diazepam
Apo-Diazepam ◆, Diastat, Novodipam ◆, Valium, Vivol ◆, Zetran

Available forms
Available by prescription only
Capsules (extended-release): 15 mg
Injection: 5 mg/ml in ampules, vials, and disposable syringes
Oral solution: 5 mg/ml, 5 mg/5 ml, 10 mg/10 ml
Rectal gel: 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg twin packs
Tablets: 2 mg, 5 mg, 10 mg

Indications and dosages
 Anxiety. Adults: Depending on severity, 2 to 10 mg P.O. b.i.d. to q.i.d. or 15 to 30 mg extended-release capsules P.O. once daily. Or, 2 to 10 mg I.M. or I.V. q 3 to 4 hours, p.r.n.
Children age 6 months and older: 1 to 2.5 mg P.O. t.i.d. or q.i.d.; increase dose gradually, as needed and tolerated.
 Acute alcohol withdrawal. Adults: 10 mg P.O. t.i.d. or q.i.d. for the first 24 hours; reduce to 5 mg t.i.d. or q.i.d., p.r.n. Or, 10 mg I.M. or I.V. initially, followed by 5 to 10 mg q 3 to 4 hours, p.r.n.
 Muscle spasm. Adults: 2 to 10 mg P.O. b.i.d. to q.i.d. or 15 to 30 mg extended-release capsules once daily. Or, give 5 to 10 mg I.M. or I.V. q 3 to 4 hours, p.r.n.
 Tetanus. Children age 5 and older: 5 to 10 mg I.M. or I.V. slowly q 3 to 4 hours, p.r.n.
Infants older than age 30 days to children age 5: 1 to 2 mg I.M. or I.V. slowly, repeated q 3 to 4 hours.
 Adjunct to convulsive disorders. Adults: 2 to 10 mg P.O. b.i.d. to q.i.d.
Children age 6 months and older: Initially, 1 to 2.5 mg P.O. t.i.d. or q.i.d.; increase dose as tolerated and needed.
 Adjunct to anesthesia, endoscopic procedures. Adults: 5 to 10 mg I.M. before surgery. Or, administer I.V. slowly just before procedure, adjusting dose to effect. Usually, less than 10 mg is used, but up to 20 mg may be given.
 Cardioversion. Adults: Administer 5 to 15 mg I.V. 5 to 10 minutes before procedure.
 Status epilepticus. Adults: 5 to 10 mg I.V. (preferred) or I.M. initially, repeated at 10- to 15-minute intervals up to a maximum dose of 30 mg. Repeat q 2 to 4 hours, p.r.n. Or, 0.2 to 0.5 mg/kg q 15 to 30 minutes for two to three doses to a maximum of 30 mg.
Children age 5 and older: 1 mg I.V. q 2 to 5 minutes up to a maximum dose of 10 mg; repeat in 2 to 4 hours, p.r.n.
Infants older than age 30 days to children age 5: 0.2 to 0.5 mg I.V. q 2 to 5 minutes up to a maximum dose of 5 mg.
 Control of acute repetitive seizure activity in patients already taking antiepileptics. Children age 12 and older: 0.2 mg/kg P.R. using applicator. A second dose may be given 4 to 12 hours after the first dose, if needed.
Children ages 6 to 11: 0.3 mg/kg P.R. using applicator. A second dose may be given 4 to 12 hours after the first dose, if needed.
Children ages 2 to 5: 0.5 mg/kg P.R. using applicator. A second dose may be given 4 to 12 hours after the first dose, if needed.
 Endoscopic procedures. Adults: Titrate 10 to 20 mg slow I.V. push just before procedure and reduce narcotic dosage by at least one-third, or possibly omit narcotic dose. Titrate to desired response, such as slurring of speech. Or, 5 to 10 mg I.M. 30 minutes before procedure.

Pharmacodynamics
Anxiolytic and sedative-hypnotic actions: Diazepam depresses the CNS at the limbic and subcortical levels of the brain. It produces an antianxiety effect by influencing the effect of the neurotransmitter gamma-aminobutyric acid on its receptor in the ascending reticular activating system, which increases inhibition and blocks cortical and limbic arousal.
Skeletal muscle relaxant action: Exact mechanism is unknown, but drug may inhibit polysynaptic afferent pathways.
Amnestic action: Exact mechanism of action is unknown.
Anticonvulsant action: Diazepam suppresses the spread of seizure activity produced by epileptogenic foci in the cortex, thalamus, and limbic structures by enhancing presynaptic inhibition.

Pharmacokinetics
Absorption: When administered orally, drug is absorbed through the GI tract. I.M. administration yields slow and erratic absorption. Drug is well absorbed rectally and reaches peak plasma levels in 1 1/2 hours.
Distribution: Distributed widely throughout the body. About 85% to 95% of an administered dose is bound to plasma protein.
Metabolism: Metabolized in the liver to the active metabolite desmethyldiazepam.
Excretion: Most metabolites of diazepam are excreted in urine, with only small amounts excreted in feces. Half-life of desmethyldiazepam is 30 to 200 hours. Duration of sedative effect is 3 hours; this may be prolonged up to 90 hours in elderly patients and in patients with hepatic or renal dysfunction. Anticonvulsant effect is 30 to 60 minutes after I.V. administration.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug; patients with angle-closure glaucoma; patients experiencing shock, coma, or acute alcohol intoxication (parenteral form); and children younger than age 6 months. Also contraindicated in patients with psychoses and in administration with ketoconazole and itraconazole because of CYP450 3A inhibition.
  Use cautiously in elderly or debilitated patients, and patients with impaired hepatic or renal function, depression, or chronic open-angle glaucoma. Avoid use in pregnancy, especially during the first trimester, and in breast-feeding women.

Interactions
Drug-drug. Antacids: Decreases the absorption of diazepam. Avoid use together.
Antidepressants, antihistamines, barbiturates, general anesthetics, MAO inhibitors, narcotics, phenothiazines: Potentiates CNS depressant effects. Avoid use together.
Cimetidine, fluoxetine, isoniazid, metoprolol, propoxyphene, propranolol, valproic acid, and possibly disulfiram: Diminishes hepatic metabolism of diazepam, which increases its plasma level. Monitor patient closely.
Digoxin: May decrease digoxin clearance. Monitor patient for digoxin toxicity.
Haloperidol: May alter seizure pattern. Benzodiazepines also may reduce serum haloperidol levels. Avoid use together.
Levodopa: May inhibit therapeutic effect of levodopa. Monitor patient carefully.
Nondepolarizing neuromuscular blockers, such as pancuronium and succinylcholine: Intensifies and prolongs respiratory depression. Don’t use together.
Oral contraceptives: May impair metabolism of diazepam. Monitor patient closely.
Ranitidine: May reduce GI absorption of diazepam. Monitor patient for effect.
Drug-lifestyle. Alcohol use: Potentiates CNS depressant effects. Discourage alcohol use.
Heavy smoking: Accelerates metabolism of diazepam, lowering clinical effectiveness. Discourage smoking.

Adverse reactions
CNS: drowsiness, slurred speech, tremor, transient amnesia, fatigue, ataxia, headache, insomnia, paradoxical anxiety, hallucinations, changes in EEG patterns, pain.
CV: hypotension, CV collapse, bradycardia, phlebitis (at injection site).
EENT: diplopia, blurred vision, nystagmus.
GI: nausea, constipation.
GU: incontinence, urine retention.
Hematologic: neutropenia.
Hepatic: jaundice.
Musculoskeletal: dysarthria.
Respiratory: respiratory depression.
Skin: rash, injection site pain.
Other: physical or psychological dependence, altered libido, acute withdrawal syndrome after sudden discontinuation in physically dependent persons.

Effects on lab test results
• May increase liver function test values. May decrease neutrophil count.

Overdose and treatment
Signs and symptoms of overdose include somnolence, confusion, coma, hypoactive reflexes, dyspnea, labored breathing, hypotension, bradycardia, slurred speech, and unsteady gait or impaired coordination.
 Support blood pressure and respiration until drug effects subside; monitor vital signs. Mechanical ventilatory assistance via endotracheal tube may be required to maintain a patent airway and support adequate oxygenation. Flumazenil, a specific benzodiazepine antagonist, may be useful, but shouldn’t be administered during status epilepticus. Use I.V. fluids and vasopressors such as dopamine and phenylephrine to treat hypotension as needed. If patient is conscious, induce emesis; use gastric lavage if ingestion was recent, but only if an endotracheal tube is present to prevent aspiration. After emesis or lavage, administer activated charcoal with a cathartic as a single dose. Dialysis is of limited value.

Special considerations
• Don’t discontinue drug suddenly; decrease dosage slowly over 8 to 12 weeks after long-term therapy.
• To enhance taste, oral solution can be mixed with liquids or semisolid foods, such as applesauce or pudding, immediately before administration.
• Extended-release capsule should be swallowed whole; don’t let patient crush or chew it.
• Shake oral suspension well before administering.
• When prescribing with opiates for endoscopic procedures, reduce opiate dose by at least one-third.
• Parenteral forms of diazepam may be diluted in normal saline solution; a slight precipitate may form, but the solution can still be used.
• Diazepam interacts with plastic. Don’t store it in plastic syringes or use plastic administration sets because doing so decreases drug availability.
• I.V. route is preferred because of rapid and more uniform absorption.
 ALERT For I.V. administration, infuse drug slowly, directly into a large vein, at no more than 5 mg/minute for adults or 0.25 mg/kg of body weight over 3 minutes for children. Don’t inject diazepam into small veins to avoid extravasation into S.C. tissue. Observe infusion site for phlebitis. If direct I.V. administration isn’t possible, inject diazepam directly into I.V. tubing at point closest to vein insertion site to prevent extravasation.
• Administration by continuous I.V. infusion isn’t recommended.
• Inject I.M. dose deep into deltoid muscle. Aspirate for backflow to prevent inadvertent intra-arterial administration. Use I.M. route only if I.V. or oral routes are unavailable.
• Patient should remain in bed under observation for at least 3 hours after parenteral administration of diazepam to prevent potential hazards; keep resuscitation equipment nearby.
• Lower doses are effective in patients with renal or hepatic dysfunction.
• Anticipate possible transient increase in frequency or severity of seizures when diazepam is used as adjunctive treatment of convulsive disorders. Impose seizure precautions.
• Don’t mix diazepam with other drugs in a syringe or infusion container.
• Use Diastat rectal gel to treat no more than five episodes per month and no more than one episode every 5 days.
Pregnant patients
• Warn woman to call immediately if she becomes pregnant.
Breast-feeding patients
• Diazepam appears in breast milk. The breast-fed infant of a woman who uses diazepam may become sedated, have feeding difficulties, or lose weight. Avoid use of drug in breast-feeding women.
Pediatric patients
• Safe use of oral diazepam in infants younger than age 6 months hasn’t been established. Safe use of parenteral diazepam in infants younger than age 30 days hasn’t been established.
• Closely observe neonates whose mothers took diazepam for a prolonged period during pregnancy; the infants may show withdrawal symptoms.
• Use of rectal diazepam during labor may cause neonatal flaccidity.
• Safety and efficacy of rectal diazepam haven’t been established in children younger than age 2.
Geriatric patients
• These patients are more sensitive to the CNS depressant effects of diazepam. Use cautiously.
• Lower doses are usually effective because of decreased elimination.
• Elderly patients who receive this drug need assistance with walking and activities of daily living when therapy starts or dosage increases.
• Parenteral administration of this drug is more likely to cause apnea, hypotension, and bradycardia in elderly patients.

Patient education
• Advise patient about risk of physical and psychological dependence with long-term use.
• Warn patient that sudden position changes can cause dizziness. Advise patient to dangle legs for a few minutes before getting out of bed to prevent falls and injury.
• Caution patient to avoid alcohol while taking diazepam.
• Advise patient not to discontinue drug suddenly.
• Teach patient’s caregiver when to use rectal gel (to control bouts of increased seizure activity) and how to monitor and record patient’s clinical response.
• Teach patient’s caregiver how to administer rectal gel.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use