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Side effects of vyvanse 40 mg: Vyvanse oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing

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Vyvanse oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing

Nausea, vomiting, constipation, stomach/abdominal pain, loss of appetite, dry mouth, headache, nervousness, dizziness, trouble sleeping, sweating, weight loss, irritability, and restlessness may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medicine because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

This medication may raise your blood pressure. Check your blood pressure regularly and tell your doctor if the results are high.

Tell your doctor right away if you have any serious side effects, including: blurred vision, fast/pounding/irregular heartbeat, mental/mood/behavior changes (such as agitation, aggression, mood swings, depression, hallucinations, abnormal thoughts/behavior, suicidal thoughts/attempts), uncontrolled movements, muscle twitching/shaking, signs of blood flow problems in the fingers or toes (such as coldness, numbness, pain, or skin color changes), unusual wounds on the fingers or toes, outbursts of words/sounds, change in sexual ability/interest, swelling ankles/feet, extreme tiredness, rapid/unexplained weight loss, frequent/prolonged erections (in males).

Get medical help right away if you have any very serious side effects, including: shortness of breath, fainting, chest/jaw/left arm pain, seizures, weakness on one side of the body, trouble speaking, confusion, sudden vision changes.

This medication may increase serotonin and rarely cause a very serious condition called serotonin syndrome/toxicity. The risk increases if you are also taking other drugs that increase serotonin, so tell your doctor or pharmacist of all the drugs you take (see Drug Interactions section). Get medical help right away if you develop some of the following symptoms: fast heartbeat, hallucinations, loss of coordination, severe dizziness, severe nausea/vomiting/diarrhea, twitching muscles, unexplained fever, unusual agitation/restlessness.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US –

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.

In Canada – Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Common and Rare Side Effects for Vyvanse oral

COMMON side effects

If experienced, these tend to have a Severe expression i

Sorry, we have no data available. Please contact your doctor or pharmacist.

If experienced, these tend to have a Less Severe expression i

  • false sense of well-being
  • difficulty sleeping
  • decreased appetite
  • nausea
  • vomiting
  • nervousness
  • irritability
  • upper abdominal pain
  • anxious feelings

INFREQUENT side effects

If experienced, these tend to have a Severe expression i

  • a hypersensitivity reaction to a drug

If experienced, these tend to have a Less Severe expression i

  • abnormal sexual function
  • altered interest in having sexual intercourse
  • feelings of hostility
  • dry mouth
  • constipation
  • urinary tract infection
  • the inability to have an erection
  • drowsiness
  • dizziness
  • low energy
  • excessive sweating
  • muscle tremors
  • taste impairment
  • weight loss
  • headache
  • heart throbbing or pounding
  • diarrhea
  • generalized weakness
  • fast heartbeat

RARE side effects

If experienced, these tend to have a Severe expression i

  • mental problems from taking the drug
  • suicidal thoughts
  • high blood pressure
  • a heart attack
  • abnormal heart rhythm
  • a stroke
  • inflammation of the liver called hepatitis
  • priapism, a prolonged erection of the penis
  • a skin disorder with blistering and peeling skin called toxic epidermal necrolysis
  • a skin disorder with blistering and peeling skin called Stevens-Johnson syndrome
  • a condition with muscle tissue breakdown called rhabdomyolysis
  • hallucinations
  • seizures
  • a significant type of allergic reaction called anaphylaxis
  • a type of allergic reaction called angioedema
  • a worsening of Tourette’s syndrome symptoms

If experienced, these tend to have a Less Severe expression i

  • manic behavior
  • grinding of the teeth
  • chronic muscle twitches or movements
  • an extreme sense of wellbeing called euphoria
  • disturbance in the ability of the eye to focus
  • double vision
  • blurred vision
  • dilated pupils
  • Raynaud’s phenomenon, a condition where blood vessels constrict too much with coldness or stress
  • hair loss
  • a type of abnormal movement disorder called dyskinesia
  • a feeling of pins and needles on skin
  • feelings of dissatisfaction, sadness, and unease
  • excessive talkativeness

What are Common Vyvanse® Side Effects? For Adult ADHD

What is the most important information I should know about VYVANSE?

VYVANSE is a federally controlled substance (Cll) because it can be abused or lead to dependence. Keep VYVANSE in a safe place to prevent misuse and abuse. Selling or giving away VYVANSE may harm others, and is against the law.

Tell your doctor if you have ever abused or been dependent on alcohol, prescription medicines or street drugs.

VYVANSE is a stimulant medicine. Some people have had the following problems when taking stimulant medicines such as VYVANSE:

1. Heart-related problems including:

  • sudden death in people who have heart problems or heart defects
  • sudden death, stroke and heart attack in adults
  • increased blood pressure and heart rate

Tell your doctor if you have any heart problems, heart defects, high blood pressure, or a family history of these problems.

Your doctor should check you carefully for heart problems before starting VYVANSE.

Your doctor should check your blood pressure and heart rate regularly during treatment with VYVANSE.

Call your doctor right away if you have any signs of heart problems such as chest pain, shortness of breath, or fainting while taking VYVANSE.

2. Mental (psychiatric) problems including:

    In Children, Teenagers, and Adults:

  • new or worse behavior and thought problems
  • new or worse bipolar illness

    In Children and Teenagers

  • new psychotic symptoms such as:
    • hearing voices
    • believing things that are not true
    • being suspicious
  • new manic symptoms

Tell your doctor about any mental problems you have, or if you have a family history of suicide, bipolar illness, or depression.

Call your doctor right away if you have any new or worsening mental symptoms or problems while taking VYVANSE, especially:

  • seeing or hearing things that are not real
  • believing things that are not real
  • being suspicious

3. Circulation problems in fingers and toes [Peripheral vasculopathy, including Raynaud’s phenomenon]:

  • Fingers or toes may feel numb, cool, painful
  • Fingers or toes may change color from pale, to blue, to red

Tell your doctor if you have numbness, pain, skin color change, or sensitivity to temperature in your fingers or toes.

Call your doctor right away if you have any signs of unexplained wounds appearing on fingers or toes while taking VYVANSE.

Dosage, side effects, alternatives, and more

Vyvanse is a brand-name prescription medication. It’s FDA-approved to treat the following conditions:*

* Vyvanse is not FDA-approved for weight loss or treatment of obesity.

Is Vyvanse a stimulant?

Yes, Vyvanse is a stimulant medication. It contains the active drug lisdexamfetamine dimesylate, which is a type of drug called an amphetamine.

Vyvanse is a controlled substance. It’s classified by the FDA as a Schedule II controlled drug.

This means it has a high potential for misuse. It also has a high risk of causing dependence (meaning your body needs the drug to function normally).

There are special rules around how Vyvanse is prescribed and dispensed. It’s important to keep it in a safe place to prevent misuse. And it’s illegal to give or sell Vyvanse to someone for whom it’s not prescribed.

Drug details

Vyvanse comes in the following forms that are taken by mouth:

  • chewable tablet, which is available in strengths of 10 milligrams (mg), 20 mg, 30 mg, 40 mg, 50 mg, and 60 mg
  • capsule, which is available in strengths of 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, and 70 mg

Vyvanse is taken once per day.

Effectiveness

For information about the effectiveness of Vyvanse, see the “Vyvanse uses” section below.

Vyvanse is available only as a brand-name medication. It’s not currently available in generic form.

A generic drug is an exact copy of the active drug in a brand-name medication. Generics usually cost less than brand-name drugs.

Vyvanse contains the active drug lisdexamfetamine dimesylate.

The Vyvanse dosage your doctor prescribes will depend on several factors. These include:

  • the type and severity of the condition you’re using Vyvanse to treat
  • other medical conditions you may have
  • how well your kidneys work
  • other medications you may take

Typically, your doctor will start you on a low dosage. Then they’ll adjust it over time to reach the amount that’s right for you. Your doctor will ultimately prescribe the smallest dosage that provides the desired effect.

The following information describes dosages that are commonly used or recommended. However, be sure to take the dosage your doctor prescribes for you. Your doctor will determine the best dosage to fit your needs.

Drug forms and strengths

Vyvanse comes in the following forms that are taken by mouth:

  • chewable tablet, available in strengths of 10 milligrams (mg), 20 mg, 30, mg, 40 mg, 50, mg, and 60 mg
  • capsule, available in strengths of 10 mg, 20 mg, 30, mg, 40 mg, 50, mg, 60 mg, and 70 mg

Dosage for binge eating disorder (BED)

For adults, the typical starting dosage for binge eating disorder (BED) is 30 mg taken once every morning.

Your doctor may increase your dose by 20 mg each week until you reach the dose that’s right for you. The recommended dosage range for BED is 50 mg to 70 mg taken once every morning. The maximum recommended dosage is 70 mg taken once every morning.

Dosage for attention deficit hyperactivity disorder (ADHD)

For adults and for children ages 6 years and older, the typical starting dosage for attention deficit hyperactivity disorder (ADHD) is 30 mg taken once every morning.

Your doctor may increase your dose by 10 mg to 20 mg each week until you reach the dose that’s right for you. The maximum recommended dosage is 70 mg taken once every morning.

Children’s dosage

Vyvanse is approved to treat ADHD in children ages 6 years and older. The recommended dosage is the same as for adults. To learn more, see the section directly above.

Vyvanse is not approved to treat binge eating disorder in children.

Dosage questions

Below are answers to some common questions you may have about taking Vyvanse.

What are the signs of having a Vyvanse dose that’s too high?

If your Vyvanse dose is too high, it may increase your risk for side effects. See the “Vyvanse side effects” section below to learn more about possible side effects of the drug.

A dose that’s too high could also cause symptoms of an overdose. To read more about the symptoms of an overdose, see the “Vyvanse overdose” section below.

If you think your Vyvanse dose is too high, talk with your doctor. They may need to lower your dosage.

What if I miss a dose?

If you miss a dose of Vyvanse in the morning, skip that dose and follow your usual schedule. Avoid taking a dose of Vyvanse in the afternoon. Doing so may cause trouble getting to sleep at night. Don’t try to make up for a missed dose by taking a double dose the next morning. Doing so can cause serious side effects, such as a fast or irregular heartbeat or increased blood pressure.

To help make sure that you don’t miss a dose, try using a medication reminder. This can include setting an alarm on your phone or downloading a reminder app. A kitchen timer can work, too.

Will I need to use this drug long term?

You might need to. Your doctor will have you taper off Vyvanse from time to time to see if your symptoms return. This is sometimes called a treatment holiday. If your symptoms come back or worsen, you may need to keep taking Vyvanse. You should always follow your doctor’s instructions for taking this drug.

Vyvanse can cause mild or serious side effects. The following lists contain some of the key side effects that may occur while taking Vyvanse. These lists do not include all possible side effects.

For more information about the possible side effects of Vyvanse, talk with your doctor or pharmacist. They can give you tips on how to deal with any side effects that may be bothersome.

Note: The Food and Drug Administration (FDA) tracks side effects of drugs it has approved. If you would like to notify the FDA about a side effect you’ve had with Vyvanse, you can do so through MedWatch.

Mild side effects

Mild side effects* of Vyvanse can include:

Most of these side effects may go away within a few days or a couple of weeks. But if they become more severe or don’t go away, talk with your doctor or pharmacist.

* This is a partial list of mild side effects from Vyvanse. To learn about other mild side effects, talk with your doctor or pharmacist, or view Vyvanse’s Medication Guide.
† For more information about this side effect, see “Side effect details” below.

Serious side effects

Serious side effects from Vyvanse aren’t common, but they can occur. Call your doctor right away if you have serious side effects. Call 911 or your local emergency number if your symptoms feel life threatening or if you think you’re having a medical emergency.

Serious side effects and their symptoms can include:

  • Cardiovascular (heart and blood vessel) problems. Examples include fast heartbeat, increased blood pressure, or in rare cases, heart attack, stroke, or sudden cardiac death (heart suddenly stops beating). Symptoms can include:
    • severe pain, pressure, or tightness in your chest, arm, throat, neck, or jaw
    • drooping on one side of the face
    • sudden weakness or numbness in one arm
    • slurred speech or trouble speaking
  • Problems with blood circulation in your fingers and toes, such as Raynaud’s syndrome. Symptoms can include:
    • pale, blue, purple, or red fingers or toes
    • cold, numb, or painful fingers or toes
    • unexplained wounds on your fingers or toes
  • Mental health conditions, such as psychosis or mania.*
  • Serotonin syndrome (a dangerous condition caused by a buildup of serotonin in your body). Symptoms can include:
    • flushing (warmth, swelling, or redness in your skin)
  • Allergic reaction.*
  • Potential for misuse and dependence.*†
  • Slowed growth in children.‡

* For more information about this side effect, see “Side effect details” below.
† Vyvanse has a boxed warning from the FDA regarding this side effect. A boxed warning is the strongest warning the FDA requires. It alerts doctors and patients about drug effects that may be dangerous.
‡ For more information about this side effect, see “Side effects in children” below.

Side effects in children

Vyvanse is used to treat ADHD in children ages 6 years and older. In clinical studies, most side effects of Vyvanse seen in children were similar to those seen in adults taking the drug. These are listed above and described in the “Side effect details” section below.

However, certain side effects may be more common in children taking this drug than in adults. These side effects are described below.

Weight loss in children

Children who take Vyvanse are more likely to have a decrease in appetite than adults who take this drug. They are also more likely to have weight loss than adults. Over time, this can lead to slowed growth in children.

In children ages 6 to 12 years who took Vyvanse every day for a year in clinical studies, weight loss led to slowed growth. This was assessed using growth charts that compare average body weight in children of the same sex and age. Before treatment, children in the study were, on average, in the 70th percentile for body weight. After taking Vyvanse for 1 year, these children were, on average, in the 47th percentile for body weight.

Children who take Vyvanse should have their height and weight regularly checked by their doctor. If your child’s growth is affected by this drug, their doctor may suggest taking a break from treatment. This will allow your child’s growth to catch up. To learn more about weight loss associated with Vyvanse, see “Weight loss” under “Side effect details” below.

Effects on personality in children

Vyvanse can sometimes cause irritability, anger, or mood changes in children. In clinical studies of children ages 6 to 12 years with ADHD:

  • 10% of children who took Vyvanse experienced irritability
  • 3% of children who took Vyvanse had mood changes

Neither of these side effects occurred in children taking a placebo in the studies. It’s not known how often irritability or mood changes occur in older children taking Vyvanse.

If your child seems irritable or angry, or has mood changes or emotional breakdowns (intense emotional distress) while taking Vyvanse, talk with their doctor. They can help you find ways to manage their symptoms, or they may suggest switching your child to a different drug.

Side effect details

You may wonder how often certain side effects occur with this drug. Here’s some detail on certain side effects this drug may cause.

Allergic reaction

As with most drugs, some people can have an allergic reaction after taking Vyvanse. However, it’s not known how often this may have occurred in clinical studies. Symptoms of a mild allergic reaction can include:

A more severe allergic reaction is rare but possible. Symptoms of a severe allergic reaction can include:

  • swelling under your skin, typically in your eyelids, lips, hands, or feet
  • swelling of your tongue, mouth, or throat
  • trouble breathing

Call your doctor right away if you have an allergic reaction to Vyvanse, as the reaction could become severe. Call 911 or your local emergency number if your symptoms feel life threatening or if you think you’re having a medical emergency.

Weight loss

Vyvanse may cause a decreased appetite or loss of appetite. For some people, this can lead to weight loss over time.

In clinical studies of ADHD, weight loss occurred in:

  • 3% to 4% of adults who took Vyvanse
  • 9% of children who took Vyvanse
  • 0% to 1% of adults and children who took a placebo (treatment containing no active drug)

After 4 weeks of treatment, the average weight loss in people who took Vyvanse was:

  • 2.8 pounds (lb) to 4.3 lb (1.3 kilograms [kg] to 2 kg) in adults
  • 2.7 lb to 4.8 lb (1.2 kg to 2.2 kg) in children ages 13 to 17 years
  • 0.9 lb to 2.5 lb (0.4 kg to 1.1 kg) in children ages 6 to 12 years

The amount of weight lost depended on dose, with more weight loss seen in people who took higher doses of Vyvanse.

In comparison, people who took a placebo in these studies tended to gain weight. After 4 weeks of treatment, the average weight gain was:

  • 0.5 lb (0. 2 kg) in adults
  • 2 lb (0.9 kg) in children ages 13 to 17 years
  • 1 lb (0.4 kg) in children ages 6 to 12 years

To learn about weight loss in adults who took Vyvanse for binge eating disorder, see the drug’s prescribing information.

If you’re concerned about weight loss with Vyvanse, talk with your doctor. For more information about weight loss in children, see the “Side effects in children” section above.

Note: Although Vyvanse can cause weight loss, it shouldn’t be taken specifically for weight loss or to treat obesity. It’s not FDA-approved or recommended for this use because of the risk of serious side effects.

Effects on personality

Vyvanse can sometimes have a temporary effect on personality, causing changes in a person’s thoughts or behavior. For instance, Vyvanse can sometimes cause irritability, anger, or mood changes, particularly in children. (See the “Side effects in children” section above to learn more about this side effect in children. )

In rare instances, stimulants such as Vyvanse can cause or worsen serious mental health conditions. These include psychosis or mania in children and adults.

In clinical studies involving different types of stimulants:

  • 0.1% of people who took stimulants had psychotic or manic symptoms
  • 0% of people who took a placebo (a treatment containing no active drug) had psychotic or manic symptoms

Symptoms of psychosis can include hallucinations, paranoia, and delusions (believing things that aren’t true). Symptoms of mania can include severe insomnia (trouble sleeping), racing thoughts, impulsive or reckless behavior, and extreme levels of happiness, excitement, or activity.

If you or your child have any of these symptoms or other changes in thoughts or behavior while taking Vyvanse, talk with your doctor right away. They may recommend stopping Vyvanse.

Suicide prevention

If you know someone at immediate risk of self-harm, suicide, or hurting another person:

  • Ask the tough question: “Are you considering suicide?”
  • Listen to the person without judgment.
  • Call 911 or the local emergency number, or text TALK to 741741 to communicate with a trained crisis counselor.
  • Stay with the person until professional help arrives.
  • Try to remove any weapons, medications, or other potentially harmful objects.

If you or someone you know is having thoughts of suicide, a prevention hotline can help. The National Suicide Prevention Lifeline is available 24 hours per day at 800-273-8255. During a crisis, people who are hard of hearing can call 800-799-4889.

Click here for more links and local resources.

Crashing

A Vyvanse crash refers to side effects that can happen when the effects of Vyvanse start to wear off. These are also known as withdrawal symptoms. They may include:

It’s not known how often crashing may occur in people who take Vyvanse. Some people who take Vyvanse in the morning may have these symptoms toward the end of the day. However, Vyvanse is a long-acting stimulant that lasts all day to treat symptoms. It’s less likely to cause a crash than short-acting stimulants that wear off after a few hours.

If you find the effects of Vyvanse wear off too soon or you have symptoms of crashing, talk with your doctor. They may suggest ways to manage this, or they may recommend a different treatment.

Headache

Vyvanse may cause headaches in some people who take this drug. Headaches are common side effects of stimulant drugs such as Vyvanse.

In clinical studies, 1% of adults who took Vyvanse stopped treatment because of headaches. It’s not known how often headaches may have occurred in children or adults who took a placebo in these studies.

If you have bothersome headaches while taking Vyvanse, talk with your doctor about ways to manage them. You can typically take acetaminophen (Tylenol) to treat a headache while taking Vyvanse.

Anxiety

Some people may have anxiety while taking Vyvanse. In clinical studies, anxiety was reported in:

  • 5% to 6% of adults who took Vyvanse, depending on the condition being treated
  • 0% to 1% of adults who took a placebo (a treatment containing no active drug)

It’s not known how often anxiety may have occurred in children who took Vyvanse in clinical studies.

If you have anxiety while taking Vyvanse, talk with your doctor. They can suggest ways to help manage this side effect.

Misuse

Vyvanse is a stimulant medication that has a high risk of drug misuse.* Drug misuse is taking a drug for a nonmedical use, or in a way that’s not approved. This is typically done to produce a “high.” Drug misuse typically involves using higher doses of a drug than are prescribed for medical uses.

Vyvanse use also has a high risk of physical and psychological dependence, meaning you need the drug to function normally. As a result, people may try to get Vyvanse illegally.

Vyvanse may have a lower risk of misuse than some other stimulant drugs. This is because it doesn’t work until it’s been activated in your body. Vyvanse doesn’t have a fast or intense effect, unlike some other stimulants.

However, you should keep Vyvanse in a safe place, such as a locked cabinet, to help prevent other people from misusing this drug. It’s illegal to give or sell Vyvanse to someone who doesn’t have a prescription for it. Misuse of Vyvanse can cause serious side effects, including heart problems and, in some cases, death.

It’s not known how often misuse or dependence may occur in people who take Vyvanse as prescribed for ADHD or binge eating disorder.

You should Vyvanse exactly as your doctor prescribes it. Don’t take a higher dose, take it more often, or take it for longer than prescribed. If you’ve ever misused or been dependent on alcohol, prescription drugs, or illegal drugs, tell your doctor before taking Vyvanse.

* Vyvanse has a boxed warning for this side effect. A boxed warning is the strongest warning the FDA requires. It alerts doctors and patients about drug effects that may be dangerous.

Other drugs are available that can treat your condition. Some may be a better fit for you than others. If you’re interested in finding an alternative to Vyvanse, talk with your doctor. They can tell you about other medications that may work well for you.

Note: Some of the drugs listed below are used off-label to treat these specific conditions. Off-label drug use means using a drug for a purpose other than what it’s been approved for by the FDA.

Alternatives for binge eating disorder (BED)

Examples of other drugs that may be used to treat binge eating disorder (BED) include:

Alternatives for attention deficit hyperactivity disorder (ADHD)

Examples of other drugs that may be used to treat attention deficit hyperactivity disorder (ADHD) include:

  • stimulant medications, such as:
  • non-stimulant medications, such as:

You may wonder how Vyvanse compares with other medications that are prescribed for similar uses. Here we look at how Vyvanse and Adderall are alike and different.

Ingredients

Vyvanse contains lisdexamfetamine, which is an inactive prodrug. A prodrug is a medication that is inactive until it’s chemically altered by your body. Lisdexamfetamine is inactive until your blood cells change it into the active drug dextroamphetamine.

Adderall contains a mixture of different forms of amphetamine and dextroamphetamine. These forms are amphetamine aspartate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate.

Vyvanse and Adderall are both stimulant medications.

Uses

Here is a list of conditions that the Food and Drug Administration (FDA) has approved Vyvanse and Adderall to treat.

  • Both Vyvanse and Adderall are FDA-approved to treat:
  • Vyvanse is also FDA-approved to treat:
  • Adderall is also FDA-approved to treat:

* For this use, Vyvanse is approved for people ages 6 years and older. Adderall is approved for people ages 3 years and older, and Adderall XR is for people ages 6 years and older.

Drug forms and administration

Vyvanse is a long-acting drug. It comes in the following forms, which are taken once per day in the morning:

Adderall comes in the following forms:

  • Adderall immediate-release tablet (this is a short-acting form that’s taken one to three times per day)
  • Adderall XR extended-release capsule (this is a long-acting form that’s taken once per day in the morning)

Side effects and risks

Vyvanse and Adderall both contain a stimulant drug. Therefore, these medications can cause very similar side effects, but some different ones as well. Below are examples of these side effects.

Mild side effects

These lists contain up to 10 of the most common mild side effects that can occur with either Vyvanse or Adderall, as well as mild side effects that both drugs may share.

  • Can occur with Vyvanse:
    • few unique mild side effects
  • Can occur with Adderall:
    • few unique mild side effects
  • Can occur with both Vyvanse and Adderall:
Serious side effects

This list contains examples of serious side effects that can occur with both Vyvanse and Adderall, as well as serious side effects that both drugs may share.

  • Can occur with both Vyvanse and Adderall:
    • slowed growth in children
    • potential for misuse and dependence*

* Both Vyvanse and Adderall have a boxed warning for this side effect. A boxed warning is the strongest warning the FDA requires. It alerts doctors and patients about drug effects that may be dangerous.

Effectiveness

The only condition both Vyvanse and Adderall are used to treat is ADHD.

These drugs haven’t been directly compared in clinical studies. However, studies have found both Vyvanse and Adderall to be effective for treating ADHD.

Vyvanse and Adderall are both stimulants. This type of medication is among the choice of drugs that doctors prescribe for ADHD. The choice of which stimulant is most suitable may vary from person to person. It typically depends on factors such as how the drug is taken and how long its effects last.

Costs

According to estimates on GoodRx.com, Vyvanse generally costs significantly more than Adderall. The actual price you’ll pay for either drug depends on your insurance plan, your location, and the pharmacy you use.

Vyvanse and Adderall are both brand-name drugs. Vyvanse isn’t currently available in generic form. Generic forms of Adderall are available. Brand-name medications usually cost more than generics.

As with Adderall (above), you may wonder how Vyvanse compares with other medications that are prescribed for similar uses. Here’s a look at how Vyvanse and Concerta are alike and different.

Ingredients

Vyvanse contains lisdexamfetamine, which is an inactive prodrug. (A prodrug is a medication that is inactive until it’s chemically altered by your body.) Your body metabolizes, or breaks down, lisdexamfetamine into the active drug dextroamphetamine after Vyvanse is absorbed into your bloodstream.

Concerta contains the active drug methylphenidate.

Vyvanse and Concerta are both stimulant medications.

Uses

Here is a list of conditions that the Food and Drug Administration (FDA) has approved Vyvanse and Concerta to treat.

  • Both Vyvanse and Concerta are FDA-approved to treat:
  • Vyvanse is also FDA-approved to treat:

Drug forms and administration

Vyvanse and Concerta are both long-acting drugs that are taken once per day in the morning.

Vyvanse comes as a chewable tablet and a capsule. People who have trouble swallowing can open the capsule and mix the powder inside with yogurt, water, or orange juice.

Concerta comes as an extended-release tablet. This must be swallowed whole.

Side effects and risks

Vyvanse and Concerta both contain a stimulant drug. Therefore, these medications can cause very similar side effects, but some different ones as well. Below are examples of these side effects.

Mild side effects

These lists contain up to 10 of the most common mild side effects that can occur with either Vyvanse or Concerta, as well as mild side effects that both drugs may share.

  • Can occur with Vyvanse:
    • few unique mild side effects
  • Can occur with Concerta:
    • few unique mild side effects
  • Can occur with both Vyvanse and Concerta:
Serious side effects

These lists contain examples of serious side effects that can occur with either Vyvanse or Concerta, as well as serious side effects that both drugs may share.

  • Can occur with Vyvanse:
    • few unique serious side effects
  • Can occur with Concerta:
    • priapism (painful and prolonged erection)
  • Can occur with both Vyvanse and Concerta:
    • slowed growth in children
    • potential for misuse and dependence*

* Both Vyvanse and Concerta have a boxed warning for this side effect. A boxed warning is the strongest warning the FDA requires. It alerts doctors and patients about drug effects that may be dangerous.

Effectiveness

The only condition both Vyvanse and Concerta are used to treat is ADHD.

These drugs haven’t been directly compared in clinical studies. However, studies have found both Vyvanse and Concerta to be effective for treating ADHD.

Vyvanse and Concerta are both stimulants. This type of medication is among the first choice of drugs that doctors prescribe for ADHD. The choice of which stimulant is most suitable may vary from person to person. It typically depends on factors such as how the drug is taken and how long its effects last.

Costs

According to estimates on GoodRx.com, Vyvanse generally costs less than Concerta. The actual price you’ll pay for either drug depends on your insurance plan, your location, and the pharmacy you use.

Vyvanse and Concerta are both brand-name drugs. Vyvanse isn’t currently available in generic form. Generic forms of Concerta are available. Brand-name medications usually cost more than generics.

Vyvanse is used to treat attention deficit hyperactivity disorder (ADHD). It’s also used for binge eating disorder (BED).

With both ADHD and BED, there seem to be changes in brain chemistry that may lead to the symptoms of these conditions.

What Vyvanse does

Vyvanse is a type of drug called a stimulant. Stimulants increase activity in your brain and other body systems. They make you more alert and focused.

It’s not fully understood how Vyvanse works in ADHD or BED. However, the drug is known to increase the levels of neurotransmitters called dopamine and norepinephrine in your brain.

Neurotransmitters are natural body chemicals that help your nerve cells communicate. Dopamine and norepinephrine are released in various nerve pathways in your brain. These include those associated with thinking, emotions, behavior, appetite, and self-control.

Vyvanse increases the amount of dopamine and norepinephrine released in your brain. In ADHD and BED, this may improve communication between nerve cells in areas of the brain that may be underactive. And this may improve symptoms of these conditions.

With ADHD, Vyvanse can improve your ability to focus, concentrate, and think. And this in turn can reduce hyperactivity and impulsive behavior.

With BED, Vyvanse can reduce obsessive and compulsive thoughts about binge eating, as well as appetite itself. And it can reduce the number of binge eating episodes you have.

How long does it take Vyvanse to work?

For ADHD, Vyvanse starts working to improve focus, attention, and behavior about 1 hour after taking a dose. For BED, you may notice the effects of Vyvanse about 1 hour after taking a dose. But you’ll likely need to take it for a few weeks before the drug starts to improve your condition.

Vyvanse contains lisdexamfetamine, which is a prodrug. (A prodrug is a medication that isn’t active until it’s chemically altered by your body.) Lisdexamfetamine is inactive until your blood cells change it into the active drug dextroamphetamine.

How long does Vyvanse last in your system?

It typically takes about 2 to 3 days before Vyvanse is fully cleared from your system. However, this may vary depending on your age, weight, genetics, kidney function, or other medications you may be taking.

The effects of Vyvanse typically last for about 10 to 12 hours after you take a dose. After the effects of Vyvanse have worn off, the levels of Vyvanse in your body continue to decrease.

Vyvanse has a half-life of about 12 hours. A drug’s half-life is the amount of time it takes for your body to remove half a dose of medication from your system. After you take a dose of Vyvanse, it takes about 12 hours for the amount of active drug in your body to decrease by half.

How long does it take for Vyvanse to peak in your system?

After you take a dose of Vyvanse, the level of the active drug in your blood gradually increases until it reaches a peak. At this peak blood level, you get the maximum effect of the dose.

The peak blood level of Vyvanse is reached about 3.5 hours after taking the Vyvanse capsule on an empty stomach. The peak level is reached about 4.4 hours after taking the Vyvanse chewable tablet on an empty stomach.

If you take Vyvanse with food, it takes about an hour longer to reach peak levels in your blood.

How long does Vyvanse stay in your urine?

Vyvanse is mainly removed from your body through your urine. The drug can be detected in your urine for about 2 to 3 days after you stop taking it.

The Food and Drug Administration (FDA) approves prescription drugs such as Vyvanse to treat certain conditions. Vyvanse may also be used off-label for other conditions. Off-label drug use means using a drug for a purpose other than what it’s been approved for by the FDA.

Vyvanse for binge eating disorder (BED)

Vyvanse is FDA-approved to treat moderate to severe binge eating disorder (BED) in adults. BED is an eating disorder that involves repeated episodes of extreme overeating. It often occurs alongside other mental health conditions, such as anxiety or depression.

With BED, episodes of overeating tend to occur in response to emotional or mental health issues. Symptoms of BED may include:

  • eating excessive amounts of food in a short time
  • eating when you’re not hungry
  • binge eating in secret
  • feeling unable to stop eating during a binge
  • feeling guilty or ashamed about your eating

People with BED don’t try to reverse episodes of overeating by vomiting, using laxatives, fasting, or exercising.

BED is considered moderate if you have four to seven episodes of binge eating per week. It’s considered severe if you have 8 to 13 episodes per week.

Vyvanse is a stimulant medication. It can help reduce the number of binge eating episodes you have. It’s typically used alongside psychotherapy. Psychotherapy can help you understand and control the thoughts, feelings, or behaviors that trigger your episodes of overeating.

Note: Vyvanse reduces appetite and can cause weight loss. However, it’s not FDA-approved or recommended for weight loss or to treat obesity. To learn more about weight loss associated with Vyvanse, see the “Vyvanse side effects” section above.

Effectiveness for binge eating disorder (BED)

Clinical studies found Vyvanse to be effective for reducing binge eating episodes in adults with moderate to severe binge eating disorder (BED).

In these studies, people took Vyvanse or a placebo (a treatment containing no active drug) for 12 weeks. The following results were seen after 12 weeks of treatment as compared with before treatment:

  • people who took Vyvanse had, on average, 3.87 to 3.92 fewer binge days* per week
  • people who took a placebo had, on average, 2.26 to 2.51 fewer binge days per week

In another study, adults took Vyvanse for 12 weeks. Those who responded to Vyvanse (people with 1 or fewer binge days per week for 4 weeks in a row) were then split into two groups.

One group kept taking Vyvanse for another 26 weeks. The other group switched to a placebo for 26 weeks. After this time, researchers assessed how many people’s BED had relapsed (gotten worse or returned). A relapse was defined as having 2 or more binge days each week for 2 weeks in a row. Those who took Vyvanse were much less likely to relapse than those who took a placebo.

* A binge day is a day with at least one episode of binge eating.

Vyvanse for attention deficit hyperactivity disorder (ADHD)

Vyvanse is FDA-approved to treat ADHD in adults and in children ages 6 years and older.

Vyvanse is a stimulant medication for ADHD. It helps people with ADHD focus, concentrate, and control their behavior. It’s typically used alongside behavioral therapy for this condition.

About ADHD

ADHD is one of the most common mental health conditions that affect children. But it can also last into adulthood. In fact, ADHD isn’t diagnosed until adulthood in some people.

Symptoms of ADHD can include:

  • Hyperactivity. People who are hyperactive find it hard to be still and calm. They may fidget, move around, or talk excessively.
  • Impulsivity. People who are impulsive act without thinking first. They may do inappropriate, or sometimes dangerous, things without thinking about the consequences.
  • Inattention. People with inattention have trouble concentrating and paying attention. These problems can cause them to lose focus quickly, be easily distracted, or make careless mistakes.

Because of these symptoms, people with ADHD may have trouble making friends or forming relationships. And they may struggle at school, at work, or in social situations.

Effectiveness for ADHD

Multiple clinical studies have found Vyvanse to be effective for treating ADHD.

For example, studies have compared Vyvanse with a placebo (a treatment containing no active drug) in different age groups. Researchers measured the effect of treatment using a scale called the ADHD Rating Scale (ADHD-RS). This scale has a minimum score of 0 and a maximum score of 54. Higher scores mean more severe ADHD symptoms.

In 4-week clinical studies, the average ADHD-RS score was reduced by:

  • 18.3 to 26.7 in children ages 6 to 17 who took Vyvanse, depending on their dose
  • 16.2 to 18.6 in adults who took Vyvanse, depending on their dose
  • 6.2 to 12.8 in children ages 6 to 17 who took a placebo
  • 8.2 in adults who took a placebo

Vyvanse was also effective in longer studies in adults and children. To learn more, see Vyvanse’s prescribing information.

Vyvanse and children

Vyvanse is used to treat ADHD in children ages 6 years and older. It’s not prescribed for any other uses in children. See the section directly above to learn about the drug’s effectiveness for treating ADHD in children.

Here are answers to some frequently asked questions about Vyvanse.

How can you intensify Vyvanse in your body?

Vyvanse doesn’t have a fast or intense effect, unlike some other stimulants. Since Vyvanse is a prodrug, it doesn’t work until it’s been metabolized in your body, which doesn’t happen right away.

You shouldn’t try to intensify the effect of Vyvanse in your body. Misuse of Vyvanse can have serious side effects, including heart problems and, in some cases, death. For more information, see “Serious side effects” in the “Vyvanse side effects” section above.

Can you take Vyvanse by snorting it?

No, you shouldn’t take Vyvanse by snorting it. This is not an approved way to take Vyvanse.

Some people who misuse Vyvanse may take it by snorting it. Misuse of Vyvanse can lead to serious side effects, including heart problems and, in some cases, death. For more information, see “Serious side effects” in the “Vyvanse side effects” section above.

Are side effects of Vyvanse different in females than they are in males?

No, side effects of Vyvanse are typically the same in both females and males.*

The only side effects specific to females are related to using the drug during pregnancy or while breastfeeding. Vyvanse can have harmful effects if used when pregnant or breastfeeding. To learn more, see the “Vyvanse and pregnancy” and “Vyvanse and breastfeeding” sections below.

* Use of the terms “female” or “male” within this article refers to a person’s sex assigned at birth.

Is Vyvanse used for depression?

Yes. Vyvanse may sometimes be used to treat depression. Several studies have looked at the use of stimulants such as Vyvanse for people with depression. In particular, stimulants have been studied as an add-on treatment for treatment-resistant depression. (This is depression that hasn’t improved with antidepressant medications.)

The research has shown conflicting results. Some studies have suggested Vyvanse may be helpful, while others found no benefit. One review of studies found that Vyvanse may ease symptoms of depression. But it also confirmed that more research is needed.

Doctors might prescribe Vyvanse off-label for treatment-resistant depression. Off-label drug use means using a drug for a purpose other than what it’s been approved for by the FDA.

If you’re interested in taking Vyvanse for depression, talk with your doctor.

Will Vyvanse make me feel ‘high’?

No. When taken at approved doses to treat attention deficit hyperactivity disorder or binge eating disorder, Vyvanse doesn’t usually cause a feeling of being “high.”

However, some people who misuse stimulants such as Vyvanse may have feelings of increased energy, excitement, self-confidence, or euphoria (an exaggerated feeling of well-being).

Drug misuse* involves taking a drug for nonmedical purposes, or in a way that’s not approved. It typically involves using higher doses of a drug than doctors prescribe. Misuse of Vyvanse can cause serious side effects, including heart problems and, in some cases, death. For more information, see “Serious side effects” in the “Vyvanse side effects” section above.

* Vyvanse has a boxed warning for misuse and dependence. A boxed warning is the strongest warning the FDA requires. It alerts doctors and patients about drug effects that may be dangerous.

Is Vyvanse a narcotic?

No, Vyvanse isn’t a narcotic. Vyvanse is a prescription stimulant medication.

Some people refer to all illegal drugs or drugs that are misused as narcotics. But according to the Drug Enforcement Administration (DEA), the term “narcotic” refers to opioid or opiate drugs. These are drugs made from the opium poppy. They include illegal drugs, such as heroin, and strong prescription pain relievers, such as morphine (Kadian, MS Contin) and oxycodone (Oxycontin, Percocet).

Can I drive while I’m taking Vyvanse?

Yes, you can likely drive while taking Vyvanse. However, some people may have certain side effects that could make it unsafe to drive. These may include dizziness and feeling jittery or anxious. Make sure you know how Vyvanse affects you before driving. And drive only if you feel it’s safe to do so.

How will my doctor monitor my health during Vyvanse treatment?

Your doctor will do various checks to monitor your health while you take Vyvanse.

Vyvanse can sometimes cause a fast heartbeat or increase your blood pressure. Your doctor will check your blood pressure and heart rate regularly while you take Vyvanse. Call your doctor right away if you have signs of a heart problem while taking Vyvanse. These may include new or worsening chest pain, fainting, or a feeling like your heart is pounding, racing, or skipping a beat.

Vyvanse can also reduce your appetite, which can lead to weight loss over time. Children taking Vyvanse should have their weight and height checked regularly by their doctor during treatment.

Vyvanse can have other side effects, including mental health conditions and circulation problems. Your doctor may ask you about possible symptoms of these at each appointment. See the “Vyvanse side effects” section above to learn about other possible side effects you may need to discuss with your doctor.

Taking Vyvanse can lead to drug dependence. It’s possible to become both psychologically and physically dependent on this drug. With psychological dependence, you feel unable to stop using a drug. With physical dependence, your body needs the drug to function normally. And you may have withdrawal symptoms if you suddenly stop taking it.

Drug dependence can make it hard to stop taking Vyvanse. And it can sometimes cause people to try to get Vyvanse illegally.

Drug dependence is more likely to occur with misuse* of Vyvanse. Misuse involves taking a drug for nonmedical purposes, or taking it in a way that’s not approved. And it typically involves using higher doses of a drug than doctors prescribe. Misuse of Vyvanse can cause serious side effects, including heart problems and, in some cases, death.

You can also develop a tolerance to Vyvanse. This can lead to a desire for larger or more frequent doses.

* Vyvanse has a boxed warning for misuse and dependence. A boxed warning is the strongest warning the FDA requires. It alerts doctors and patients about drug effects that may be dangerous.

Withdrawal symptoms

If you’ve been taking high doses of Vyvanse for a long time, you may have withdrawal symptoms if you suddenly stop taking the drug. This is sometimes called a Vyvanse crash.

Withdrawal symptoms may include:

If you want to stop taking Vyvanse, talk with your doctor about the best way to do this. They may recommend that you slowly stop taking the medication to help avoid withdrawal symptoms.

You should avoid drinking alcohol while you’re taking Vyvanse. Vyvanse can mask the effects of alcohol in your body. This can make it hard for you to know how much you’ve had to drink.

If you have certain side effects with Vyvanse, such as nausea, dizziness, or diarrhea, drinking alcohol could make them worse.

If you’ve ever misused or been dependent on alcohol, you could be more likely to misuse* or become dependent on Vyvanse. Talk with your doctor about whether Vyvanse is right for you.

If you have questions about drinking alcohol while taking Vyvanse, talk with your doctor or pharmacist.

* Vyvanse has a boxed warning for misuse and dependence. A boxed warning is the strongest warning the FDA requires. It alerts doctors and patients about drug effects that may be dangerous.

Vyvanse can interact with several other medications. It can also interact with certain supplements and certain foods.

Different interactions can cause different effects. For instance, some interactions can interfere with how well a drug works. Other interactions can increase side effects or make them more severe.

Vyvanse and other medications

Below is a list of medications that can interact with Vyvanse. This list doesn’t contain all drugs that may interact with Vyvanse.

Before taking Vyvanse, talk with your doctor and pharmacist. Tell them about all prescription, over-the-counter, and other drugs you take. Also tell them about any vitamins, herbs, and supplements you use. Sharing this information can help you avoid potential interactions.

If you have questions about drug interactions that may affect you, ask your doctor or pharmacist.

Vyvanse and MAOIs

You shouldn’t take Vyvanse with drugs called monoamine oxidase inhibitors (MAOIs). Taking Vyvanse with MAOIs can cause a dangerous increase in blood pressure.

Both Vyvanse and MAOIs can also increase your serotonin levels. Taking these drugs together can raise your risk for a serious side effect called serotonin syndrome. To learn more, see the “Vyvanse and drugs that increase serotonin levels” section below.

MAOI drugs you shouldn’t take with Vyvanse include:

  • the antibiotic linezolid (Zyvox)
  • a blood disorder treatment called methylene blue (ProvayBlue)
  • MAOI antidepressants, such as:
    • tranylcypromine (Parnate)

Do not take Vyvanse if you’ve taken an MAOI drug in the last 14 days. If you currently take or have recently taken any of these drugs, talk with your doctor about different treatment options.

Vyvanse and drugs that increase serotonin levels

Vyvanse may interact with drugs that increase the level of serotonin in your body. Serotonin is a chemical in your body that affects mood, digestion, and sleep.

Vyvanse raises the level of serotonin in your body. If you take Vyvanse with other drugs that also have this effect, your serotonin level can rise even higher. This can raise your risk for a serious side effect called serotonin syndrome. This is a dangerous condition caused by a buildup of serotonin in your body.

Examples of drugs that can raise the risk of serotonin syndrome if taken with Vyvanse include:

  • selective serotonin reuptake inhibitor (SSRI) antidepressants, such as:
  • serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressants, such as:
  • lithium (Lithobid), a drug for bipolar disorder and depression
  • buspirone, a drug for anxiety
  • triptan medications for migraine, such as:
  • certain pain medications, such as:
    • fentanyl (Duragesic, Subsys, Actiq, others)
  • other amphetamine drugs, such as:
    • amphetamine (Evekeo, Adzenys, Dynavel)
  • monoamine oxidase inhibitors (MAOIs), such as:

If you take any of these drugs, talk with your doctor before taking Vyvanse. They may prescribe a lower dose of Vyvanse.

Vyvanse and Lexapro

Lexapro is an SSRI antidepressant that contains the active drug escitalopram. Both Vyvanse and Lexapro can increase your serotonin levels. Taking these drugs together can raise your risk for a serious side effect called serotonin syndrome. To learn more, see the “Vyvanse and drugs that increase serotonin levels” section above.

If you take Lexapro, talk with your doctor before taking Vyvanse. They may prescribe a lower dose of Vyvanse.

Vyvanse and Prozac

Prozac is an SSRI antidepressant that contains the active drug fluoxetine. Taking Vyvanse with Prozac can cause Vyvanse to build up in your body. This can raise your risk for Vyvanse side effects.

Both Vyvanse and Prozac can also increase your serotonin levels. Taking these drugs together can raise your risk for a serious side effect called serotonin syndrome. To learn more, see the “Vyvanse and drugs that increase serotonin levels” section above.

If you take Prozac, talk with your doctor before taking Vyvanse. They may prescribe a lower dose of Vyvanse.

Vyvanse and Wellbutrin

Wellbutrin is an antidepressant that contains the active drug bupropion. Taking Vyvanse with Wellbutrin can cause Vyvanse to build up in your body. This can raise your risk for Vyvanse side effects.

If you take Wellbutrin, talk with your doctor before taking Vyvanse. They may prescribe a lower dose of Vyvanse.

Vyvanse and drugs that inhibit CYP2D6

Vyvanse may interact with drugs that inhibit CYP2D6. Vyvanse is metabolized (broken down) by CYP2D6, which is an enzyme in your liver. Certain drugs can reduce the activity of this enzyme. These are known as CYP2D6 inhibitors. If you take Vyvanse with one of these drugs, it can cause Vyvanse to build up in your body. This can raise your risk for side effects with Vyvanse.

Examples of CYP2D6 inhibitors that can cause Vyvanse to build up in your body include:

If you take any of these drugs, talk with your doctor before taking Vyvanse. They may prescribe a lower dose of Vyvanse.

Vyvanse and tricyclic antidepressants

Vyvanse may interact with tricyclic antidepressants. Both Vyvanse and tricyclic antidepressants can have side effects that affect your heart, such as a fast or irregular heartbeat. Taking these drugs together can raise your risk for these side effects even more.

Both Vyvanse and tricyclic antidepressants can also increase your serotonin levels. Taking these drugs together can raise your risk for a serious side effect called serotonin syndrome. To learn more, see the “Vyvanse and drugs that increase serotonin levels” section above.

Examples of tricyclic antidepressants include:

If you take one of these drugs, talk with your doctor before taking Vyvanse. They may prescribe a lower dose of Vyvanse. Or they may recommend alternative treatments.

Vyvanse and drugs that make urine more alkaline

Vyvanse may interact with certain drugs that can make urine more alkaline. Taking these drugs with Vyvanse can cause Vyvanse to build up in your body. This could increase your risk for Vyvanse side effects.

Examples of drugs that make urine more alkaline and can raise your risk for Vyvanse side effects include:

  • acetazolamide
  • sodium bicarbonate (baking soda)

If you take one of these drugs, your doctor may recommend different treatment options for you.

Vyvanse and drugs that make urine more acidic

Vyvanse may interact with certain drugs that can make urine more acidic. Taking these drugs with Vyvanse can lower the amount of Vyvanse in your blood and make it less effective.

Examples of drugs that make urine more acidic and can reduce the effect of Vyvanse include:

  • methenamine (Hiprex, Urex)
  • ascorbic acid (vitamin C)

If you take one of these drugs, your doctor may recommend taking a higher dose of Vyvanse.

Vyvanse and drugs that contain caffeine

Vyvanse may interact with certain drugs that contain caffeine. Vyvanse is a stimulant medication, and caffeine is also a stimulant. Caffeine is found in certain drugs used for headache, cold and flu, or pain.

Taking medications that contain caffeine might add to the stimulant effects of Vyvanse. This can increase the risk of stimulant-related side effects such as anxiety, fast heartbeat, insomnia (trouble sleeping), feeling jittery, and others.

It’s best to avoid taking medications that contain caffeine while you’re taking Vyvanse. Your doctor or pharmacist can usually recommend a suitable alternative.

Vyvanse and herbs and supplements

Vyvanse can interact with certain herbs or supplements, including those listed below.

Vyvanse and St. John’s wort

Vyvanse may interact with an herbal supplement called St. John’s wort. This is because both St. John’s wort and Vyvanse can raise your serotonin levels.

Taking Vyvanse with St. John’s wort can raise your risk for a serious side effect called serotonin syndrome. This can occur if levels of serotonin get too high in your body.

If you take St John’s wort, talk with your doctor before taking Vyvanse. They may prescribe a lower dose of Vyvanse.

Vyvanse and tryptophan

Vyvanse may interact with tryptophan supplements. This is because both Vyvanse and tryptophan can raise your serotonin levels.

Taking Vyvanse with tryptophan raises the risk of a serious side effect called serotonin syndrome. Serotonin syndrome can occur if levels of serotonin get too high in your body.

If you take tryptophan, talk with your doctor before taking Vyvanse. They may prescribe a lower dose of Vyvanse.

Vyvanse and foods or beverages

Vyvanse can interact with certain food and beverages that contain caffeine.

Vyvanse and caffeine

Consuming caffeine in foods and drinks might add to the stimulant effects of Vyvanse. This can increase the risk of stimulant-related side effects such as anxiety, fast heartbeat, insomnia (trouble sleeping), feeling jittery, and others.

While taking Vyvanse, you should avoid consuming large amounts of foods or drinks that contain caffeine. Caffeine is found in foods such as chocolate. It’s also found in drinks such as coffee, certain teas, and sodas.

You may want to try decaffeinated versions of these drinks. However, if you feel you need some caffeine, talk with your doctor. They can tell you how much is safe to have while taking Vyvanse.

As with all medications, the cost of Vyvanse can vary. To find current prices for Vyvanse tablets or capsules in your area, check out GoodRx.com.

The cost you find on GoodRx.com is what you may pay without insurance. The actual price you’ll pay depends on your insurance plan, your location, and the pharmacy you use.

Before approving coverage for Vyvanse, your insurance company may require you to get prior authorization. This means that your doctor and insurance company will need to communicate about your prescription before the insurance company will cover the drug. The insurance company will review the prior authorization request and decide if the drug will be covered.

If you’re not sure if you’ll need to get prior authorization for Vyvanse, contact your insurance company.

Financial and insurance assistance

If you need financial support to pay for Vyvanse, or if you need help understanding your insurance coverage, help is available.

Takeda Pharmaceutical Company Limited, the manufacturer of Vyvanse, offers a savings program that may help lower the cost of the drug. For more information and to find out if you’re eligible for support, visit the program website for:

Mail-order pharmacies

Vyvanse may be available through a mail-order pharmacy. Using this service may help lower the drug’s cost and allow you to get your medication without leaving home. However, since Vyvanse is a controlled substance, this option may not be available in all areas.

Some Medicare plans may help cover the cost of mail-order medications.

If you don’t have insurance, you can ask your doctor or pharmacist about online pharmacy options.

Generic version

Vyvanse isn’t available in a generic form. A generic drug is an exact copy of the active drug in a brand-name medication. Generics tend to cost less than brand-name drugs.

It’s not known if Vyvanse is safe to take during pregnancy. This medication hasn’t been studied during pregnancy.

However, Vyvanse is an amphetamine and stimulant drug. Amphetamines are known to increase the risk of certain problems if used during pregnancy. These problems include:

If you’re pregnant or planning to become pregnant, talk with your doctor about the risks and benefits of taking Vyvanse.

It’s not known if Vyvanse is safe to take during pregnancy. If you’re sexually active and you or your partner can become pregnant, talk with your doctor about your birth control needs while you’re using Vyvanse.

For more information about taking Vyvanse during pregnancy, see the “Vyvanse and pregnancy” section above.

Breastfeeding isn’t recommended while taking Vyvanse. If taken while breastfeeding, Vyvanse may pass into breast milk. It could also affect the way your body makes breast milk.

Vyvanse may cause serious side effects in a breastfed child. These include feeding problems, slowed growth, increased blood pressure, fast heartbeat, and serious cardiovascular (heart and blood vessel) problems.

If you’re currently breastfeeding or planning to breastfeed, talk with your doctor. They may suggest that you take a medication other than Vyvanse.

Using more than the recommended dosage of Vyvanse can lead to serious side effects.

Do not use more Vyvanse than your doctor recommends.

Overdose symptoms

Symptoms of an overdose can include:

What to do in case of overdose

If you think you’ve taken too much of this drug, call your doctor. You can also call the American Association of Poison Control Centers at 800-222-1222 or use their online tool. But if your symptoms are severe, call 911 or your local emergency number, or go to the nearest emergency room right away.

You should take Vyvanse according to your doctor’s or healthcare provider’s instructions.

When to take

Vyvanse should be taken once daily in the morning. Don’t split your dose to spread it over the day.

You shouldn’t take Vyvanse in the afternoon, because this can lead to insomnia (trouble sleeping) at night.

To help make sure that you don’t miss a dose, try using a medication reminder. This can include setting an alarm on your phone or downloading a reminder app. A kitchen timer can work, too.

Taking Vyvanse with food

You can take Vyvanse either with or without food.

Can Vyvanse be crushed, split, or chewed?

Vyvanse comes as a capsule and a chewable tablet.

Vyvanse capsules should be swallowed whole. It shouldn’t be chewed or crushed. However, if you have trouble swallowing the capsule whole, it can be split open. You should thoroughly mix the powder inside with yogurt, water, or orange juice, and take it right away.

There may be a film left in the glass or container after you take the mixture. This doesn’t contain the active drug, so this residue does not need to be taken.

Vyvanse chewable tablets should be chewed thoroughly before swallowing. The tablet shouldn’t be crushed or split.

This drug comes with several precautions.

FDA warning: Potential for drug misuse and dependence

This drug has a boxed warning. This is the most serious warning from the Food and Drug Administration (FDA). A boxed warning alerts doctors and patients about drug effects that may be dangerous.

Vyvanse is an amphetamine and stimulant medication. It has a high risk of drug abuse, which is also called drug misuse. It also has a high risk of psychological and physical dependence, meaning the person needs the drug to function normally.

Before you start taking Vyvanse, your doctor will ask you if you’ve ever misused or been dependent on alcohol, prescription drugs, or illegal drugs. They’ll also monitor you during your treatment to see if you develop any signs of misusing or becoming dependent on Vyvanse.

For more information on this side effect, see “Misuse” under the “Side effect details” section above.

Other precautions

Before taking Vyvanse, talk with your doctor about your health history. Vyvanse may not be right for you if you have certain medical conditions or other factors affecting your health. These include:

  • Allergic reaction. If you’ve ever had an allergic reaction to amphetamine drugs, or to Vyvanse or any of its ingredients, you shouldn’t take Vyvanse. Ask your doctor what other medications are better options for you.
  • Heart conditions. You shouldn’t take Vyvanse if you have a serious heart condition such as a heart defect, irregular heartbeat, or coronary artery disease. This is because Vyvanse can increase blood pressure and heart rate. In rare cases, it can also cause serious cardiovascular side effects, including heart attack, stroke, and sudden cardiac death (heart suddenly stops beating). These side effects are more likely in people with serious heart conditions. If you have a heart condition, talk with your doctor about whether Vyvanse is right for you. They may want to check your heart function before prescribing Vyvanse.
  • High blood pressure. Vyvanse can increase blood pressure. If you already have high blood pressure, Vyvanse could make your condition worse. Talk with your doctor about whether Vyvanse is right for you. Your doctor will check your blood pressure regularly while you take Vyvanse.
  • Mental health conditions. Vyvanse cancause or worsen symptoms of psychosis and mania. If you or a close family member have ever had depression, bipolar disorder, mania, or psychosis, ask your doctor if Vyvanse is right for you.
  • Circulation problems in fingers and toes. Vyvanse can cause problems with blood circulation in your fingers and toes, such as Raynaud’s phenomenon. If you already have one these problems, taking Vyvanse can make it worse. Talk with your doctor about whether Vyvanse is right for you.
  • Kidney problems. Your kidneys help remove Vyvanse from your body. If your kidneys don’t work well, this can cause Vyvanse to build up in your body. This can raise your risk for side effects. If you have kidney problems, your doctor may prescribe a lower dose of Vyvanse.
  • Pregnancy. It’s not known if Vyvanse is safe to take during pregnancy. For more information, see the “Vyvanse and pregnancy” section above.
  • Breastfeeding. Vyvanse passes into breast milk. You shouldn’t breastfeed while taking this drug. For more information, see the “Vyvanse and breastfeeding” section above.

Note: For more information about the potential negative effects of Vyvanse, see the “Vyvanse side effects” section above.

When you get Vyvanse from the pharmacy, the pharmacist will add an expiration date to the label on the bottle. This date is typically 1 year from the date they dispensed the medication.

The expiration date helps guarantee that the medication is effective during this time. The current stance of the Food and Drug Administration (FDA) is to avoid using expired medications. If you have unused medication that has gone past the expiration date, talk to your pharmacist about whether you might still be able to use it.

Storage

How long a medication remains good can depend on many factors, including how and where you store the medication.

Vyvanse tablets and capsules should be stored at room temperature (68°F to 77°F or 20°C to 25°C). However, if needed, the drug can be kept at a temperature of 59°F to 86°F (15°C to 30°C) for short periods of time. Store the tablets and capsules in a tightly sealed container away from light. Avoid storing this medication in areas where it could get damp or wet, such as bathrooms.

It’s important to store Vyvanse in a safe place. This is to lower the risk of the drug being misused by someone who doesn’t have a prescription for it. To learn more, see the FDA warning in the “Vyvanse precautions” section above.

Disposal

If you no longer need to take Vyvanse and have leftover medication, it’s important to dispose of it safely. This helps prevent others, including children and pets, from taking the drug by accident. It also helps keep the drug from harming the environment. And it prevents potential misuse of this drug. Ask your doctor or pharmacist about a medicine take-back program in your area.

This article provides several useful tips on medication disposal. You can also ask your pharmacist for information about how to dispose of your medication.

Disclaimer: Medical News Today has made every effort to make certain that all information is factually correct, comprehensive, and up-to-date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or other healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.

Vyvanse Side Effects, Uses, Dosages, Interactions: ADHD Medication

What is Vyvanse? Is Vyvanse a Narcotic?

Vyvanse (Generic Name: lisdexamfetamine dimesylate) is a once-daily, timed-release stimulant ADHD medication primarily used to treat attention deficit hyperactivity disorder (ADHD or ADD) in children ages 6-12, adolescents, and adults. Vyvanse is not a narcotic, but according to the FDA, it is a federally controlled substance (CII) because it can be abused or lead to dependence. It is an amphetamine.

Vyvanse may improve focus for people with inattentive ADHD (aka ADD), and decrease impulsivity and hyperactive behavior — hallmark ADHD symptoms for many patients. It is not known if it is safe for children under the age of 6. Vyvanse has been available since 2007, when the FDA approved the medication for the treatment of ADHD.

Vyvanse is also used to treat binge eating disorder in adults.

Is Vyvanse Better Than Adderall?

Adderall and Vyvanse are both schedule II amphetamine-based central nervous system stimulant medications used to treat ADHD. Adderall comes in both immediate- and extended-release form; Vyvanse is available as an extended-release medication only. The immediate-release version of Adderall has a duration of action of 4 to 6 hours; the extended-release version lasts approximately 12 hours. The duration of effects for Vyvanse is 10 to 14 hours.

Vyvanse is a prodrug – an inert substance that is metabolized in the body to become active – which means it’s side effects are considered less harsh. Both drugs are classified by the FDA as Schedule II stimulants because they can be abused or lead to dependence, however Vyvanse is considered to carry a lower risk since it takes longer to metabolize in the system than does Adderall.

What Is the Best Vyvanse Dosage to Treat ADHD Symptoms?

The optimal dosage of Vyvanse varies by patient. Vyvanse capsules are available in 5mg, 10mg, 20mg, 30mg, 40mg, 50mg, 60mg and 70mg dosages. Vyvanse chewable tablets are available in 5mg, 10mg, 20mg, 30mg, 40mg, 50mg, and 60mg dosages. The time-release formulation is designed to maintain a steady level of medicine in the body throughout the day.

Your doctor may adjust your dosage weekly by 10mg or 20mg increments until you or your child experiences the best response — that is, the lowest dosage at which you experience the greatest improvement in symptoms without side effects. The maximum dose is typically 70mg daily.

As with all medications, follow your Vyvanse prescription instructions exactly. Vyvanse is taken orally, with or without food, once daily. The first dose is typically taken first thing in the morning; it should be taken at the same time each day for the best results.

Capsules should be swallowed whole with water or other liquids. If your child is unable to swallow the capsule, it can be opened and stirred into yogurt, water, or orange juice. Taken this way, the mixture should be swallowed entirely at once. Chewable tablets should be completely chewed before swallowing, then followed with a glass of water or other liquid.

During treatment, your doctor may periodically ask you to stop taking your Vyvanse so that he or she can monitor ADHD symptoms; check vital statistics including blood, heart, and blood pressure; or evaluate height and weight. If any problems are found, your doctor may recommend discontinuing treatment.

Some patients report developing a tolerance to Vyvanse after long-term use. If you notice that your dosage is no longer controlling your symptoms, talk to your doctor to plan a course of action.

What are the Side Effects of Vyvanse?

Most people taking Vyvanse do not experience any side effects. That said, the most common side effects associated with Vyvanse are as follows:

Vyvanse Side Effects When Treating ADHD:

  • anxiety
  • decreased appetite
  • diarrhea
  • dizziness
  • dry mouth
  • irritability
  • loss of appetite
  • nausea
  • trouble sleeping
  • upper stomach pain
  • vomiting
  • weight loss

Vyvanse Side Effects When Treating Binge Eating Disorder:

  • dry mouth
  • trouble sleeping
  • decreased appetite
  • increased heart rate
  • constipation
  • feeling jittery
  • anxiety

Another serious side effect is slowed growth in children.

Vyvanse and Weight Loss

Vyvanse should not be taken off-label to help you lose weight. Weight loss is not an approved use for this medication.

Vyvanse and Driving

Taking Vyvanse may impair your or your teenager’s ability to drive, operate machinery, or perform other potentially dangerous tasks. This side effect usually wears off with time. If side effects are bothersome, or do not go away, talk to your doctor. Most people taking this medication do not experience any of these side effects.

Vyvanse and Heart or Blood Pressure Related Problems

Report to your doctor any heart-related problems or a family history of heart and blood pressure problems. Patients with structural cardiac abnormalities and other serious heart problems have experienced sudden death, stroke, heart attack, and increased blood pressure while taking Vyvanse. Stimulants can increase blood pressure and heart rate. Physicians should monitor these vital signs closely during treatment. Call your doctor immediately if you or your child experiences warning signs such as chest pain, shortness of breath, or fainting while taking Vyvanse.

Vyvanse and Mental Illness

Disclose to your physician all mental health issues including any family history of suicide, bipolar illness, or depression. The FDA manufacturer recommends evaluating patients for bipolar disorder prior to stimulant administration. Vyvanse may create new or exacerbate existing behavior problems, or bipolar illness. It can cause psychotic or manic symptoms in children and teenagers. Call your doctor immediately if you or your child experiences new or worsening mental health symptoms including hallucinations or sudden suspicions.

Vyvanse and Circulation Problems

Discuss circulation problems with your doctor before taking Vyvanse, which has been known to cause numbness, coolness, or pain in fingers or toes, including Raynaud’s phenomenon. Report to your doctor any new blood-flow problems, pain, skin color changes, or sensitivities to temperature while taking Vyvanse.

Vyvanse and Substance Abuse

Stimulants like Vyvanse have a high potential for abuse and addiction, especially among people who do not have ADHD. It is a “Schedule II Stimulant,” a designation that the Drug Enforcement Agency uses for drugs with a high potential for abuse. Other Schedule II drugs include Dexedrine, Ritalin, and cocaine. People with a history of drug abuse should use caution when trying this medication. Taking the medication exactly as prescribed can reduce potential for abuse.

The above is not a complete list of potential side effects. If you notice any health changes not listed above, discuss them with your doctor or pharmacist.

Who Can Take Vyvanse? Medication Precautions

You should not take Vyvanse if you are allergic to any of the ingredients in Vyvanse, or if you have taken a monoamine oxidase inhibitor (MAOI) within 14 days.

If you’re thinking of becoming pregnant, discuss the use of Vyvanse with your doctor. It is not known if it can cause fetal harm. Vyvanse is passed through breastmilk, so it is recommended that mothers do not nurse while taking it.

The safety of Vyvanse for children under age six has not been established. Store Vyvanse in a secure place out of the reach of children, and at room temperature. Do not share your Vyvanse prescription with anyone, even another person with ADHD. Sharing prescription medication is illegal, and can cause harm.

Interactions Associated with Vyvanse

Before taking Vyvanse, discuss all other active prescription medications with your doctor. Vyvanse can have a dangerous, possibly fatal, interaction with antidepressants including MAOIs.

Vyvanse is similar to amphetamine and dextroamphetamine. You should avoid taking these medications concurrently with Vyvanse.

Share a list of all vitamin or herbal supplements, and prescription and non-prescription medications you take with the pharmacist when you fill your prescription, and let all doctors and physicians know you are taking Vyvanse before having any surgery or laboratory tests. Vyvanse can cause false steroid results.

The above is not a complete list of all possible drug interactions.

Sources:

What is Vyvanse. https://www.vyvanse.com/

Allen, Shari. Adderall XR and VyvanseTM. Mental Health Clinician (2014) https://meridian.allenpress.com/mhc/article/4/1/8/37052/Adderall-XRR-and-VyvanseT

Adderall vs. Vyvanse: What’s the Difference? American Addiction Centers (2019). https://americanaddictioncenters.org/adderall/vs-vyvanse

Cardiovascular Effects of Stimulant and Non-Stimulant Medication for Children and Adolescents with ADHD. CNS Drugs (2017). https://link.springer.com/article/10.1007%2Fs40263-017-0410-7

Drelich, Jordan. Is Lisdexamfetamine Dimesylate Safe and Effective in Reducing ADHD Symptoms? Psychiatry Commons (2017). https://digitalcommons.pcom.edu/pa_systematic_reviews/397/

More Information on Vyvanse and Other ADHD Medications:

Free Download: The Complete Guide to ADHD Medications

The Top ADHD Medications for Children — Rated by Readers

Primer: The Stimulant Medications Used to Treat ADHD

Vyvanse for Treating ADHD in Children

Vyvanse is a stimulant medication for attention deficit hyperactivity disorder (ADHD). Stimulants (also known as psychostimulants) are the first line of medications due to their effectiveness in treating ADHD symptoms. Vyvanse was approved by the U.S. Food and Drug Administration in July 2007.

Vyvanse for ADHD

Vyvanse is a once-a-day treatment for adults and children who are 6 years old and older with ADHD. It’s also approved to treat binge-eating disorder in adults. The main ingredient in Vyvanse is lisdexamfetamine dimesylate.

The drug acts on the central nervous system to boost the levels of two brain chemicals, dopamine and norepinephrine. This, in turn, improves focus and attention and decreases impulsivity and hyperactive behavior.

Advantages of Vyvanse

Vyvanse is unique in that it’s a prodrug or forerunner of the drug dextroamphetamine, an amphetamine that’s one of the main ingredients in Adderall, Adderall XR, and Dexedrine Spansules.

This means Vyvanse isn’t active in its ingested form but must be metabolized by the body’s enzymes to become converted to dextroamphetamine and become an active drug. That delayed action—it can take one to two hours to take effect versus a half-hour for Adderall—can stretch out how long the drug works.

In studies, Vyvanse lasted up to 14 hours, compared with other long-acting ADHD medicines that tend to last 10 to 12 hours. The delay also means Vyvanse is much less likely to be abused than conventional ADHD medicines.

Research shows that up to 10% of high school students and up to 35% of college students misuse or divert ADHD stimulant medication.

Because it’s released at the same levels over time and produces a slow, steady therapeutic effect throughout the day, Vyvanse is often described as “smoother” than Adderall—there’s no “kick” or “jolt” to the system when the medication starts to work.

An analysis of studies on Vyvanse reported that this smoothness potentially avoids the large and fast increases in dopamine that are associated with the reinforcing effects of drug abuse.

Vyvanse may be an especially good option if your child’s current medication isn’t lasting long enough throughout the day, or if you’re worried your child may be abusing his or her medicine.

Dosage

Vyvanse is available in seven dosage strengths: 10mg, 20mg, 30mg, 40mg, 50mg, 60mg, and 70mg. Although most children will start Vyvanse at the 30mg dosage, a higher starting dose may be more appropriate if your child is switching to Vyvanse from another ADHD stimulant.

Vyvanse is taken orally once daily. The first dose is typically taken first thing in the morning; it should be taken at the same time each day for best results. Vyvanse can be taken either with or without food.

If your child doesn’t like chewable drugs and has trouble swallowing the Vyvanse capsules whole, you can open them and either sprinkle the beads onto a small amount of food or stir them into a few ounces of water or orange juice. This is another benefit over other “beaded” ADHD stimulant medicines, which don’t dissolve in liquids.

Side Effects

Side effects of Vyvanse are similar to other ADHD stimulants and most commonly include:

  • Abdominal pain
  • Decreased appetite
  • Headaches
  • Insomnia
  • Irritability
  • Vomiting
  • Weight loss

Precautions

Like other stimulant medications, Vyvanse should not be used or used with caution by children with certain conditions, including the following:

  • Glaucoma
  • Heart disease or hardening of the arteries
  • High state of anxiety, tension, or agitation
  • Hyperthyroidism
  • Moderate to severe high blood pressure

Vyvanse should also not be used by kids who are taking or have taken within the past 14 days an anti-depression medicine (monoamine oxidase inhibitor or MAOI), and used with significant caution in those who are sensitive to, allergic to, or had a reaction to other stimulant medicines.

Vyvanse Drug / Medicine Information

 

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine,
speak to your doctor or pharmacist.

 

WARNING: Important safety information is provided in a boxed warning in the full CMI. Read before using this medicine.

Why am I using VYVANSE?

VYVANSE contains the active ingredient lisdexamfetamine dimesilate. VYVANSE is used
to treat 1) Attention Deficit Hyperactivity Disorder (ADHD) AND 2) Binge Eating Disorder
(BED).

What should I know before I use VYVANSE?

Do not use if you: have ever had an allergic reaction to VYVANSE or any of the ingredients
listed at the end of the CMI; taking a medicine called a ‘monoamine oxidase inhibitor’
(MAOI) or have taken an MAOI in the last 14 days; have a thyroid problem; feel unusually
excited, over-active, or un-inhibited; have ever had heart problems.

Talk to your doctor if you have any other medical conditions, take any other medicines,
or are pregnant or plan to become pregnant or are breastfeeding.

What if I am taking other medicines?

How do I use VYVANSE?

Take VYVANSE capsule once a day in the morning with or without food. The usual starting
dose is 30 mg once a day, your doctor may change the dose until it is right for you.
If you have trouble swallowing capsules, you may open your VYVANSE capsule and pour
all of the powder into a soft food such as yogurt, water or orange juice; mix completely
and consume mixed contents right away.

Follow all directions given to you by your doctor or pharmacist carefully.

What should I know while using VYVANSE?

Things you should do

Remind any doctor or dentist you/your child visit/s that you/your child are/is using
VYVANSE. If you/your child become/s pregnant while using this medicine, tell the doctor
immediately.

Things you should not do

Do not stop using this medicine or change dosage without checking with your/your child’s
doctor.

Driving or using machines

Be careful driving or operating machinery until you/your child know/s how VYVANSE
affects you/your child.

Drinking alcohol

Be careful when drinking alcohol while taking VYVANSE, it could make some of the unwanted
side effects of VYVANSE worse.

Looking after your medicine

Store VYVANSE in a cool dry place where the temperature is below 25°C. Keep the container
tightly closed.

Are there any side effects?

Common side effects include decreased appetite, insomnia, dry mouth, headache, upper
abdominal pain, weight decreased, feeling tired. Serious side effects include allergic
reaction, chest pain, shortness of breath, mood changes, confusion, seizures.
For more information, including what to do if you have any side effects, see Section
6. Are there any side effects? in the full CMI.

 

WARNING: VYVANSE can be abused or lead to dependence. VYVANSE is a controlled substance
and should be handled responsibly. It is illegal for anyone prescribed VYVANSE to
sell or give it to other people. Keep VYVANSE in a safe place to prevent misuse and
abuse.

Active ingredient: lisdexamfetamine dimesilate

Consumer Medicine Information (CMI)

This leaflet provides important information about using VYVANSE. It does not take
the place of talking to your doctor or pharmacist. You should also speak to your doctor or pharmacist if you would like further information
or if you have any concerns or questions about using VYVANSE.
The information in this leaflet was last updated on the date listed on the final
page. More recent information on the medicine may be available. You should ensure
that you speak to your pharmacist or doctor to obtain the most up to date information
on this medicine. You can also download the most up to date leaflet from www.takeda.com/en-au . Those updates may contain important information about the medicine and its use of
which you should be aware.

Where to find information in this leaflet:

Why am I using VYVANSE?

The main ingredient in VYVANSE is lisdexamfetamine dimesilate which itself is not
active (such medicines are sometimes called a pro-drug). After VYVANSE is taken, it
is converted in the blood to dexamphetamine which is the active ingredient.
VYVANSE is a central nervous system stimulant.

VYVANSE is used to treat:

Attention Deficit Hyperactivity Disorder (ADHD). VYVANSE increases attention and decreases
impulsiveness and hyperactivity in patients with ADHD.

Binge Eating Disorder (BED). VYVANSE may help to reduce the number of binge eating
days in patients with moderate to severe BED.

VYVANSE is not for weight loss.

It is not to be taken by children with ADHD under 6 years of age or in patients with
BED under 18 years of age. VYVANSE should be used as part of a comprehensive treatment
program which usually includes psychological, educational and social therapy. For
BED, VYVANSE should only be prescribed by a psychiatrist as part of a comprehensive
treatment program.

What should I know before I use VYVANSE?

Warnings

Do not use VYVANSE if you:

have a disease of the arteries due to cholesterol deposits e.g. atherosclerosis

are allergic to amphetamines, or any of the ingredients listed at the end of this
leaflet. Always check the ingredients to make sure you can use this medicine.

have heart disease such as angina or myocardial infarction (heart attack)

have moderate to severe high blood pressure

have hyperthyroidism (hyperactive thyroid)

have an eye condition called glaucoma

have a tumour of the adrenal gland tissue (phaeochromocytoma)

have tics (muscle twitching usually in the face and shoulders)

have Tourette’s syndrome

have severe depression, suicidal ideation or behaviour, thoughts or acts of self-harm
or mental illness

have periods of severe anxiety, tension or agitation

suffer with drug dependence or abuse alcohol

are taking or have taken an antidepressant called a monoamine oxidase inhibitor (MAOI)
within the past 14 days.

Check with your doctor if you:

are allergic to any other medicines, or any foods, dyes or preservatives

take any medicines for any other condition

have any other medical conditions or heart problems, including ischemic heart disease
(such as angina or myocardial infarction), suspicion or presence of any cardiac or
heart-related abnormalities, irregular heartbeats or rate, family history of sudden/cardiac
death

suffer from blood pressure and/or taking medications to treat blood pressure

disorders of the blood vessels of the brain e.g. stroke

suffer from depression, bipolar illness, or schizophrenia or other mental illness

have liver or kidney disease. Your doctor may lower the dose if you have kidney disease.

have epilepsy or other seizures or have had an abnormal brain wave test (EEG)

have circulation problems in fingers and toes

During treatment, you may be at risk of developing certain side effects. It is important
you understand these risks and how to monitor for them. See additional information
under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any
medicines, vitamins or supplements that you buy without a prescription from your pharmacy,
supermarket or health food shop.

Some medicines may interfere with VYVANSE and affect how it works.

It is especially important to tell your doctor or pharmacist if you or your child
is taking medicines to treat any of the following conditions:

depression including class of medicines called monoamine oxidase inhibitor (MAOI)

anxiety, mania or bipolar disorder

high blood pressure

schizophrenia or schizophrenia-like illness

strong pain

In addition, the following medicines may also interact with VYVANSE:

Urinary acidifying agents e.g. ascorbic acid (Vitamin C), ammonium chloride, sodium
acid phosphate

Urinary alkalinising agents e.g. sodium bicarbonate, acetazolamide, some thiazides

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins
or supplements you are taking and if these affect VYVANSE.

How do I use VYVANSE?

How much to take

The usual starting dose for children, adolescents and adults is 30 mg once a day.
Your doctor may increase the dose until it is right for you or your child. For treatment
of BED your psychiatrist will assess the response to VYVANSE after 12 weeks.

Follow the instructions provided and use VYVANSE until your doctor tells you to stop.

When to take VYVANSE

Take VYVANSE once a day in the morning.

How to take VYVANSE

VYVANSE can be taken with or without food.

If you have trouble swallowing capsules, you may open your VYVANSE capsule and pour
all of the powder into a soft food such as yogurt, water or orange juice.

Use all of the VYVANSE powder from the capsule so you get all of the medicine.

Using a spoon, break apart any powder that is stuck together. Stir the VYVANSE powder
and yogurt, water or orange juice until they are completely mixed together.

Consume all of the yogurt, water or orange juice right away after it has been mixed.
Do not store the yogurt, water or orange juice after it has been mixed with VYVANSE.

Do not worry if there is a film or residue left in the glass or container afterwards
– this is not the active ingredient.

From time to time, your doctor may stop VYVANSE treatment for a while to check your/your
child’s ADHD or your BED symptoms.

If you forget to use VYVANSE

VYVANSE should be used regularly in the morning each day. If you miss your dose, then
take VYVANSE as usual the next morning. Avoid taking VYVANSE in the afternoon or evening
as it can cause an inability to sleep.

Do not take a double dose to make up for the dose you missed.

A Dosage Chart is provided on the VYVANSE carton to help track the capsules are taken
properly. Cross off a symbol each time a capsule is taken.

If you use too much VYVANSE

If you think that you have used too much VYVANSE, you may need urgent medical attention.

You should immediately:

phone the Poisons Information Centre
(by calling
13 11 26 in Australia; 0800 POISON or 0800 764766 in New Zealand), or

contact your doctor, or

go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

What should I know while using VYVANSE?

Things you should do

VYVANSE should be taken in the morning

Make sure that all of your doctors, dentists, ophthalmologists, psychologists and
pharmacists know you/your child are taking VYVANSE. Remind them if any new medicines
are about to be started.

Like all stimulants, VYVANSE may become habit-forming and can be abused by some people.
If it is taken correctly as instructed by your doctor, this should not happen, either
now or later in life.

Be sure to keep all doctors’ appointments so that you/your child’s progress can be
checked.

Your doctor will want to check your/your child’s blood pressure and pulse.

Tell your doctor immediately if you/your child become pregnant while on VYVANSE.

Things you should not do

Do not stop treatment or change the dosage without checking with your doctor.

Do not give VYVANSE to anyone else, even if they have the same condition as you/your
child. It may not be safe for another person to take VYVANSE.

Do not take VYVANSE to treat any other complaints unless your doctor tells you to.
It may not be safe to use VYVANSE for another complaint.

Do not take VYVANSE for a longer time than your doctor has prescribed.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how VYVANSE
affects you.

VYVANSE may cause dizziness, drowsiness and blurry or double vision. This is uncommon;
but if affected, you/your child should avoid driving or using heavy machinery. Check
with your doctor if driving is advisable for you/your child while you/your child are
taking VYVANSE.

Drinking alcohol

Tell your doctor if you drink alcohol.

Alcohol may make some of the unwanted side effects of VYVANSE worse. Your doctor may
suggest that you avoid alcohol completely or reduce the amount you drink while you
are taking VYVANSE.

Looking after your medicine

Keep the capsules in the bottle until it is time to take them. Store VYVANSE in a
cool dry place where the temperature is below 25°C. Keep the container tightly closed.

Do not store it in the bathroom or near a sink, or in the car or on windowsill.

Do not use this medicine after the expiry date.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy
for safe disposal. Do not keep unused or expired VYVANSE as it can be abused or taken
by someone else. Do not throw out with your household waste.

It is illegal for anyone prescribed VYVANSE to sell or give it to other people.

Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of
them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you
have any further questions about side effects.

Less serious side effects

Serious side effects

Tell your doctor or pharmacist if you notice anything else that may be making you
feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can
report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems . By reporting side effects, you can help provide more information on the safety of
this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop
taking any of your medicines.

Product details

This medicine is only available with a doctor’s prescription.

What VYVANSE contains

Active ingredient

(main ingredient)

Lisdexamfetamine dimesilate

Other ingredients

(inactive ingredients)

Microcrystalline cellulose, croscarmellose sodium and magnesium stearate.

The capsule shells contain gelatin, titanium dioxide (E171) (all strengths) erythrosine
(E127) (30 mg and 70 mg), brilliant blue (E133) (40 mg, 50 mg, 60 mg and 70 mg), iron
oxide yellow (20 mg and 40 mg), iron oxide black (40 mg) and TekPrint SW-9008 (all
strengths).

Do not take this medicine if you are allergic to any of these ingredients.

What VYVANSE looks like

VYVANSE 20 mg capsule (AUST R 284019): ivory opaque body and ivory opaque cap, printed
‘S489′ and ’20 mg’ in black ink.

VYVANSE 30 mg capsule (AUST R 199227): white opaque body and pink opaque cap, printed
‘S489′ and ’30 mg’ in black ink.

VYVANSE 40 mg capsule (AUST R 284020): white opaque body and blue/green opaque cap,
printed ‘S489′ and ’40 mg’ in black ink.

VYVANSE 50 mg capsule (AUST R 199226): white opaque body and blue opaque cap, printed
‘S489′ and ’50 mg’ in black ink.

VYVANSE 60 mg capsule (AUST R 284021): aqua blue opaque body and aqua blue opaque
cap, printed ‘S489′ and ’60 mg’ in black ink.

VYVANSE 70 mg capsule (AUST R 199228): blue opaque body and pink opaque cap, printed
‘S489′ and ’70 mg’ in black ink.

VYVANSE is supplied in bottles of 30 capsules, inside a cardboard box.

Who distributes VYVANSE

Takeda Pharmaceuticals Australia Pty Ltd

Level 39

225 George Street

Sydney NSW 2000

Australia

Phone: 1800 012 612

www.takeda.com/en-au

 

This leaflet was prepared in October 2020.

 

VYVANSE® and the VYVANSE Logo® are registered trademarks of Takeda Pharmaceuticals U.S.A., Inc.

90,000 Clinical Study Attention Deficit Hyperactivity Disorder: Methylphenidate Hydrochloride, Lisdexamfetamine Dimesylate – Clinical Trials Registry

Inclusion Criteria:

1. Pediatrics: Male patients or non-pregnant, non-lactating women aged 6 to less than 18. Adults: Men non-pregnant, non-lactating women aged 18 and over.

2. Diagnosis of ADHD (inattentive, hyperactive or combined) considered eligible for treatment with FOQUEST or VYVANSE according to the relevant product Monograph.

3. Is mentally and physically competent to give informed consent or consent and is able and willing to comply with the research protocol, including the duration of the research.

Exclusion Criterion:

Potential Patients meeting any of the contraindications or warnings outlined in the Relevant Canadian Product Monographs were excluded from participation in the study:

1. True allergy to methylphenidate, amphetamines or sympathomimetic amines, history of serious adverse reactions or methylphenidate amphetamines or known not to respond to treatment with methylphenidate or amphetamine.No response is defined as methylphenidate or amphetamine used in varying doses over a phase of at least four weeks with each dose with little or no clinical benefit over the past 10 years.

2. Pregnant women of childbearing age (FOCP) planning to become pregnant or breastfeeding.

3. A history of hyperthyroidism, thyrotoxicosis, severe atherosclerosis. renal failure or glaucoma.

4. Presence of structural heart abnormalities, symptomatic cardiovascular disease or moderate to severe hypertension.

5. You are currently taking MAO inhibitors or within the last 14 days.

6. Initial diagnosis of bipolar disorder at visit 1.

7. You are currently receiving any investigational drug or have received investigational drug. in the previous month.

8. A history of drug or alcohol abuse or dependence.

9. At present, the investigator considers the risk of suicide.

Ritalin and its analogues in Israel | Treatment in Israel with IS-med

“Ritalin” and its analogue “Concert”

If Ritalin does not help: there are other drugs, explains the doctor
# Ritalin and # Concert are the most popular drugs in Israel for the treatment of hyperactivity.But for some, they do not help or cause side effects. Is there an alternative?

“Ritalin” and its analogue “Concert” have become the most popular drugs for hyperactivity disorder and attention deficit disorder (in Hebrew this diagnosis is called “beayot keshev verikuz”, in Russian – ADHD). However, in about a quarter of patients, they do not help, and sometimes side effects, especially in children, force them to stop taking. Common side effects are headache, nervousness, loss of appetite, nervous tics, and weight loss.

But there are other drugs that a neurologist or psychiatrist can prescribe if Ritalin does not give the desired effect.

# Adderall, # Attent

Adderall is a popular stimulant medication for the treatment of attention deficit disorder in the USA. It is sold in Israel under the name Attent. Similar to Ritalin, this amphetamine increases the production of dopamine in the brain, which improves focus and concentration.

There are fast-acting and prolonged versions of the drug: regular Adderall lasts 6 hours, and Adderall XR – 12 hours.

Unlike Ritalin, this agent has fewer side effects, in particular due to the lower dosage. They appear less frequently and less pronounced. The dosage is selected individually, in most cases – 40 mg, similar to Ritalin, but in the USA it is used in higher doses.

Attent with 6 hours action is included in the state health basket and is prescribed to children with Ritalin ineffectiveness and concerts.

Long-acting XR is not included in the health basket.

# Dexedrine

Includes, like Adderall, dexamphetamine, and has no particular advantages over the named drug.

# Vyvanse

Contains amphetamine derivatives. It is activated after splitting in the blood, therefore it is not suitable for drug addicts.

Since assimilation is gradual, its concentration in the blood does not increase abruptly. This helps to avoid the side effects caused by the rapid increase in concentration.If the child cannot swallow the capsule, it can be opened and the contents dissolved in water.

Due to the slow growth of action, the effect of the drug is more delicate, and side effects are less common.

# Focalin

This is an isomer of the active ingredient Ritalin, but with a different molecular structure. The change in the structure allows you to reduce the dose in comparison with Ritalin by 2 times. As a result, side effects are less pronounced.

The usual form of the drug acts for 4 hours, the XR form, like Ritalin LA with a slow release of the active principle – 12 hours.

# Daytrana

Stickers with methylphenidate (the active ingredient in Ritalin). The substance is absorbed directly into the bloodstream and is not decomposed by the liver, as when taking pills. (Decomposition products in themselves cause side effects, and this process forces an increase in the dose.)

The sticker allows you to enter into the patient’s body lower doses. The skin stores the substance and slowly releases it into the blood, so the concentration in the blood rises slowly, which prevents side effects.

The sticker can be removed at any time, thereby adjusting the duration. This is important, for example, for food intake, because Ritalin suppresses appetite.

The sticker is designed for up to 12 hours, causing a small number of side effects. The sticker is attached for 9 hours, after removal, the effect lasts for 2-3 hours.

# Atomoxetine

Sold under the brand name Strattera. Refers to norepinephrine reuptake inhibitors, that is, to a class of drugs other than Ritalin.

Medicines of this class are also used as an antidepressant. They must be taken daily, but the effect, like that of antidepressants, appears only after 3 weeks.

Advantages of the medicine: does not suppress appetite, can be taken at any time of the day, does not cause, like Ritalin and a concert, nervous tics, on the contrary, it helps to get rid of existing ones.

But there are also disadvantages: the drug is effective only for 60% of those who take it, it is necessary to take it constantly, including weekends and holidays, and it affects behavior more than concentration.

# Guanfacine

Originally intended for the treatment of hypertension and sold in the United States under the Tenex and other generic brands. On its basis, the drug Intunice was created for the treatment of ADHD.

The direct effect on the syndrome is insignificant, but the remedy eliminates tics, reduces impulsivity and improves sleep. Therefore, doctors often prescribe the drug in parallel with stimulants.

How do you choose the right remedy for hyperactivity and ADHD?

Choosing a drug is not easy, there are 11 dosages of methylphenidate alone, and other drugs have their own dosage options.

Selection of the type of medicine and dose takes a long time and is accompanied by communication between the doctor and the patient. A common mistake among patients is to stop treatment if the first drug prescribed does not help. Sometimes the result is achieved by changing the dose, this also affects the side effects. The doctor should explain this to the patient and set him up for a long process of adjusting the medicine to the body.

In Israel, treatment is usually started with the appointment of Ritalin at a dose of 10 mg. These tablets are easy to cut and patients can take a quarter at a time.Then they move on to long-acting Ritalin LA or to a concert – depending on the required duration of the effect.

If a medicine does not help or causes severe side effects, the doctor selects another one, also from the group of stimulants. Each drug has its own characteristics, and the patient may not give the desired reaction to the classic options – Ritalin or a concert. In most cases, they then switch to Focalin, Vyvanse or Attent.

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Opioid analgesics in the treatment of pain syndromes

Opioid analgesics are by far the most controversial drugs. They are extremely inconvenient to use both in hospitals and in outpatient practice due to unreasonably complex and contradictory rules for their accounting and control, their inherent side properties, fear of causing iatrogenic drug addiction in patients, etc.d.

However, it is obvious that opioid analgesics cannot be dispensed with yet. For millennia, opioids have continued to be the mainstay of the pharmacotherapy of severe pain syndromes.

Opium and its derivatives were used by mankind for thousands of years BC. Poppy seeds were discovered by archaeologists during excavations of Neanderthal settlements, indicating that it was probably used in Europe as early as 30 thousand years ago. Mentions of the use of opium in medicine are found in the history of all outstanding ancient civilizations: Egyptians, Sumerians, Hindus, Persians, Greeks, Romans, etc.There is evidence that Arab doctors used it under the name “afjun”, a word that later became the term “opium” and used it mainly for coughing.

In Europe in the Middle Ages, on the basis of opium, Paracelsus created his famous “magic elixir” – Laudanum Paracelsus. This universal drug was used to treat various pains, agitation, insomnia, cough, weakness, exhaustion, bleeding, diarrhea, etc. in both adults and children.

And only at the beginning of the XIX century.Friedrich Sertürner from Hanover succeeded in isolating a pure substance from opium juice, which he called morphine (1804). From this began a systematic scientific study of this opioid, which led to the discovery of the opioid system of the body, its role not only in controlling the sensation of pain, but also in the functioning of the endocrine and immune systems, the digestive tract, as well as in the process of consciousness and thinking.

Over the following years, thousands of new molecules of opioid drugs were created and continue to be created, hundreds of which are used in medical practice.Most doctors do not have a clear distinction between the definitions of “drugs” and “opioids”, although these words are not complete synonyms. Therefore, it is necessary to give definitions to the terms used in the following, which are often used in the literature as interchangeable, but are not.

The term “ drugs ” comes from the Greek word “ναρκωτικός” – immersion in numbness, numbness, insensibility. They mean any substances that can cause a psychotropic effect and are associated with mental and physical dependence, addiction and abuse (for example, morphine, opium, methadone, heroin, marijuana, phencyclidine, LSD, etc.).

For the most part, this is a legal and social, not a medical term, which is used by legislative and executive authorities, the media. For example, in the United States, drugs include all poppy opium derivatives, synthetic opioids, alcohol and cocaine, adding to the confusion in terms. According to the international definition on the INCB (International Narcotics Control Board) lists, alcohol is classified as a drug.

When describing the medical and pharmacological aspects of the action of these substances, the terms “opiates” and “opioids” should be used instead of the term “drug”. Opiates are natural derivatives of poppy (morphine, codeine, thebaine, oripavine), and opioids are all synthetic and natural substances (including opiates) that directly affect opioid receptors, regardless of the type of exposure. They include molecules that fully (eg morphine, fentanyl) or partially (eg buprenorphine) stimulate or block (eg naltrexone) opioid receptors.

Opioids bind to specific receptors, which are G-proteins on the surface of cell membranes, with which opioids interact as ligands.The analgesic function of opioids is carried out mainly at the level of the cortex and brain stem structures, although opioid receptors can be found in virtually all tissues of the body.

The highest concentration of these receptors is found in the rostral part of the anterior singular gyrus and in the middle part of the anterior insula. The second area with the highest concentration of opioid receptors is in the intestines. Structurally, somatostatin receptors and opioid receptors coincide by 40%, therefore opioids affect the growth of tissues (in the experiment), including malignant ones.

The first publication that suggested the existence of opioid receptors was published in 1971, and in 1973 their presence was proved. Currently, there are many types and categories of opioid receptors. The International Union of Fundamental and Clinical Pharmacology (IUPHAR) admits the use of the generally accepted Greek classification, but recommends 3 classical receptors (μ-, δ-, κ-) with the designation of the nociceptin receptor as MOR, DOR, KOR and NOR, respectively.

Previously, sigma receptors were also referred to as opioid receptors due to their antitussive effect, but later it turned out that endogenous opioids do not act on them, and in their structure they differ significantly from opioid receptors. Currently, sigma receptors have been removed from the opioid receptor class. Instead, an introduction to the classification of the zeta (ζ-) receptor, also called the opioid growth factor receptor, is contemplated. Another, epsilon (ε-) receptor, has been under study for more than 30 years and, possibly, represents a subtype of one of the already known receptors.

The name of the receptors comes from those substances that were originally discovered as substances that interact with this receptor. Thus, the “mu receptor” comes from the first letter of morphine, the “kappa receptor” from ketocyclazosine, the “delta receptor” was named after the “vas defference” (vas deferens) of the mice where this receptor was originally found.

Simplifying, we can say that all opioid receptors are supramolecular complexes built into the plasma membrane that interact in isolation with specific ligands – opioids of endogenous or exogenous origin.

Conventionally, the mechanism of activation of mu-opioid receptors can be described as a series of sequential changes on the surfaces of the neuronal synapse. Interaction of an opioid ligand (for example, morphine) and a mu receptor triggers the synthesis of a secondary messenger enzyme, cAMP. As a consequence, this leads:

  • to the closure of voltage-dependent calcium (Ca ++) channels on the presynaptic membrane of the neuron, then to a decrease in the release of excitatory neurotransmitters (glutamate), causing a weakening of pain impulses;
  • to the opening of potassium (K +) channels on the surface of the postsynaptic membrane, to stimulation of the release of potassium into the intersynaptic cleft, which leads to hyperpolarization of the postsynaptic membrane and reduces the sensitivity of the neuron to the excitatory action of neurotransmitters;
  • as a result, neuronal excitability sharply decreases, the transmission of nerve impulses is inhibited and the release of neurotransmitters is inhibited;
  • The flow of pain impulses is weakened or interrupted.

This is just a simplified diagram of a complex process. Currently, the process of excitation and inhibition of nociceptive receptors has been studied in sufficient detail, more than 35 different substances are involved in it, including potassium and hydrogen ions, nitric oxide molecules, tissue and plasma algogens, as well as neuropeptides (substance P, neurokinin A, calciotonin-gene) related peptide, etc.).

In addition to the ability to control the conduction of pain impulses, opioid receptors are involved in many other physiological and pathophysiological processes, such as membrane ion homeostasis, cell growth and division, emotional component, seizures, appetite, obesity, cardiovascular and respiratory control.This is an incomplete list of the effects of the opioid system on the human body.

Opioid receptors are involved in animal hibernation (a period of deep numbness in cold climates) and, as has been identified in recent years, have a powerful neuro- and cardioprotective function. Stimulation of delta receptors enhances neuronal resistance to hypoxia and ischemia, increasing neuronal survival and antioxidant activity. All this explains the effectiveness of opioid treatment in such fatal conditions as stroke and myocardial infarction.

Three main types of opioid receptors are most relevant to analgesia: mu, delta, kappa. These receptors are concentrated on the surface of the neurons of the dorsal horns of the spinal cord (I and II plates) and in numerous centers of the overlying parts of the brain, although opioid receptors are also present on the surface of cells of the immune system, in joints, in various organs (for example, in the intestinal wall) and peripheral tissues.

The effect of opioids on mu, delta and kappa receptors is not the same.Some drugs stimulate (agonists), others block (antagonists) these receptors. There is a group of substances that simultaneously exert stimulating and blocking effects on the same receptors. These opioids are commonly referred to as agonists / antagonists. Representatives of the latter group (partial agonists) stimulate only a certain type of receptor, while they are not able to cause maximum excitation of the mu receptor.

The effectiveness of an opioid depends mainly on how strongly the substance binds to opioid receptors.This is most often correlated with the level of analgesia. Based on a variety of laboratory studies, the degree of affinity (affinity) of receptors and various opioids has been established, however, these data are quite contradictory, since various laboratory animal models were used in the studies, and different indicators were studied. Therefore, the potency of opioids is indicated in a certain range, and these figures are approximate. For example, morphine binds mu receptors by about 68%, fentanyl by 81%, and carfentanyl by 98%.

The analgesic effect in the experiment is investigated on laboratory animals, using either thermal (hot plates), mechanical or chemical action. The lower the dose of the opioid is able to effectively relieve pain, the more “potent” the drug. These studies do not take into account the individual characteristics and emotional aspects of pain inherent in a person.

Due to the fundamentally different physiology of acute and chronic pain, the effectiveness of opioids is being investigated in acute pain.In the case of chronic pain, the relative effectiveness of an opioid is extremely difficult to calculate, as the emotional and cognitive mechanisms are not well understood.

Opioids can be roughly divided into three groups: weak opioids, medium-power opioids, strong opioids. This division is subjective, and there is currently no full consensus of opinion on where this or that opioid belongs. The gold standard for opioid efficacy is the analgesic effect of 10 mg parenterally administered morphine.This drug is the most studied and has been used for a long time. Accordingly, its analgesic effect is taken as a unit, as in the SI system, units are 1 meter or 1 gram. Accordingly, a drug with an indicator of “1.5: 1” is one and a half times stronger than morphine; “5: 1” is five times stronger, a “0.2: 1” is five times weaker, “0.1: 1” is 10 times weaker, etc.

Buprenofine is considered one of the strongest analgesics, it is 30-50 times more effective than morphine. Oxycodone is 1.5-2.0 times higher than morphine, and tramadol and codeine are 5 and 10 times weaker, respectively.

Characterization of selected opioids

Morphine

Morphine is the gold standard for opioids. This does not mean that it is better, more powerful, safer or cheaper than other drugs in this group. Its effect is the most studied and accepted as the standard, since historically morphine was the first opioid analgesic isolated in pure form from opium juice in 1804 in Germany, thanks to the work of Friedrich Serterner.

Since 1827, morphine has been commercially available as a drug and since the invention of the syringe in 1857 has been widely used as a powerful analgesic. The name comes from the name of the Greek god of dreams Morpheus, the son of the god of sleep – Hypnos. The entire morphine molecule was synthesized by Robert Woodvodrom in 1952, but the complexity of this process (originally 17 steps were included) makes its commercial use impractical. Even now, when simpler methods of synthesis exist, natural morphine is still significantly cheaper than synthetic one.

Its properties and characteristics are in many ways inferior to more modern opioids. One of its individual properties is the gradual accumulation of the toxic metabolite morphine-3-glucuronide (M3G). With long-term use, morphine M3G poorly binds to opioid receptors and can cause peripheral neuropathies and encephalopathy, in contrast to M6G, which is 20-45 times more active than the parent substance when administered epidurally and 4 times when administered subcutaneously. In addition, it is an important cumulative component in morphine pain relief.

Morphine is metabolized in the liver, kidneys and brain through the process of glucuronidation bypassing the liver enzymes of the cyprohexadine series and is excreted mainly by the kidneys, and also to a small extent – with bile. Up to 87% of the dose taken is eliminated within the first 72 hours, but with renal failure, this process is delayed, leading to the accumulation of toxic metabolites and increasing the likelihood of respiratory depression and other opioid-dependent side effects. The half-life of morphine averages 1.9 hours (in tolerant individuals, this indicator may vary).Up to 8% of the administered dose is excreted unchanged.

Morphine is poorly absorbed when taken by mouth due to low intestinal absorption and the “first pass” effect through the liver. Only ⅓ of morphine taken orally enters the systemic circulation. Liquid forms of morphine (1% and 2% solutions – for oral administration) have the same onset of action as tablet forms, since absorption occurs in the same areas of the intestine and practically does not occur in the oral cavity.

In medical practice, only water-soluble salts of morphine (sulfate and hydrochloride) are used, which poorly penetrate the blood-brain barrier. This leads to the fact that the concentration of morphine in the central nervous system rises later than in the blood plasma, which can lead to errors in forensic examination (in particular, in establishing the cause of death). In addition, when morphine is metabolized in small amounts, normorphine, codeine and hydromorphone are formed, which can also lead to erroneous conclusions about the drugs taken by the patient.

Methods of introducing morphine into the body include all possible routes except transdermal.

Codeine

Codeine is the most widely used opioid in medical practice worldwide. It is the second most potent opium alkaloid and is the prototype of such opioids as tramadol, dextropropoxyphene, hydrocodone and oxycodone. It was first isolated in France by Pierre Robiquet in 1832.

The codeine molecule has no analgesic effect, but about 10% of codeine is metabolized to morphine, which in turn controls pain.A significant part of the codeine is immediately glucoronized and excreted by the kidneys as an inactive substance. The rest is metabolized through the cytochrome C450 2D6 system to morphine, norcodeine, hydromorphone, and codeine-6-glucoronate.

If this process is disrupted by the introduction of drugs that block 2D6 (for example, paroxetine, fluoxetine and duloxetine, etc.), then morphine is not produced, and codeine instead of pain relief causes a number of side effects. Rifampicin and dexamethasone, on the other hand, stimulate 2D6 and lead to increased synthesis of morphine, thus enhancing the main analgesic effect of codeine.

Due to the peculiarities of genetic polymorphism, 10-15% of Europeans have a low activity of the 2D6 enzyme. Therefore, in a significant number of Caucasian populations, codeine is ineffective as a pain reliever.

Due to the weak analgesic effect of codeine, it is used mainly in the treatment of cough, diarrhea, and less often to reduce labor pains. Despite the described features of elimination, the drug is widely used throughout the world in the treatment of moderate and non-cancer pain.The most commonly used combinations of codeine in doses of 8-30 mg with paracetamol, less often with NSAIDs, aspirin or sodium metamizole.

Dihydrocodeine – a semi-synthetic analogue of codeine, in some countries (for example, in England) is used for the treatment of moderate pain. It is usually used in combination with paracetamol or aspirin. It is often prescribed as an antitussive agent. In Russia, dihydrocodeine tablets are registered but never supplied.

Fentanyl

Fentanyl is a true mu agonist and one of the most potent opioid analgesics used in daily clinical practice.The drug was first synthesized in 1959 by Paul Janssen, the creator of such well-known drugs as haloperidol and droperidol.

Since the release of fentanyl in injectable form in 1962 by specialists from the Belgian company Janssen Pharmaceutical and is still widely used in anesthesiology, since it is 100 times more analgesic than morphine, while at the same time it has a unique controllability, a short onset of action (within 45- 60 s after intravenous administration) and a number of other qualities that make it indispensable for achieving powerful analgesia during surgical interventions.

The use of fentanyl for the treatment of severe chronic pain syndrome in oncology was associated with the invention of a new non-invasive dosage form – a transdermal therapeutic system (TTS) for application to the skin, which provides gradual dosed absorption and entry of the drug into the systemic circulation, followed by a long-term analgesic effect – 72 hours .

The drug metabolism occurs mainly in the liver (N-dealkylation and hydroxylation), as well as in the kidneys, intestines and adrenal glands with the formation of inactive metabolites, which are excreted mainly in the urine (75%) and feces (9%).No more than 10% of the dose taken is excreted unchanged in the urine.

Fentanyl is extensively metabolized by cytochrome P-450 CYP3A4 in the liver. Since the metabolic process involves only a small part of the enzyme’s activity, even with liver disease, as a rule, no dose adjustment of fentanyl is required. At the same time, this opioid should be used with caution in people with low P-450 CYP3A4 function or with the concurrent use of such inhibitors of this enzyme as ketoconazole, fluvoxamine, erythromycin, grapefruit juice, etc.as this can lead to unpredictable accumulation of fentanyl in blood and tissues. On the other hand, tobacco, carbamazepine, phenobarbital, modafinil, etc., accelerate the metabolism of fentanyl, leading to a decrease in its level and effectiveness.

In contrast to morphine, fentanyl metabolites are inactive, although in case of liver disease in elderly, debilitated or debilitated patients, the metabolism of the drug may be delayed.

Fentanyl is considered to be the drug of choice for patients with impaired renal function.A number of specific qualities of fentanyl (high analgesic activity, lipophilicity, moderate sedative effect on the central nervous system and depressive effect on the cardiovascular system) make its use in the form of TTS beneficial for the treatment of chronic pain syndrome in cancer patients.

However, it should be borne in mind that the drug is deposited in adipose tissue, therefore, after the termination of administration (including transdermal), its effect continues until the concentration of the drug in adipose tissue is depleted.This process is individual and can fundamentally differ in different patients from several hours to several days (average duration 24 hours).

Due to its high lipophilicity, this drug quickly penetrates into the central nervous system, which is associated with numerous cases of overdose, such as, for example, accidental contact of the contents of the first generation patch on the skin of children. TTS of the matrix type have now been created, in which the substance is incorporated into the polymer, which makes it possible to even cut TTS without losing fentanyl.

Sufentanil, alfentanil, remifentanil, lofentanil, etc. were synthesized on the basis of fentanyl.

Fentanyl is applied in the form of patches, intravenously, under the tongue in the form of tablets or buccal in the form of special plates on the buccal mucosa, in the form of a spray for spraying in the nasal cavity or the floor of the mouth, or through an inhaler – intratracheally. Epidural and intrathecal administration are also possible.

Intravenous fentanyl is used for general anesthesia.Fentanyl patches are used to treat moderate to severe chronic pain, including in children (there are no indications for use in children in Russia).

All other non-invasive routes of administration give a quick and short-term effect (1-3 hours), therefore they are used for pain breakouts, mainly in cancer patients. In the United States, a spray of pure fentanyl (not associated with citrate, as in all other drugs) is used under the tongue, with an onset of action within 5 minutes (Subsis).Registration of this drug in Russia is not considered.

An interesting new way of using fentanyl for postoperative pain relief using a patch with a button for iophoresis, which is pressed by the patient himself when he experiences pain, which is analogous to patient-controlled analgesia. Fentanyl is less likely to cause nausea, vomiting, and constipation than morphine. Has less effect on histamine receptors and less likely to cause itching and bronchospasm.

Sufentanil

This is a potent mu-opioid agonist analogous to fentanyl.It is used only during operations for intravenous and epidural administration under general anesthesia. It is about 1,000 times more potent than morphine.

Unlike fentanyl, it practically does not accumulate in tissues, or rather, its high tissue affinity (due to lipophilicity) contributes to its rapid redistribution into inactive tissues (fat, skeletal muscles), which significantly limits the time of its action, especially at low doses.

In terms of its clinical and pharmacological characteristics, the drug is similar to fentanyl, but has a more pronounced sedative effect; miosis, respiratory depression, bradycardia, nausea, vomiting and smooth muscle spasm may develop more often.

Less than 1% of unchanged sufentanil is excreted in the urine. Sufentanil metabolites are excreted in both urine and feces. About 30% of the released metabolites are conjugated.

Used as sufentanil citrate for general anesthesia and postoperative pain relief. There are no enteral dosage forms, but transdermal systems (patches) with sufentanil are being tested.

Methadone

This synthetic opioid was developed in 1937.in Germany, in preparation for war. Since 1947, this drug has been approved for use in the United States. The unique pharmacological features make this opioid especially dangerous in clinical use. Only 5% of patients with chronic pain use methadone in the United States, but it is associated with 30% of all opioid-related deaths (legal and illegal) in this country.

The low cost of this opioid is the main reason for its widespread use. Methadone is approved not only for the treatment of pain, but also for substitution therapy for heroin addiction in the United States and European countries, as well as in Belarus, Ukraine, and Georgia.In Russia, this opioid is prohibited for medical use, as are all types of substitution therapy in the treatment of drug addiction.

Methadone is a racemic mixture of right- and levorotatory isomers presented in equal proportions. Methadone dextrorotatory molecules block NMDA receptors, which is especially effective in the treatment of neuropathic pain. The levorotatory isomer acts only on opioid receptors. Therefore, a racemic mixture of molecules is used in pain syndromes, and levomethadone is used in the treatment of drug addicts.

The left-handed molecule also blocks the absorption of serotonin and norepinephrine. Thus, cyclic antidepressants, MAO inhibitors cannot be combined with methadone, and the use of all selective antidepressants should be extremely careful with it.

This preparation has both water and fat soluble properties. The syndrome of prolonged QT interval and polymorphic ventricular tachycardia is one of the serious side effects of methadone.

The greatest danger of this opioid is its unpredictable half-life, which ranges from 3 to 72 hours (some sources suggest half-life up to 150 hours) and varies due to many factors, with the danger of reaching lethal plasma concentration even with regular use …This is the main contraindication for the use of methadone in the treatment of acute pain.

Usually drugs without active metabolites, like methadone, have a predictable duration of action. One of the unusual properties of methadone is that the duration of its pain-relieving effect is not correlated with the pain-relieving effect. Despite its long presence in the blood, the duration of the methadone dose in terms of pain control does not exceed 4-6 hours, and it is prescribed to be taken at least 3-4 times a day.

Methadone is metabolized in the liver through the cytochrome P450 C YP3A4 system, like fentanyl. Unlike fentanyl, methadone is also an inhibitor of the P450 CYP3A4 enzyme. Thus, this opioid exhibits non-linear pharmacodynamics, disproportionately increasing efficacy with dose escalation.

The efficacy of methadone is likely to continue to improve as doses are increased, reaching a 15-fold increase over morphine at 500 mg / day and 20-fold at over 1,000 mg.Selected examples of drugs that inhibit or stimulate CYP3A4 are given above when describing fentanyl.

Similarly, CYP3A4 stimulants, when given with methadone, can cause withdrawal. The combined use of CYP3A4 inhibitors can significantly increase the plasma concentration of methadone and cause an overdose, which often occurs in real clinical practice. If a patient takes a drug that stimulates CYP3A4 (for example, phenobarbital) while on methadone therapy, then methadone intoxication may also develop if this stimulant is canceled.

The positive aspects of using methadone are its cytotoxic properties, which are being actively investigated for the treatment of leukemia and tolerance to chemotherapy with conventional drugs. It causes less euphoria compared to morphine, which, in particular, explains its use in the treatment of drug addiction.

Hydrocodone

Hydrocodone is a semi-synthetic opioid. Synthesized in Germany in 1920Karl Mannich and Helena Lowenheim and has been used in the United States since 1943. It is the most commonly used opioid in the United States. It is mainly available in combination with acetaminophen (paracetamol) or ibuprofen, and in these mixtures until 2015 was less controlled than other mu-agonist opioids, with the exception of buprenorphine.

Pure hydrocodone has always been controlled at the same level as morphine; 99% of the world’s total consumption of this opioid is in North America. Increased control of the combination hydrocodone preparations was introduced in connection with an epidemic of abuse of this drug.

Opinions about the potency of this drug differ, and different experts estimate its potency from 60 to 130% of the potency of morphine. This is because, although hydrocodone, when administered intravenously, exhibits only 40% of the potency of morphine, when administered orally, the potency of hydrocodone is higher due to its higher bioavailability during gastrointestinal absorption.

Cases of ototoxicity of hydrocodone have been described, although it is believed that this is the effect of paracetamol, and not hydrocodone.

This opioid in its pure form has a rather weak analgesic effect and must undergo biotransformation to active metabolites. It is metabolized by the cytochrome P450 CYP2D6 system in the liver and gastrointestinal mucosa to hydromorphone (the main metabolite) and morphine. Another enzyme, CYP3A4, produces norhydrocodone. Substances that enhance CYP2D6 function increase the strength of hydrocodone (by producing more hydromorphone). Inhibitors of this enzyme can reduce the strength of hydrocodone.

A case of death in a child who had a naturally weak CYP2D6 and was prescribed a drug that inhibits CYP3A4 was described. In Indianapolis, USA, a child died from respiratory failure after routine tonsil removal. The child received a small dose of codeine in the postoperative period, but due to congenital hyperactivity of the 2D6 enzyme, the high production of hydromorphone and morphine in his body caused respiratory arrest.

Due to the metabolic process described above, hydrocodone can give false positive data on urinalysis, indicating the presence of morphine, codeine, hydromorphone and the false presence of cocaine.In Belgium, France, Germany, the Netherlands and Sweden, this opioid is not licensed for legal use.

Hydromorphone

Hydrocodone metabolite. It was first produced in Germany in 1924 from morphine and is about 8 times more potent than morphine. It is more lipophilic than morphine and therefore has a faster onset of action. Hydromorphone causes less constipation than its predecessor. These properties of hydromorphone contribute to its widespread use in many countries.

Like morphine, hydromorphone can be used in many forms, from tablets to intrathecal administration using implanted pumps. Unlike morphine, this opioid has been successfully administered subcutaneously as an alternative to intravenous administration.

Hydromorphone is metabolized in the liver by glucuronidation, with the formation of toxic, but no analgesic substances: hydromorphone-6 and hydromorphone-3 glucoronates. Hydromorphone is excreted from the body by the kidneys and should be used with caution in renal failure.

Hydromorphone is associated with a strong feeling of euphoria and is extremely dangerous in case of an overdose. In the United States in Ohio, this opioid is used intramuscularly (in combination with midazolam) to carry out a death sentence if there is no access to a vein.

The stimulating effect of hydromorphone causes not only euphoria, but also myclonic convulsions and hyperalgesia. Alcohol increases the dumping effect of hydromorphone, which can lead to accidental overdose.Because of this effect, long-acting hydromorphone drugs have been banned in the United States.

Oxycodone

Semisynthetic opioid manufactured by Frund and Spreyer in Germany in 1916 shortly after Bayer’s discontinuation of medicinal heroin. Oxycodone has been in clinical use in Europe since 1917 and in the United States since 1939.

One of the most interesting opioids from the point of view of studying the properties of opioid addiction, most likely due to the action on kappa receptors.According to a number of researchers, oxycodone, unlike other opioids, has a more powerful effect on the kappa receptors, and not only on the mu receptors, although this point of view has not been definitively proven. The effect on the kappa receptor, in particular, is associated with euphoria and a variety of other stimulatory effects.

Metabolism is carried out through cytochrome P450 2D6, which converts oxycodone to oxymorphone and noroxycodone (the latter is a weak analgesic). This biotransformation pathway should be considered by clinicians when combining oxycodone with medications or foods that stimulate or inhibit this enzyme by altering the blood oxycodone concentration.The most dangerous is the inhibition of CYP 2D6, which leads to the accumulation of oxycodone in the body, therefore it is better to avoid drugs such as paroxetine, fluoxetine and duloxetine.

It is the oxycodone molecule, and not its metabolites, that has a powerful analgesic effect, therefore, like fentanyl, it is the drug of choice for impaired renal function, although it is excreted mainly in the urine, and renal excretory function directly affects the level of oxycodone in the blood.

Oxycodone is widely used either in combination with paracetamol or as a pure substance.Unlike hydrocodone, oxycodone combination products have always been controlled in the United States in the same way as pure oxycodone.

The potency of oxycodone in relation to morphine is estimated from 1: 1 to 2: 1, but due to the euphoric effect, patients often prefer oxycodone. Approximately 82% of the oxycodone produced worldwide is consumed in the United States. According to 2007 data, Canada, Germany, Australia and France together account for 13%. In recent years, the use of oxycodone in America has increased even more, has become epidemic, which has become one of the major national problems.

In order to reduce the serious side effects of oxycodone, mainly from the gastrointestinal tract (GIT), at the end of the last century, a combined drug oxycodone with naloxone was created, where naloxone was assigned the role of an antidote in the effect of the opioid oxycodone on intestinal excretory function. Since naloxone has a greater affinity for opioid mu-2 receptors, which are located in the intestinal wall, it blocks them and prevents oxycodone from interacting with them.

Thus, oxycodone is actively absorbed in the gastrointestinal tract (up to 75%) and enters the systemic circulation, where it has the main analgesic effect, and naloxone, which is practically not absorbed in the gastrointestinal tract (3%), provides good intestinal passage while taking a strong opioid.

It is used in non-cancer patients with moderate to severe pain, in cancer patients for long-term opioid therapy. The drug under the brand name Targin is widely used in Europe, it is also registered in Russia and will go for use in 2017.

Oxymorphone

This is the first synthetic opioid produced in Germany in 1914, but it did not appear on the medical market until the late 1950s. Only 10% of oxymorphone enters the bloodstream after passing through the liver, but it is about 5 times more potent than morphine. Oxymorphone metabolism occurs by conjugation with glucuronide and does not affect P450. The metabolites are non-toxic. At the same time, it is itself a metabolite of oxycodone after its biotransformation by CYP 2D6.

Unlike oxycodone, which binds to mu, kappa and delta opioid receptors, oxymorphone interacts only with mu receptors. Alcohol causes unexpected changes in the concentration of oxymorphone in the blood when taken concurrently. The concentration can be halved or increased many times in the presence of alcohol, which can lead to overdose. Taking oxymorphone with food, especially fatty foods, significantly increases plasma opioid levels and is therefore recommended for use on an empty stomach.Misoprostol slows down the absorption of oxymorphone.

Oxymorphone has a high lipophilicity, therefore, research is currently underway on its intranasal application in the form of a spray, as well as in the form of a transdermal patch. At equianalgesic doses, oxymorphone is more toxic than morphine, but safer than synthetic opioids such as methadone and meperidine (pethidine). Oxymorphone is less likely to cause seizures than most other opioids. An important feature is less pronounced drowsiness compared with morphine.

In early July 2017, long-acting oxymorphone (Opana ER) was withdrawn from the US medical market due to the high risk of overdose and abuse.

Levorphanol

This is a left-handed isomer of the synthetic substance “morphinan”, from which nalbuphine, butorphanol, dextromethorphan, etc. were also synthesized. It was first described in Germany in 1948. In 1971, in the United States, Candice Perth used it in research that led to the discovery of opioid receptors.Levorphanol metabolism occurs through glucoronidation without the mediation of P450 and without the production of active metabolites.

Levorphanol is 4-8 times more potent than morphine and has a longer half-life. Some academic sources estimate the potency of levorphanol 12 times that of morphine, but this does not correlate with observations in clinical practice. Levorphanol is administered orally, intravenously and subcutaneously. Due to its long-term effect, it is recommended to use it not for the treatment of acute pain, but mainly for the treatment of chronic pain.

A unique property of this opioid is its action not only on mu, kappa and delta receptors, but also on sigma receptors. In addition, it blocks NMDA receptors and is quite effective in blocking the reuptake of serotonin and especially norepinephrine.

As a result, levorphanol is known to be effective in treating neuropathic pain and is potent in improving mood. Unfortunately, all of this is associated with an increased risk of abuse.Its combination with antidepressants can lead to side effects, including serotonin syndrome.

Tramadol

One of the weakest mu agonists, tramadol hydrochloride was synthesized in 1962 in Germany and entered the market in 1977.

Tramadol, like methadone, is a racemic mixture of two enantomers, which are involved in analgesic action in different ways. One isomer, O-desmethyltramadol, is a pure opioid receptor agonist that is 200 times more potent as an analgesic than tramadol.Another isomer inhibits the neuronal uptake of serotonin and norepinephrine, activates the central descending noradrenergic system, which disrupts the transmission of pain impulses to the gelatinous substance of the spinal cord. Thus, both isomers act synergistically.

The analgesic activity of tramadol to morphine is 0.5: 1 or 0.1: 1 when administered orally. When administered intravenously, the analgesic efficacy of tramadol is comparable to that of morphine. The tramadol molecule is not an active analgesic and the drug is metabolized by the cytochrome P450 2D6 system to active metabolites.Like codeine, in 6% of the population, which by nature have an increased activity of this cytochrome system, the effect of tramadol will be much higher, and in 8-10% of people in whom this enzyme is weakened, pain relief will be ineffective. The same is true for substances that inhibit or activate this liver enzyme.

Thus, the metabolism of tramadol and codeine is quite similar. Although tramadol is weak when administered enterally, when given intravenously, it can be compared to morphine and therefore poses a risk of abuse.According to its pharmacological parameters, it is modeled like levorphanol, only with a weak effect on the mu receptor.

But it is molecularly similar to the antidepressant venlafaxine and acts as an inhibitor of the reuptake of serotonin and partially norepinephrine. Because of these properties, tramadol has a mild analgesic but strong antidepressant effect, and the level of illegal use when taken orally is low. In the United States, it is the only opioid not controlled until 2015.at the federal level, with the exception of some states that have introduced controls on tramadol.

The tramadol molecule is somewhat similar to codeine. When combined with paracetamol or anti-inflammatory nonsteroidal drugs, the analgesic efficacy of both substances increases, therefore, in some countries, combined drugs are produced (the combination with paracetamol is especially often used). The products of tramadol metabolism are excreted by the kidneys, and the dose of the drug should be reduced in case of renal failure.

The combination of tramadol with any serotonergic substances can be dangerous, and the combination with MAO inhibitors is contraindicated.

Tramadol can provoke seizures, even in small doses, so the use of this opioid in patients with epilepsy is best avoided. The occurrence of seizures can be explained by the fact that tramadol blocks GABAd receptors. The withdrawal syndrome of this opioid is similar to that of other opioids, but is milder, or as after the withdrawal of antidepressants.

The drug is widely used all over the world, including Russia. The combined preparation of tramadol and paracetamol tablets in Russia is registered under the brand name Zaldiar.

Tapentadol

Like tramadol, this opioid was developed by the German firm Grunental, but with the participation of Johnson & Johnson. It is the most recent opioid analgesic to hit the American and European markets from 2009-2010.

The mechanism of action of tapentadol is similar to tramadol, it binds to mu-opioid receptors and simultaneously blocks the reuptake of norepinephrine in synapses. With the opioid antagonist naloxone, the analgesic effect of tapentadol is only halved, thus it is assumed that 50% of the analgesic effect is not via the opioid system but via descending norepinephrine inhibition at the level of the spinal cord.

Unlike tramadol, the tapentadol molecule has a direct analgesic effect, the effectiveness of the drug does not depend on the primary metabolism in the liver.The drug is slightly more effective than tramadol and significantly weaker than morphine and oxycodone. A number of publications indicate a high analgesic potential of the drug in the treatment of neuropathic pain.

Tapentadol is characterized by less pronounced side effects from the gastrointestinal tract (nausea, vomiting, constipation), as well as from the central nervous system (drowsiness, weakness, dizziness). Unlike most opioids, the drug does not lengthen the QT interval, does not affect heart rate or blood pressure, and has minimal narcogenic potential.However, isolated hallucinatory reactions have been described, probably due to excessive accumulation of norepinephrine in synapses. Due to the powerful effect on serotonin and norepinephrine, the combination of tapentadol with antidepressants can be dangerous, and the combination with MAO inhibitors is contraindicated.

This opioid is metabolized by conjugation and does not pass through the cytochrome P450 system. It has no active metabolites and is excreted by the kidneys. Precautions are recommended for kidney disease.

Meperidine (pethidine)

Like many other opioids, meperidine was synthesized in Germany. Chemist Otto Eislib developed this opioid in 1932 as a cure for muscle spasms, and it was only years later that the analgesic properties of meperidine, which is about 10 times weaker than morphine, were revealed. In the XX century. meperidine has been widely used in medical practice.

The initial opinion that this opioid is safer than morphine did not come true, on the contrary, with the accumulation of knowledge and experience with the use of meperidine, it turned out that this is one of the most toxic opioids, causing convulsions, delirium and destructive neurocognitive effects due to the accumulation of a toxic half-life product – normeperidine.An analogue of meperidine, trimeperidine, has been produced in Russia since 1952 under the name promedol.

Combined with mild analgesic and short-acting, problems with concomitant use with many medications, meperidine use has dropped dramatically. Many countries have imposed government restrictions on the use of this opioid. The death of patient Libby Zion, who was injected with meperidine while taking the antidepressant fluosetine (Prozac) in an emergency room in a New York hospital, led to major changes in both legislation and medical education in the United States.

Meperidine stimulates mu receptors and, unfortunately, kappa receptors, which causes neurodegenerative and psychotic reactions. It has only a mild relaxing effect on smooth muscles, so the hopes that it might be more effective than morphine for gallbladder spasms and renal colic did not come true. Structurally, this opioid is somewhat similar to atropine, which gives it many side effects, especially anticholinergic ones.

Meperidine blocks the transport of dopamine and norepinephrine, its combination with antidepressants, especially with MAO inhibitors, can lead to death. Numerous cases of serotonin syndrome, which is caused by meperidine, are known, even without a combination with other drugs.

Sodium channel inhibition is another adverse effect of meperidine associated with cardiac arrhythmias. The psychotropic effect of meperidine is sometimes compared to that of cocaine. It is metabolized by several cytochromes P450 and, by conjugation with glucuronide (glucoronidation), is converted to normperidine, which is 50% weaker for the treatment of pain, but many times more toxic than meperidine itself. The half-life of meperidine is approximately 3 hours, and that of normeperidine is 8-12 hours.High levels of toxic metabolites can accumulate even during the first two days of therapy.

This opioid is more lipophilic and acts faster than morphine, but has less pain suppression than morphine. It can be used orally, intramuscularly and intravenously.

Meperidine and its metabolites are excreted by the kidneys, therefore, caution should be exercised when using it in patients with renal insufficiency. The metabolites of trimeperidine (promedol) are the same as that of meperidine (normeperidine), which is why its long-term use in the treatment of chronic pain is contraindicated.

Propoxyphene

This opioid was first patented in the United States in 1955 by Eli Lilly, was used since 1957 and withdrawn from the European market between 2005-2009, and was subsequently banned in the United States in 2010 due to serious cardiotoxic complications. associated with cardiac arrhythmias (and in part due to the association with suicide).

This synthetic opioid is structurally similar to methadone, is comparable in strength to codeine (10 times weaker than morphine) and is metabolized in the liver into a toxic and very long-acting metabolite, norpropoxyphene.The drug caused not only arrhythmias, but also convulsions and psychosis. According to available information, this opioid is currently not approved for use in almost all countries.

Buprenorphine

Perhaps one of the safest and most effective opioid analgesics for the treatment of chronic pain. It was synthesized for the treatment of heroin addiction. The British company, now called Reckitt Benckiser, began trials of this semi-synthetic opioid in 1971.and in 1978 it was marketed in the UK as an intramuscular injection for the treatment of severe pain. Since 1982, it has been used in the form of a tablet under the tongue.

In the United States, this drug has been approved for use in the form of injections for the treatment of pain since the early 1980s, and for substitution treatment of patients with opioid dependence – since 2002 (in sublingual form). The European Union has approved the use of buprenorphine for substitution therapy since 2006.For the treatment of pain, buprenorphine transdermal systems (patches) have been used in Europe since 2001

Registered doses 35; 52.5 and 70 mcg / h, they are distinguished from the transdermal therapeutic system (TTS) of fentanyl by a long duration of action – up to 96 hours and a “ceiling” effect – a maximum dose of 140 mcg / h.

In Russia, patches with buprenorphine have been used for a short time since 2003. In addition, a patch has been developed for the treatment of non-oncological pain mainly in the elderly (Butrans), which lasts up to 7 days and has a minimum dose of 5, 10, 15, 20 μg / h …

In the United States, doses of TTS of buprenorphine in excess of 20 mcg / h (approximately 0.5 mg / day) are currently not approved for pain management due to concerns about arrhythmias. Another form – under the tongue – is allowed at a dose of up to 1.8 mg / day (Belbuca). At the same time, without much logic, buprenorphine is approved for replacement therapy up to 24 mg / day.

In May 2016, Braeburn Pharmaceuticals began manufacturing Probufin, a subcutaneous buprenorphine implant. The implant, about the size of a match, contains 74.2 mg of buprenorphine and is implanted on the inside of the arm.Up to four implants are allowed to be implanted at the same time. The duration of the implant is 3-6 months. Implants in the United States are approved for drug substitution treatment rather than pain management, but are sometimes used in clinical practice for pain relief.

Buprenorphine has a high lipophilicity, but it is not a complete but a partial agonist of opioid receptors. In terms of pain control, it is 30-50 times stronger than morphine, but causes much less depression of the respiratory center.Other positive properties of buprenorphine are a lesser effect on the gastrointestinal tract (less constipation and spasm of the intestines, spasms of the sphincter of Oddi) and a minimal negative effect on the cognitive abilities of the brain.

Unlike all other opioids, it does not activate, but inhibits the kappa receptor, thus improving mood, reducing anxiety, not causing drowsiness and contributing to a lower risk of abuse. In addition, buprenorphine benefits from its duration of action and slow dissociation from opioid receptors.Thus, the withdrawal syndrome it produces is milder than that of morphine or fentanyl.

Another unique and beneficial property of buprenorphine is the absence of the effects of immunosuppression, which complicates the life of many patients who take opioids.

The low level of euphoria makes this substance unpopular among drug addicts, although there is evidence of a fairly high level of illegal use of buprenorphine, especially in the Scandinavian countries.As a rule, drug addicts use buprenorphine not for the purpose of euphoria, but as self-medication for withdrawal syndrome (if access to regular opioids or heroin is temporarily impossible) or to control pathological cravings for heroin, since if euphoria occurs when using buprenorphine, then this reaction stops after several doses and does not resume when the dose is increased.

There is a risk of misuse of buprenorphine, like tramadol, when it is administered intravenously but not orally.To reduce the risk of such administration of the drug, buprenorphine is produced in a mixture with naloxone (drug Saboxon, etc.). When administered orally, naloxone is not absorbed and remains neutral. When intravenous administration is attempted, naloxone is absorbed and may cause acute withdrawal.

In Russia, buprenorphine + naloxone sublingual tablets are produced under the name Bupraxone, which is registered for the treatment of acute pain (after burns or postoperative pain).

Buprenorphine is a partial agonist of opioid receptors.The term “partial agonist” is not always clear. A partial agonist in the case of buprenorphine means that it stimulates the mu and delta receptors, but blocks the kappa receptors. That is, only part of the opioid receptors are excited under its action (mu- and delta-), and some are not excited (kappa-). At the same time, buprenorphine has a higher affinity for mu receptors than fentanyl, so it is able to displace fentanyl in receptor interaction.

As mentioned above, in the treatment of opioid dependence, buprenorphine is used in combination with the opioid antagonist naloxone to prevent intravenous administration of the drug for abuse.This combination does not actually reduce the likelihood of abuse, but improves the analgesic properties of such a combination drug and reduces side effects from the gastrointestinal tract.

A distinctive feature of buprenorphine is the “Ceiling” effect. Increasing the dose over 24-32 mg / day does not lead to increased analgesia, but increases the number and severity of side effects. The recommended maximum therapeutic dose of buprenorphine in Russia is 2.4 mg / day (when taken as a combined drug Bupraxone).

Buprenorphine is used in the USA as TTS for the treatment of pain in doses up to 20 μg / h (0.48 mg / day) or under the tongue up to 900 μg twice a day (1.8 mg / day). This dose fully controls pain in 10-15% of patients. For the treatment of drug addiction, higher doses are used – up to 24 mg / day.

Higher doses of buprenorphine (rarely up to 32 mg / day) are commonly used in the United States for the treatment of chronic pain. Basically, patients are prescribed from 6 to 24 mg / day.At these doses, pain is controlled in most patients. The majority of these patients receive the drug within 1-2 years and cancel it completely.

It should be remembered that the use of large doses of buprenorphine can reduce the analgesic effect of injected morphine (and other mu-agonists) to the level inherent in buprenorphine. As with methadone, buprenorphine’s long half-life (36 hours) does not mean that the substance helps control pain when taken once a day and when taken orally, not once, but 2-3 times a day.

Buprenorphine is metabolized in the liver by the P450 ZA4 system and is excreted in the bile through the intestine mainly unchanged, a small part is excreted by the kidneys in the form of metabolites. Thus, it is the drug of choice for renal failure. Naloxone only partially attenuates the effects of buprenorphine (even in high doses) and is not a complete antagonist; this is in contrast to opioid analgesics of full mu agonists. The metabolism of buprenorphine and its drug interactions associated with the activation and blockade of P450 ZA4 follow the same pattern as described above in the “methadone” or “fentanyl” sections.

The unique properties of buprenorphine are the ability to enhance the effects of mu receptors (as a result, the same receptors control pain better than under the influence of other opioids) and cause the migration of mu receptors to the neuron membrane, which also enhances the effect of analgesia. Buprenorphine is more versatile than, for example, fentanyl, and is able to control various types of pain, including hyperalgesia, which can be caused by all other mu agonists. This is most likely due to a blockade of kappa receptors.

Due to its favorable clinical and pharmacological profile, buprenorphine is increasingly used in the treatment of cancer pain and in palliative care in general. The negative properties of buprenorphine are the likelihood of lengthening the QT interval on the electrocardiogram and displacing other opioids if added to them, causing withdrawal.

With the addition of buprenorphine to any other opioid already taken, withdrawal syndrome often occurs (since buprenorphine has a greater tropism for opioid receptors), but in the opposite situation (the addition of any opioid to buprenorphine) withdrawal syndrome does not occur, since there is no dissociation of buprenorphine from opioid receptors (since buprenorphine has a greater tropism for opioid receptors).

The combination of buprenorphine with drugs that induce drowsiness can be dangerous. This is especially true for benzodiazepines and barbiturates. Their concomitant use with buprenorphine is contraindicated. In 2016, the United States introduced a universal warning not to combine any opioid with any benzodiazepine.

Kappa receptor agonists and mu receptor antagonists

A group of antagonist agonists, such as nalbuphine, butorphanol, pentazocine, dezocine, has not found wide application in the treatment of chronic pain syndrome due to rapidly growing addiction, pronounced side effects of these drugs, often unpredictable psychotropic manifestations, incompatibility with other mu-agonists.In this publication, the description of these drugs is considered inappropriate. Their use in the treatment of acute pain, especially chronic pain, is not recommended.

Combined opioid and non-medical protection drugs

Opioids are most commonly used as monopreparations, although some medications are also available in combination. For example, in the US on the pharmaceutical market, you can find more than 50 such combination drugs, and in Russia there are more than 20 registered drugs (these are mostly drugs containing low doses of codeine).

Combinations of opioids are designed for different purposes:

  • increasing the effectiveness of analgesia;
  • reduced side effects of opioids;
  • Prevention of non-medical use of the drug.

The main goal, as a rule, is to increase the analgesic efficacy of an opioid, which is achieved in different ways.

Combination of two opioid analgesics

Since different opioids act on different opioid receptors, theoretically the combination of the two opioids should be more effective than either alone.Experimental work carried out on a model of acute pain in mice supports this theory. It should be noted that active research is currently underway on a drug consisting of a combination of morphine and oxycodone.

Combination of opioid and non-opioid analgesic

Cumulation of the analgesic effect is also observed when using combinations of an opioid with non-steroidal anti-inflammatory drugs or with paracetamol.As a rule, these combinations are used only for the treatment of moderate pain, relief of individual pain attacks, but not for the long-term treatment of chronic pain. The following drug combinations are used in clinical practice:

  • hydrocodone + ibuprofen,
  • hydrocodone + paracetamol,
  • oxycodone + ibuprofen,
  • oxycodone + aspirin,
  • oxycodone + paracetamol,
  • codeine + paracetamol,
  • pentazocine + paracetamol,
  • Propoxyphene + Paracetamol,
  • tramadol + paracetamol.

When treating headache, it is not recommended to use opioids due to its possible intensification with frequent use of the drug (more than 5-7 doses per month), when the so-called abusal headache occurs. However, in the United States, combination drugs of codeine are widely available and widely used for the treatment of headaches, despite numerous studies showing the dangers of such treatment. Codeine in a dose of 8 to 60 mg is an integral part of these medicines, which also contain paracetamol, caffeine and aspirin, antispasmodics, etc.

Quite often, codeine with guaifenesin and other drugs is used to treat cough and pain in the following combinations:

  • codeine + paracetamol,
  • codeine + paracetamol + caffeine (FIORICET),
  • codeine + butalbutal + paracetamol + araofein (Fioricet with codeine),
  • codeine + butalbutal + aspirin + caffeine (FIORINAL with codeine),
  • butalbutal + barbiturate.

In addition to codeine, a combination of the weak opioid tramadol (37.5 mg) and paracetamol (325 mg), registered by Grunental, has been widely used over the past 10 years.The rationale and rationality of this combination of two analgesics is that the analgesic effect develops quite quickly (after 20-30 minutes) due to the initiating action of paracetamol. In the future, it is supported and enhanced by tramadol, the effect of which is much more powerful and longer (4-6 hours). As a result of the combined action of both drugs, the strength of the analgesic effect of the drug is sufficient to treat moderate pain, and the side effects are much less pronounced than with tramadol monotherapy.

To improve the safety and efficacy of preparations containing opioids, it is very important to reduce the risks of abuse. For this purpose, the following combinations are used:

Combinations of an opioid agonist with opioid antagonists are designed to prevent intravenous administration of an opioid and to prevent addictive behavior.

As a rule, opioid antagonists are poorly absorbed in the gastrointestinal tract, but easily penetrate into the nervous system when administered intravenously.However, when a significantly higher dose than recommended is taken, the amount of the antagonist that is absorbed can be high enough to cause withdrawal, thus reducing the potential for drug abuse.

In such combinations, medium and high doses of opioid antagonists are used. In the United States and other countries, the following combinations are in use or in preparation for market launch:

  • morphine + naltrexone,
  • buprenorphine + naloxone,
  • pentazocine + naloxone,
  • nalbuphine + naloxone.

To prevent addictive effect, opioids are combined with microdoses of opioid antagonists. An extremely low dose, as a rule, cannot lead to a withdrawal syndrome, but it helps to prevent addiction and allows the patient to use the dose of the drug without increasing it for many years. In addition, this combination leads to an increase in the analgesic effect of the opioid and to a decrease in other opioid stimulatory effects, especially edema, nausea and seizure reactions.The following drugs are currently being actively studied:

  • methadone + naltrexone,
  • morphine + naltrexone.

In 2010, the FDA approved Embeda containing morphine sulfate (20 to 100 mg) in combination with naltrexone (0.8 to 4 mg) , in the form of special tablets, where naltrexone constitutes the “inner core”, which is not absorbed during normal administration, but this occurs when the tablet is destroyed (when chewing or crushing).This drug has been temporarily banned from use since 2011 due to “drug instability”, but has reappeared on the market since 2014

The oxycodone + naloxone extended-release tablet combination is registered and used in Europe under the name Targin (Mundipharma). The dose of oxycodone in 1 tablet is from 5 to 40 mg, naloxone – from 2.5 to 20 mg. Since only 3-5% of naloxone is absorbed during enteral administration, its addition to oxycodone does not reduce the analgesic effect of the main opioid, but reduces the number of gastrointestinal and other disorders.After taking large doses of opioids, oxycodone + naloxone can also partially cause withdrawal symptoms. The drug is registered in Russia and will be used from the second half of 2017

Combinations of an opioid with substances that can cause side effects in case of an overdose:

  • oxycodone + nicotinic acid,
  • morphine + ipecac derivatives.

Morphine in combination with emetogenic additives (derivatives of ipecac, which induce violent vomiting) is expected to be deprived of the possibility of uncontrolled dose escalation and non-medical use.The use of standard doses of oxycodone with small doses of niacin should not lead to an overdose of the latter component, however, when taken on an empty stomach or in individuals with individual intolerance, reddening of the face and upper half of the body, dizziness, a feeling of blood flow to the head, urticaria, parasthesias, numbness, etc. Project

There are ethical contradictions in this approach. Is it possible, knowing in advance that this situation is likely or often occurs, to prescribe such a medicine? In addition, taking such drugs with food usually reduces the side effects of the additives so much that all the meaning of this “control additive” is lost.

Although several drugs based on a combination of opioids with “restraining” additives have been investigated, none of them have been released to the market.

Combinations with substances that cause side effects if the route of administration of the opioid is changed (for example, if the tablet is ground and inhaled into the nose). For this, morphine in tablets is combined with sodium sulfate (sodium sulfate causes irritation of the nasal mucosa) or, in another embodiment, morphine is combined with polyethylene oxide in order to transform the tablet when combined with moisture into jelly, which excludes the intravenous administration of the main substance.

Combination drugs of this class, in addition to positive features, have many negative ones. They often lead to increased side effects. The number of complications caused by paracetamol (liver damage), anti-inflammatory drugs (gastrointestinal tract, liver, kidney damage, agranulocytosis), opioid antagonists (liver damage and risk during pregnancy) and other listed supplements are higher than problems caused by the opioids themselves.

Such supplements also lead to an increased risk of drug interactions and a decreased predictive rate of treatment.The choice of such drugs in a clinical situation depends on a significant number of factors and should be based on the individual needs of the patient.

Developing Safe Opioid Delivery Systems

This is one of the most promising approaches in which the drug is not active until it has been converted by the body into an active agent. For example, a drug may soon appear on the market that secretes an opioid only in the gastrointestinal tract under the influence of lipase.Thus, intravenous administration, smoking and inhalation of this drug are not possible.

Another approach is to create a prodrug that has no opioid properties until activated, for example, by a liver enzyme. A mixture of opioids with L-lysine is also being tested. The addition of lysine to the opioid molecule turns it into an inactive drug, and only in the blood does this mixture undergo biotransformation, lysine is cleaved off, and the opioid becomes an active substance. A similar technology has long been used to prevent dextroamphetamine abuse and is marketed in the US under the name Vyvanse.

Conclusion

Despite the small list of opioid drugs registered in Russia, interest in these drugs has been growing in recent years. Currently, clinical trials of a number of domestic opioid drugs are being carried out, the studies have already been completed and are ready for use in clinical practice, TTS fentanyl and domestically produced buprenorphine + naloxone tablets, were registered in 2017.tapentadol and oxycodone + naloxone will be supplied from abroad.

The authors hope that the presented publication, based on a review of scientific publications, as well as many years of practical experience from both the American and Russian sides, will prove the unity of views on the problem of pain therapy. We hope that the review will be useful for the entire medical community and will raise the awareness of medical professionals in the field of the safe and effective use of opioid analgesics.

D.M. Arbukh, G.R. Abuzarova, G.S. Alekseeva

2017

VYVANSE – HEALTH – 2021

Contents:

Generic name: Lisdexamfetamine (lis dex am FET a meen)

Drug class: CNS stimulant

Table of Contents

  • Overview
  • How to take it
  • Side effects
  • 9025 Warnings and precautions 902 Dosage and missed dose
  • Storage location
  • Pregnancy or lactation
  • Additional information

Review

Vyvanse (Lisdexamfetamine) is used in patients to treat attention deficit hyperactivity disorder (ADHD) in adults and children (6 years and older).It is a medicine that stimulates the central nervous system (CNS). It can improve the ability to stop fidgeting, pay attention, and maintain concentration.

Doctors may also prescribe this drug for other conditions, such as moderate to severe eating disorder (BED) in adults.

This information is for educational purposes only. Not all known side effects, side effects, or drug interactions are listed in this database.If you have questions about your medications, talk to your doctor.

It works by helping to change certain chemicals in the brain, which professionals call “neurotransmitters”. It is not yet fully understood why altering these neurochemicals leads to symptomatic relief of conditions for which this drug is commonly prescribed.

How to take it

Follow the directions for use of this medication provided by your doctor. Vyvanse should be taken in the morning with or without food.

Side effects

Side effects that may occur with this medication include:

  • dry mouth
  • loss of appetite
  • weight loss
  • feeling irritable
  • nausea
  • vomiting
  • with dizziness

  • problems with dizziness such as insomnia

Seek immediate medical attention if you experience:

  • chest pain
  • paranoia
  • erection that is painful or lasts 4 hours or longer
  • numbness
  • red, irritated eyes unexplained wounds

  • skin color changes
  • muscle pain
  • hallucinations
  • swelling or swelling of the eyelids

Warnings and Precautions

  • If you have any serious side effects, including chest, jaw, or arm pain, difficulty breathing, cramps, or fainting, seek immediate medical attention.
  • Vyvanse SHOULD NOT be taken by children with heart conditions, including heart disease or irregular heartbeat. It can cause stroke, heart attack, and even sudden death.
  • NOT Use this medication if you have taken an MAO inhibitor in the past 2 weeks.
  • While taking Vyvanse, check your blood pressure regularly. This medication may raise blood pressure.
  • NOT Allow someone else to use this medicine that has been prescribed for you.Vyvanse can be habit-forming. Should never be used without a prescription.
  • Men taking Vyvanse may experience erections that last longer than usual and occur more frequently.
  • In case of overdose, seek medical advice immediately. In the event of an emergency, contact your local or regional poison control center at 1-800-222-1222.

Drug Interactions

Before taking any new prescription or over-the-counter medicine, talk to your doctor or pharmacist.This includes supplements and herbal products.

Dosage and Missed Dose

Follow your doctor’s instructions when taking this medication. Vyvanse can be taken with or without food. Your doctor may change the dose based on your reaction to it. Vyvanse is available in capsule form in 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, and 70 mg capsules.

Typical starting dose for adults is 30 mg every morning.

Children 6 to 12 years old may initially take 30 mg per day.This dosage can also be changed by your pediatrician depending on how your child reacts to it.

Take the next dose as soon as you remember. If it’s time to take your next dose, skip the missed dose and go back to your normal schedule. Do not double doses or take additional medications to make up for a missed dose.

Storage area

Store this medicine in the container in which it came, tightly closed and out of reach of children.Store it at room temperature, away from excess heat and moisture (preferably not in the bathroom). Throw away any medications that are outdated or no longer needed.

Pregnancy / Nursing

If you plan to become pregnant, talk with your doctor about the benefits and risks of this medication during pregnancy. It is recommended NOT to breastfeed while taking this medication, unless your doctor or pediatrician has told you to.

More information

For more information, contact your doctor, pharmacist or healthcare provider, or visit this website https: // www.See nlm.nih.gov/medlineplus/druginfo/meds/a607047.html for more information from the manufacturer of this drug.

90,000 Why Modafinil Is Becoming More Popular Among Office Workers in the West – Future on vc.ru

All available information about the drug that is gaining popularity in the West and banned in Russia.

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Still from the film “Areas of Darkness”

Relativity Media

Browser vc.ru has collected all the available information about the drug that is gaining popularity in the West and the modafinil banned in Russia, which is used by military, police and office workers to improve their performance. The material describes the principle of the drug’s action, provides research and expert opinions on its effectiveness and side effects.

600 milligrams – this is how much modafinil it took for the US Air Force pilots to spend 40 hours awake.At the same time, the speed of their reaction and accuracy remained practically at the same level.

In Maryland, the drug is used in long-term operations by police officers to improve concentration, and the Journal of the Canadian Medical Society claims that modafinil is present in the astronauts’ first aid kit on the ISS in order to “optimize performance during fatigue.”

Modafinil is a drug from the class of analeptics. The task of drugs of this class is to influence the centers of the medulla oblongata in order to stimulate the vital functions of respiration and blood circulation. In other words, Modafinil invigorates.

Modafinil, as well as Adderall and Ritalin, are most often prescribed for patients with attention deficit disorder and narcolepsy.But in the case of modafinil, it is often used as a cognitive enhancer.

Almost like allergy

Modafinil increases histamine levels and affects the neurotransmitter system of the brain, improving concentration.A similar effect should be familiar to those suffering from allergies. In such cases, antihistamines are prescribed, which act exactly the opposite – they lower the level of histamine in the body. For the same reason, allergy sufferers are strictly prohibited from drinking Modafinil.

Scientists from the University of Oxford collected all studies of modafinil and based on them conducted a meta-analysis of its effects.Of the 267 studies, 92 were screened out because they were animal tested. Then another 151 because there was no placebo test. Of the 24 remaining studies, 24 gave the same results: subjects performed better on tests related to flexibility of thought, information handling, and concentration.

Meta-analysis methodology

One of the researchers, Anna-Katharine Brem, told The Atlantic that another effect was noticed:

The longer and more difficult the task, the better the results of the subjects taking Modafinil.

Drug or not

The drug is often used by American students during sessions, as well as by people who want to increase their productivity. In the United States, modafinil is sold in pharmacies, but in Russia it cannot be bought in this way – the drug has not passed the registration of the Ministry of Health of the Russian Federation and is illegal.

Scientists and doctors agree that the drug has practically no side effects. University of California psychiatrist James McGough says the effects of modafinil overdose are the same as coffee overdose – nervousness and abdominal pain. According to him, the drug is not addictive.However, he explains:

If you stop taking Modafinil, there will be no painful side effects. But after experiencing its influence and the absence of side effects, many do not see the point in abandoning the drug.

It is impossible to find statistics on those who take the drug for obvious reasons – it is not typical for people to admit to taking doping.Even if it is harmless. In 2011, the BBC conducted an anonymous survey asking readers if they were taking cognitive enhancers, specifically Modafinil. 38% of the respondents answered “Yes”. Of these, 40% said they bought the drug online, and 92% said they would try it again. In total, about a thousand people took part in the survey. Reviews of the drug ranged from neutral to admiring:

I wrote a 22-page piece in one day.I reviewed it after a couple of days and passed it, having received an A (the highest mark – ed.). Normally, I would only be able to give birth to a draft, and then in a week.

The drug did not help in any way. But for fifteen hours I could not sit still and felt anxious and agitated at the same time.

Some scientists still advise against taking Modafinil.The reason is simple: if you do not feel enough energy or vigor in yourself, then why increase their level with drugs? Modafinil can be compared to taking painkillers – if you have a headache for a week, you will not take pills, but try to find out the cause of the disease.

Professor at the University of Cambridge, Barbara Sahakian, is more loyal to the drug.Her team began to study its effects on patients with Alzheimer’s and Parkinson’s, and then conducted several tests on healthy people.

Their study proved that surgeons who were sleep deprived for a long time did better when taking Modafinil. Professor Sakhakyan recommends using the drug for those whose work is stressful or stressful at a particular moment.

I believe we underestimate drugs like Modafinil. A study by the Academy of Medical Sciences showed that even a slight improvement in memory by 10% will dramatically increase the ability to consume new information. As a society, we can probably move forward if everyone has access to safe cognitive enhancers.

The representative of the Russian medical holding “Atlas” is more cautious.

I will speak from the position of a neurosurgeon.

Any drug has indications for use. Use not according to indications (as well as the use of the drug in doses exceeding the recommended ones) is an inappropriate risk in the game with one’s own health.

In the 24 studies described, not enough time has passed to assess the long-term results (to the question of safety).

All stimulants deplete the nervous system, plus their effect varies greatly depending on the type of nervous system and the presence of concomitant diseases.

Conclusion: if you really need it, once you can. And on an ongoing basis, you need to look for “legal” energy (I write in quotes, because I mean everything that does not “hack” our own “bank” of dopamine and serotonin in the brain) – sex, sports, creativity, and so on.

Pavel Likhachev

Sales Director of the Atlas Medical Center, neurosurgeon by education

Happiness Price

Writer and columnist Maria Hyland (M.J. Hyland described her experiences with the drug in an article on The Guardian. According to her, in the first weeks of use, she felt “happy and constantly in a good mood.” However, she attributed this not so much to modafinil as to the placebo effect.

The euphoric effect stopped after a month, but concentration and the ability to work without stopping remained.Hyland took 400 milligrams of the drug daily with no ill effects and believes he hasn’t made her smarter. But I made it more productive.

In a column, Highland mentioned that she has been taking the drug for six months now, as it has proven effective against the symptoms of multiple sclerosis that she suffers from. Improving cognitive skills, she calls only a pleasant bonus.

A daily dosage of 400 milligrams is too much. According to the Drugs.com portal, you should not exceed the limit of one dose per day. Depending on the manufacturer, one dose equals from 80 to 200 milligrams of the active substance.

Buying Modafinil in the USA is not a problem.There is even a site called ModafinilCat that specializes in selling modafinil in different forms and from different manufacturers. The cost of a daily dose ranges from $ 1 when you buy the drug for a year to $ 2 when you buy a monthly amount. Here you can also pay with bitcoins and receive a 20% discount.

In Russia, the drug should be looked for in online stores. Most often, it can be found in sports nutrition stores, where modafinil is positioned as an energy drink.The cost of the drug is almost the same as in the United States.

Scientists agree that the drug will become more and more popular. Psychiatrist James McGow even suggests employers will prioritize employees who accept cognitive enhancers, thereby showing how important the job is to them. Any manager wants to get a kind of “Hulk” – an employee who can work 16 hours without slowing down.

90,000 What are Nootropics? – PureNootropics.ru

The word nootropic comes from the Greek words noos, meaning mind, and trope, meaning rotation. Basically, nootropics serve one function: they “turn” your mind to enhance your cognitive abilities and improve your mental state in one form or another.

Different groups classify different drugs as nootropics, but for the most part everyone agrees that nootropics have two defining characteristics:

  1. They improve your cognitive abilities; and also
  2. When used at recommended doses, they have very few or no side effects.

Keep in mind that nootropics are not vitamins and minerals. These are usually synthetic chemicals produced in laboratories. They are not important to your body’s functions.They are “add-ons” in the sense that you use them and feel better, but if you don’t, it doesn’t mean that your body is missing something else. We truly advocate getting the right amount of essential nutrients and minerals as a starting point for improved cognitive health. We’ll talk about the overall optimization of brain health (your cognitive baseline) through sleep, diet, and exercise in a later post.

We’re relatively vague here because there is a wide variety of nootropics available today.And they all claim to do different things for you. It’s up to you to choose the right nootropic for what you want to achieve. Subsequent articles will explore the different types of nootropics, as well as specific nootropics that can be used in certain scenarios – for study, for sharpness, for party recovery, etc.

After understanding what nootropics are, the next question arises: “How do they work?”

How do nootropics work?

How Nootropics Work Each nootropic affects your body in a different way.It is important to note the distinction between “outcomes” and those commonly referred to as “operating mechanisms”. One thing we also want to point out is that nootropics are a very subjective experience, and while one person may have great results with a particular nootropic, another person may not have an effect with the same nootropic.

If the mechanism of action of enhancers is known, we know exactly how it affects your body. For example, if you swallow enhancer A, it will affect the X, Y, and Z receptors.This modification of the X, Y, and Z receptors produces effects B, C and D.

If the working mechanism of the enhancer is unknown, then we only know A, B, C and D in the above example. For most nootropics, there are speculations about working mechanisms, but there was no conclusive evidence for these claims. Thus, the discussed working mechanisms are theories and not facts.

Don’t let this distract you from nootropics as a safe way to improve your mental function.The human body is incredibly complex, and we haven’t even begun to understand how all the pieces of the puzzle fit together. We don’t even know how some of the most popular amplifiers sold around the world work.

Take acetaminophen (the active ingredient in Tylenol), for example. Tens of thousands of studies have been conducted with this enhancer, and after multiple studies of the human response to it, we came to three conclusions:

  1. Acetaminophen helps relieve minor body aches and pains
  2. Acetaminophen helps relieve headaches
  3. Acetaminophen does not help with inflammation

You might think that after tens of thousands of studies, a working mechanism would be found, right? Unfortunately not – the mechanism of action of acetaminophen is unknown and it doesn’t look like we’ll know exactly how it works anytime soon.

Take this example and apply it to nootropics. The working mechanisms are usually unknown, but after observing the empirical data over and over again, we can come to some fairly consistent conclusions about them.

Are Nootropics Legal? Legality of Nootropics

Are nootropics legal? We now know what you are thinking; If these enhancers claim to improve your cognitive abilities, but the working mechanisms are not 100% known, are they legal?

The answer is yes and no.

Yes : Most nootropics are perfectly legal. This means that if a police officer saw you taking one and stopped you, he would probably be suspicious (nootropics are often in the form of a white powder), but if he was field testing on him, you would not would be arrested or not fined. Your package will not be accepted if it is checked by customs, etc.

None : Like dietary supplements, most nootropics are not FDA approved .All countries differ on the legality of nootropics. In Russia, most of them are legal , and many are available on prescription. We suggest that you check the laws in your country regarding the availability of a specific nootropic before placing an order. These are just two examples. Always check your country’s laws before purchasing any nootropic supplements.

What can I expect from nootropics?

The cool (and sometimes repulsive) thing about nootropics is that everyone reacts differently to everyone.This is pretty standard for enhancers in general – if we take marijuana as an example, it relaxes some people, while it causes anxiety and paranoia in others. This is your personal reaction.

Giving 110 percent As a rule, nootropics have a rather weak effect. They are not intended to be used as stimulants such as Adderall, Ritalin, Vyvanse, or Gig. Instead, they seek to take your “baseline” of cognitive performance and raise it. Move from being able to give 100% when you are not taking nootropics to being able to give 105% or 110% when you are taking.If you focus on how nootropics affect you, you can tell, but with the vast majority of nootropics you won’t feel overstimulation or anything like that, sometimes the effects will be quite minor. One thing we suggest is to track the effectiveness of the nootropics you are taking to really determine the value you get from the nootropics; this will be discussed later.

Also, you shouldn’t expect a break or a lift. Nootropics work in the background.When you take a dose, you don’t feel hot flashes (although some report a “tingling sensation”), and when the nootropic’s effects begin to fade, you don’t feel like you are crumbling. Instead, you will slowly ascend to where your cognitive ability improves and then gradually weaken that as the chemical is depleted until you reach your normal baseline mental state.

Different types / categories of nootropics

Each nootropic can be attributed to a specific subset of nootropics.Here are the main ones – all popular nootropics will fall into one of these categories. We’ll talk about some of the more specific nootropics later. If you want to jump straight to the best nootropics for beginners click here

Racetams (one of our favorites)

All racetams (about 20 in total, depending on who you ask) are sourced from piracetam. After being synthesized in the early 1970s, piracetam quickly took its place at the forefront of the nootropic movement – if you ask someone to name a nootropic, piracetam will usually be the first answer.

Piracetam’s formula is C6h20N2O2 and most of its derivatives such as Aniracetam, Oxiracetam and Pramiracetam contain certain elements added or removed from this basic structure. Racemates can provide a wide range of cognitive enhancements, including improved memory, improved speech articulation, improved long-term and short-term memory, and more.

Most often, racetam is the backbone of any nootropic stack. Users often add other nootropics to enhance the effects of racetam.

If you are into nootropics and want a win-win bet, choose Racetam.

Choline (usually in combination with racetams)

Choline is not usually used on its own in the nootropic landscape, but it is a very common addition to any nootropic combination (stack). There are two reasons for this: choline itself provides additional cognitive enhancements, and choline supplementation is believed to enhance the effects of any racemate that increases the absorption of acetylcholine.Choline was once classified as vitamin B4 and was later reclassified as an essential nutrient and is metabolized by the body to acetylcholine.

Before going any further, I want to point out that acetylcholine is an important neurotransmitter thought to be responsible for decision making and certain types of learning. Many nootropics have some effect on how the body processes or interacts with acetylcholine, and these effects tend to have cognitive benefits when used responsibly.

Simply put, adding a source of choline means that you have an increased amount of acetylcholine in your body. Having a lot of acetylcholine in and of itself is said to improve cognitive functions, but they are usually enhanced when another nootropic is added to the mixture.

In addition, there have been studies that suggest racemates deplete acetylcholine in your brain. If your body is lacking in acetylcholine, you end up with frequent headaches.The same thing works in the other direction, which is another reason almost no one adds a source of choline without adding a nootropic, as too much acetylcholine (or whatever for that matter) is usually not very good. They balance each other perfectly to improve cognition and prevent headaches; it is a symbiotic relationship that needs to be balanced.

You will notice that two terms are mentioned here – sources of acetylcholine and choline.The sources of choline are the supplements you are taking, and after ingestion, they raise your acetylcholine levels. Each choline source produces a different amount of acetylcholine. Alpha-GPC is considered to be the most potent drug with the highest bioavailability. An elementary search will get you on the right track – see what other users have combined with their specific nootropics to properly balance acetylcholine levels. For more information on choline, check out our guide to choline for beginners.

Natural

Natural nootropics are no different from what you call “natural herbs” or “natural remedies”; they are naturally occurring elements (from plants) that, when taken internally, provide cognitive enhancing effects.

The effects of natural nootropics vary greatly, and in general, users have completely different experiences with each one. Some claim they are straight placebos, while others think they may be even more powerful than their human-made ones.However, by all accounts, they are less effective than synthetic nootropics.

This should not distract you from them altogether. While some natural nootropics are less effective, they have benefits that cannot be matched by synthetic ones. In general, since natural nootropics are (by definition) derived from nature, they are often available at a lower cost than synthetic nootropics. No laboratories, purity tests, etc. Not required.

BrahmiBacopi Monneri tea is one of the most common natural nootropics.It acts as a memory and anxiety aid, but the effects usually appear after 6-8 weeks – this is a great example of natural nootropics being less effective than synthetic memory or anxiety remedies, which can occur in as little as a couple of days. or even right away. It’s also a great example of how you can work in a way that its synthetic counterpart cannot – while sedative nootropics are usually borderline sedatives, users report that Bacopi Monneri works “in the background” so you don’t want to be under the influence.

Other popular natural nootropics are Huperzine-A and Ginkgo Biloba. If you’re interested in nootropics but aren’t a fan of lab-made ones, these three are great starting points.

Smart amplifiers

Smart enhancer is where the borderline between nootropic and enhancer is tested; some believe that smart enhancers are nootropics, while others believe they should be tightly regulated, just like prescription drugs.

Modafinil is the best example of a smart amplifier. It is prescribed in some countries, prohibited in some, and completely legal in others. It promises a full-fledged energy boost similar to Adderall, but without the euphoria or other side effects.

Many people think that smart boosters like Modafinil are not nootropics because of the way they affect you. If you take a standard nootropic like racetam for a month and then stop abruptly, you may notice that the nootropic is not present, but you will not have any real side effects.On the other hand, constantly taking a smart booster like Modafinil and then suddenly stopping it can lead to insomnia, loss of focus, and more.

We are not saying that smart amplifiers are necessarily bad. We’re just saying that you shouldn’t expect the subtle effects that other nootropics give you. When you take one of them, you will easily notice the effects, and when you discard it, you will easily notice that you are not on it.

Vitamin B and Vitamin B derivatives

B vitamins B vitamins are unique in the way they affect us.One of the most popular energy drinks, 5 Hour Energy, contains vitamin B6 as its main ingredient (albeit 10,000 times the RDA) due to the energy boost it gives us.

Naturally, with such effects, B vitamins are considered as nootropics. It is important to note that vitamin B derivatives are not the same as B vitamins; they have been modified in some way and turned into something other than a natural vitamin. As of 2015, vitamin B derivatives are relatively new.Sulbutiamine is a vitamin B1 derivative that was originally developed by the Japanese to combat fatigue and has the largest user base of all. Picamillion is also a Group B nootropic as it combines niacin (B3) with GABA. More research is needed to draw any conclusions about B vitamins, but if you’ve been successful with a B complex or an energy drink like 5 Hour Energy, it’s worth investigating.

Ampakides

Ampakids are commonly regarded as racemates in the 80s and 90s – interesting but not fully researched.In fact, of all types of nootropics, ampakids are the least researched.

They appear to work by antagonizing the AMPA and NDMA receptors in your body; this, in turn, leads to an increase in the amount of glutamate available for your brain to use. Glutamate is said to increase memory capacity and focusing ability. But again, there hasn’t been a lot of research done on ampakids or how they will affect you in the long term. Use ampakids only if you are a researcher and are willing to ingest something that has not yet been fully explored.

Peptides

Peptides are interesting in that they act similarly to racetams, but they are not the same thing. There is not much on the market today besides Noopept.

Noopept quickly earned a reputation 1,000 times more potent than Piracetam for similar effects. This means that the dosage is much smaller – while you need 1.6 to 4.8 grams of piracetam per day, you only need 10 to 40 mg of Noopept per day.

Although the peptides are not as popular as the racetams, they are well worth studying.Many users report similar effects to racetams, but not identity. Some people prefer peptides, while others stick to racemates. If you don’t like how you feel from a particular racetam, peptides are worth looking into.

Blends

Many companies have taken up the nootropic footrest and created nootropic blends. These blends are just a bunch of nootropics combined into one pill, which is similar to adding nootropics on your own – just easier.

It is important to pay attention to the ingredients of each mixture you are considering. Sometimes there will be ingredients that are not nootropics, and sometimes there will be a mixture of ingredients that you can easily make yourself for a fraction of the price. They often do not contain the right dosage of ingredients to make them useful.

Most Popular Nootropic Blend – Alpha Brain by Onnit; you can check out our full Alpha Brain review and analysis here. By and large, people see success in this combination, but a lot of marketing effort has gone into it – it’s hard to get objective information when you look online.We recommend starting with pure nootropics first, and if you find one that you like, perhaps get a blend that has the nootropics of your choice as ingredient # 1. If we missed something, please let us know so that we can provide our clients with the most up-to-date information.

In the next blog post, we’ll introduce you to the best nootropics for beginners, and from there, we’ll look at some popular combinations of individual nootropics in our post on the best nootropic stacks.

Lisdexamfetamine – Lisdexamfetamine – other.wiki

Chemical compound

91 492 91 489 91 499
Liability for dependency 91 500

Lisdexamphetamine
Trade names 91,500

Vivans, Tivens, Elvans and others
Other names (2 S ) -2,6-Diamino- N – [(2 S ) -1-phenylpropan-2-yl] hexanamide
N – [(2 S ) -1- Phenyl-2-propanyl] – L- lysinamide
AHFS / Drugs.com Monograph
MedlinePlus a607047
License data
Pregnancy category 91 492 91 489 91 499
Liability for dependency 91 500

Moderate Moderate
Administration paths Inside (capsules)
ATC code
Legal status
  • AU : S8 (Controlled Drug)
  • BR : class A3 (psychoactive drugs)
  • CA : Schedule I
  • DE : Anlage III (special prescription form required)
  • UK : class B
  • USA : Schedule II
  • EC : only for recipes
  • In general: ℞ (prescription only)
Bioavailability 91,500

96.4% 91 491
Metabolism Initially, hydrolysis of red blood cells by enzymes.
Subsequent metabolism is consistent with amphetamine pharmacokinetics #.
Start of validity 2 h
Elimination Half-life ≤1 h (prodrug molecule)
9-11 h (dextroamphetamine)
Duration of action 10-12 h
Excretion Kidney: ~ 2%
  • (2 S ) -2,6-Diamino- N – [(1 S ) -1-methyl-2-phenylethyl] hexanamide

CAS number
PubChem CID
IUPHAR / BPS
DrugBank
ChemSpider
UNII
KEGG
CHEMBL
CompTox control panel ( EPA )
Formula C 15 H 25 N 3 O
Molar mass 263.385 g mol -1
3D model (JSmol)
  • O = C (N [C @ H] (Cc1ccccc1) C) [C @@ H] (N) CCCCN

  • InChI = 1S / C15h35N3O / c1-12 (11-13-7-3-2-4-8-13) 18-15 (19) 14 (17) 9-5-6-10-16 / h3- 4, 7-8.12.14H, 5-6.9-11.16-17h3.1h4, (H, 18.19) / t12-, 14- / m0 / s1 Y
  • Key: VOBHXZCDAVEXEY-JSGCOSHPSA-N Y
N Y (what is this?) (Check)

Lisdexamphetamine , sold inter alia under the trade name Vyvanse , is an amphetamine derivative drug.It is mainly used to treat attention deficit hyperactivity disorder (ADHD) in people over the age of five, and moderate to severe binge eating disorder in adults. Lisdexamphetamine is taken by mouth. In the United Kingdom, it is generally less preferred than methylphenidate. Its action usually begins within 2 hours and lasts up to 14 hours.

Common side effects of lisdexamphetamine include loss of appetite, anxiety, diarrhea, trouble sleeping, irritability, and nausea.Rare but serious side effects include mania, sudden cardiac death in people with heart disease, and psychosis. He has a high substance abuse potential according to the DEA. Serotonin syndrome can occur when used with certain other medications. Its use during pregnancy may harm the baby, and its use while breastfeeding is not recommended by the manufacturer. Lisdexamphetamine is a central nervous system (CNS) stimulant that works after the body is converted to dextroamphetamine.Chemically, lisdexamfetamine is composed of lysine L amino acids, attached to dextroamphetamine.

Lisdexamphetamine was approved for medical use in the United States in 2007. In 2018, it was the 82nd most commonly prescribed drug in the United States, with over 10 million prescriptions. It is a Schedule II controlled substance in the United Kingdom and a Schedule II controlled substance in the United States.

Uses

Medical

30 mg Vyvanse capsule

Lisdexamphetamine is used primarily for the treatment of attention deficit hyperactivity disorder (ADHD) and binge eating disorder; it has similar intended uses as that of other pharmaceutical amphetamines. Individuals over the age of 65 have not usually been tested in clinical trials with lisdexamphetamine for the treatment of ADHD. Long-term exposure to amphetamine at high enough doses is known to cause abnormal dopamine development or nerve damage in some species, but in people with ADHD, therapeutic doses of pharmaceutical amphetamines appear to improve brain development and nerve growth.Reviews of magnetic resonance imaging (MRI) studies show that long-term treatment with amphetamine reduces abnormalities in brain structure and function found in subjects with ADHD, and improves function in several parts of the brain, such as the right caudate nucleus from the basal ganglia.

Reviews of stimulant clinical trials have established the safety and efficacy of long-term continuous use of amphetamine for the treatment of ADHD. Randomized controlled trials of continuous stimulant therapy for ADHD for 2 years have demonstrated the efficacy and safety of the treatment.Two reviews have shown that long-term, continuous stimulant therapy for ADHD is effective in reducing the main symptoms of ADHD (i.e., hyperactivity, inattention, and impulsivity), improving quality of life and academic achievement, and improving a wide range of functional capabilities. results across 9 outcome categories related to learning, antisocial behavior, driving, non-drug use of drugs, obesity, occupation, self-esteem, service use (eg, academic, professional, medical, financial and legal services), and social function.One review highlighted a nine-month randomized controlled trial of amphetamine treatment for ADHD in children, which found an average 4.5 IQ increase, a sustained increase in attention, and a continued decrease in disruptive behavior and hyperactivity. Another review found that, based on the longest follow-up studies conducted to date, the lifespan of stimulant therapy that begins in childhood is consistently effective to control ADHD symptoms and reduce the risk of developing substance use as an adult.

Current models of ADHD suggest that it is associated with functional impairments in some neurotransmitter systems in the brain; These functional impairments include impaired dopamine neurotransmission in the mesocorticolimbic projection and norepinephrine neurotransmission in noradrenergic projections from the macula blue to the prefrontal cortex. Psychostimulants such as methylphenidate and amphetamine are effective in treating ADHD because they increase the activity of neurotransmitters in these systems.Approximately 80% of those who use these stimulants see an improvement in their ADHD symptoms. Children with ADHD who take stimulant medications tend to communicate better with peers and family members, do better in school, are less distracted and impulsive, and have longer attention span. Cochrane Reviews of Pharmaceutical Amphetamines Treatment of ADHD in Children, Adolescents and Adults indicate that short-term studies have shown that these drugs reduce the severity of symptoms, but they have a higher withdrawal rate than non-stimulant drugs because of their adverse effects.side effects . A Cochrane review of the treatment of ADHD in children with tic disorders such as Tourette’s syndrome found that stimulants do not generally worsen tics, but high doses of dextroamphetamine can exacerbate tics in some people.

Increased productivity

Cognitive performance

In 2015, a systematic review and meta-analysis of high-quality clinical trials showed that, when used at low (therapeutic) doses, amphetamine produced moderate but definitive improvements in cognitive function, including working memory, long-term episodic memory, inhibitory control, etc.D. and some aspects of attention in normal healthy adults; These cognitive-enhancing effects of amphetamine are known to be mediated in part by indirect activation of both the dopamine D receptor 1 and and the α adrenergic receptor 2 in the prefrontal cortex. A systematic review in 2014 found that low doses of amphetamine also improved memory consolidation, which in turn resulted in better information perception.Therapeutic doses of amphetamine also increase the effectiveness of the cortical network, an effect that improves working memory in all people. Amphetamine and other ADHD stimulants also improve task release (motivation to complete a task) and increase arousal (wakefulness), in turn promoting purposeful behavior. Stimulants such as amphetamine can improve the performance of difficult and boring tasks and are used by some students to aid their studies and examinations.Based on self-reported studies of the illegal use of stimulants, 5–35% of college students use distracted ADHD stimulants, which are primarily used to improve academic performance rather than as a recreational drug. However, high doses of amphetamine in excess of the therapeutic range can impair working memory and other aspects of cognitive control.

Physical performance

Some athletes use amphetamine for its psychological and athletic performance enhancing effects such as increased stamina and alertness; however, the non-medical use of amphetamine is prohibited in sporting events that are regulated by collegial, national and international anti-doping agencies.In healthy individuals, in therapeutic doses, oral amphetamine has been shown to increase muscle strength, acceleration, anaerobic athletic performance, and endurance (i.e., delay the onset of fatigue), while improving reaction time. Amphetamine improves endurance and reaction time, primarily by inhibiting the reuptake and release of dopamine in the central nervous system. Amphetamine and other dopaminergic drugs also increase power output at fixed levels of perceived voltage, bypassing the “safety switch,” allowing the core temperature to be raised to gain access to reserve power that is normally prohibited.At therapeutic doses, the side effects of amphetamine do not impair athletic performance; however, at much higher doses, amphetamine can cause effects that seriously impair performance, such as rapid muscle breakdown and increased body temperature.

Contraindications.

The pharmaceutical lisdexamphetamine dimesylate is contraindicated in patients with hypersensitivity to amphetamine products or any of the inactive ingredients of the drug.It is also contraindicated in patients who have used a monoamine oxidase inhibitor (MAOI) in the past 14 days. Amphetamine-containing products are contraindicated by the US Food and Drug Administration (USFDA) for people with a history of drug abuse, heart disease, extreme agitation or anxiety, and those currently suffering from atherosclerosis, glaucoma, hyperthyroidism, or severe hypertension.The USFDA advises anyone with bipolar disorder, depression, high blood pressure, liver or kidney problems, mania, psychosis, Raynaud’s phenomenon, seizures, thyroid problems, tics, or Tourette’s syndrome to control their symptoms while taking amphetamine. Amphetamine is classified in pregnancy category C in the United States. This means that fetal damage has been observed in animal studies and that adequate human studies have not been performed; Amphetamine can still be prescribed to pregnant women if the potential benefits outweigh the risks.Amphetamine has also been shown to pass into breast milk, which is why the USFDA advises mothers to avoid breastfeeding while taking it. Because of the potential for stunted growth, the USFDA recommends monitoring the height and weight of children and adolescents who are prescribed amphetamines. A prescribing information approved by the Australian Therapeutic Goods Administration is also a contraindication for anorexia.

Side effects

Products containing lisdexamphetamine have a safety profile comparable to those containing amphetamine.

Interactions

  • Acidifying agents: Drugs that acidify the urine, such as ascorbic acid, increase the excretion of dextroamphetamine in the urine, thereby decreasing the half-life of dextroamphetamine in the body.
  • Alkalizing agents: Urine alkalizing drugs, such as sodium bicarbonate, decrease the urinary excretion of dextroamphetamine, thereby increasing the half-life of dextroamphetamine in the body.
  • Monoamine oxidase inhibitors: Concomitant use of MAOIs and central nervous system stimulants such as lisdexamphetamine can cause a hypertensive crisis.

Pharmacology

Mechanism of Action

Pharmacodynamics of amphetamine in dopamine neuron

Amphetamine enters the presynaptic neuron through the neuronal membrane or through DAT . Once inside, it binds to TAAR1 or enters the synaptic vesicles through VMAT2 .When amphetamine enters synaptic vesicles via VMAT2, it disrupts the vesicular pH gradient, which in turn triggers the release of dopamine into the cytosol (light brown area) via VMAT2. When amphetamine binds to TAAR1, it decreases the rate of dopamine neuron firing through potassium channels and activates protein kinase A (PKA) and protein kinase C (PKC), which subsequently phosphorylate DAT. PKA phosphorylation causes DAT to go into the presynaptic neuron (internalize) and stop transport.PKC-phosphorylated DAT can either act in the opposite direction or, like PKA-phosphorylated DAT, internalize and stop transport. Amphetamine is also known to increase intracellular calcium, an effect that is associated with DAT phosphorylation through the CAMKIIα-dependent pathway, which in turn induces dopamine efflux.

Lisdexamphetamine is an inactive prodrug that is converted in the body to dextroamphetamine, a pharmacologically active compound that is responsible for the drug’s activity.After oral administration, lisdexamphetamine is broken down by red blood cell enzymes to form L- lysine, a naturally occurring essential amino acid, and dextroamphetamine. The conversion of lisdexamphetamine to dextroamphetamine is independent of gastrointestinal pH and is unlikely to be affected by changes in normal gastrointestinal transit time.

These optical isomers of amphetamine, ie, dextroamphetamine and levamphetamine, are TAAR1 agonists and vesicular monoamine transporter 2 inhibitors that can introduce monoamine neurons; this allows them to release monoamine neurotransmitters (among others, dopamine, norepinephrine and serotonin) from their storage sites in the presynaptic neuron, and also prevent the reuptake of these neurotransmitters from the synaptic cleft.

Lisdexamphetamine was formulated to provide long-term effects that last throughout the day, while reducing the likelihood of abuse. The attachment of the amino acid lysine slows down the relative amount of dextroamphetamine available into the bloodstream. Because lisdexamphetamine capsules lack free dextroamphetamine, dextroamphetamine is not available through mechanical manipulation such as crushing or simple extraction. The production of dextroamphetamine from lisdexamphetamine requires a relatively complex biochemical process.Unlike Adderall, which contains roughly equal parts of the racemic amphetamine and dextroamphetamine salts, lisdexamfetamine is the one-enantiomer formula of dextroamphetamine. Studies show that lisdexamphetamine dimesylate may have less abuse potential than dextroamphetamine, and the abuse profile is similar to diethylpropion at dosages approved by the FDA for ADHD, but still has a high abuse potential when this dosage is exceeded by more than 100%.

Pharmacokinetics.

The oral bioavailability of amphetamine depends on the pH of the gastrointestinal tract; it is well absorbed from the intestine, and the bioavailability of dextroamphetamine usually exceeds 75%. Amphetamine is a weak base with p K a 9.9; hence, when pH is basic, more drug is in its lipid-soluble free base form, and more is absorbed across lipid-rich cell membranes from intestinal epithelium.Conversely, an acidic pH means that the drug is predominantly in a water-soluble cationic (salt) form and is less absorbed. Approximately 20% of the amphetamine circulating in the bloodstream binds to plasma proteins. Once absorbed, amphetamine is readily distributed to most body tissues, with high concentrations found in cerebrospinal fluid and brain tissue.

The half-lives of amphetamine enantiomers vary and depend on urine pH.At normal urine pH, the half-lives of dextroamphetamine and levoamphetamine are 9-11 hours and 11-14 hours, respectively. Strongly acidic urine shortens the half-life of the enantiomer to 7 hours; highly alkaline urine increases the half-life to 34 hours. The immediate release and prolonged release variants of the salts of both isomers reach peak plasma concentrations 3 and 7 hours after dosing, respectively. Amphetamine is excreted through the kidneys, while 30–40% of the drug is excreted unchanged at normal urine pH.When urine pH is alkaline, amphetamine is in free base form, so less is excreted. When urine pH is abnormal, urinary recovery of amphetamine can range from 1% to 75%, mainly depending on whether the urine is too alkaline or acidic, respectively. After oral administration, amphetamine appears in the urine within 3 hours. Approximately 90% of ingested amphetamine is excreted 3 days after the last oral dose.

The prodrug lisdexamphetamine is not as sensitive to pH as amphetamine when absorbed from the gastrointestinal tract; after being absorbed into the bloodstream, it is converted by enzymes associated with red blood cells to dextroamphetamine through hydrolysis.The half-life of lisdexamphetamine is usually less than 1 hour.

CYP2D6, dopamine β-hydroxylase (DBH), flavin-containing monooxygenase 3 (FMO3), butyrate-CoA ligase (XM-ligase) and glycine- N- acyltransferase (GLYAT) are enzymes that are known to , metabolize amphetamine or its metabolites in the human body. Amphetamine contains many metabolic products, including 4-hydroxyamphetamine, 4-hydroxyephedrine, 4-hydroxyphenylacetone, benzoic acid, hippuric acid, norephedrine, and phenylacetone.Among these metabolites, the active sympathomimetics are 4-hydroxyamphetamine, 4-hydroxyephedrine, and norephedrine. Major metabolic pathways include aromatic para-hydroxylation, aliphatic alpha and beta hydroxylation, N- oxidation, N- dealkylation, and deamination. Known metabolic pathways, detectable metabolites and metabolizing enzymes in humans include the following:

Metabolic pathways of amphetamine in humans

Para –
hydroxylation

Para –
hydroxylation

Para –
hydroxylation

unidentified

Beta
hydroxylation

Beta
hydroxylation

Oxidative
deamination

Oxidation

unidentified

Glycine conjugation

The main active metabolites of amphetamine are 4-hydroxyamphetamine and norephedrine; at normal urine pH, about 30-40% of amphetamine is excreted unchanged and about 50% is excreted as inactive metabolites (bottom row).The remaining 10–20% are excreted as active metabolites. Benzoic acid is metabolized by XM ligase to an intermediate product, benzoyl-CoA, which is then metabolized by GLYAT to hippuric acid.

Chemistry

Lisdexamfetamine is a substituted amphetamine with an amide bond formed by condensation from dextroamphetamine with a carboxylate group from the essential amino acid L lysine.The reaction proceeds with preservation of the stereochemistry, therefore the product lisdexamphetamine exists as a single stereoisomer. There are many possible names for lisdexamphetamine based on the IUPAC nomenclature, but it is commonly referred to as N – [(2 S ) -1-phenyl-2-propanyl] – L- lysinamide or (2 S ) -2, 6-diamino- N – [(1 S ) -1-methyl-2-phenylethyl] hexanamide. The condensation reaction occurs with the loss of water:

( S ) – PhCH
2 CH (CH
3 ) NH
2 + ( S ) – HOOCCH (NH
2 ) CH
2 CH
2 CH
2 CH
2 NH
2 → ( S , S ) – PhCH
2 CH (CH
) NHC 3 917 (O) CH (NH
2 ) CH
2 CH
2 CH
2 CH
2 NH
2 + H
2

Amine functional groups are vulnerable to oxidation in air and therefore pharmaceutical preparations containing them are usually prepared in the form of salts, where this fragment has been protonated.This increases the stability, solubility in water and, by converting a molecular compound into an ionic compound, increases the melting point and thereby provides a solid product. In the case of lisdexamfetamine, this is achieved by reacting with two equivalents of methanesulfonic acid to give the di-mesylate salt, a water-soluble (792 mg ml -1 ) powder from a white to off-white color.

PhCH
2 CH (CH
3 ) NHC (O) CH (NH
2 ) CH
2 CH
2 CH
2 CH

2 NH
2 + 2 channels
3 TAK
3 H → [PhCH
2 CH (CH
3 ) NHC (O) CH (NH +
3 ) CH
2 CH
2 CH
2 CH
2 NH +
3 ] [CH
3 TAK 937 3 ]
2

Comparison with other formulations

Lisdexamphetamine dimesylate is one of the marketed drugs that deliver dextroamphetamine.The following table compares the drug to other amphetamine-based pharmaceuticals.

Amphetamine base in marketed amphetamine preparations
medication formula molecular weight amphetamine base amphetamine base
in equal doses
doses with
equal to
base content
(g / mol) (percent) (Dose 30 mg)
total base general right left right left
dextroamphetamine sulfate (C 9 H 13 N) 2 • H 2 SO 4

368.49

270.41

73.38%

73.38%

22.0 mg

30.0 mg

amphetamine sulfate (C 9 H 13 N) 2 • H 2 SO 4

368.49

270.41

73.38%

36.69%

36.69%

11.0 mg

11.0 mg

30.0 mg

Adderall

62.57%

47.49%

15.08%

14.2 mg

4.5 mg

35.2 mg

25% dextroamphetamine sulfate (C 9 H 13 N) 2 • H 2 SO 4

368.49

270.41

73.38%

73.38%

25% amphetamine sulfate (C 9 H 13 N) 2 • H 2 SO 4

368.49

270.41

73.38%

36.69%

36.69%

25% dextroamphetamine saccharate (C 9 H 13 N) 2 • C 6 H 10 O 8

480.55

270.41

56.27%

56.27%

25% amphetamine aspartate monohydrate (C 9 H 13 N) • C 4 H 7 NO 4 • H 2 O

286.32

135.21

47.22%

23.61%

23.61%

lizdexamphetamine dimesylate C 15 H 25 N 3 O • (CH 4 O 3 S) 2

455.49

135.21

29.68%

29.68%

8.9 mg

74.2 mg

amphetamine-based suspension C 9 H 13 N

135.21

135.21

100%

76.19%

23.81%

22.9 mg

7.1 mg

22.0 mg

History, society and culture

Lisdexamphetamine was developed by New River Pharmaceuticals, which was acquired by Takeda Pharmaceuticals through the acquisition of Shire Pharmaceuticals shortly before it was marketed.It was developed with the aim of creating a more durable and less used version of dextroamphetamine, as the need to be converted to dextroamphetamine by enzymes in red blood cells delays the onset of its action, regardless of the route of administration.

On April 23, 2008, the FDA approved lisdexamphetamine for the treatment of ADHD in adults. On August 4, 2009, Health Canada approved the sale of 30 and 50 mg lisdexamphetamine capsules for prescription use.

In January 2015, lisdexamphetamine was approved by the US Food and Drug Administration for the treatment of binge eating disorder in adults.

The US production quota for 2016 was 29,750 kilograms.

Names

Lisdexamphetamine is the abbreviation for L- lysine – dextroamphetamine.

Elvanse Adult 50 mg and 70 mg capsules on the package (in German)

As of July 2014, lisdexamphetamine was marketed under the following brands: Elvanse, Samexid, Tyvense, Venvanse and Vyvanse.

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Depression

Several clinical trials in which lisdexamphetamine has been used as adjunctive therapy with selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrine reuptake inhibitor (SNRI) for the treatment of resistant depression have shown that it is no more effective than SSRIs or SNRIs …one. Other studies have shown that psychostimulants enhance the effects of antidepressants and are not prescribed for the treatment of persistent depression. In these studies, patients showed significant improvements in energy, mood, and psychomotor performance. In February 2014, Shire announced that two late clinical trials showed Vyvanse was not an effective treatment for depression.

Notes

Reference Notes

Recommendations

External links

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