Is diazepam a muscle relaxer. How does diazepam compare to Flexeril for treating back pain and muscle spasms. What are the key differences and side effects of diazepam and Valium. When should you seek emergency help while taking diazepam.

Understanding Diazepam: Uses and Applications

Diazepam, commonly known by its brand name Valium, is a versatile medication belonging to the benzodiazepine family. It’s primarily prescribed for treating various conditions, including anxiety, muscle spasms, and seizures. But is diazepam a muscle relaxer? While not technically classified as such, it does have muscle-relaxing properties that make it effective for certain muscular conditions.

Diazepam’s applications extend beyond its primary uses. Healthcare professionals may prescribe it for:

• Managing alcohol withdrawal symptoms
• Pre-operative relaxation (as a “pre-med”)
• Treating epilepsy

Available only by prescription, diazepam comes in various forms to suit different needs:

• Tablets
• Rectal tubes
• Injectable form (administered in hospitals)

Several brand names exist for diazepam, including Anxicalm, Diazemuls, and Stesolid Rectal tubes. Its versatility in addressing multiple conditions makes it a frequently prescribed medication, but it’s crucial to understand its proper use and potential risks.

Diazepam vs. Flexeril: Comparing Muscle Relaxants

When it comes to treating muscle spasms and back pain, both diazepam and Flexeril (cyclobenzaprine) are often considered. However, they work differently and have distinct characteristics.

How do diazepam and Flexeril differ in their mechanism of action?

Diazepam, a benzodiazepine, works by enhancing the effects of GABA, a neurotransmitter that reduces brain activity. This results in muscle relaxation, among other effects. Flexeril, on the other hand, is a tricyclic muscle relaxant that acts on the brain stem to reduce muscle spasms without directly affecting the muscles.

Which is more effective for back pain?

The effectiveness can vary depending on the individual and the specific cause of back pain. Flexeril is often preferred for acute muscle spasms, while diazepam might be chosen when anxiety is also a factor in muscle tension. Your healthcare provider will consider your specific situation when prescribing either medication.

Are there differences in side effects?

Both medications can cause drowsiness and dizziness. However, diazepam carries a higher risk of dependence and withdrawal symptoms, especially with long-term use. Flexeril may cause dry mouth and constipation more frequently than diazepam.

Recognizing Serious Side Effects of Diazepam

While diazepam is generally well-tolerated, it’s crucial to be aware of potential serious side effects that require immediate medical attention.

When should you contact your GP urgently while taking diazepam?

• If your breathing becomes very slow or shallow
• If your skin or the whites of your eyes turn yellow
• If you experience significant memory difficulties
• If you have hallucinations or delusions
• If you notice increased falls
• If you experience excessive talkativeness or excitation
• If you feel unusually agitated, restless, irritable, or aggressive

These symptoms could indicate serious adverse reactions to diazepam and should not be ignored. Prompt medical evaluation is essential to ensure your safety and adjust your treatment if necessary.

Diazepam Overdose: Recognizing the Signs and Taking Action

Diazepam overdose is a serious medical emergency that requires immediate attention. The amount that can lead to an overdose varies from person to person, making it crucial to adhere strictly to prescribed dosages.

What are the signs of a diazepam overdose?

Look out for the following symptoms:

• Poor coordination
• Confusion
• Slurred speech
• Extreme drowsiness
• Slow or irregular heartbeat
• Uncontrolled eye movements
• Muscle weakness
• Paradoxical excitation

If you suspect a diazepam overdose, it’s crucial to seek emergency medical help immediately. Call 999 or 112 or go to the nearest emergency department. Do not attempt to drive yourself; either have someone else drive you or call for an ambulance.

Allergic Reactions to Diazepam: When to Seek Emergency Care

Although rare, diazepam can cause serious allergic reactions, including anaphylaxis. Recognizing the signs of an allergic reaction is crucial for prompt treatment.

What are the symptoms of a serious allergic reaction to diazepam?

Be alert for the following signs:

• Itchy, red, swollen, or blistered rash
• Wheezing
• Tightness in the chest or throat
• Difficulty breathing or talking
• Swelling of the mouth, face, lips, tongue, or throat

If you experience any of these symptoms after taking diazepam, seek emergency medical care immediately by calling 112 or 999 or going to an emergency department. Anaphylaxis is a life-threatening condition that requires immediate treatment.

Starting Diazepam Treatment: What to Expect

When beginning diazepam treatment, it’s essential to follow your healthcare provider’s instructions carefully. The medication is typically prescribed for short-term use, usually up to 4 weeks, to minimize the risk of dependence.

How quickly does diazepam start working?

The onset of action can vary depending on the condition being treated:

• For seizures: Rectal tubes should start working within 10 minutes
• For anxiety: You may start feeling better within a few hours, but it can take up to 2 weeks to experience the full effect
• For muscle spasms: Pain relief may begin after 15 minutes, but the full effect may take longer

Your healthcare provider will determine the most appropriate dosage based on your specific condition and individual factors. It’s crucial to take diazepam exactly as prescribed and not to adjust the dose without consulting your doctor.

Diazepam Suitability: Who Should Avoid This Medication?

While diazepam is effective for many conditions, it’s not suitable for everyone. Certain medical conditions and factors may increase the risk of adverse effects or interactions.

Who should avoid taking diazepam?

Diazepam may not be suitable if you:

• Have a history of allergic reactions to diazepam or other benzodiazepines
• Suffer from liver or kidney problems
• Have breathing difficulties or sleep apnea
• Are diagnosed with myasthenia gravis
• Have severe depression or thoughts of self-harm
• Have a history of substance abuse
• Are over 65 years old
• Have arteriosclerosis (hardening of the arteries)
• Have low levels of albumin in your blood

Always inform your healthcare provider about your complete medical history and any medications you’re currently taking before starting diazepam treatment. This ensures that the benefits of the medication outweigh any potential risks in your specific case.

Diazepam and Pregnancy: Weighing the Risks and Benefits

The use of diazepam during pregnancy requires careful consideration due to potential risks to the developing fetus. If you’re pregnant, planning to become pregnant, or suspect you might be pregnant, it’s crucial to discuss your medication use with your healthcare provider.

What are the risks of taking diazepam during pregnancy?

The safety of diazepam use during pregnancy is not fully established. Potential risks include:

• Withdrawal symptoms in newborns
• Possible birth defects (although the risk is considered low)
• Sedation effects on the fetus

However, in some cases, the benefits of continuing diazepam treatment during pregnancy may outweigh the potential risks, especially if it’s essential for managing severe anxiety or seizures. Your healthcare provider will help you weigh the pros and cons based on your individual situation.

Can diazepam be used while breastfeeding?

Generally, diazepam use is not recommended during breastfeeding due to the potential for the drug to pass into breast milk and affect the baby. However, in some cases, your healthcare provider may determine that the benefits outweigh the risks. Always consult with your doctor or nurse before using diazepam while breastfeeding.

If you’re currently taking diazepam and discover you’re pregnant or planning to breastfeed, don’t stop the medication abruptly. Consult your healthcare provider to develop a safe plan that considers both your health needs and the well-being of your baby.

Long-term Use of Diazepam: Risks and Considerations

While diazepam can be highly effective for short-term treatment of various conditions, long-term use carries significant risks that need to be carefully considered.

What are the risks associated with long-term diazepam use?

Prolonged use of diazepam can lead to several potential issues:

• Tolerance: The body may become accustomed to the drug, requiring higher doses to achieve the same effect
• Dependence: Physical and psychological dependence can develop, making it difficult to stop using the medication
• Withdrawal symptoms: Abrupt discontinuation can lead to severe withdrawal effects
• Cognitive impairment: Long-term use may affect memory and cognitive function
• Increased risk of falls and accidents, especially in older adults

Due to these risks, healthcare providers typically prescribe diazepam for short periods, usually not exceeding 4 weeks. If you’ve been using diazepam for an extended period, it’s crucial to work closely with your healthcare provider to develop a safe tapering plan if discontinuation is appropriate.

How can the risks of long-term diazepam use be minimized?

To reduce the potential negative effects of long-term diazepam use, consider the following strategies:

• Regular review of medication necessity with your healthcare provider
• Exploring alternative treatments for long-term management of your condition
• Implementing lifestyle changes that may help manage symptoms (e.g., stress reduction techniques for anxiety)
• Gradual tapering of the medication under medical supervision if discontinuation is recommended

Remember, never stop taking diazepam abruptly without consulting your healthcare provider, as this can lead to severe withdrawal symptoms.

Diazepam Interactions: Medications and Substances to Avoid

Diazepam can interact with various medications and substances, potentially altering its effectiveness or increasing the risk of side effects. Understanding these interactions is crucial for safe use of the medication.

Which medications can interact with diazepam?

Diazepam may interact with several types of medications, including:

• Other central nervous system depressants (e.g., opioids, barbiturates)
• Certain antidepressants (e.g., fluoxetine, fluvoxamine)
• Antipsychotics
• Antihistamines
• Anticonvulsants
• Some antibiotics and antifungal medications

Always inform your healthcare provider about all medications you’re taking, including over-the-counter drugs and herbal supplements, to avoid potential interactions.

How does alcohol affect diazepam use?

Combining alcohol with diazepam can be dangerous. Both substances depress the central nervous system, and their effects can be additive, leading to:

• Increased sedation
• Impaired coordination and judgment
• Respiratory depression
• Increased risk of overdose

It’s strongly advised to avoid alcohol consumption while taking diazepam. If you’re concerned about alcohol use while on this medication, discuss it with your healthcare provider for personalized advice.

Alternatives to Diazepam: Exploring Other Treatment Options

While diazepam can be effective for various conditions, it’s not always the most appropriate choice for everyone. Exploring alternative treatments can be beneficial, especially for long-term management of chronic conditions.

What are some non-pharmacological alternatives to diazepam for anxiety?

Several non-drug approaches can be effective in managing anxiety:

• Cognitive Behavioral Therapy (CBT)
• Mindfulness and meditation practices
• Regular exercise
• Stress management techniques
• Dietary changes and reducing caffeine intake
• Adequate sleep hygiene

These methods can be used alone or in combination with medication, depending on the severity of symptoms and individual preferences.

Are there alternative medications for muscle spasms?

Several other medications can be used to treat muscle spasms, including:

• Cyclobenzaprine (Flexeril)
• Baclofen
• Tizanidine
• Methocarbamol
• Non-steroidal anti-inflammatory drugs (NSAIDs)

The choice of medication depends on the underlying cause of the muscle spasms, individual patient factors, and potential side effects. Your healthcare provider can help determine the most appropriate option for your specific situation.

What about alternative treatments for seizures?

For seizure disorders, several other anticonvulsant medications are available, such as:

• Carbamazepine
• Valproic acid
• Phenytoin
• Levetiracetam
• Lamotrigine

In some cases, dietary approaches like the ketogenic diet or vagus nerve stimulation may be considered as adjunct therapies for seizure management. The choice of treatment depends on the type of seizures, individual patient factors, and response to therapy.

When considering alternatives to diazepam, it’s essential to work closely with your healthcare provider to find the most appropriate treatment plan for your specific needs and circumstances. Never discontinue or change your medication regimen without professional medical advice.

Diazepam: medicine to treat anxiety, muscle spasms and fits

Diazepam is used to treat anxiety, muscle spasms and fits (seizures), such as epilepsy.

It belongs to a group of medicines called benzodiazepines. It is available only on prescription.

Diazepam is also used to treat alcohol withdrawal symptoms, such as sweating or difficulty sleeping.

It is sometimes used to help you relax before a medical operation. This is known as a ‘pre-med.’

Types of diazepam

Diazepam comes in tablets or a rectal tube (medicine that’s squeezed into your bottom).

It can also be given as an injection in hospital.

Brand names include:

• Anxicalm
• Diazemuls
• Stesolid Rectal tubes
• Diazepam Rectubes
• Diazepam Desitin

It’s also known as valium.

Get emergency help

You might need emergency help if you get serious side effects, take too much or have a serious allergic reaction (anaphylaxis).

Serious side effects

Serious side effects from taking diazepam are rare.

Urgent advice: Contact your GP straight away if:

• your breathing becomes very slow or shallow
• your skin or the whites of your eyes turn yellow
• you find it difficult to remember things
• you see or hear things that are not there
• you think things that are not true
• you keep falling over
• you talk too much or feel over excited
• you feel agitated or restless
• you feel irritable or aggressive

If you take too much

The amount of diazepam that can lead to an overdose varies from person to person. You may need to go to the emergency department (ED).

Emergency action required: Phone 999 or 112, or go to your nearest ED if:

• you’ve taken more than your dose of diazepam, even if you feel OK

Emergency action required: It’s especially important to get emergency help if you’ve taken more than your dose and:

• have poor coordination
• feel confused
• have slurred speech
• have trouble speaking
• feel sleepy
• have a slow or irregular heartbeat
• have uncontrolled eye movements
• feel your muscles are weak
• feel over excited

Do not drive yourself to the ED. Get someone else to drive or call for an ambulance.

Take your remaining medication and any leaflets with you.

Serious allergic reaction

It’s rare that diazepam causes a serious allergic reaction (anaphylaxis).

Emergency action required: Call 112 or 999 or go to an ED if:

• you get a rash that’s itchy, red, swollen or blistered
• you’re wheezing
• you get tightness in your chest or throat
• you have trouble breathing or talking
• your mouth, face, lips, tongue or throat start swelling

When you start taking diazepam

Diazepam is usually taken 1 to 3 times a day. It’s important to take your dose exactly as your GP says.

If you are unsure, read the patient information leaflet that comes with your medicine or ask your GP or pharmacist.

You should take diazepam tablets for as short a period of time as possible. It is usually only recommended for use up to 4 weeks.

The amount of time it takes before diazepam starts to work will depend on your conditions. Your GP will prescribe the best dose for you.

Fits

Rectal tubes should start to work within 10 minutes.

Anxiety

You should start to feel a bit better in a few hours, but it may take up to 2 weeks to feel the full effect.

Muscle spasms

You should begin to feel less pain after 15 minutes, but it may take longer to feel the full effect.

Check if you can take diazepam

Diazepam is suitable for adults aged 18 years and over.

If prescribed by a doctor, it can also be taken by children aged 1 month or older for muscle spasms.

It may not be suitable if you:

• have had an allergic reaction to diazepam or other medicines
• have liver or kidney problems
• are breathless or have difficulty breathing
• suffer from obsessions or phobias (a fear of a particular object or situation)
• are over 65
• have a condition that causes muscle weakness (myasthenia gravis)
• have a condition that causes breathing problems during sleep (sleep apnoea)
• have depression or thoughts of harming yourself
• have a personality disorder
• have current or past problems with alcohol or drugs
• have recently had a loss or bereavement
• have a condition that affects the blood flow to your brain (arteriosclerosis)
• have low levels of protein called albumin
• are going to be put to sleep for an operation

Pregnancy

If you are pregnant, think you might be pregnant or are planning to have a baby, ask your GP or pharmacist for advice before taking diazepam. You may need to keep taking it to remain well.

We don’t know if diazepam is safe to use in pregnancy. It can give your newborn baby withdrawal symptoms.

Your GP can explain the risks and benefits and will help you choose the best treatment for you and your baby.

Breastfeeding

Usually, you should not breastfeed while using diazepam, but your GP or nurse will let you know if it is safe for your baby.

If your baby is healthy it can be used in a low dose for a short time. Larger amounts can build up in your breast milk and make your baby too tired to feed.

If you take diazepam while breastfeeding, make sure your baby is feeding, sleeping and breathing normally.

Talk to your GP or public health nurse as soon as possible if you have concerns.

Contraception and fertility

Diazepam does not affect contraception including the combined pill or emergency contraception.

Some contraceptive pills can keep diazepam in your body for longer and increase its effect. You can also get bleeding in between your periods if you take diazepam and contraceptive pills together.

There is currently no evidence to suggest that taking diazepam will reduce fertility in either men or women.

How and when to take it

Rectal tube

Diazepam rectal tubes can be used if you or your child is having a fit.

If it’s for you, a family member, friend or caregiver must know how to give this medicine.

Make sure your GP or pharmacist shows them how to use it.

Tablets

Take diazepam tablets with water. You can take them with or without food.

If you forget to take it

If you’re taking diazepam regularly take the missed dose as soon as you remember, unless it’s time for the next one.

In this case skip the missed dose and take your next one as normal.

Never take 2 doses at the same time or an extra dose to make up for a forgotten one.

Side effects

Keep taking the medicine but talk to your GP if side effects get worse or do not go away after a few days.

Side effects may include:

• feeling sleepy or drowsy
• confusion
• problems with coordination or controlling your movements
• shaky hands (tremors)

See the patient information leaflet that comes with your medicine for a full list of side effects.

Report side effects

You can report any suspected side effects to the the Health Products Regulatory Authority (HPRA): report an issue – hrpa. ie

Long term use

Usually, you should not take diazepam for longer than 4 weeks. Do not stop taking your medicine without talking to your GP.

If you’re prescribed diazepam for longer, your dose may be reduced gradually when coming off it to prevent withdrawal symptoms.

Addiction

There is a risk you might become addicted to diazepam, but the risk is small if you take a low dose for 2-4 weeks.

Addiction is more likely if you have past or current problems with alcohol or drugs.

Coming off diazepam

If you have been taking a high dose or have been taking diazepam for a long time, your GP will probably recommend reducing your dose gradually.

If you suddenly stop taking it, you may experience some side effects such as:

• confusion
• anxiety
• panic attacks
• palpitations
• loss of appetite
• insomnia
• fits
• depression
• feeling nervous or irritable
• sweating
• diarrhoea

Food and drink

Avoid grapefruit juice as it may increase the amount of diazepam in your blood.

Also avoid caffeine as it is a stimulant and may reduce the calming effects of diazepam.

Driving and operating machinery

Do not drive a car, ride a bike or operate machinery if taking diazepam:

• makes you sleepy
• gives you blurred vision
• makes it difficult to concentrate or make decisions

These effects may continue for several days even after you stop taking diazepam.

Taking diazepam with other medicines

Tell your GP or pharmacist that you are on diazepam before you take any new medicines.

Before you take diazepam for the first time, tell your GP or pharmacist if you:

• are taking any other medication
• have recently taken any medication
• might take any other medicines in the near future

This includes medicines you can get without a prescription.

Non-urgent advice: Check with your GP if you’re already taking:

• antipsychotics for mental health problems
• anticonvulsants or other medicines for epilepsy
• antidepressants
• oral contraceptives (the pill)
• corticosteroids
• levodopa – used to treat Parkinson’s disease
• medicines used to treat stomach problems
• hypnotics for anxiety or sleep problems
• drowsy or sedating antihistamines such as chlorphenamine or promethazine
• strong painkillers such as codeine, methadone, morphine, oxycodone, pethidine or tramadol
• HIV medicines such as ritonavir, atazanavir, efavirenz or saquinavir
• antifungal medicines such as fluconazole
• muscle relaxants such as baclofen and tizanidine
• rifampicin for bacterial infections
• theophylline for asthma or other breathing problems

Herbal remedies or supplements

Do not take herbal medicines for anxiety or insomnia, such as valerian or passionflower.

They can increase the drowsy effects of diazepam and may have other side effects.

Similar medicines

If diazepam does not work or gives you side effects, your GP may suggest you try different medicines for treating anxiety or fits.

For anxiety your GP may recommend a type of antidepressants called selective serotonin reuptake inhibitors (SSRI). Brand names include sertraline, paroxetine or escitalopram.

For fits, a medicine called midazolam can be used. It comes as a pre-filled syringe and is given inside the mouth between the cheek and the gum.

This can be used instead of rectal diazepam.

Alcohol

Do not drink alcohol while you’re on diazepam – it can make you go into a very deep sleep.

There’s a risk you will not be able to breathe properly and may have difficulty waking up.

Recreational drugs

Using cannabis, heroin or methadone with diazepam will increase the drowsy effects. It can make you go into a very deep sleep and may cause your breathing to stop. This could lead to death.

There’s a risk you will not be able to breathe properly or have difficulty waking up.

Using cocaine or other stimulants like MDMA (ecstasy) and amphetamines with diazepam can also lead to drowsiness.

Talk to your GP if you think you might use recreational drugs while taking diazepam.

Fact check

This content was fact checked by a pharmacist, a GP, the National Medication Safety Programme (Safermeds) and the Health Products Regulatory Authority (HPRA).

This project has received funding from the Government of Ireland’s Sláintecare Integration Fund 2019 under Grant Agreement Number 123.

Page last reviewed: 24 September 2021

Next review due: 24 September 2024

Diazepam – StatPearls – NCBI Bookshelf

Continuing Education Activity

Diazepam is a benzodiazepine medication that is FDA approved for the management of anxiety disorders, short-term relief of anxiety symptoms, spasticity associated with upper motor neuron disorders, adjunct therapy for muscle spasms, preoperative anxiety relief, management of certain refractory epilepsy patients, and adjunct in severe recurrent convulsive seizures, and an adjunct in status epilepticus. Off-label (non-FDA approved) use for diazepam includes sedation in the ICU and short-term treatment of spasticity in children with cerebral palsy. This activity will highlight the mechanism of action, adverse event profile, approved and off-label uses, dosing, pharmacodynamics, pharmacokinetics, monitoring, and relevant interactions of diazepam, pertinent for interprofessional team members using diazepam for any of its intended indications.

Objectives:

• Identify the indications for using diazepam.

• Summarize the adverse effects of diazepam.

• Review the mechanism of action of diazepam.

• Outline the importance of improving care coordination among the interprofessional team to enhance the delivery of care for patients when using diazepam.

Access free multiple choice questions on this topic.

Indications

Diazepam is an anxiolytic benzodiazepine, first patented and marketed in the United States in 1963. It is a fast-acting, long-lasting benzodiazepine commonly used to treat anxiety disorders and alcohol detoxification, acute recurrent seizures, severe muscle spasms, and spasticity associated with neurologic disorders. In acute alcohol withdrawal, diazepam is useful for symptomatic relief of agitation, tremor, alcoholic hallucinosis, and acute delirium tremens.[1] Benzodiazepines have largely replaced barbiturates in treating anxiety and sleep disorders because of their improved safety profile, fewer side effects, and flumazenil(antagonist) availability that can reverse oversedation in cases of benzodiazepine intoxication. [2][3]

Diazepam is FDA approved for the management of anxiety disorders, short-term relief of anxiety symptoms, spasticity associated with upper motor neuron disorders, adjunct therapy for muscle spasms, preoperative anxiety relief, management of certain refractory epilepsy patients, and adjunct in severe recurrent convulsive seizures, and an adjunct in status epilepticus. Off-label (non-FDA approved) use for diazepam includes sedation in the ICU and short-term treatment of spasticity in children with cerebral palsy.[4]

Mechanism of Action

Benzodiazepines exert their effects by facilitating the activity of gamma-aminobutyric acid(GABA) at various sites. Specifically, benzodiazepines bind at an allosteric site at the interface between the alpha and gamma subunits on GABA-A receptor chloride ion channels. The allosteric binding of diazepam at the GABA-A receptor increases the frequency at which the chloride channel opens, leading to an increased conductance of chloride ions. This shift in charge leads to a hyperpolarization of the neuronal membrane and reduced neuronal excitability.[5]

Specifically, the allosteric binding within the limbic system leads to the anxiolytic effects seen with diazepam. Allosteric binding within the spinal cord and motor neurons is the primary mediator of the myorelaxant effects seen with diazepam. Mediation of the sedative, amnestic, and anticonvulsant effects of diazepam is through receptor binding within the cortex, thalamus, and cerebellum.[6]

Pharmacokinetics

Absorption: After oral administration of diazepam >90%  is absorbed, the average time to achieve peak plasma concentrations is 1 to 1.5 hours. Absorption is delayed and decreased when administered with a meal. There is an increase in the mean time to achieve peak concentrations to approximately 2.5 hours in the presence of food. 

Distribution: Diazepam is highly lipophilic. While there is a moderately quick onset of action, the drug quickly redistributes.  Diazepam and its metabolites have high plasma protein binding.(diazepam 98%). Diazepam and metabolites penetrate the blood-brain and placental barriers and are found in breast milk. The volume of distribution is 0.8 to 1.0 L/kg. 

Metabolism: Diazepam is mostly broken down by the microsomal enzymes CYP2C19 and CYP3A4 enzymes to several active metabolites, mainly desmethyldiazepam. Other minor active metabolites include oxazepam and temazepam. The average half-lives of oral diazepam and desmethyldiazepam are about 46 and 100 hours, respectively.[6]

Excretion: The initial distribution is followed by a prolonged terminal elimination(half-life ~ 48 hours). Additionally, the terminal elimination half-life of the active metabolite N-desmethyldiazepam is up to 100 hours. Diazepam and its metabolites are excreted predominantly in the urine. Diazepam accumulates upon multiple dosing; consequently, the terminal elimination half-life of diazepam is slightly prolonged.

Administration

Diazepam is available in multiple formulations, including oral tablets, intramuscular injections (IM), intravenous injections (IV), or rectal gel. Oral tablets have a more reliable absorption and controlled release when compared to IM. When administered intravenously, diazepam has an onset of action within 1 to 3 minutes, while oral dosing onset ranges between 15 to 60 minutes. In addition, diazepam is long-lasting, with a duration of action of more than 12 hours.

• Treatment of acute ethanol withdrawal: Initial dosing should be 10 mg IM or IV. If needed, a follow-up dose of 5 to 10 mg is permissible 3 to 4 hours later. If using the oral tablet, dosing is 10 mg every 6 to 8 hours within the first 24 hours, then 5mg every 6 to 8 hours after that as needed.[4]

• Treatment of anxiety: 2 to 10 mg can be given orally 2 to 4 times daily. If given parentally, dosing can be 2 to 10 mg and repeated in 3 to 4 hours, if needed.[7]

• Treatment of muscle spasms: 2 to 10 mg can be given orally 3 to 4 times daily. If given parentally, an initial dose of 5 to 10 mg can be followed by another 5-10mg dose in 3 to 4 hours, if necessary. [8]

• Treatment of preoperative anxiety: Dosing is 10 mg IM before surgery.[9]

• For sedation in the ICU: Loading dose of 5 to 10 mg for initial administration, followed by a maintenance dose of 0.03 to 0.10 mg/kg every 0.5 to 6 hours. (Barr 2013)

• Treatment of seizures: 2 to 10 mg orally dosed 2 to 4 times daily as adjunctive maintenance therapy. Rectal gel 0.2mg/kg is an option for intermittent management of seizures. It may be repeated in 4 to 12 hours if needed. Do not exceed five uses per month or more than one dose every five days.

• Skeletal muscle relaxant: 2 to 10 mg, dosed 3 to 4 times daily as an adjunct therapy. 

• Treatment of status epilepticus: 0.15 to 0.20 mg/kg IV per dose and may be repeated once needed. Do not exceed 10 mg per single dose. Rectal administration of 0.2 to 0.5 mg/kg administered one time. Do not exceed 20 mg per dose.[10]

Use in Specific Patient Populations

Patients with Renal impairment: Clinicians should exercise caution when prescribing diazepam to the older population as they tend to have decreased renal function and clearance; therefore, this population is at an increased risk of diazepam accumulation and its major metabolites. The recommendation is to limit the dosage to the smallest effective amount. Paradoxical reactions of CNS hyperactivity have also been reported when using benzodiazepines in the elderly, manifesting as hyperactivity, aggressive behavior, irritability, anxiety, and hallucinations. Discontinuation of diazepam is recommended if there is a presence of paradoxical agitation.[11][12][13]

Patients with Hepatic Impairment: In mild and moderate cirrhosis, the mean half-life of diazepam is increased. In addition, the volume of distribution also increases, and average clearance decreases by almost half. Mean half-life is also increased with hepatic fibrosis by approximately 90 hours, chronic active hepatitis by 60 hours, and acute viral hepatitis to about 74 hours.

Pregnancy Considerations: Diazepam is classified as a former FDA pregnancy category D, indicating positive evidence of human fetal risk. Still, the benefits from use in pregnant women may be acceptable despite the risk. The use of diazepam and other benzodiazepines in pregnancy correlates with an increased risk of congenital malformations, premature birth, low birth weight, and other neurodevelopmental abnormalities. However, additional studies are needed to confirm. Diazepam readily crosses the placental barrier, and use during pregnancy may result in neonatal withdrawal soon after birth. Symptoms of neonatal withdrawal include high-pitched cry, hypertonia, tremor, irritability, feeding difficulties, sleep/wake disturbances, gastrointestinal and autonomic disturbances, respiratory problems, and failure to thrive. The onset of withdrawal in a neonate whose mother has taken diazepam during the pregnancy could be anywhere from the first days of life to the first few weeks. During the last trimester of pregnancy, diazepam use can result in “floppy infant syndrome,” characterized by hypotonia, hypothermia, lethargy, respiratory distress, and suckling difficulties.[14][15]

Breastfeeding Considerations: Diazepam and its metabolites are excreted in breast milk and may affect the nursing infant. Some studies have shown diazepam’s relative infant dose (RID) to be approximately 9%. The relative infant dose (RID) is the dose received via breast milk relative to the mothers. A relative dose below 10% is within an acceptable range regarded as reasonably safe in the short term. However, due to diazepam’s long half-life, metabolites may accumulate in a breastfed infant. Therefore, the clinician should monitor an infant breastfed by a mother receiving diazepam for drowsiness, decreased feeding, lethargy, and failure to thrive. Discontinue breastfeeding in cases with high doses of diazepam or when repeated administration will be necessary. However, when a single dose of diazepam is required for a procedure or seizure, the clinician should advise the mother to wait six to eight hours before resuming nursing, particularly with a preterm infant.[16][17]

Adverse Effects

Like most benzodiazepines, the adverse reactions of diazepam include CNS and respiratory depression, dependence, and benzodiazepine withdrawal syndrome. [18]

Serious adverse effects of diazepam include:

• Respiratory depression

• Suicidality[19]

• Dependency and abuse

• Withdrawal symptoms

• Cardiovascular collapse

• Bradycardia 

• Hypotension

• Syncope

• Paradoxical CNS stimulation[20]

Common adverse effects of diazepam include:

• Sedation

• Fatigue

• Confusion

• Anterograde amnesia

• Depression

• Ataxia

• Irritability

• Disinhibition

• Local injection site reaction

• Headache

• Tremor

• Dystonia

• Urinary retention

• Incontinence

• Nausea

• Constipation

• Diplopia

• Libido changes

• Rash

• Menstrual irregularities

• ALT and/or AST elevation[21]

Drug Interactions: 

• Potent inhibition of the CYP2C19 enzyme by certain drugs (fluoxetine and chloramphenicol) and CYP3A4 enzymes by certain medications (ketoconazole, protease inhibitors, erythromycin) may cause increased levels of diazepam.

• Inducers of CYP2C19 (rifampicin and prednisone) and CYP3A4 (carbamazepine, topiramate, phenytoin, St. John’s wort, rifampin, or barbiturates) may cause lower levels.[22]

Contraindications

Contraindications to diazepam include patients with a known hypersensitivity to diazepam. Diazepam is also contraindicated in patients under six months of age. Other contraindications to diazepam include patients with severe respiratory insufficiency, myasthenia gravis, sleep apnea syndrome, and severe hepatic insufficiency. It is permissible in patients with open-angle glaucoma receiving appropriate therapy but is contraindicated in acute narrow-angle glaucoma.[23][24] The persistent and chronic use of benzodiazepines, including diazepam, can lead to physical dependence if used more frequently than recommended.[25]

US Boxed Warning

Simultaneous use of benzodiazepines and opioids may result in respiratory depression, profound sedation, coma, and death—Reserve concomitant prescribing of these drugs for patients with inadequate alternative treatment options. Minimize dose to the minimum to prevent fatal respiratory depression.[26]

Monitoring

Monitoring respiratory and cardiovascular status, blood pressure, heart rate, and anxiety symptoms in patients taking diazepam is crucial. With long-term use, monitor liver enzymes, CBC, and for signs of propylene glycol toxicity, including serum creatinine, BUN, serum lactate, and osmolality gap. With critically ill patients, monitor the depth of sedation.[27]

Monitor the patient for benzodiazepine use disorder (BUD) and recommend appropriate referral. The use of mandatory prescription drug monitoring programs results in a substantial decrease in controlled substance prescriptions and misuse, including opioids and benzodiazepines.[28]

Toxicity

Diazepam Overdose

The toxic-to-therapeutic ratio of benzodiazepines is very high, making them relatively safe medications. However, the potential of overdose from diverted diazepam always exists when combined with opioids, alcohol, or other centrally acting agents. Overdose in adults frequently involves the co-ingestion of other CNS depressants, which work synergistically to increase toxicity. In the case of single-agent diazepam overdose, symptoms manifest as CNS depression and are very rarely fatal. In mild cases, lethargy, drowsiness, and confusion are common symptoms. In cases of severe overdose, symptoms manifest as ataxia, diminished reflexes, hypotonia, hypotension, respiratory depression, coma (rarely), and death (rarely).[14]

Treatment of benzodiazepine overdose involves protecting the airway, fluid resuscitation, and the use of flumazenil if indicated. Flumazenil works via competitive antagonism at the benzodiazepine receptor and can rapidly reverse coma. However, in patients with benzodiazepine tolerance, flumazenil can precipitate acute withdrawal symptoms, autonomic instability, and seizures.[3] 

Potential for Diazepam Abuse and Dependence

Diazepam is a Schedule IV controlled substance with the potential for abuse. Development of dependence and tolerance can occur in addiction-prone, long-term treatment or those patients taking high doses. Thus, these individuals should be under careful supervision; once an individual develops dependence, the risk of developing withdrawal symptoms increases. Signs of benzodiazepine withdrawal include tremors, rebound anxiety, perceptual disturbances, dysphoria, psychosis, agitation, irritability, restlessness, sweating, headache, confusion, myalgias, abdominal pain, and vomiting. In long-term use and abrupt cessation, there is potential for hallucinations and epileptic seizures to occur.[29][25]

Propylene Glycol Toxicity

Propylene glycol toxicity is a rare toxidrome associated with the parenteral use of diazepam. Propylene glycol is a common diluent used in the suspension of IV diazepam. Large doses or long-term infusions of IV diazepam can cause accumulation of propylene glycol and subsequent anion gap metabolic acidosis. Signs of propylene glycol poisoning include the development of serum hyperosmolality, hemolysis, cardiac dysrhythmias, hypotension, lactic acidosis, seizure, acute kidney injury, and multisystem organ failure. [30]

Enhancing Healthcare Team Outcomes

Diazepam is a fast-acting potent anxiolytic popular due to its broad therapeutic index, low toxicity, and improved safety profile. Nonetheless, diazepam is still a drug with a high potential for use disorder associated with severe adverse/toxic effects. Therefore, clinicians should identify the proper indication for the prescription of diazepam. Psychiatrist consultation is necessary in the cases of anxiety disorders. Neurologists should prescribe diazepam in spasticity and status epilepticus, considering the risk vs. benefit ratio for the individual patients. The pharmacists are responsible for the proper dosing of diazepam, medication reconciliation, and patient counseling. The pharmacist should report to the clinician or nurse if there are significant interactions.[31][32]

In acute overdose of diazepam, triage nurses and emergency department physicians are responsible for rapid diagnosis and stabilization of the patient. Critical care physicians should manage respiratory depression, which can be life-threatening if not treated promptly. In ICU, regular assessment of RASS(Richmond agitation-sedation scale) and CAM-ICU (confusion assessment method for the ICU) scoring should guide the proper use of sedatives. Consulting the psychiatrist is especially important if the diazepam overdose is intentional.[33]

A randomized controlled trial, EMPOWER (Eliminating Medications Through Patient Ownership of End Results), for reducing inappropriate benzodiazepine prescriptions for older adults through direct patient education was conducted to compare the result of a direct-to-consumer educational intervention against usual care on benzodiazepine discontinuation in older adults. At the end of six months, 27% of the intervention group discontinued benzodiazepine compared to 5% in the control group using the stepwise tapering protocol.[34] [Level 1]

As illustrated above, managing patients on diazepam requires an interprofessional team approach consisting of clinicians (MDs, DOs, NPs, PAs), specialists, nurses, pharmacists, and other healthcare providers. As stated previously, prescribing clinicians should be responsible for checking state and federal controlled substance databases to detect benzodiazepine use disorder, diversion, and prevent improper drug use.[28] An interprofessional team approach would achieve maximum efficacy and minimize potential adverse drug reactions for the patients requiring diazepam, which can translate to better patient outcomes. [Level 5]

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Figure

Chemical Structure of Diazepam. Contributed by US National Library of Medicine

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Taran Z, Namadian M, Faghihzadeh S, Naghibi T. The Effect of Sedation Protocol Using Richmond Agitation-Sedation Scale (RASS) on Some Clinical Outcomes of Mechanically Ventilated Patients in Intensive Care Units: a Randomized Clinical Trial. J Caring Sci. 2019 Dec;8(4):199-206. [PMC free article: PMC6942649] [PubMed: 31915621]

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Tannenbaum C, Martin P, Tamblyn R, Benedetti A, Ahmed S. Reduction of inappropriate benzodiazepine prescriptions among older adults through direct patient education: the EMPOWER cluster randomized trial. JAMA Intern Med. 2014 Jun;174(6):890-8. [PubMed: 24733354]

Disclosure: Jaberpreet Dhaliwal declares no relevant financial relationships with ineligible companies.

Disclosure: Alan Rosani declares no relevant financial relationships with ineligible companies.

Disclosure: Abdolreza Saadabadi declares no relevant financial relationships with ineligible companies.

Diazepam | is… What is diazepam?

Diazepam (Valium) is a commonly used sedative and anti-anxiety drug in the benzodiazepine group. White or white with a slight yellowish tinge, fine crystalline powder, practically insoluble in water, hardly soluble in alcohol.

The drug has a sedative, hypnotic, anti-anxiety, anticonvulsant, muscle relaxant (relaxes muscles) and amnestic action. Enhances the effect of sleeping pills, narcotic, neuroleptic, analgesic drugs, alcohol.

Long-term use of diazepam may lead to dependence on the drug.

Diazepam is on the WHO Essential Medicines List, which defines the minimum set of medicines needed in a health care system. The drug is used, in particular, for the treatment of anxiety, insomnia, epileptic convulsions, muscle spasms, alcohol dependence. In preparation for some medical procedures, such as endoscopy, diazepam is used to sedate the patient or for anesthesia.

General information

Diazepam is one of the main benzodiazepine tranquilizers, which has found wide application in medical practice.

The drug has a sedative, hypnotic, anti-anxiety, anticonvulsant, muscle relaxant (relaxes the muscles) and amnestic action. Enhances the effect of sleeping pills, narcotic, neuroleptic, analgesic drugs, alcohol.

The drug and its major metabolites are excreted primarily in the urine.

Therapeutic effects and indications for use

Diazepam is prescribed for various neuropsychiatric diseases: neurosis, psychopathy, as well as neurosis-like and psychopathic conditions in schizophrenia, organic brain lesions, including cerebrovascular diseases, somatic diseases accompanied by signs of emotional stress, anxiety, fear, increased irritability, senestohypochondriac, obsessive and phobic disorders, sleep disorders. It is also used to relieve psychomotor agitation and anxious agitation in these diseases.

In pediatric neuropsychiatric practice, diazepam is prescribed for neurotic and neurosis-like conditions, accompanied by the above phenomena, as well as headaches, enuresis, mood and behavioral disorders.

Diazepam is used in epilepsy for the treatment of convulsive paroxysms, mental equivalents, for the relief of status epilepticus. In connection with the muscle relaxant effect, the drug is also used in various spastic conditions.

In combination with other drugs, diazepam is prescribed for the treatment of withdrawal syndrome in alcoholism.

Used in anesthetic practice for preoperative preparation of patients.

In dermatological practice, it is used for itchy dermatoses.

The drug reduces the nocturnal secretion of gastric juice, which can play an important role when it is prescribed as a sedative and hypnotic agent for patients with gastric ulcer

The drug also has an antiarrhythmic effect.

Diazepam is used for premedication and ataralgesia before endoscopy and surgery in combination with analgesics and other neurotropic drugs.

Diazepam is an ingredient in the hypnotic drug reladorm (see Cyclobarbital).

Methods of administration

Use diazepam by mouth, intravenously or intramuscularly. A sedative effect is observed within a few minutes after intravenous and 30-40 minutes after intramuscular administration of diazepam, a therapeutic effect is observed after 3-10 days. After removing the acute manifestations of the disease, diazepam is prescribed orally.

Diazepam solution should not be administered in the same syringe with other drugs to avoid precipitation.

Dosage

When taken orally, it is recommended to prescribe the drug to adults, starting with a dose of 0.0025-0.005 g (2.5-5 mg) 1-2 times a day, and then gradually increase it. Usually a single dose for adults is 0.005-0.01 g (5-10 mg). In some cases (with increased arousal, fear, anxiety), a single dose can be increased to 0. 02 g (20 mg). When treated in a hospital and with careful medical supervision, the daily dose can reach 0.045 g (45 mg). In outpatient treatment, it is not recommended to prescribe more than 0.025 g (25 mg) per day.

Maximum daily dose 0.06 g (60 mg). The daily therapeutic dose is given in 2-3 doses.

Weakened and elderly people are recommended to take the drug in reduced doses (0.0025 g (2.5 mg) 1-2 times a day).

For sleep disorders, adults are prescribed 2.5-5 mg at bedtime.

For children, diazepam is prescribed orally in the following doses:

• aged 1 to 3 years – a single dose of 1 mg, a daily dose of 2 mg.
• 3 to 7 years – single dose 2 mg, daily dose 6 mg.
• 7 years and older – single dose 3-5 mg, daily dose 8-10 mg.

Older children can increase the daily dose to 0.014-0.016 g (14-16 mg) if necessary.

Cancellation of diazepam should be carried out by gradually reducing the dose. Due to the possible development of psychological dependence, the duration of a continuous course of treatment should not exceed 2 months. Before a second course of treatment, a break of at least 3 weeks.

Intravenously (drip or jet) and intramuscularly, the drug is administered to adults mainly in diseases accompanied by psychomotor agitation, convulsions, in the relief of status epilepticus, in the treatment of acute anxiety-phobic, anxiety-depressive conditions, including alcoholic psychoses and withdrawal symptoms. The average single dose is 10 mg (2 ml of a 0.5% solution), the average daily dose is 30 mg. Maximum dose: single 30 mg, daily 70 mg.

For status epilepticus, diazepam is administered slowly intravenously at a dose of 10 to 40 mg. It is possible, if necessary, to repeat intravenous or intramuscular administration every 3-4 hours (3-4 times). The highest effect is observed with the early appointment of diazepam in the first 3 hours after the onset of the status in the form of generalized seizures.

Contraindications

Possible complications, contraindications and precautions are basically the same as for chlosepid. With intravenous administration of a solution of diazepam, local inflammatory processes may occur, and therefore it is recommended to change the injection site.

Drug interactions

Simultaneous use of diazepam with other psychotropic or antispasmodic drugs (anesthesia, barbiturates, phenothiazines, analgesics, MAO inhibitors and other antidepressants, ethanol) increases the effect of diazepam. With the simultaneous use of diazepam with muscle relaxants, the risk of apnea increases.

Pharmacokinetic interaction With prolonged use of cimetidine or omeprazole, the clearance of diazepam decreases. Drugs that cause the induction of liver enzymes, including antiepileptic drugs (carbamazepine, phenytoin), can accelerate the excretion of diazepam.

Pharmaceutical interactions

Diazepam solution is not compatible in the same syringe with any other drugs (precipitation is possible).

Non-medical use

Due to the relative availability of diazepam (despite the prescription of the drug), addicts very often use this drug along with tramadol (tramal retard) when withdrawal develops, to stop the withdrawal. People who suffer from alcoholism often use diazepam to enhance the effects of ethanol on the body.

Doctors in Primorye prescribed Valium for themselves

12:01, February 6, 2012
Incidents

In Primorye, a criminal case has been initiated against the chief physician of the municipal budgetary healthcare institution “Central City Hospital” in the city of Ussuriysk and the head of the medical center “Polyclinic No. 2” of the same medical institution.

According to the investigation, in November 2011, the head physician of the Central City Hospital of Ussuriysk illegally ordered her subordinate, the head of the Polyclinic No. 2 medical center, to write out two prescriptions for a drug that includes the potent substance Diazepam and is included in the corresponding list potent substances.

– Prescriptions had to be written out in the name of the head and in the name of any patient for whose medical reasons it was possible to prescribe this drug, – Avrora Rimskaya, senior assistant to the head of the regional TFR, told Vladnews. – The head of the medical center prepared prescriptions and handed them over to the head, who, in turn, received the drug indicated in them at the pharmacy according to fake prescriptions, after which she transferred it to third parties.

Currently, the investigation of the criminal case is ongoing, investigative actions are being carried out aimed at establishing all the circumstances of the incident: an inspection of the scene was carried out, documentation was confiscated, witnesses are being interrogated.

Diazepam (Valium) is a widely used sedative and anti-anxiety medication. The drug has a sedative, hypnotic, anti-anxiety, anticonvulsant, muscle relaxant (relaxes muscles) and amnestic action. Enhances the effect of sleeping pills, narcotic, neuroleptic, analgesic drugs, alcohol. Taking diazepam for a long time can lead to dependence on the drug.

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