Diazepam

Diazepam Uses, Dosage, Side Effects, Food Interaction and all others data.

Diazepam, like other members of the benzodiazepine family, binds to receptors in various regions of the brain, such as the spinal cord, brain stem, cerebellum, limbic system and cerebral cortex. Binding of diazepam to the benzodiazepine receptor potentiates the inhibitory actions of gamma-aminobutyric acid (GABA) mediated through chloride channel, thereby enhancing GABA-facilitated, inhibitory synaptic transmission.

Diazepam is a benzodiazepine that exerts anxiolytic, sedative, muscle- relaxant, anticonvulsant and amnestic effects . Most of these effects are thought to result from facilitation of the action of gamma aminobutyric acid (GABA), an inhibitory neurotransmitter in the central nervous system .

Trade Name Diazepam
Availability Prescription only
Generic Diazepam
Diazepam Other Names Diazepam, Methyl diazepinone
Related Drugs Valtoco, Nayzilam, Diastat, escitalopram, alprazolam, duloxetine, cyclobenzaprine, clonazepam, Lexapro, lorazepam
Weight 2mg, 5mg, 10mg/2ml, , 5mg/ml, 5mg/5ml, 10mg, 10mg/dose, 15mg/dose, 20mg/dose, 5mg/dose, 2.5mg, 20mg
Type Tablet, Injection, Oral Concentrate, Oral Solution, Oral Tablet, Injectable Solution, Nasal Spray, Rectal Kit
Formula C16H13ClN2O
Weight Average: 284.74
Monoisotopic: 284.071640755
Protein binding

Despite high binding to plasma proteins (98-99%) - mainly albumin and to a lesser extent α1-acid glycoprotein - diazepam is widely distributed into tissues and crosses the blood-brain barrier and is highly lipid soluble, which causes the initial effects to decrease rapidly as it is redistributed into fat deposits and tissues .

Groups Approved, Illicit, Investigational, Vet approved
Therapeutic Class Benzodiazepine sedatives, Centrally acting Skeletal Muscle Relaxants, Primary anti-epileptic drugs
Manufacturer Efroze Chemical Industries (pvt) Ltd, , Albion Pharmaceuticals Ltd, Essential Drugs Company Ltd, Popular Pharmaceuticals Ltd, Renata Limited, Sandoz Limited, Farmasi,  meprofarm, Mersifarma Tirmaku Mercusana, Reagan Remedies Limited
Available Country Pakistan, Bangladesh, United Kingdom, United States, Indonesia, Netherlands, Nigeria
Last Updated: September 19, 2023 at 7:00 am
Diazepam
Diazepam

Uses

Diazepam is used for the management of anxiety disorders or for the shortterm relief of the symptoms of anxiety. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. In acute alcohol withdrawal, Diazepam may be useful in the symptomatic relief of acute agitation, tremor, impending or acute delirium tremens and hallucinosis.

Diazepam is a useful adjunct for the relief of skeletal muscle spasm due to reflex spasm to local pathology (such as inflammation of the muscles or joints, or secondary to trauma), spasticity caused by upper motor neuron disorders (such as cerebral palsy and paraplegia), athetosis, and stiff-man syndrome.

Oral Diazepam may be used adjunctively in convulsive disorders, although it has not proved useful as the sole therapy.

The effectiveness of Diazepam in long-term use, that is, more than 4 months, has not been assessed by systematic clinical studies. The physician should periodically reassess the usefulness of the drug for the individual patient.

Diazepam is also used to associated treatment for these conditions: Alcohol Withdrawal Syndrome, Anxiety, Anxiety Disorders, Refractory Epilepsy, Intermittent distinct from a patient’s usual seizure pattern, stereotypic episode Epileptic seizure, Refractory seizure disorders, Skeletal muscle spasm, Sedation, Perioperative management therapy

How Diazepam works

Diazepam is a benzodiazepine tranquilliser with anticonvulsant, sedative, muscle relaxant and amnesic properties .

Benzodiazepines, such as diazepam, bind to receptors in various regions of the brain and spinal cord. This binding increases the inhibitory effects of gamma-aminobutyric acid (GABA) . GABAs functions include CNS involvement in sleep induction. Also involved in the control of hypnosis, memory, anxiety, epilepsy and neuronal excitability .

Dosage

Diazepam dosage

Dosage should be individualized for maximum beneficial effect. While the usual daily dosages given below will meet the needs of most patients, there will be some who may require higher doses. In such cases dosage should be increased cautiously to avoid adverse effects.

ADULTS:

Management of Anxiety Disorders and Relief of Symptoms of Anxiety: Depending upon severity of symptoms 2 mg to 10 mg, 2 to 4 times daily

Symptomatic Relief in Acute Alcohol Withdrawal: 10 mg, 3 or 4 times during the first 24 hours, reducing to 5 mg, 3 or 4 times daily as needed

Adjunctively for Relief of Skeletal Muscle Spasm: 2 mg to 10 mg, 3 or 4 times daily

Adjunctively in Convulsive Disorders: 2 mg to 10 mg, 2 to 4 times daily

Geriatric Patients, or in the presence of debilitating disease: 2 mg to 2.5 mg, 1 or 2 times daily initially; increase gradually as needed and tolerated

PEDIATRIC PATIENTS:

Because of varied responses to CNS-acting drugs, initiate therapy with lowest dose and increase as required. Not for use in pediatric patients under 6 months: 1 mg to 2.5 mg, 3 or 4 times daily initially; increase gradually as needed and tolerated

Side Effects

Drowsiness and light headedness the next day; confusion and ataxia (specially in the elderly); amnesia may occur; dependence; paradoxical increase in aggression; occasionally headache, vertigo, hypotension, gastrointestinal disturbances, visual disturbances, dysarthria, tremor, changes in libido, incontinence, urinary retention, blood disorders and jaundice reported.

Toxicity

The symptoms of diazepam overdose are mainly an intensification of the therapeutic effects (ataxia, drowsiness, dysarthria, sedation, muscle weakness, profound sleep, hypotension, bradycardia, nystagmus) or paradoxical excitation . In most cases only observation of vital functions is required .

Extreme overdosage may lead to coma, areflexia, cardio-respiratory depression and apnoea, requiring appropriate countermeasures (ventilation, cardiovascular support) .

Benzodiazepine respiratory depressant effects are more serious in patients with severe chronic obstructive airways disease . Severe effects in overdose also include rhabdomyolysis and hypothermia . Overdose of benzodiazepines in combination with other CNS depressants (including alcohol) may be fatal and should be closely monitored .

In general, the use of diazepam in women of childbearing potential, and more specifically during known pregnancy, should be considered only when the clinical situation warrants the risk to the fetus . The possibility that a woman of childbearing potential may be pregnant at the time of institution of therapy should be considered . If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus . Patients should also be advised that if they become pregnant during therapy or intend to become pregnant they should communicate with their physician about the desirability of discontinuing the drug .

Special care must be taken when diazepam is used during labor and delivery, as high single doses may produce irregularities in the fetal heart rate and hypotonia, poor sucking, hypothermia, and moderate respiratory depression in the neonates . With newborn infants it must be remembered that the enzyme system involved in the breakdown of the drug is not yet fully developed (especially in premature infants) .

Diazepam passes into breast milk . Breastfeeding is therefore not recommended in patients receiving diazepam .

Safety and effectiveness in pediatric patients below the age of 6 months have not been established .

In elderly patients, it is recommended that the dosage be limited to the smallest effective amount to preclude the development of ataxia or oversedation (2 mg to 2.5 mg once or twice daily, initially to be increased gradually as needed and tolerated) . Extensive accumulation of diazepam and its major metabolite, desmethyldiazepam, has been noted following chronic administration of diazepam in healthy elderly male subjects. Metabolites of this drug are known to be substantially excreted by the kidney, and the risk of toxic reactions may be greater in patients with impaired renal function . Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function .

Decreases in clearance and protein binding, and increases in volume of distribution and half-life has been reported in patients with cirrhosis . In such patients, a 2- to 5- fold increase in mean half-life has been reported . Delayed elimination has also been reported for the active metabolite desmethyldiazepam . Benzodiazepines are commonly implicated in hepatic encephalopathy . Increases in half-life have also been reported in hepatic fibrosis and in both acute and chronic hepatitis .

Precaution

Diazepam is not recommended for use in patients with depressive disorders or psychosis. Patients should be advised against the concurrent use of alcohol and other CNS depressant drugs. Patients with known or presumed dependence from alcohol or drugs should not take benzodiazepines.

Since Diazepam has a CNS depressant effect, patients should be warned against driving, operating dangerous machinery, or engaging in other hazardous activities requiring mental alertness and physical coordination.

Interaction

Diazepam may potentiate or interact with the effects of other CNS acting drugs such as alcohol, narcotics, hypnotics, sedative antihistamines, antipsychotics, anxiolytics/ sedatives, anesthetics, antidepressants and anticonvulsants. Besides these diazepam may interact with phenytoin, cimetidine, levodopa, lithium.

Food Interaction

  • Avoid alcohol.
  • Take on an empty stomach. Food may decrease absorption and time to therapeutic effect.

[Moderate] GENERALLY AVOID: Acute alcohol ingestion may potentiate the CNS depression and other CNS effects of many benzodiazepines.

Tolerance may develop with chronic ethanol use.

The mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic enzyme inhibition.

Also, it has been suggested that the cognitive deficits induced by benzodiazepines may be increased in patients who chronically consume large amounts of alcohol.



MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme.

However, the interaction seems to affect primarily those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability), presumably due to the fact that grapefruit juice inhibits intestinal rather than hepatic CYP450 3A4.

Because pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability, the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients should be advised to avoid alcohol during benzodiazepine therapy.

Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of drugs that undergo significant presystemic metabolism by CYP450 3A4.

Grapefruit and grapefruit juice should be avoided if an interaction is suspected.

Orange juice is not expected to interact with these drugs.

Volume of Distribution

In young healthy males, the volume of distribution at steady-state is 0.8 to 1.0 L/kg .

Elimination Route

After oral administration, it is considered that diazepam is rapidly and completely absorbed from the gastrointestinal tract as >90% of diazepam is absorbed and the average time to achieve peak plasma concentrations is 1 – 1.5 hours with a range of 0.25 to 2.5 hours .

Absorption is delayed and decreased when administered with a moderate fat meal . In the presence of food mean lag times are approximately 45 minutes as compared with 15 minutes when fasting . There is also an increase in the average time to achieve peak concentrations to about 2.5 hours in the presence of food as compared with 1.25 hours when fasting . This results in an average decrease in Cmax of 20% in addition to a 27% decrease in AUC (range 15% to 50%) when administered with food .

Half Life

Diazepam has a biphasic half-life with an initial rapid distribution phase followed by a prolonged terminal elimination phase of 1 or 2 days; its action is further prolonged by the even longer half-life of 2-5 days of its principal active metabolite, desmethyldiazepam (nordiazepam), the relative proportion of which increases in the body on long-term administration . The plasma half-life of diazepam is prolonged in neonates, in the elderly, and in patients with kidney or liver disease .

Clearance

The clearance of diazepam is 20 to 30 mL/min in young adults .

Elimination Route

Diazepam and its metabolites are excreted mainly in the urine, predominantly as their glucuronide conjugates .

Pregnancy & Breastfeeding use

Category D: The use of Diazepam during the first trimester of pregnancy should almost always be avoided as it bears a risk of congenital malformation.

Diazepam has been detected in breast milk. If possible the use of diazepam should be avoided during lactation.

Contraindication

Patients with known hypersensitivity to benzodiazepines, & myasthenia gravis are contraindicated to diazepam.

Acute Overdose

Symptoms: Somnolence, ataxia, confusion, dysarthria, little or no resp depression, hypotension, muscular weakness, deep coma, severe depression, diminished reflexes. 

Management: Symptomatic and supportive treatment. Empty stomach by vomiting or gastric lavage. Activated charcoal may help reduce absorption. Flumazenil may be used for the complete or partial reversal of the sedative effects but there is a risk of seizure esp in long-term benzodiazepine users and in cyclic antidepressant overdose.

Storage Condition

Store between 15-30°C. Protect from light. Inj: Avoid freezing.

Innovators Monograph

You find simplified version here Diazepam

Diazepam contains Diazepam see full prescribing information from innovator Diazepam Monograph, Diazepam MSDS, Diazepam FDA label

FAQ

What is Diazepam used for?

Diazepam is commonly used to treat a range of conditions, including anxiety, seizures, alcohol withdrawal syndrome, benzodiazepine withdrawal syndrome, muscle spasms, insomnia, and restless legs syndrome. It's used to treat anxiety, muscle spasms and fits (seizures). It's also used in hospital to reduce alcohol withdrawal symptoms, such as sweating or difficulty sleeping.

How safe is Diazepam?

Diazepam has a risk for abuse and addiction, which can lead to overdose and death. Taking this, to lower your risk, your doctor should have you take the smallest dose of Diazepam that works, and take it for the shortest possible time.

How does Diazepam work?

Diazepam works by increasing the levels of a calming chemical in your brain.

What are the common side effects of Diazepam?

Common side effects of

  • drowsiness
  • dizziness
  • tiredness
  • muscle weakness
  • headache
  • dry mouth
  • nausea
  • constipation
  • confusion
  • difficulty urinating
  • frequent urination
  • changes in sex drive or ability

Is Diazepam safe during pregnancy?

Diazepam is safe to take Diazepam during pregnancy but not during lactation because it can cause lethargy, sedation, and weight loss in infants.

Is Diazepam safe during breastfeeding?

Small amounts of Diazepam are expected to enter the breast milk. However, Diazepam stays in the body longer than some other benzodiazepines do. If you use Diazepam regularly while breastfeeding there is a chance it could build up in the baby's system and cause sleepiness or affect your child's weight gain.

Can I drink alcohol with Diazepam?

Diazepam and alcohol are both central nervous system depressants. Therefore, the effects of mixing Diazepam and alcohol can be unpleasant and life-threatening.

Can I drive after taking Diazepam?

If you take Diazepam and feel sleepy, do not drive or use tools or machines. Do not drink alcohol while taking Diazepam.

When should be taken of Diazepam?

If you are taking Diazepam to help you sleep, you should take it just before bedtime.

Can I take Diazepam on an empty stomach?

Take Diazepam tablets or liquid with a drink of water. You can take them with or without food.

How often can I take Diazepam?

You'll usually take your Diazepam 1 to 3 times a day.

How long does Diazepam take to work?

Diazepam starts to work very quickly in your body, and you should get calming effects within two hours of taking it.

How long can I take Diazepam ?

It is usual to take Diazepam for no longer than 2 to 4 weeks. If you're prescribed Diazepam for more than 4 weeks, your dose may be reduced gradually when coming off it to prevent withdrawal symptoms.

Is Diazepam safe for long term use?

Long-term use of Diazepam can lead to chemical dependency and, eventually, to severe addiction.

Who should not take Diazepam?

You should not use this medicine if you are allergic to Diazepam or similar medicines, or if you have myasthenia gravis, severe liver disease, narrow-angle glaucoma, a severe breathing problem, or sleep apnea.

What should I do if I missed a dose of Diazepam ?

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

What happens if I overdose on Diazepam?

Overdose symptoms may include extreme drowsiness, loss of balance or coordination, limp or weak muscles, slow breathing, or coma. If you think you or someone else may have overdosed on: Diazepam, call your doctor or the Poison Control center

Can Diazepam affects my heart ?

Diazepam produced no change in baroreceptor sensitivity; however, there was a significant rise in heart rate and a significant fall in aortic systolic and left ventricular end-diastolic pressures. Cardiac index was unchanged, whereas stroke volume fell significantly.

Can Diazepam effects my kidney?

Diazepam is removed from your body by your kidneys. If you have kidney problems, more of the Diazepam may stay in your body for longer, putting you at risk for side effects.

Can Diazepam affects my liver?

Clinically apparent liver injury from Diazepam is exceedingly rare.

*** Taking medicines without doctor's advice can cause long-term problems.
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