What are the common side effects of phentermine and topiramate. How can patients manage potential risks associated with this medication combination. When should individuals seek immediate medical attention while taking phentermine and topiramate. What long-term effects should be monitored in patients using this weight loss treatment.

Overview of Phentermine and Topiramate Combination Therapy

Phentermine and topiramate are two medications that, when combined, are used as a weight loss treatment for individuals struggling with obesity. This combination therapy is designed to suppress appetite and increase feelings of fullness, ultimately leading to reduced caloric intake and weight loss. However, as with any medication, there are potential side effects and risks that patients and healthcare providers must be aware of.

Common Side Effects of Phentermine and Topiramate

While phentermine and topiramate can be effective for weight loss, they may cause a range of side effects. Some of the more common side effects include:

• Change in taste or loss of taste
• Difficulty having bowel movements
• Ear congestion
• Fear or nervousness
• Memory problems
• Stuffy or runny nose
• Trouble sleeping
• Back pain
• Dry eyes
• Hair loss
• Irritability

Are these side effects permanent? In most cases, these side effects are temporary and may subside as your body adjusts to the medication. However, if they persist or become bothersome, it’s important to consult with your healthcare provider.

Serious Side Effects Requiring Immediate Medical Attention

While less common, some side effects of phentermine and topiramate can be more serious and require immediate medical attention. These include:

• Chest pain or discomfort
• Fast, irregular, or pounding heartbeat
• Shortness of breath
• Severe mood changes or mental disturbances
• Seizures or increase in seizure frequency
• Severe skin reactions (blistering, peeling)
• Vision changes or eye pain
• Unusual bleeding or bruising

Can these serious side effects be life-threatening? Yes, in some cases, these side effects may indicate a severe reaction to the medication and could potentially be life-threatening if left untreated. It’s crucial to seek immediate medical care if you experience any of these symptoms.

Cardiovascular Concerns with Phentermine and Topiramate

One of the primary concerns with phentermine use is its potential impact on the cardiovascular system. Phentermine is a stimulant that can affect heart rate and blood pressure. Patients taking this medication may experience:

• Increased heart rate
• Elevated blood pressure
• Palpitations
• Chest pain

Is it safe for patients with pre-existing heart conditions to take phentermine? Generally, phentermine is not recommended for patients with a history of cardiovascular disease, uncontrolled hypertension, or other serious heart conditions. Your healthcare provider will carefully evaluate your medical history before prescribing this medication.

Neurological and Psychiatric Effects of Topiramate

Topiramate, originally developed as an anticonvulsant, can have various effects on the central nervous system. Some patients may experience:

• Cognitive impairment (difficulty with concentration, memory)
• Mood changes (depression, anxiety)
• Suicidal thoughts or behaviors
• Dizziness or balance problems

How can patients manage the cognitive side effects of topiramate? If you experience cognitive issues while taking topiramate, discuss them with your healthcare provider. They may adjust your dosage or suggest strategies to cope with these effects, such as taking the medication at bedtime or implementing memory aids.

Metabolic and Endocrine Considerations

The combination of phentermine and topiramate can affect various metabolic processes in the body. Patients should be aware of potential issues such as:

• Changes in blood sugar levels
• Alterations in electrolyte balance
• Increased risk of kidney stones
• Decreased sweating and increased body temperature

How often should patients on phentermine and topiramate have their metabolic parameters checked? Regular monitoring is essential. Your healthcare provider may recommend blood tests every 3-6 months to check electrolytes, kidney function, and blood sugar levels. More frequent monitoring may be necessary for patients with pre-existing metabolic conditions.

Pregnancy and Breastfeeding Considerations

The use of phentermine and topiramate during pregnancy and breastfeeding is a significant concern due to potential risks to the fetus or infant. Key points to consider include:

• Increased risk of birth defects, particularly cleft lip and palate
• Potential for fetal growth restriction
• Unknown effects on breastfed infants

What precautions should women of childbearing age take when using this medication? Women of childbearing potential should use effective contraception while taking phentermine and topiramate. If pregnancy occurs, the medication should be discontinued immediately, and the healthcare provider should be notified.

Long-term Effects and Monitoring

While phentermine and topiramate combination therapy is typically prescribed for short-term use, some patients may require longer treatment periods. Long-term effects that should be monitored include:

• Changes in bone density
• Potential for dependency or withdrawal symptoms
• Chronic effects on cognitive function
• Impact on cardiovascular health over time

What follow-up care is recommended for patients on long-term phentermine and topiramate therapy? Patients should have regular check-ups with their healthcare provider, including periodic assessments of weight loss progress, side effect management, and evaluation of the need for continued treatment. Bone density scans and cardiovascular assessments may be recommended for long-term users.

Managing Side Effects and Optimizing Treatment

To maximize the benefits of phentermine and topiramate therapy while minimizing risks, patients should:

• Follow dosing instructions carefully
• Stay well-hydrated to reduce the risk of kidney stones
• Report any new or worsening side effects promptly
• Engage in regular physical activity and maintain a balanced diet
• Avoid alcohol and other central nervous system depressants

How can patients determine if the benefits of treatment outweigh the risks? This decision should be made in consultation with a healthcare provider, considering factors such as the degree of weight loss achieved, the presence and severity of side effects, and the patient’s overall health status.

Drug Interactions and Precautions

Phentermine and topiramate can interact with various medications, potentially altering their effectiveness or increasing the risk of side effects. Some important interactions to be aware of include:

• Other weight loss medications
• Antidepressants, particularly MAOIs
• Certain antiepileptic drugs
• Oral contraceptives (may be less effective)
• Drugs that affect kidney function or electrolyte balance

Why is it crucial to inform all healthcare providers about phentermine and topiramate use? Disclosing all medications, including over-the-counter drugs and supplements, to healthcare providers helps prevent potentially dangerous drug interactions and ensures comprehensive care.

Alternative Weight Loss Strategies

For individuals who cannot tolerate phentermine and topiramate or prefer non-pharmacological approaches, alternative weight loss strategies include:

• Behavioral therapy and lifestyle modifications
• Structured diet and exercise programs
• Other FDA-approved weight loss medications
• Bariatric surgery for severe obesity

How do the risks and benefits of these alternatives compare to phentermine and topiramate? Each approach has its own set of advantages and potential drawbacks. A healthcare provider can help determine the most appropriate weight loss strategy based on individual health status, preferences, and weight loss goals.

Patient Education and Support

Successful weight loss with phentermine and topiramate requires more than just taking medication. Patients benefit from comprehensive education and support, including:

• Detailed information about the medication and potential side effects
• Guidance on healthy eating habits and portion control
• Encouragement to engage in regular physical activity
• Strategies for managing stress and emotional eating
• Regular follow-up appointments to monitor progress and address concerns

What resources are available for patients seeking additional support while on phentermine and topiramate? Many healthcare providers offer support groups, nutritional counseling, or referrals to weight loss specialists. Online communities and educational materials can also provide valuable information and peer support.

Discontinuation and Withdrawal

When it’s time to stop taking phentermine and topiramate, patients should be aware of potential withdrawal symptoms and the importance of gradual discontinuation. Key points include:

• Tapering the medication under medical supervision
• Possible rebound weight gain
• Monitoring for mood changes or increased appetite
• Implementing strategies to maintain weight loss after stopping the medication

How long does it typically take to safely discontinue phentermine and topiramate? The duration of the tapering process can vary depending on the individual and the length of time they’ve been on the medication. It may take several weeks to months to gradually reduce the dosage and discontinue the medication safely.

Future Developments in Weight Loss Pharmacotherapy

Research in the field of weight loss medications continues to evolve. Emerging areas of interest include:

• Development of new drug combinations with fewer side effects
• Personalized medicine approaches to weight loss treatment
• Long-term studies on the safety and efficacy of existing medications
• Exploration of novel targets for appetite suppression and metabolism modulation

How might future developments impact the use of phentermine and topiramate? As new treatments become available and our understanding of obesity physiology improves, the role of phentermine and topiramate may evolve. However, it’s likely to remain an important option in the arsenal of weight loss treatments for the foreseeable future.

In conclusion, phentermine and topiramate combination therapy can be an effective tool for weight loss in appropriate candidates. However, it requires careful consideration of potential side effects, close medical supervision, and a comprehensive approach to weight management. Patients and healthcare providers must work together to balance the benefits of treatment with the potential risks, ensuring the safest and most effective use of this medication.

Phentermine And Topiramate (Oral Route) Side Effects

Side Effects

Drug information provided by: IBM Micromedex

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

Less common

1. 
   Chest discomfort
2. 
   convulsions
3. 
   decreased urine
4. 
   fast, irregular, pounding, or racing heartbeat or pulse
5. 
   loss of appetite
6. 
   mood changes
7. 
   muscle pain or cramps
8. 
   nausea or vomiting
9. 
   numbness or tingling in the hands, feet, or lips
10. 
    shortness of breath
11. 
    unusual tiredness or weakness

Rare

1. 
   Blood in the urine
2. 
   pain in the groin or genitals
3. 
   sharp back pain just below the ribs

Incidence not known

1. 
   Blistering, peeling, or loosening of the skin
2. 
   blisters on the mouth, trunk, scalp, or other areas
3. 
   blurred or decreased vision
4. 
   chest pain
5. 
   chills or shivering
6. 
   clumsiness
7. 
   continuing nausea or vomiting
8. 
   cough or sore throat
9. 
   dark urine
10. 
    diarrhea or light-colored stools
11. 
    dizziness
12. 
    headache
13. 
    increase in the frequency of seizures
14. 
    irregular heartbeat
15. 
    itching
16. 
    joint or muscle pain
17. 
    loss of appetite
18. 
    low body temperature
19. 
    muscle aches or weakness
20. 
    pain in the shoulders, arms, jaw, or neck
21. 
    red skin lesions, often with a purple center
22. 
    red, irritated eyes
23. 
    shakiness in the legs, arms, hands, or feet
24. 
    sores, ulcers, or white spots in the mouth or on the lips
25. 
    sweating
26. 
    swelling of the face
27. 
    tiredness and weakness
28. 
    trouble thinking, speaking, or walking
29. 
    upper right abdominal or stomach pain
30. 
    weak or feeble pulse
31. 
    weight gain
32. 
    yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

1. 
   Back pain
2. 
   change in taste
3. 
   difficulty having a bowel movement (stool)
4. 
   ear congestion
5. 
   fear or nervousness
6. 
   loss of taste
7. 
   loss of voice
8. 
   memory problems
9. 
   pain or tenderness around the eyes and cheekbones
10. 
    sneezing
11. 
    stuffy or runny nose
12. 
    trouble sleeping

Less common

1. 
   Belching
2. 
   cramps
3. 
   decreased appetite
4. 
   dry eyes
5. 
   eye pain
6. 
   hair loss
7. 
   heartburn or indigestion
8. 
   heavy bleeding
9. 
   irritability
10. 
    rash
11. 
    stomach discomfort, upset, or pain

Incidence not known

1. 
   Bloating
2. 
   false or unusual sense of well-being
3. 
   feeling that others are watching you or controlling your behavior
4. 
   feeling that others can hear your thoughts
5. 
   feeling, seeing, or hearing things that are not there
6. 
   hives or welts
7. 
   change in sexual ability, desire, drive, or performance
8. 
   severe mood or mental changes
9. 
   unusual behavior

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Portions of this document last updated: July 01, 2021

Copyright © 2021 IBM Watson Health. All rights reserved. Information is for End User’s use only and may not be sold, redistributed or otherwise used for commercial purposes.

.

Important Safety Information I ADIPEX-P® (phentermine HCl) CIV

ADIPEX-P^® (phentermine hydrochloride USP) CIV is used for a short period of time (a few weeks), as part of a weight reduction treatment plan that includes exercise, behavioral changes, and a low-calorie diet, for obese people with a body mass index greater than or equal to 30 kg/m² or a body mass index greater than or equal to 27 kg/m² and other risk factors (e.g., controlled high blood pressure, diabetes, high cholesterol).

Do not take ADIPEX-P if you:

• Have a history of heart disease (e.g., coronary artery disease, stroke, arrhythmias, congestive heart failure, uncontrolled high blood pressure)
• Are taking certain medicines called monoamine oxidase inhibitors (MAOIs) or have taken MAOIs in the past 14 days
• Have thyroid problems (hyperthyroidism)
• Have glaucoma (increased pressure in the eyes)
• Have experienced agitated states or have a history of drug abuse
• Are pregnant or are nursing
• Are allergic to sympathomimetic amines such as phentermine, or any of the ingredients

Use with Other Medicines for Weight Loss. Taking ADIPEX-P with other drugs used for weight loss is not recommended.

Primary Pulmonary Hypertension. A rare but often fatal disease of the lungs, has been reported in patients taking phentermine and phentermine-like products. Tell your doctor if you have shortness of breath, chest or heart pain, or experience fainting or swelling in your lower legs. Contact your doctor immediately if you experience any decrease in the amount of exercise you are normally able to tolerate.

Heart Value Disease. Serious heart valve problems or disease have been reported in patients taking phentermine or other phentermine-like products for weight loss. The possibility of an association cannot be ruled out.

Tolerance. There is the potential for tolerance to develop, where the same dose might not work as well as it did in the beginning. If this happens, the recommended dose should not be increased, but instead the drug should be discontinued.

Motor Impairment. ADIPEX-P may impair your ability to operate machinery or drive a motor vehicle.

Risk of Abuse and Dependence. Keep ADIPEX-P in a safe place to prevent theft, accidental overdose, misuse or abuse.

Use With Alcohol. Do not use ADIPEX-P with alcohol as it may result in an adverse drug reaction.

Patients with High Blood Pressure. ADIPEX-P may cause an increase in blood pressure. Tell your doctor if you have or have had high blood pressure.

Patients with Diabetes. A decrease in the dose of insulin or other oral hypoglycemic medications may be required. Talk to your physician if you are taking medications for diabetes.

Patients with Renal Impairment. Avoid use if you have impaired kidney function or are on dialysis.

Tell your doctor about all of your medical conditions and about all of the medications you are taking, including over-the-counter or herbal treatments.

Some side effects of ADIPEX-P include pulmonary hypertension, heart disease, palpitations, increased heart rate or blood pressure, insomnia, restlessness, dry mouth, diarrhea, constipation, and changes in sexual drive. Tell your healthcare provider if you have any side effect that bothers you or does not go away.

These are not all of the possible side effects of ADIPEX-P. For more information, ask your healthcare provider or pharmacist.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please see full Prescribing Information.

Phentermine; Topiramate extended-release capsules

What is this medicine?

Phentermine; topiramate (FEN ter meen; toe PYRE a mate) is a combination of two medicines and is used to help people lose weight and maintain weight loss. It is used with a reduced-calorie diet and exercise.

This medicine is only available through certified pharmacies enrolled in a special program. Your healthcare professional will tell you where you can get your medicine. If you have additional questions, you can visit the manufacture’s website at www.QsymiaREMS.com or contact them by phone at 1-888-998-4887.

This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.

COMMON BRAND NAME(S): Qsymia

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:

• agitation
• diarrhea
• depression or other mental illness
• diabetes
• glaucoma
• heart disease
• high or low blood pressure
• history of anorexia or other eating disorder
• history of substance abuse
• kidney stones or kidney disease
• liver disease
• lung disease like asthma, obstructive pulmonary disease, emphysema
• metabolic acidosis
• on a ketogenic diet
• scheduled for surgery or a procedure
• suicidal thoughts, plans, or attempt; a previous suicide attempt by you or a family member
• taken an MAOI like Carbex, Eldepryl, Marplan, Nardil, or Parnate in last 14 days
• thyroid disease
• an unusual or allergic reaction to phentermine, topiramate, other medicines, foods, dyes, or preservatives
• pregnant or trying to get pregnant
• breast-feeding

How should I use this medicine?

Take this medicine by mouth with a glass of water. Follow the directions on the prescription label. Do not crush or chew. This medicine is usually taken with or without food once per day in the morning. Avoid taking this medicine in the evening. It may interfere with sleep. Take your doses at regular intervals. Do not take your medicine more often than directed.

A special MedGuide will be given to you by the pharmacist with each prescription and refill. Be sure to read this information carefully each time.

Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed.

Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.

NOTE: This medicine is only for you. Do not share this medicine with others.

What if I miss a dose?

If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.

What may interact with this medicine?

Do not take this medicine with any of the following medications:

• MAOIs like Carbex, Eldepryl, Marplan, Nardil, and Parnate

This medicine may also interact with the following medications:

• acetazolamide
• amitriptyline
• antihistamines for allergy, cough and cold
• atropine
• birth control pills
• carbamazepine
• certain medicines for bladder problems like oxybutynin, tolterodine
• certain medicines for depression, anxiety, or psychotic disturbances
• certain medicines for Parkinson’s disease like benztropine, trihexyphenidyl
• certain medicines for stomach problems like dicyclomine, hyoscyamine
• certain medicines for travel sickness like scopolamine
• dichlorphenamide
• digoxin
• diltiazem
• diuretics
• hydrochlorothiazide
• ipratropium
• lithium
• medicines for diabetes
• medicines for pain, sleep, or muscle relaxation
• methazolamide
• phenytoin
• pioglitazone
• stimulant medicines for attention disorders, weight loss, or to stay awake
• valproic acid
• zonisamide

This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

What should I watch for while using this medicine?

Visit your doctor or health care professional for regular checks on your progress. This medicine is intended to be used in addition to a healthy diet and appropriate exercise. The best results are achieved this way. Do not increase or in any way change your dose without consulting your doctor or health care professional.

Do not take this medicine within 6 hours of bedtime. It can keep you from getting to sleep. Avoid drinks that contain caffeine and try to stick to a regular bedtime every night.

Do not stop taking this medicine suddenly. This increases the risk of seizures.

This medicine can decrease sweating and increase your body temperature. Watch for signs of deceased sweating or fever. Avoid extreme heat, hot baths, and saunas. Be careful about exercising, especially in hot weather. Contact your health care provider right away if you notice a fever or decrease in sweating.

You should drink plenty of fluids while taking this medicine. If you have had kidney stones in the past, this will help to reduce your chances of forming kidney stones.

If you have stomach pain, with nausea or vomiting and yellowing of your eyes or skin, call your doctor immediately.

You may get drowsy or dizzy. Do not drive, use machinery, or do anything that needs mental alertness until you know how this medicine affects you. Do not stand or sit up quickly, especially if you are an older patient. This reduces the risk of dizzy or fainting spells. Alcohol may increase dizziness and drowsiness. Avoid alcoholic drinks.

This medicine may affect blood sugar levels. If you have diabetes, check with your doctor or health care professional before you change your diet or the dose of your diabetic medicine.

Patients and their families should watch out for worsening depression or thoughts of suicide. Also watch out for sudden changes in feelings such as feeling anxious, agitated, panicky, irritable, hostile, aggressive, impulsive, severely restless, overly excited and hyperactive, or not being able to sleep. If this happens, especially at the beginning of treatment or after a change in dose, call your health care professional.

If you notice blurred vision, eye pain, or other eye problems, seek medical attention at once for an eye exam.

This medicine may increase the chance of developing metabolic acidosis. If left untreated, this can cause kidney stones, bone disease, or slowed growth in children. Symptoms include breathing fast, fatigue, loss of appetite, irregular heartbeat, or loss of consciousness. Call your doctor immediately if you experience any of these side effects. Also, tell your doctor about any surgery you plan on having while taking this medicine since this may increase your risk for metabolic acidosis.

Women who become pregnant while using this medicine should contact their physician immediately. You should also contact The Qsymia Pregnancy Surveillance Program which is a program that monitors pregnancies that occur during treatment. Contact the program by calling 1-888-998-4887.

What side effects may I notice from receiving this medicine?

Side effects that you should report to your doctor or health care professional as soon as possible:

• allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
• blood in the urine
• changes in vision
• chest pain or chest tightness
• confusion
• depressed mood
• difficulty breathing
• dizziness
• fast or irregular heartbeat
• feeling anxious
• irritable
• loss of appetite
• low blood pressure
• pain in the lower back or side
• pain, tingling, numbness in the hands or feet
• pain when urinating
• palpitations
• redness, blistering, peeling or loosening of the skin, including inside the mouth
• shortness of breath
• suicidal thoughts or other mood changes
• trouble passing urine or change in the amount of urine
• trouble walking, dizziness, loss of balance or coordination
• unusually weak or tired
• vomiting

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):

• change in sex drive or performance
• changes in vision
• constipation
• diarrhea
• dry mouth
• headache
• nausea
• tremors
• trouble sleeping
• upset stomach

This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Where should I keep my medicine?

Keep out of the reach of children. This medicine can be abused. Keep your medicine in a safe place to protect it from theft. Do not share this medicine with anyone. Selling or giving away this medicine is dangerous and against the law.

This medicine may cause accidental overdose and death if taken by other adults, children, or pets. Mix any unused medicine with a substance like cat litter or coffee grounds. Then throw the medicine away in a sealed container like a sealed bag or a coffee can with a lid. Do not use the medicine after the expiration date.

Store at room temperature between 15 and 25 degrees C (59 and 77 degrees F).

NOTE: This sheet is a summary. It may not cover all possible information. If you have questions about this medicine, talk to your doctor, pharmacist, or health care provider.

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How Long Does Adipex (Phentermine) Stay in Your System?

Adipex (phentermine) is a prescription medication given to assist people with weight loss. It works by decreasing the appetite and is usually prescribed for three to six weeks (though can be used for up to 12 weeks) to people who are exercising and eating a low-calorie diet.

Phentermine is also the active ingredient in other prescription drugs including Fastin, Ionamin, and Zantryl and is one of the two ingredients in Qsymia. These medications are the most prescribed diet pills on the market. Because these drugs are similar to amphetamines and act as a stimulant, they are a controlled substance and are often sold illicitly.

Knowing how phentermine acts in your system and for how long can help you avoid drug interactions and side effects. It’s also important to note that phentermine has the potential to become addicting.

Adipex can be detected in the blood, urine, and hair. The SAMHSA amphetamine test on the 5-panel urine test is the most common test administered. Hair follicle tests and blood tests are less common but may also be used.

 Verywell / Gary Ferster 

How Long Does It Take to Feel Effects?

Phentermine acts similarly to amphetamines by suppressing the appetite, stimulating the central nervous system, and elevating blood pressure. Phentermine is absorbed through the gastrointestinal tract and reaches peak concentrations in the blood in three to 4.4 hours, by which time you should start feeling the effects, alerting you that the drug is working.

The short-term effects of Adipex may include:

• Decreased appetite
• Euphoria
• Hyperactivity
• Anxiety, irritability
• Chest pain

It is taken either as an extended-release capsule, which is taken once per day in the morning, or tablets, which are taken a half hour before meals, three times per day.

Phentermine increases levels of norepinephrine, dopamine, and serotonin, producing an effect similar to amphetamine. For this reason, phentermine is a controlled substance and only available legally via a prescription.

How Long Does Adipex Last?

Adipex has a half-life of about 20 hours, which is the time it takes for half of the dosage to be metabolized by the liver or excreted unchanged in the urine. It takes five to six half-lives for Adipex to be completely eliminated from your system.

A typical dose of Adipex is one 37.5mg capsule in the morning before breakfast. Adipex capsules contain the active ingredient phentermine hydrochloride, of which 70% to 80% is excreted in the urine unchanged. The rest undergoes N-oxidation and N-hydroxylation to form corresponding metabolites.

Blood

Adipex is detected via blood test for up to 24 hours.

Urine

Adipex is detected for one to four days by the SAMSHA 5-panel’s amphetamine test. Urine tests are the most common, so it’s fairly safe to stop taking Adipex a week before the drug test and expect for it to not show up on the test.

Hair

The hair follicle drug test can detect Adipex for several months.

False Positive Testing

Since phentermine has a similar structure to amphetamines, it can turn up a false positive on urine drug screens for amphetamines or MDMA, as confirmed by a 2016 study. A positive result will signal the need for a confirmatory test, which will then show that it was phentermine and not amphetamine or methamphetamine. The original result will then be ruled a false positive.

If you have a prescription for phentermine, you should disclose that to the testing lab so your results can be appropriately interpreted.

Factors That Affect Detection Time

The amount of phentermine detected in tests and how long it stays in your system is dependent on a number of factors.

Age

Metabolism of Adipex may take longer in an older person.

Dosage

If you are taking more than the recommended dose and using it off-label, Adipex may stay in your system longer.

Metabolism

A person of average build and metabolism can expect phentermine to be present in urine for three to five days. It may be longer for an older person

How to Get Adipex Out of Your System

It is recommended to taper Adipex use rather than immediately stopping. Adipex will generally be out of your system about two days after the last time you take it.

Phentermine is stored in body fat and burning fat may support elimination. That said, there is no healthy way to speed up this process. If you are expecting to be tested for Adipex, disclose that you are taking it or stop using it prior to being tested. People prescribed Adipex for weight loss often expect to take it for several weeks. Plan ahead.

Keep in mind that if you are using the drug as prescribed by your doctor, it is not a problem for Adipex to show up on a drug test.

Symptoms of Overdose

Phentermine has stimulant properties and can impact neurotransmitters including dopamine, norepinephrine, and serotonin. This is very similar to amphetamines. For this reason, prescriptions are tightly regulated and often only allowed for short periods of time. It is not recommended for people with a history of stimulant use disorder.

Some of the serious side effects of Adipex include increased blood pressure, heart palpitations, restlessness, dizziness, tremor, insomnia, shortness of breath, chest pain, and swelling of the legs and ankles.

Adipex overdose symptoms, on the other hand, may include:

• Confusion
• Panic
• Hallucinations
• Extreme restlessness
• Nausea
• Vomiting
• Diarrhea
• Stomach cramps
• Feeling tired or depressed
• Irregular heartbeats
• Weak pulse
• Seizure
• Slow breathing (breathing may stop)

If you think someone has overdosed on any phentermine medication, call the poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call 911 immediately.

Drug Interactions

It is important that you discuss all of your medications and supplements with your doctor to avoid drug interactions. Drugs of special concern include those used to treat depression and similar conditions, including:

Your doctor should also be made aware of any previous heart conditions, including high blood pressure and arteriosclerosis, or if you have hyperthyroidism. It’s also best to avoid using alcohol while taking Adipex as the combination can intensify the effects.

Getting Help

Withdrawal symptoms from Adipex use tend to peak within the first couple of days and diminish over the next week. Common withdrawal symptoms from Adipex include:

• Headaches
• Lack of energy
• High blood pressure
• Diarrhea
• Stomach pain
• Vomiting
• Menstrual irregularities
• Insomnia
• Irritability
• Memory loss
• Heart palpitations

If you are taking Adipex regularly at a high dose and stop taking it too soon, you can be at risk for more serious problems, including:

• Congestive heart failure
• Cardiac arrest
• Strokes
• Tremors
• Seizures
• Nerve damage

Adipex and other phentermine-containing medications may be available by prescription and can help with your weight loss goals. However, it is important to realize that there are potential risks involved, including developing a dependence and even a stimulant use disorder.

It could become difficult for you to concentrate without taking Adipex. You could enter into unhealthy cycles of taking more and less of the drug that put dangerous strain on your cardiovascular system.

Cravings for Adipex that end up interfering with your everyday life are cause for speaking with a mental health professional. Counseling or group therapy can help you understand the reasons for your Adipex use and develop alternatives and strategies to slowly stop using. Harm reduction psychotherapy and abstinence-based programs are both available depending on what you feel is best for you.

If you or a loved one is experiencing symptoms of Adipex addiction, help is available. Treatment providers can be found using the Substance Abuse and Mental Health Services Administration’s Behavioral Health treatment services locator.

2 Popular Diet Pills Linked to Problems With Heart Valves

”Presently, there is no conclusive evidence establishing a causal relationship between these two products and valvular disease,” the F.D.A. letter said. ”However, given the seriousness of the reported valvular disease and its rare occurrence in otherwise healthy women in this age range, we believe that patients and health care professionals should be notified of this information.”

In a telephone interview, Dr. Friedman acknowledged that ”these are immensely popular drugs.” But the Acting Commissioner added, ”For those physicians who wish to prescribe these two drugs in an off-label manner and for patients who wish to take them, there may well be significant and unanticipated risks.”

The most dangerous complication, primary pulmonary hypertension, which can be almost impossible to treat and can kill patients by asphyxiation, was already known to be a rare complication of fenfluramine, but it was thought to occur in just 40 to 50 patients per million. The finding of eight women with the disorder in such a small geographic area was unexpected.

Dr. Heidi M. Connolly, a cardiologist at the Mayo Clinic, said she and her colleagues first became suspicious of the diet drugs a year ago, when a 40-year-old woman was referred to the clinic for heart surgery. Her mitral valve had developed serious leakage and her heart could no longer function effectively, leaving her tired and short of breath.

Dr. Hartzell V. Schaff, the surgeon who replaced the woman’s valve, remarked to Dr. Connolly that the valve was glistening and white, and looked like those that had been damaged when patients took ergotamine for long periods of time. The woman had not been taking that drug, but she mentioned to the surgeon that she had taken fenfluramine and phentermine.

Dr. Schaff went to the Mayo Clinic’s pharmacy and asked whether the diet drugs resembled serotonin and whether anyone had ever reported that they caused mitral valve problems. The answer, he was told, was no.

”We couldn’t say it was cause and effect,” Dr. Connolly said. ”But then we saw additional patients,” and a pattern emerged.

Phentermine and Alcohol | Midwood Addiction Treatment

Are Phentermine and Alcohol Safe to Combine? – Phentermine (Adipex-P, Pro-Fast) is a weight loss agent prescribed by health providers to help their patients lose weight. It’s primarily used among those who are obese or who have medical conditions are related to being overweight.

Phentermine is in of a class of drugs known as sympathomimetic amines.

When a patient uses phentermine, the drug will activate the release of three hormones in their body: epinephrine, adrenaline, and norepinephrine. This action suppresses a person’s appetite, and therefore, they tend to eat less. It may also increase a person’s energy and activity levels.

Phentermine is classified by the FDA as a schedule IV controlled substance and is designed for short-term use. It’s generally only prescribed for people with a body mass index (BMI) of greater than 30.

Side effects of phentermine may include:

• Decreased libido
• Bowel movement issues
• Dry mouth
• False sense of well-being

• Itching
• Erectile dysfunction
• Skin redness and hives
• Insomnia

• Gastrointestinal issues
• Heart palpitations
• Hyperactivity
• Tremors and restlessness

More severe side effects include dizziness, fainting, chest pain, accelerated heart rate, headache, numbness or tingling in the extremities, and breathing problems.

Phentermine and Alcohol Abuse

Even without combining it with alcohol, those who use phentermine may potentially abuse it or become addicted. It is a stimulant drug, and it can be used to produce a high, especially when it is used large doses. If a person takes phentermine more often or for longer than instructed, they can become dependent or addicted. They will then experience unwanted withdrawal symptoms when they try to quit.

Potentially severe phentermine withdrawal symptoms include the following:

• Depression
• High blood pressure
• Diarrhea
• Nausea

• Vomiting
• Glaucoma
• Memory loss
• Heart failure

• Cardiac arrest
• Strokes
• Seizures
• Nerve damage

NOTE: People with a prior history of drug or alcohol abuse are cautioned not to use phentermine.

Mixing Alcohol and Phentermine

Patients are generally advised against using alcohol and phentermine in conjunction with one another. The side effects of combining alcohol and phentermine are likely to be more severe than those of either substance used on its own. For example, phentermine side effects include dry mouth, nausea, sleep disturbances, and elevated heart rate and blood pressure. All of these can be made worse when the two substances are combined.

Moreover, because alcohol is known to irritate the stomach, gastrointestinal side effects are common amongst those who drink while taking phentermine. This action can lead to nausea, vomiting, stomach aches, and heartburn.

The manufacturers of phentermine caution that when consuming alcohol and phentermine, you may be at an increased risk of cardiovascular side effects, including chest pains and elevated blood pressure. Also, even having only a small amount of alcohol can increase the risk of heart attack or stroke in those who are obese or have heart disease and are using phentermine.

Using alcohol and phentermine together can increase the risk of addiction to both substances.

Both substances are addictive on their own, and, if used together, they may be more likely to be abused.

Phentermine and alcohol have two competing effects on the body. Phentermine is a central nervous system stimulant, and alcohol is a depressant. Therefore, when a person combines alcohol and phentermine, the medication may not be as effective as it would have been otherwise.

In fact, there are many ways that alcohol can undermine weight loss efforts. For one, alcohol contains a large amount of sugar and mostly empty calories. Also, it tends to make people tired and less likely to be physically active—both while drinking and the day after during a hangover. Because alcohol affects the liver, it may also make it more difficult for the body to burn fat. Finally, alcohol reduces inhibitions, and a person who is drinking may be more likely to make dietary food choices.

It is best for a patient who is using phentermine to stop drinking alcohol to minimize these risks and prevent other complications from occurring.

Treatment for Alcoholism

If you are using phentermine and feel as if you are unable to stop drinking alcohol on your own, you should consider seeking professional help. Harmony Treatment and Wellness offers comprehensive services for the treatment of alcohol and drug addiction. Our programs feature evidence-based modalities vital for the process of recovery, including psychotherapy, counseling, psychoeducation, peer support groups, medication-assisted treatment, and more.

We employ highly-skilled staff who provide clients with the tools, resources, and support they need to experience a full recovery! We believe that everyone—regardless of their addiction—is entitled to happiness and wellness. We urge those who need help to reach out as soon as possible!

If you or someone you love is struggling with alcohol abuse and are ready to begin a new life, contact us today! We are dedicated to helping people liberate themselves from the chains of addiction for life!

90,000 Opportunities of drug therapy for obesity yesterday and today | Khorosheva G.A., Melnichenko G.A.

MMA named after I.M. Sechenov

In , the present obesity has ceased to be considered only from an aesthetic point of view and has moved into the category of medical problems. This is due to the fact that obesity is associated with increased mortality and diseases such as hypertension, hyperglycemia, dyslipidemia, coronary heart disease, osteoarthritis, gallbladder disease, sleep apnea and some types of malignant neoplasms (breast, prostate, endometrial, colon ) [one]. For example, over 50% of Americans can be classified as overweight or obese. As a result, the expected death rate in the United States could increase to 300,000 per year [2]. Indeed, despite the fact that the exact linkage mechanism by which obesity contributes to arterial hypertension is not known, according to population studies, at least 75% of cases of arterial hypertension are associated with obesity [3]. In the literature, there is abundant evidence that blood pressure rises with weight gain and decreases with weight loss, and is also responsible for the activation of the sympathetic nervous system, which can ultimately lead to changes in the structure and function of the kidneys [3,4].Obesity also affects lipoprotein metabolism. Weight gain leads to an increase in triglyceride and low-density lipoprotein (LDL) levels, and a decrease in high-density lipoprotein (HDL) levels. With weight loss, there is an opposite effect on the level of lipoproteins in overweight individuals [3,4]. A similar relationship is also observed with respect to the sensitivity of insulin receptors in type 2 diabetes mellitus. In more than 50% of cases, insulin sensitivity is directly related to obesity [3].With increasing weight, insulin resistance increases, with weight loss, an improvement in glycemic control is noted [3,4,5,6].

When examining obese patients, it is necessary to evaluate three indicators: body mass index (BMI), waist circumference and absolute risk status . BMI is an indicator of the relationship between height and weight, it is calculated as the ratio of body weight in kg to the square of height in meters.In June 1998, The National Institutes of Health (NIH) approved clinical guidelines for the diagnosis and treatment of obesity [3]. This guideline defines overweight people as having a BMI of 25–29.9 kg / m ² and obese people with a BMI of 30 kg / m ² and above. The classification of obesity depending on BMI is presented in table 1

The guidelines emphasize that patients 18 years of age or older with a BMI of 25 kg / m2 ² and above have a higher risk of developing secondary complications such as hypertension, type 2 diabetes mellitus, coronary heart disease and hyperlipidemia.

Waist circumference is an indicator of the degree of abdominal (central, visceral) obesity. It has been proven that the central type of obesity is an independent risk factor for concomitant diseases. The following three groups include individual cardiovascular risk factors according to the classification proposed by the NIH:

1. Patients with comorbidities, such as type 2 diabetes mellitus, coronary heart disease, other diseases associated with atherosclerotic vascular lesions, sleep apnea syndrome, belong to the group with a very high risk of complications and mortality.

2. Patients with three of the following cardiovascular risk factors: hypertension (systolic blood pressure> = 140 mm Hg or diastolic blood pressure> = 90 mm Hg, or receiving antihypertensive therapy), dyslipidemia (LDL> = 160 mg / dL or HDL <35 mg / dL), impaired fasting glucose (110-125 mg / dL), smoking, family history of cardiovascular disease at a young age (myocardial infarction or sudden death at age <= 55 for father or brother, or <= 65 for mother or sister), age (men> = 45 and women> = 55 or postmenopausal) are at high risk.

3. Patients with other diseases such as gynecological pathology, osteoarthritis, cholelithiasis.

NIH recommends patients with a BMI> = 30 kg / m2 ² , as well as patients with a BMI between 25 and 29.9 kg / m2 ² , or men with a waist circumference greater than 102 cm and women over 88 cm with two or more of the above risk factors for weight loss. The initial target should be 10% loss of baseline body weight in 6 months .It can be achieved through lifestyle modifications that include a reduced calorie diet and increased physical activity. If the change in lifestyle is not enough to achieve the goal or does not allow maintaining the achieved result for a long time, then pharmacotherapy may be prescribed. Over the past few years, the arsenal of weight loss drugs has dwindled. Fenfluramine, dexfenfluramine, phenylpropanolamine are withdrawn from the market due to serious side effects.To date, only the sympathomimetics sibutramine and orlistat have been approved by the Food and Drug Administration (FDA) for weight loss. The choice of a particular drug depends on the concomitant pathology and therapy, ease of use and cost. Before prescribing a particular drug, the physician should have complete information about the various classes of drugs used for weight loss today, about their pharmacodynamics, side effects and possible interactions with other drugs.

Medicines for weight loss

Recently withdrawn from the market

Fenfluramine hydrochloride and its isomers, dexfenfluramine hydrochloride, increase satiety by increasing serotonin levels in the central nervous system (CNS). This is accomplished by two different mechanisms. Both drugs inhibit the reuptake of serotonin in the central nervous system and, at the same time, when they are metabolized to norfenfluramine, serotonin is released [7].Fenfluramine is effective in reducing body weight and has long been used as monotherapy. Then it was found that the combination of low doses of fenfluramine with low doses of phentermine ((in the English-language literature “fen-phen”), phentermine will be discussed below) is more effective than each drug alone, and the side effects are much less [8].

Dexfenfluramine was effective in reducing weight by 10% of baseline in obese patients.Since its effectiveness has been proven in clinical studies, the FDA approved its use in April 1996 [7]. Thereafter, about 85,000 prescriptions per week of this drug were noted in the United States. The use of fenfluramine and fenluramine-phentermine (“fen-phen”) has also increased. Most appointments were made to slightly overweight patients to lose a few pounds than to obese patients. After several clinical studies have shown that dexfenfluramine is effective for weight loss throughout the year, it was recommended for long-term use in the treatment of obesity [9].

In Europe, widespread use of fenfluramine and dexfenfluramine has been noted since the early 90s [7]. During this period of increasing use of these drugs, a large number of cases of dexfenfluramine-induced pulmonary hypertension were reported throughout Europe. Fenfluramine-induced pulmonary hypertension was reported before 1981 [10]. In the International Primary Pulmonary Hypertension Study (IPPHS) case-control design, it was found that the use of anorectics, mainly derivatives of fenfluramine, was associated with a 10-fold increased risk of primary pulmonary hypertension compared with the control group [ eleven].In patients taking anorectics for more than 3 months, there was a 23-fold increase in risk compared with the control group.

Pulmonary hypertension was not the only serious side effect reported with fenfluramine and dexfenfluramine. According to many reports, lesions of the heart valves have also been associated with the use of these two drugs, and especially their combination with phentermine. In the summer of 1997, the FDA requested voluntary withdrawals of fenfluramine and dexfenfluramine [12].Theoretically, the pharmacological action of fenfluramine-containing drugs was the cause of damage to the lungs and heart valves. Moreover, not only the action of fenfluramine and dexfenfluramine in inhibiting the reuptake of seretonin in the central nervous system, as well as their active metabolite norfenfluramine, which increases the release of serotonin, led to the activation of serotonin receptors. Serotonin is a potent vasoconstrictor and can lead to pulmonary vasoconstriction [7]. Moreover, high serotonin levels are the cause of histological changes in heart valves in patients receiving fenfluramine-containing drugs.

Phenylprpanolamine, a synthetic catecholamine, was the active ingredient in weight loss supplements sold without a prescription, and is also part of the combination therapy for the symptomatic treatment of rhinitis and upper respiratory tract inflammation. Decreased appetite during its intake occurs as a result of stimulation of the release of norepinephrine and dopamine in the center of hypothalamic saturation [13]. Since the late 1970s, many FDA publications and reports have linked phenylpropanolamine intake to hemorrhagic stroke.As a number of reports were submitted by Yale University, the FDA and phenylpropanolamine manufacturers joined the Hemorrhagic Stroke Project, a case-control study, to establish a correlation between phenylpropanolamine use and the risk of hemorrhagic stroke [14]. It was concluded that an increased risk of hemorrhagic stroke exists for women taking anorexics containing phenylpropanolamine. Although the risk of hemorrhagic stroke was lower among those taking phenylpropanolamine, the FDA recommended that phenylpropanolamine-containing drugs be removed from the trade [15].This request was complied with as the benefits did not outweigh the risks of taking these drugs.

Medicines currently used to treat obesity

Sympathomimetics. Sympathomimetics suppress appetite by stimulating the release of norepinephrine and dopamine by nerve endings in the saturation center of the hypothalamus. Other effects caused by sympathomimetics, such as suppression of gastric secretion and increased energy expenditure, may also contribute to appetite suppression and weight loss [13].Benzfetamine, diethylpropion, phendimetrazine, and phentermine are licensed sympathomimetics for weight loss in the United States. Moreover, phentermine is the most prescribed drug. In clinical studies, phentermine has been shown to exhibit the same activity in terms of weight loss both with continuous daily use and with the appointment of short courses. At the same time, weight loss ranged from 5 to 15% of the baseline in 60% of patients [16,17].Those taking phentermine in combination with a hypocaloric diet achieved more significant weight loss compared to patients on a hypocaloric diet alone [18]. However, weight loss with phentermine was usually 0.5 kg over a week compared with placebo, and tolerance was often developed to it [13]. After the results of long-term studies appeared in which phentermine was prescribed for 36 weeks [16], it is recommended for short-course therapy.

Phentermine therapy should be limited and should be prescribed to patients with a BMI> 30 kg / m ² or to patients with a BMI> 27 kg / m ² with risk factors [19]. The most common side effects of phentermine are nervousness, dry mouth, constipation, and hypertension. In this regard, the appointment of phentermine is not recommended for patients with hypertension and concomitant cardiovascular pathology.Also, with caution, phentermine should be prescribed to patients with anxiety and depression, as it can aggravate their manifestations. The structure and pharmacological action of phentermine are similar to those of amphetamine. Hence, phentermine can cause physical and mental addiction. In this regard, patients with a history of drug dependence should not be prescribed phentermine.

There is evidence that there is a relationship between taking phentermine and the development of pulmonary hypertension, damage to the heart valves [20].However, most of these patients also took fenfluramine and dexfenfluramine in combination with phentermine. Although it is believed that side effects from the lungs and heart are caused by taking fenfluramine derivatives, researchers cannot unequivocally rule out the effects of phentermine on these organs. In this regard, patients receiving phentermine should immediately stop taking it and consult a doctor if shortness of breath, chest tightness, fainting, and decreased exercise tolerance appear. The doctor, in turn, will need to assess the functions of the respiratory and cardiovascular systems. Phentermine should not be taken during treatment with monoamine oxidase (MAO) inhibitors, and, at least, in the next 2 weeks after its termination, as the risk of developing a hypertensive crisis increases [13]. The combined use of phentermine with tricyclic antidepressants leads to an increase in norepinephrine stimulation, which can cause the development of arterial hypertension and various types of arrhythmias.Due to the possibility of developing pulmonary hypertension and damage to the heart valves, it is not recommended to take phentermine in patients receiving drugs that inhibit serotonin reuptake. Phentermine can reduce the hypotensive effect of clonidine, guanethidine and methyldopa, as well as potentiate the metabolic effect of thyroid hormones. The usual dose of phentermine is 8 mg 3 times a day 30 minutes before meals, or 15–37.5 mg once [20]. To avoid insomnia, it is recommended to take the last dose 6 hours before bedtime [13]. Taking the drug with a single use is made either before breakfast, or 1-2 hours after it.

Sibutramine . Sibutramine hydrochloride inhibits the reuptake of norepinephrine, serotonin and dopamine in the central nervous system. Moreover, the inhibition of the seizure of norepinephrine (norepinephrine) and serotonin is three times stronger than that of dopamine. The two active metabolites of sibutramine also inhibit the reuptake of norepinephrine and serotonin. Increased levels of norepinephrine and serotonin in the central nervous system lead to increased satiety, which in turn contributes to lower calorie intake.One study suggests that sibutramine may also increase basal metabolic rate. However, this assumption was not confirmed in subsequent studies [13]. In clinical trials, it has been demonstrated that taking sibutramine can achieve greater weight loss compared to placebo [21-25]. Weight loss was noted even in those patients who took sibutramine without following a hypocaloric diet and did not seek lifestyle modifications. Nevertheless, weight loss of 5–10% of baseline was achieved with great success in those patients in whom sibutramine was combined with a hypocaloric diet and lifestyle modification [21].

Studies have shown that the greatest weight loss is achieved after approximately 6 months taking the drug and remains unchanged for almost a year [21-23]. Since the effects of sibutramine persist for at least 12 months, it can be recommended for long-term treatment of obesity.In one study, weight loss after a year was 5% or more in 40% of patients receiving sibutramine, compared with 8-10% of patients receiving placebo. A weight loss of 10% or more was noted in 13% in the group of patients receiving sibutramine versus 5% receiving placebo [22]. Another small study showed that 86% of patients who combined sibutramine with a very low-calorie diet achieved 5% or more weight loss, compared with 55% of patients taking placebo.At the same time, 75% of patients receiving sibutramine maintained the obtained result for a year compared with 42% of patients receiving placebo [23]. Studies have also shown that against the background of weight loss achieved by taking sibutramine, there is an improvement in blood glucose, lipid profile, uric acid levels and a decrease in abdominal obesity [21,22,25].

In studies investigating the effect of sibutramine, an increase in the levels of systolic and diastolic pressure was noted by an average of 1-3 mm Hg.Art. and heart rate by 4-5 beats / min. in the group receiving the active substance compared with placebo [19]. Patients with inadequate compensation for hypertension, coronary heart disease, other cardiac pathology, arrhythmias, as well as those who have had a stroke, should not take sibutramine. Before the appointment, as well as in the process of taking sibutramine, it is necessary to monitor the level of blood pressure and heart rate. An increase in blood pressure and / or an increase in heart rate during sibutramine therapy is a reason for reducing the dose of the drug and even discontinuing it.Other common side effects of sibutramine include dry mouth, anorexia, insomnia, and constipation. Unlike fenfluramine and dexfenfluramine, there are currently no known cases of pulmonary hypertension and lesions of the cardiac valves caused by taking sibutramine. Although, like fenfluramine, sibutramine inhibits serotonin reuptake, it does not have the ability to further stimulate the release of serotonin from nerve endings [13].

Sibutramine should not be taken during and in the next 2 weeks after treatment with MAO inhibitors because of the risk of increased norepinephrine activity and, as a consequence, the development of hypertensive crisis, as well as due to the possibility of increased serotonin activity and the risk of developing “serotonin syndrome” …Taking sibutramine with drugs that inhibit serotonin reuptake can also lead to the development of “serotonin syndrome”. In addition, it is not recommended to take sibutramine with drugs that can cause an increase in blood pressure. Sibutramine is metabolized by cytochrome P-450 isoenzyme 3A4. Its metabolism can be inhibited by ketoconazole and erythromycin. However, this interaction is believed to be of no clinical relevance.

Sibutramine should be prescribed to patients with a BMI> = 30 kg / m ² or to patients with a BMI> = 27 kg / m ² with risk factors [19].It is recommended to combine taking sibutramine with a hypocaloric diet. The starting dose is 10 mg once in the morning. If the weight loss in 4 weeks was not more than 1.5 kg, then the dose of the drug can be increased to 15 mg. Physicians need to be aware of the importance of controlling blood pressure and heart rate when adjusting the dose of sibutramine.

Orlistat (Xenical) . Unlike other drugs for weight loss, orlistat is an inhibitor of gastrointestinal lipases [19].Orlistat covalently binds to the active site of the enzyme, inactivating it. This prevents hydrolysis and subsequent absorption of dietary fats. A decrease in fat intake leads to a decrease in energy intake and, in the future, to a loss of extra pounds. Since the main action of orlistat is realized in the gastrointestinal tract, a very small amount of the drug enters the systemic circulation.

Recently, the results of three large, randomized, double-blind, placebo-controlled trials have been published that investigated the efficacy of orlistat [26-28].In all three studies, patients on both orlistat and placebo followed a hypocaloric diet during the first year. In order to maintain the achieved result as much as possible, in the second year all patients were transferred to a eukaloric diet. All three studies demonstrated significant weight loss at the end of the first year in the groups receiving orlistat (average 9%) compared with placebo (average weight loss 5%). In addition, all studies showed significantly less weight gain during the second year in the groups receiving orlistat.After the first year, 30–65% of patients receiving orlistat experienced a weight loss of 5% or more versus 30–43% of patients receiving placebo. Weight loss of 10% or more was achieved by 28–38% of those receiving orlistat versus 11–24% of those taking placebo. After the second year, weight loss persisted> = 10% in 18–34% of those on orlistat, and in 6–17. 5% of those taking placebo. In addition to weight loss during treatment with orlistat, these studies revealed a significant reduction in obesity-associated risk factors , such as arterial hypertension, hyperglycemia, hypercholesterolemia, and abdominal obesity.Two studies reported a significant decrease in insulin levels in patients taking orlistat for two years [27,28], while in the third study, not only a decrease in insulin levels was recorded, but also an improvement in fasting glucose levels [26]. Hollander et al. studied the effects of orlistat in combination with a moderately hypocaloric diet in patients with type 2 diabetes mellitus [6]. As in previous studies, they also showed a significant decrease in body weight in patients taking orlistat.In addition, in patients with type 2 diabetes mellitus taking orlistat for 1 year, there was a decrease in fasting glycemia and an improvement in glycosylated hemoglobin compared with the placebo group. However, there were no significant differences in fasting insulin levels between the two groups. All patients randomized in this study received therapy with second-generation sulfonylureas (glyburide or glipizide). A dose reduction of sulfonylurea was required in 43% of patients on orlistat and 28% on placebo.

In all three studies, there was a significant decrease in total cholesterol and LDL cholesterol levels during treatment with orlistat [26-28]. It is believed that the improvement in lipid metabolism is not due to weight loss per se. This is associated with the ability of orlistat to disrupt lipid absorption. Accordingly, their entry into the liver decreases, which ultimately leads to an increase in the sensitivity of hepatocyte receptors to LDL cholesterol [29].I would like to note that, unlike other drugs for weight loss, Medicaid primarily recommends orlistat, precisely because of its positive effect on blood lipid composition, which is not associated with a decrease in body weight [30].

Since orlistat is not absorbed into the systemic circulation, it does not have the side effects typical of other drugs for weight loss. The most common symptoms are from the gastrointestinal tract, as the excretion of fats increases [19].Side effects such as abdominal pain, fecal incontinence, flatulence, increased frequency of bowel movements and stool volume, “fat” stools and others, occur in 95% of patients taking orlistat. In most patients, these symptoms resolve within four weeks, but in some they may persist for up to 6 months or longer. It is possible to reduce bowel manifestations by applying a low-fat diet (daily fat intake should not exceed 30% of total calories). Although taking orlistat is not recommended for patients with cholestasis, there is no evidence of the possibility of gallstones forming while taking it.Orlistat is also not recommended for patients with malabsorption syndrome.

Treatment with orlistat may impair the absorption of fat-soluble vitamins (A, D, E and K) and b-carotene [31]. In this regard, it is recommended to take multivitamins during orlistat therapy. Moreover, they should be taken 2 hours before or 2 hours after taking orlistat. It is believed that when orlistat is taken together with warfarin, the pharmacokinetics of the latter should not change [32]. Despite this, due to the fact that orlistat reduces the absorption of vitamin K, the anticoagulant effect of warfarin may increase over time [29].Since dietary fat is known to increase absorption of cyclosporins, the opposite effect can be expected as a result of the reduction in dietary fat caused by taking orlistat. Although there are no publications on studies that would study the interaction of cyclosporins and orlistat, there is evidence that six patients while taking orlistat had subtherapeutic levels of cyclosporins in their blood [33]. One small study showed that pravastatin and orlistat increased the lipid-lowering effect of pravastatin [19] and there was a slight increase in pravastatin blood levels.Nevertheless, it is believed that the additive hypolipidemic effect is more due to the mechanism of action of orlistat than to a change in the pharmacokinetics of pravastatin. Small studies have shown that orlistat does not affect the pharmacokinetics of digoxin, glibutide, nifedipine, oral contraceptives, and phenytoin [19,34,35].

In combination with a hypocaloric diet, orlistat is used for long-term treatment of obesity in patients with BMI> = 30 kg / m ² or BMI> = 27, with risk factors [13,19].and also to maintain the achieved result. It is taken three times a day at 120 mg during or within 1 hour after a meal containing fat. If a meal is skipped or it does not contain fat, then the drug should not be taken. Patients should be recommended multivitamins, which are best taken two hours before or 2 hours after taking orlistat. It should also be reminded of the importance of following a low fat diet to avoid side effects.

Conclusion

Many studies have shown that even a slight decrease in body weight reduces the risk of developing cardiovascular and other complications [3,26-28,36].The obesity treatment guidelines indicate that the initial goal of treatment is to lose 5–10% of body weight and maintain weight, rather than achieving ideal body weight . If within 6 months it is not possible to achieve weight loss by 5-10% with the help of diet, exercise, lifestyle changes, then it is advisable to prescribe drug therapy, especially for patients with risk factors such as hyperlipidemia, hypertension, diabetes mellitus. Although drug therapy results in a loss of only 5–15% of body weight in most patients, even such a decrease in weight leads to significant improvements in health status.In addition, as mentioned above, the results of a number of studies suggest that drug therapy in combination with dietary modification increases the long-term effectiveness of obesity treatment and makes it possible to maintain body weight for a long time after weight loss.

Patients choosing drug therapy need to be educated that obesity is a chronic disease. Therefore, in order to prevent a return to their original weight, they need long-term treatment [37].In this regard, for obese patients, phentermine will not be a first-line drug, since most patients quickly develop tolerance to its therapeutic effect. Since orlistat and sibutramine are suitable for long-term use and their therapeutic effect lasts for at least 1 year, they are the drugs of choice for the treatment of obesity.

When deciding on the appointment of drug treatment for obesity, it is necessary to take into account the presence of combined pathology and concomitant drug therapy.Brief characteristics of drugs for the treatment of obesity, their side effects and contraindications to the appointment are listed in Table 2.

Literature:

1. Pi – Sunyer FX. Medical hazards of obesity. Ann Intern Med. 1993; 119: 655-60.

2. McGinnis JM, Foege WH. Actual causes of death in the United States. JAMA. 1993; 270: 2207-12.

3. Krauss RM, Winston M. Obesity: impact on cardiovascular disease. Circulation.1998; 98: 1472-6.

4. Expert Panel on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. Executive summary of the clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults. Arch Intern Med. 1998; 158: 1855–67.

5. Heymsfield SB, Segal KR, Hauptman J et al. Effects of weight loss with orlistat on glucose tolerance and progression to type 2 diabetes in obese adults. Arch Intern Med. 2000; 160: 1321-6.

6. Hollander PA, Elbein SC, Hirsch IB et al. Role of orlistat in the treatment of obese patients with type 2 diabetes: a 1 – year randomized double – blind study. Diabetes Care. 1998; 21: 1288–94.

7. Langleben D. Relearning the lessons of history: anorexigens and pulmonary hypertension. Chest. 1998; 114: 55S-7S.

8. Weintraub M, Hasday JD, Mushlin AI et al. A double – blind clinical trial in weight control: use of fenfluramine and phentermine alone and in combination.Arch Intern Med. 1984; 144: 1143-8.

9. Guy-Grand B, Apfelbaum M, Crepaldi G et al. International trial of long – term dexfenfluramine in obesity. Lancet. 1989; 2: 1142-5.

10. Douglas JG, Munro JF, Kitchin AH et al. Pulmonary hypertension and fenfluramine. Br Med J. 1981; 283: 881-3.

11. Abenhaim L, Moride Y, Brenot F et al. Appetite – suppressant drugs and the risk of primary pulmonary hypertension. International Primary Pulmonary Hypertension Study Group.N Engl J Med. 1996; 335: 609-16.

12. Cardiac valvulopathy associated with exposure to fenfluramine or dexfenfluramine: U.S. Department of Health and Human Services interim public health recommendations, November 1997. MMWR Morb Mortal Wkly Rep. 1997; 46: 1061-6.

13. USP DI – volume I: drug information for the health care professional. 21st ed. Englewood, CO: Micromedex; 2001.

14. Kernan WN, Viscoli CM, Brass LM et al. Phenylpropanolamine and the risk of hemorrhagic stroke.N Engl J Med. 2000; 343: 1826–32.

15. Food and Drug Administration. Washington, DC: U.S. Department of Health and Human Services 2000 Nov 6. (Talk Paper T00-58.)

16. Munro JF, MacCuish AC, Wilson EM et al. Comparison of continuous and intermittent anorectic therapy in obesity. Br Med J. 1968; 1: 352-4.

17. Truant AP, Olon LP, Cobb S. Phentermine resin as an adjunct in medical weight reduction: a controlled, randomized, double-blind prospective study.Curr Ther Res Clin Exp. 1972; 14: 726-38.

18. Langlois KJ, Forbes JA, Bell GW et al. A double – blind clinical evaluation of the safety and efficacy of phentermine hydrochloride (Fastin) in the treatment of exogenous obesity. Curr Ther Res Clin Exp. 1974; 16: 289-96.

19. Schrefer J, ed. Mosby GenRx: a comprehensive reference for generic and brand prescription drugs. 11th ed. St. Louis: Mosby; 2001.

20. McEvoy GK, ed. AHFS drug information. Bethesda, MD: American Society of Health – System Pharmacists; 2000.

21. Wadden TA, Berkowitz RI, Sarwer DB et al. Benefits of lifestyle modification in the pharmacologic treatment of obesity. Arch Intern Med. 2001; 161: 218-27.

22. McMahon FG, Fujioka K, Shingh BN et al. Efficacy and safety of sibutramine in obese white and African American patients with hypertension: a 1 – year, double – blind, placebo – controlled, multicenter trial. Arch Intern Med. 2000; 160: 2185-91.

23. Apfelbaum M, Vague P, Ziegler O et al.Long – term maintenance of weight loss after a very – low – calorie diet: a randomized blinded trial of the efficacy and tolerability of sibutramine. Am J Med. 1999; 106: 179–84.

24. Hanotin C, Thomas F, Jones SP et al. Efficacy and tolerability of sibutramine in obese patients: a dose – ranging study. Int J Obes Relat Metab Disord. 1998; 22: 32-8.

25. McNeely W, Goa KL. Sibutramine: a review of its contribution to the management of obesity. Drugs. 1998; 56: 1093-124.

26. European Multicenter Orlistat Study Group. Randomized placebo – controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. Lancet. 1998; 352: 167-72.

27. Davison MH, Hauptman J, DiGirolamo M et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. JAMA. 1999; 281: 235–42.

28. Hauptman J, Lucas C, Boldrin MN et al. Orlistat in the long – term treatment of obesity in primary care settings.Arch Fam Med. 2000; 9: 160-7.

29. Cada DJ, Baker DE, Levien T. Orlistat. Hosp Pharm. 1999; 34: 1195-213.

30. National Association of Chain Drug Stores. Fast facts – Medicaid and Xenical. Chain Pharm Pract Memo. 2000; 4 (6): 4.

31. Collazo-Clavell ML. Safe and effective management of the obese patient. Mayo Clin Proc. 1999; 74: 1255-60.

32. Zhi J, Melia AT, Guerciolini R et al. The effect of orlistat on the pharmacokinetics and pharmacodynamics of warfarin in healthy volunteers.J Clin Pharmacol. 1996; 36: 659-66.

33. Colman E, Fossler M. Reduction in blood cyclosporine concentrations by orlistat. N Engl J Med. 2000; 342: 1141-2. Letter.

34. Melia AT, Mulligan TE, Zhi J. The effect of orlistat on the pharmacokinetics of phenytoin in healthy volunteers. J Clin Pharmacol. 1996; 36: 654-8.

35. Melia AT, Mulligan TE, Zhi J. Lack of effect of orlistat on the bioavailability of a single dose of nifedipine extended – release tablets in healthy volunteers.J Clin Pharmacol. 1996; 36: 352-5.

36. Stevens VJ, Obarzanek E, Cook NR et al. Long – term weight loss and changes in blood pressure: results of the trials of hypertension prevention, phase II. Ann Intern Med. 2001; 134: 1-11.

37. Atkinson RL. A 33 – year – old woman with morbid obesity. JAMA. 2000; 283: 3236-43.

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Pharmacotherapy of obesity: what’s new? | Troshina

Introduction

The rate of prevalence of obesity in both economically developed and developing countries is comparable to the scale of the epidemic.The catastrophic increase in the prevalence of obesity, according to published data from WHO [1], led to the fact that in 2014 more than 1.9 billion adults (18 years and older) were overweight, of whom 600 million were obese. If these trends continue, then by 2030 about 60% of the world’s population, i. e. 3.3 billion people may be overweight (2.2 billion) or obese (1.1 billion) [2]. Obesity-related diseases such as type 2 diabetes mellitus (DM 2), arterial hypertension (AH), coronary heart disease, etc., represent a global medical problem associated with a significantly increasing risk of morbidity and mortality, a significant increase in health care costs and significantly worsening the quality of life of patients [1, 3]. WHO lists obesity as one of the top five risk factors for death. Treatment of diseases associated with obesity accounts for about 70% of health care costs. The mortality risk increases significantly with a body mass index (BMI)> 30 kg / m2. With a BMI> 40 kg / m2, mortality in the 35-45 age group increases 6 times; in the 25-30 age group, the mortality rate is 12 times higher than in persons of the same age without obesity.

Since weight loss can reduce the risk of developing diseases associated with obesity, significantly influence the timing of their manifestation or contribute to their more favorable course [4-7], the issues of conservative treatment of obesity are becoming extremely urgent.

Lifestyle modification based on dietary adjustments and increased physical activity is the cornerstone of the treatment of obese patients, including morbid ones. However, not all patients manage to change their deep-rooted dietary and lifestyle habits and achieve positive treatment results.

It is known that obese patients complicated by concomitant diseases (type 2 diabetes, hypertension, atherosclerosis, obstructive sleep apnea syndrome, arthrosis, gout, etc.) find it more difficult to reduce body weight, since such conditions make it difficult to follow medical recommendations on nutrition and physical loads. It is these difficulties that dictate the need to include pharmaceuticals in the complex treatment of obesity. Pharmacotherapy makes it possible to achieve a more effective reduction in body weight, facilitates the implementation of dietary recommendations, helps in the development of new eating habits, and promotes long-term retention of a reduced body weight.

Since obesity is a chronic disease with frequent relapses, requiring long-term life-long treatment and follow-up, short-term therapy is ineffective.

In patients with complicated obesity, treatment should be continued, even if a slight decrease in body weight is accompanied by an improvement in health and metabolic parameters.

Therefore, the main objectives of pharmacotherapy include the achievement of effective weight loss (more than 10% of the initial), compensation of existing metabolic disorders, improvement of treatment tolerance and adherence to it, as well as prevention of relapse of the disease.

Drugs for the treatment of obesity should have a known mechanism of action, significantly reduce body weight, have a positive effect on metabolic disorders associated with obesity (dyslipidemia, diabetes mellitus, hypertension, etc.), have an acceptable tolerance profile, not cause dependence, be effective and safe for long-term use.

Modern pharmacotherapy of obesity

Until recently, only two drugs for the treatment of obesity, orlistat and sibutramine, were presented on the Russian pharmaceutical market [5-8].

Orlistat

The drug has a peripheral action, has a therapeutic effect within the gastrointestinal tract (GIT) and does not have a systemic effect. As a specific, long-acting inhibitor of gastrointestinal lipases, orlistat prevents the breakdown and subsequent absorption of fats from food (about 30%), thereby creating an energy deficit, which leads to a decrease in body weight. At the same time, it reduces the amount of free fatty acids and monoglycerides in the intestinal lumen, thus reducing the solubility and subsequent absorption of cholesterol, helping to reduce hypercholesterolemia, regardless of the degree of weight loss.Side effects of the drug include fatty stools, oily discharge from the rectum, urge to defecate, increased frequency of bowel movements and fecal incontinence, abdominal pain, gas with some intestinal discharge.

The severity and duration of side effects directly depend on patient adherence to treatment and adherence to recommendations for restricting dietary fat. The side effects of orlistat further encourage patients to follow these guidelines.Adverse events become more frequent with an increase in the fat content in the diet, occur in the early stages of treatment (the first 3 months), and, subject to restriction of fats in food, are poorly expressed and transient.

The optimal dose of the drug is 120 mg 3 times a day with meals or no later than an hour after it. Increasing the dose does not increase efficacy. Dose adjustment in elderly patients and with impaired liver or kidney function is not required. The drug is contraindicated in exacerbation of pancreatitis and diseases accompanied by diarrhea, malabsorption syndrome, cholestasis, with hypersensitivity to the drug itself or any of its components.

The use of orlistat leads to an effective decrease in body weight and BMI in more than 80% of patients. While taking the drug, there is a decrease in risk factors and diseases associated with obesity. The safety of long-term use (up to 4 years of continuous use), as well as the effectiveness of the prevention of type 2 diabetes were demonstrated in the XENDOS study (Xenical in the Prevention of Diabetes in Obese Subjects). Long-term use of the drug in combination with lifestyle changes led to a more pronounced decrease in body weight and statistically significantly reduced the incidence of diabetes mellitus 2 compared with only one change in lifestyle.In addition, the treatment led to a significant and persistent decrease in cardiovascular risk factors such as blood pressure (BP) and the level of atherogenic lipid fractions, and a positive effect on the lipid spectrum was provided not only by a decrease in body weight, but also by direct, independent of the degree of its reduction by the effect of the drug on the absorption of cholesterol [5]. We also obtained data on the positive effect of orlistat on carbohydrate metabolism: treatment with the drug leads to a decrease in the severity of such components of the metabolic syndrome as fasting hyperglycemia, hyperinsulinemia and insulin resistance.S. Heymsfield et al. [7] showed that in the group of patients taking orlistat, impaired glucose tolerance with the subsequent development of diabetes mellitus 2 was recorded half as often as in the group receiving placebo (3.0 and 7.6%, respectively). At the same time, the number of patients whose carbohydrate metabolism normalized while taking the drug, on the contrary, turned out to be significantly higher (71.6 and 49.1%, respectively).

Since the mechanism of action of orlistat is to limit the absorption of fats, its long-term use can potentially lead to a deficiency of fat-soluble vitamins, in particular vitamin 25 (OH) D, and, as a consequence, to impaired calcium metabolism.In some studies, it was shown that in postmenopausal women, treatment of obesity with orlistat does not change the content of 25 (OH) D, however, with a longer use of the drug (12 months), there was a significant decrease in the vitamin content [8, 9]. Therefore, all patients receiving orlistat treatment, especially postmenopausal women, are advised to take a multivitamin supplement, including calcium and 25 (OH) D, and orlistat and vitamins should not be taken at the same time.

Orlistat increases the likelihood of gallstones formation, since inhibition of lipolysis reduces the release of fatty acids into the intestinal lumen, which is necessary to stimulate cholecystokinin secretion and contraction of the gallbladder.Since orlistat inhibits the breakdown of only 30% of dietary fats, rational consumption of fats does not lead to a decrease in gallbladder motility.

Sibutramine

Sibutramine, a dual-acting obesity drug, is an inhibitor of the reuptake of serotonin, norepinephrine and, to a lesser extent, dopamine at the synapses of the central nervous system. The drug enhances and prolongs the feeling of fullness, thereby reducing the amount of food consumed.On the other hand, sibutramine increases the body’s energy expenditure, which together leads to a negative energy balance. Thus, the drug makes it easier for patients to follow medical advice on nutrition.

While taking sibutramine, 1/3 of patients manage to reduce their weight by more than 10% [6].

As an initial dose, sibutramine is prescribed 10 mg in the morning, every day, regardless of food intake. If the body weight in the first month of treatment has decreased by less than 2 kg, it is recommended to increase the dose to 15 mg, provided that the drug is well tolerated.If after the next month the body weight has decreased by less than 2 kg, or in 3 months of admission by less than 5% of the initial, the treatment is considered ineffective. The maximum period of sibutramine therapy is 2 years. In the presence of type 2 diabetes, treatment begins immediately with 15 mg. A loss of less than 2 kg in the first month of therapy does not require discontinuation of the drug, since patients with type 2 diabetes lose weight more slowly. At the same time, even a slight decrease in body weight is accompanied by an improvement in carbohydrate metabolism indicators. As shown by the STORM study, about 54% of patients decreased body weight by more than 10% within 6 months of admission, and the reduced body weight during this period was maintained for 2 years of treatment.Having a positive effect on anthropometric parameters, sibutramine has a beneficial effect on metabolic disorders. Its use is accompanied by a decrease in triglyceride levels by 20% and an increase in high-density lipoprotein levels by 21%, which significantly reduces cardiovascular risk [10].

Considering, however, such possible side effects of the drug as an increase in blood pressure by 1-3 mm Hg. and an increase in heart rate by 3-7 beats. per minute, it is possible to prescribe the drug to patients with obesity and often accompanying hypertension only after the correction of the latter.The drug should not be prescribed to patients with uncontrolled hypertension, ischemic heart disease, decompensated heart failure, heart rhythm disturbances, cerebrovascular diseases (stroke, transient cerebrovascular accidents), severe liver and kidney damage, as well as with simultaneous administration or earlier than 2 weeks after withdrawal of monoamine oxidase inhibitors or other drugs acting on the central nervous system (including antidepressants).

Side effects such as nausea, loss of appetite, constipation, dry mouth, change in taste, insomnia, headache, agitation, sweating are usually mild, are noted only at the beginning of treatment and, as a rule, do not require discontinuation of therapy.

Sibutramine treatment requires medical supervision. Blood pressure and pulse should be monitored in all patients before starting treatment, then from the 1st to the 3rd months of treatment every 2 weeks, from the 4th to 6th months – monthly, from 6th to 12th months – every 3 months

The drug is canceled if the heart rate increases by more than 10 beats / min, the blood pressure rises by more than 10 mm Hg, as well as if the blood pressure is> 140/90 mm Hg. in persons with previously compensated hypertension, with progression of shortness of breath, chest pain or joint swelling.

A predictor of successful weight loss and long-term maintenance of body weight is a loss of more than 2 kg in the first months of treatment or more than 5% of the initial weight in 3 months. In women, especially young women, treatment success is recorded more often than in men. The higher the baseline BMI, the more intense weight loss can be expected. The presence of concomitant diseases of obesity predetermines slow weight loss.

Of interest is the early completed SCOUT study [11], the first prospective study of the relationship between weight loss in long-term pharmacotherapy of obesity (sibutramine) and cardiovascular outcomes (cardiovascular death, angina pectoris, myocardial infarction, stroke).Results from a randomized, double-blind, placebo-controlled study involving 10,744 overweight or obese people (mean age 63 years) in 300 centers in 17 countries showed that patients with preexisting cardiovascular disease who had long-term use of sibutramine had an increased risk of non-fatal myocardial infarction and nonfatal stroke, but not cardiovascular or all-cause deaths. These results have led to the recall of sibutramine in the European Union and the United States.

The drug has not been withdrawn in Russia at the present time; it remains an approved treatment for obesity. Since January 2008, sibutramine has been on the government-approved list of potent drugs, which means prescription only.

Liraglutide 3 mg

The availability in our country of only two drugs for the treatment of obesity with the need for strict adherence to indications and contraindications to their appointment extremely limited the possibility of treating this condition.In the spring of 2016, the first analogue of glucagon-like peptide-1 (GLP-1) for the treatment of obesity, liraglutide at a dose of 3 mg (Saxenda), was registered in Russia. Prior to this, liraglutide at doses of 1.2 and 1.8 mg per day was used under the name Victoza for the treatment of diabetes 2. GLP-1 is a physiological regulator of appetite and food intake. Liraglutide at the level of the hypothalamus activates GLP-1 receptors, increasing satiety signals and attenuating hunger signals, which contributes to weight loss. In addition, liraglutide stimulates glucose-dependent insulin secretion and reduces paradoxical hyperglucagonism (typical for patients with carbohydrate metabolism disorders), and also contributes to the preservation of a functioning pool of ß-cells.

The efficacy and safety of liraglutide at a dose of 3 mg per day in the treatment of obese patients was investigated in a series of randomized, double-blind, placebo-controlled studies included in the SCALE program (the Satiety and Clinical Adiposity – Liraglutide Evidence in nondiabetic and diabetic individuals). This program, which covered more than 5,000 patients, served as the evidence base that allowed the drug to be registered in the USA, Europe and Russia. The program included 4 studies – “SCALE, obesity and prediabetes”, “SCALE, diabetes”, “SCALE, maintenance of body weight” and “SCALE, sleep apnea”.

The study “SCALE, obesity and prediabetes” lasting 56 weeks was conducted on the basis of 191 clinical centers in 27 countries of the world with the participation of 3731 patients with obesity or overweight in combination with dyslipidemia and / or hypertension. 160 patients participated in Russia. All patients were randomized in a 2: 1 ratio to receive either liraglutide 3 mg (n = 2487) or placebo (n = 1244) as an adjunct to diet and exercise. The peer endpoints were changes in body weight and the proportion of patients whose body weight decreased by ≥5%.After 56 weeks, the average weight loss in the liraglutide group was 8.0 ± 6.7% (8.4 ± 7.3 kg) versus 2.6 ± 5.7% (2.8 ± 6.5 kg) in the placebo group.

A decrease in body weight of 5% or more was achieved in 63.2% of patients in the liraglutide group and in 27.1% of patients in the placebo group; a decrease in body weight by 10% was noted, respectively, in 33.1 and 10.6% of patients (p <0.001). The prevalence of prediabetes among patients with an initially established diagnosis after 56 weeks in the liraglutide group decreased by half (from 61.4 to 30.8%), while in the placebo group it increased (from 60.9 to 67.3%) [12] ...After 56 weeks, patients with baseline prediabetes continued to participate in the study for a total duration of 3 years and were re-randomized in a 2: 1 ratio to liraglutide 3 mg (n = 1505) or placebo (n = 749). Over 3 years, DM 2 was recorded in 26 (2%) people who received liraglutide 3 mg, and in 46 (6%) in the placebo group. In addition, the time to the onset of DM 2 in patients receiving liraglutide was 2.7 times longer than in the placebo group, which indicated a significant decrease in the risk of developing DM 2 while taking liraglutide - by 80% (OR = 0.21 ; 95% CI 0.13-0.34).Over 3 years, the weight loss in patients treated with liraglutide 3 mg and placebo was, respectively, 6.1 and 1.9% of the baseline [13].

The SCALE, Obesity and Prediabetes Study also assessed the dynamics of cardiometabolic risk factors during weight loss. After 56 weeks of therapy, systolic blood pressure decreased in the liraglutide 3 mg group by 4.2 ± 12.2 mm Hg, which was significantly more than in the placebo group (1.5 ± 12.4 mm Hg). In addition, in the liraglutide group, there was a more pronounced improvement in such cardiometabolic parameters as blood lipid spectrum, the level of highly sensitive C-reactive protein, plasminogen activator inhibitor-1 and adiponectin compared to placebo.

The 56-week SCALE, weight maintenance study, conducted at 36 research centers with the participation of 422 patients, evaluated the effectiveness of liraglutide 3 mg in maintaining body weight after weight loss using a low-calorie diet in obese or overweight patients in combined with dyslipidemia and / or hypertension. During the introductory period lasting from 4 to 12 weeks, diet therapy was carried out (daily calorie intake of 1200-1400 kcal) and an increase in physical activity was recommended (brisk walking for at least 150 minutes per week).After the induction period, patients who achieved weight loss of 5% or more were randomized in a 1: 1 ratio to either liraglutide 3 mg or placebo for 56 weeks. Against the background of the use of liraglutide at a dose of 3 mg, an additional decrease in body weight averaged 6.2% (0.2% on placebo). Among those who received liraglutide 3 mg, the proportion of participants who retained the 5% or more weight loss achieved during the introductory period was significantly higher (81.4%) than in the placebo group (48.9%). After completion of the study for 12 weeks in the group of patients receiving liraglutide 3 mg, the achieved weight loss was maintained (by 4.1%), while among patients receiving placebo, weight gain was observed (+ 0.3%) [14] …Thus, the efficacy of liraglutide at a dose of 3 mg 1 time per day in combination with lifestyle changes was confirmed in relation to long-term maintenance of clinically significant weight loss. In addition, liraglutide 3 mg reduced several cardiovascular risk factors (waist circumference, fasting plasma glucose, blood pressure, etc.).

In the study “SCALE, diabetes”, 56 weeks long, conducted on the basis of 126 clinical centers from 9 countries with the participation of 846 patients, the efficacy of various doses of liraglutide (3 and 1.8 mg) was assessed in terms of weight loss in patients with diabetes mellitus 2.By the end of the study, the decrease in body weight was 6.1% at a dose of 3 mg, 4.7% at a dose of 1.8 mg, 1.9% at a placebo. The number of patients who achieved weight loss of 5% or more was also significantly higher in the group of patients taking liraglutide at a dose of 3 mg. The proportion of patients who achieved an HbA1c level <7% during therapy with liraglutide 3 mg was 69.2% (compared with 27.2% for placebo) [15].

In the SCALE, Sleep Apnea Study, 32 weeks long, conducted at 40 clinical sites in 359 obese patients with moderate to severe obstructive sleep apnea, after randomization in a 1: 1 ratio, participants received either liraglutide 3 mg , or a placebo.In the main group, along with a more significant decrease in body weight (by 5.7% of the initial versus 1.6% on placebo), a more significant decrease in the apnea / hypopnea index was achieved (-12.2 episodes / h versus –6.1 episodes / hour on placebo) [16].

Thus, these clinical trials programs have demonstrated the high efficacy of liraglutide at a dose of 3 mg in relation to weight loss and maintenance of the achieved results in obese and overweight individuals, regardless of the presence of DM 2 and other concomitant diseases.This was accompanied by a significant reduction in cardiovascular risk with a good tolerance and safety profile.

According to the instructions, the drug is injected subcutaneously once a day at any time, regardless of food intake, into the abdomen, thigh or shoulder area. The starting dose is 0.6 mg per day. The dose is increased by 0.6 mg at intervals of at least one week to improve gastrointestinal tolerance until a therapeutic dose of 3 mg per day is reached. In the absence of a decrease in body weight for 12 weeks by 5% of the original, treatment is discontinued.Among the side effects, there are primarily dyspeptic phenomena (decreased appetite, nausea, vomiting, constipation, diarrhea), which usually occur in the first weeks of treatment and in most cases are transient, without requiring discontinuation of therapy.

Since liraglutide can induce medullary thyroid cancer in rodents, the drug is contraindicated in patients with a history of medullary thyroid cancer, as well as in type 2 multiple endocrine neoplasia syndrome.In obesity and in cases of severe weight loss, the concentration of cholesterol in the bile increases and the contractile function of the gallbladder decreases (which increases the risk of gallstones), patients with a history of cholelithiasis should be prescribed with caution.

Drugs not registered on the Russian pharmaceutical market

In Europe and the USA, other drugs are also used for the treatment of obesity, which are currently not registered in Russia.

Lorcaserin is a serotonin 5HT2c receptor agonist that reduces appetite. The drug is approved for use in the United States, rejected in the European Union. The efficacy and safety of the drug was evaluated in the BLOOM, BLOOM-DM and BLOSSOM studies, which showed a decrease in body weight after a year of treatment by an average of 3.6% and an improvement in metabolic parameters. There were no statistically significant differences in the incidence of cardiac valvulopathy between the placebo and lorcaserin groups. The most common side effects of lorcaserin were decreased vision, dizziness, drowsiness, headache, and gastrointestinal disturbances.The results of the ongoing study of cardiovascular outcomes CAMELLIA TIMI 61 will determine the role of lorcaserin in the primary prevention of diabetes mellitus 2 in overweight or obese individuals and the possibility of using this drug at high cardiovascular risk [17].

The combination of phentermine and topiramate is used to achieve an effect with less toxicity of drugs. Phentermine, an atypical analogue of amphetamine and sympathomimetic, suppresses appetite at the CNS level. Topiramate is an anticonvulsant drug, the mechanism of influence of which on appetite may include a decrease in the activity of carbonic anhydrase or a modification of the effect of gamma-aminobutyric acid.The efficacy and safety of the combination drug was evaluated in the EQUIP, CONQUER, SEQUEL and EQUATE studies. Average body weight loss ranged from 6.6 to 8.6% per year. Adverse effects included dry mouth, constipation, insomnia, palpitations, dizziness, paresthesias, impaired attention, metabolic acidosis and kidney stones, headache, taste distortion, alopecia, and hypokalemia. Treatment is contraindicated during pregnancy because of the possible teratogenic effect [17].

In the combination of bupropion with naltrexone, the first agent is a selective norepinephrine and dopamine reuptake inhibitor used in the treatment of depression and nicotine addiction. Naltrexone, an opioid receptor antagonist, is widely used in the treatment of alcohol and opiate addiction. The anorexigenic effect of the bupropion / naltrexone combination may be due to the activation of neurons in the arcuate nucleus of the hypothalamus and the release of α-melanocyte-stimulating hormone. The efficacy and safety of the drug was evaluated in the COR-I, COR-II, COR-BMOD and COR-DM studies.The average body weight loss for 1 year of therapy was 4.8%. The most common side effects when taking the combined drug were nausea, vomiting, headache, dizziness, and insomnia [17].

Conclusion

The heterogeneity of obesity and the presence of associated diseases require a personalized approach to treatment. The most important tasks, along with a decrease in body weight, are the prevention of the development and progression of diseases associated with obesity, the correction of already existing metabolic disorders.Therefore, when determining the tactics of treatment, not only the degree of obesity should be taken into account, but also the age of the patient, his psychological characteristics, the range of concomitant diseases, reproductive function, and family history. Treatment that improves the overall health of the patient can be considered successful. Since obesity is a chronic disease with frequent relapses, treatment should be long-term, often lifelong. Replenishment of the arsenal of drugs for the pharmacotherapy of obesity with new drugs, for example, liraglutide at a dose of 3 mg (Saxenda), which fundamentally differ in the mechanism of action from the two used in the Russian Federation (orlistat and sibutramine) and have an acceptable safety and tolerance profile, even with prolonged use, significantly expands the possibilities treatment of patients with obesity, including morbid and complicated, and the accumulation of clinical experience will make it possible to comprehensively assess the scope of application of such drugs and their likely pleiotropic effects.

Additional information

Conflict of interest . The authors declare no obvious and potential conflicts of interest related to the publication of this article.

Contribution of authors : E.A. Troshina – development of the concept of the manuscript, analysis of foreign and Russian literature, editing of the manuscript; E.V. Ershova – analysis of foreign and Russian literature, writing a draft of the manuscript, preparation of the final version of the manuscript.

90,000 reasons in Irkutsk at the Expert Clinic

It can be a sign of life-threatening conditions, so it is important to know its basic characteristics in order to seek medical help in a timely manner.Pain in the region of the heart. What is it like? Is it always an indicator of heart pathology?

Natalya Aleksandrovna Shelest, a cardiologist, Clinic Expert, Irkutsk, tells about the characteristics of pain in the region of the heart, the possible reasons for their occurrence.

– Natalya Alexandrovna, is chest pain always a sign of heart disease?

– No, not always. Chest pain, along with diseases of the cardiovascular system, can also manifest diseases of bones, joints, muscles (Titze syndrome, anterior scalene muscle syndrome, fibromyositis, dorsopathy), changes in the lungs and pleura (pleurisy, spontaneous pneumothorax, pulmonary infarction, tumors ), digestive tract organs (esophagitis, cardiospasm, diaphragmatic hernia, stomach and duodenal ulcers, cholecystitis), some neurological disorders (shingles, neurocirculatory dystonia), breast diseases.

Among the pathologies that cause chest pain, there are both life-threatening, requiring immediate intervention (in particular, myocardial infarction, dissecting aortic aneurysm, thromboembolism of the pulmonary artery and its branches, pneumothorax), and less serious pathologies – for example, anterior thoracic syndrome walls, anxiety-depressive state. They, of course, also require correction, but they are not classified as urgent conditions.

– For what reasons can there be true pain in the region of the heart?

– The cause of such pain can be increased blood pressure, increased heart rate, heart rhythm disturbances, excessive physical and emotional stress.Alcohol abuse, smoking, heavy food intake, and drug use can also cause heart pain.

– If a patient complains of pain in the heart when taking a deep breath, what can this talk about?

– First of all, about diseases of the musculoskeletal system – intercostal neuralgia, fibromyalgia, inflammation of the sternocostal joints (Titze syndrome), chest injuries. The appearance of soreness in the region of the heart with these pathologies is caused by irritation or infringement of the intercostal nerves, an excursion (movement) of the chest as a result of the act of inhalation and exhalation, and a change in body position.

A number of pulmonary diseases, such as pneumothorax, pleurisy, pneumonia, can also be accompanied by painful sensations when inhaling, often additional symptoms are fever, shortness of breath and tachycardia.

– And if the pain in the heart appears at rest?

– In this case, there is a high probability of developing a serious pathology, in particular, dissecting aortic aneurysm, pulmonary embolism, cardiac tamponade.

Sometimes banal muscle pains in the chest can also bother a person at rest due to excessive static loads or improper body position.

– Which doctor should I see if there is pain in the region of the heart?

– If the pain in the heart occurs for the first time, catching by surprise, and is accompanied by a deterioration in well-being, a person should immediately consult any doctor who is nearby and explain what worries him. Regardless of qualifications and specialization, each doctor is able to navigate how to act in a particular case, provide first aid, if necessary, and refer you to the right specialist.

If the patient can get to the polyclinic, you should contact the therapist It is he who will decide on the necessary stages of medical care, including in the consultation of narrow specialists – a cardiologist, gastroenterologist, neurologist, surgeon and other doctors.

– What characteristics of chest pain require emergency medical attention?

Chest pain should always be treated with caution. It is important not to miss such conditions as acute coronary syndrome, an attack of angina pectoris (commonly referred to as “angina pectoris”).They are characterized by paroxysmal squeezing, bursting, pressing, burning pains behind the sternum and / or in the left half of the chest (precordial region), can spread into the axillary and subscapular region on the left, into the left arm and shoulder, into the left half of the neck and lower jaw, last no more than 10 minutes, may be accompanied by a feeling of shortness of breath, shortness of breath. It should be remembered that most often these symptoms appear in the background or immediately after physical or emotional stress. There is a quick effect of taking nitroglycerin within 5 minutes.

If these pains last more than 20 minutes and intensify when the load is resumed, you should definitely call an ambulance. A dangerous condition is also a combination of these pains with a decrease in blood pressure, a decrease (less than 50 beats per minute) or an increase (more than 120 beats per minute) in the heart rate, with interruptions in the heart rate, profuse cold sweating, pallor of the skin, severe weakness, nausea, light-headedness, or even loss of consciousness.If these symptoms are present, the patient needs urgent medical attention.

– How is heart pain diagnosed?

– First of all, we assess vital functions – we determine whether the patient is conscious, what are the indicators of respiration, hemodynamics (blood circulation). If there are signs of breathing disorders, very low or high blood pressure, heart rhythm disturbances, then emergency assistance is needed: calling an ambulance and urgent hospitalization.

The second stage of diagnosis is the identification of risk factors for coronary heart disease. In the presence of pain of the type of angina pectoris, the patient is given a nitroglycerin tablet under the tongue, an electrocardiogram (ECG) is taken, and the clinical effect of the drug taken is evaluated. If there is a suspicion of pulmonary embolism, pneumothorax, dissecting aneurysm, it is necessary to take an ECG, conduct echocardiography, determine markers of myocardial damage, take a chest x-ray, and assess blood oxygen saturation.

At the next stage of diagnosis (after excluding life-threatening pathologies), they move on to the search for other causes that can cause pain in the region of the heart. In this case, complaints are detailed, a more thorough examination, an algorithm for laboratory and instrumental studies is developed: blood tests, Holter ECG, 24-hour blood pressure (BP) monitoring, chest and spinal X-ray, abdominal ultrasound, fibrogastroduodenoscopy, if necessary CT scan.

– Natalya Alexandrovna, tell our readers about the tactics of treating pain in the heart area.

– Pain in the region of the heart can occur with a number of pathologies, both heart and non-heart. Therefore, therapeutic measures will depend on the background of which disease these pains are noted.

In the event of pressing, bursting, burning pains behind the sternum, which arose against the background of physical or emotional overload, or at rest (which happens much less often), it is necessary to stop any load, take a sitting position with the legs down (to reduce the venous return of blood to the heart) and call an ambulance.

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For information:

Shelest Natalya Alexandrovna

In 2000 she graduated from Irkutsk State Medical University with a degree in General Medicine.