Diazepam

Indications
 Oral
Severe anxiety
Adult: 2 mg tid. Max: 30 mg daily.
Elderly: Dose reduction may be required.
Renal impairment: Dosage adjustments may be needed.
Oral
Insomnia associated with anxiety
Adult: 5-15 mg at bedtime.
Child: and adolescents (12-18 yr): 1-5 mg at bedtime to control night terrors and sleepwalking.
Elderly: Dose reduction may be required.
Renal impairment: Dosage adjustments may be needed.
Oral
Premedication before anaesthesia
Adult: 5-20 mg given before general anaesthesia.
Child: 1 mth-18 yr: 200-300 mcg/kg, may be given 45-60 min beforehand. Max: 10 mg (up to 12 yr); 20 mg (up to 18 yr).
Elderly: Dose reduction may be required.
Renal impairment: Dosage adjustments may be needed.
Oral
Adjunct in seizures
Adult: 2-60 mg daily in divided doses.
Elderly: Dose reduction may be required.
Renal impairment: Dosage adjustments may be needed.
Oral
Muscle spasms
Adult: 2-15 mg daily in divided doses, may increase up to 60 mg daily in severe spastic disorders e.g. cerebral palsy.
Child: 1-12 mth: 250 mcg/kg; 1-5 yr: 2.5 mg; 5-12 year: 5 mg; 12-18 yr: 10 mg (max: 40 mg/day). Dose can be given twice daily.
Elderly: Dose reduction may be required.
Renal impairment: Dosage adjustments may be needed.
Oral
Alcohol withdrawal syndrome
Adult: 5-20 mg repeated after 2-4 hr if necessary. Alternatively, 10 mg 3-4 times daily on the 1st day, reducing to 5 mg 3-4 times daily as required.
Elderly: Dose reduction may be required.
Renal impairment: Dosage adjustments may be needed.
Parenteral
Muscle spasms
Adult: 10 mg IM/IV repeated if necessary after 4 hr. Higher doses may be used in tetanus: 100-300 mcg/kg every 1-4 hr via IV inj; alternatively 3-10 mg/kg may be given over 24 hr by continuous IV infusion or by nasoduodenal tube using a suitable liquid oral dosage form.
Child: ≥1 mth: Higher doses may be used in tetanus: 100-300 mcg/kg every 1-4 hr via IV inj; alternatively 3-10 mg/kg may be given over 24 hr by continuous IV infusion or by nasoduodenal tube using a suitable liquid oral dosage form.
Elderly: Dose reduction may be required.
Renal impairment: Dosage adjustments may be needed.
Intravenous
Premedication before anaesthesia
Adult: Usual dose: 100-200 mcg/kg.
Child: >1 mth: 100-200 mcg/kg. Max: 1 mth-12 yr: 5 mg/day; 12-18 yr: 20 mg/day.
Elderly: Dose reduction may be required.
Renal impairment: Dosage adjustments may be needed.
Parenteral
Alcohol withdrawal syndrome
Adult: 10-20 mg IM/IV if symptoms are severe and if delirium tremens has developed.
Elderly: Dose reduction may be required.
Renal impairment: Dosage adjustments may be needed.
Parenteral
Severe anxiety
Adult: Up to 10 mg may be used, repeat if needed after 4 hr. Dose can be given via IM or IV inj.
Renal impairment: Dosage adjustments may be needed.
Intravenous
Sedation in minor surgical and medical procedures
Adult: 10-20 mg given via IV inj over 2-4 min.
Child: ≥1 mth: 100-200 mcg/kg via IV inj over 2-4 min, to be given immediately before the procedure. Max: 5 mg (up to 12 yr); 20 mg (up to 18 yr).
Renal impairment: Dosage adjustments may be needed.
Intravenous
Adjunct in seizures
Adult: 10-20 mg at a rate of 5 mg/min, repeat if needed after 30-60 min. Once the seizures have been controlled, up to 3 mg/kg may be given via slow IV infusion over 24 hr to prevent recurrence.
Child: 1 mth-12 yr: 300-400 mcg/kg over 3-5 min, repeat after 10 min if needed.
Renal impairment: Dosage adjustments may be needed.
Rectal
Severe anxiety
Adult: As rectal solution: 500 mcg/kg, repeated after 12 hr if necessary. As suppository: 10-30 mg.
Elderly: Dose reduction may be required.
Renal impairment: Dosage adjustments may be needed.
Rectal
Premedication before anaesthesia
Adult: As a rectal solution: 500 mcg/kg.
Child: As a rectal solution: Dose is based on age. 1-3 yr: 5 mg; 3-12 yr: 5-10 mg; 12-18 yr: 10 mg.
Elderly: Dose reduction may be required.
Renal impairment: Dosage adjustments may be needed.
Rectal
Adjunct in seizures
Adult: As rectal gel: 200-500 mcg/kg, repeated after 4-12 hr if necessary. Rectal solution may be appropriate for febrile convulsions, status epilepticus and convulsions due to poisoning; suppositories are not suitable due to slow absorption. Typical dose for rectal solution: 500 mcg/kg, repeated every 12 hr if needed; use other anticonvulsive measures is recommended if convulsions are not controlled by the 1st dose.
Child: >2 yr: As rectal gel: 200-500 mcg/kg, repeated after 4-12 hr if necessary. Rectal solution may be appropriate for febrile convulsions, status epilepticus and convulsions due to poisoning; suppositories are not suitable due to slow absorption. Typical rectal solution dose for children >10 kg: 500 mcg/kg, repeated every 12 hr if needed; recommended to use other anticonvulsive measures if convulsions are not controlled by the 1st dose.
Elderly: Dose reduction may be required.
Renal impairment: Dosage adjustments may be needed.
Rectal
Muscle spasms
Adult: As a rectal solution: 500 mcg/kg, repeat every 12 hr if needed.
Child: >10 kg: As a rectal solution: 500 mcg/kg, repeat every 12 hr if needed.
Elderly: Dose reduction may be required.
Renal impairment: Dosage adjustments may be needed.

Special Populations: Max dose for elderly and debilitated patients is ½ the adult dose. Reduce dose in patients with liver or kidney dysfunction.

Reconstitution: Do not mix IV product with other medications.
Incompatibility: Y-site incompatibility: Dexmedetomidine, diltiazem, fluconazole, foscarnet, gatifloxacin, heparin, heparin with hydrocortisone sodium succinate, hetastarch, hydromorphone, potassium chloride, propofol, vecuronium, vitamin B complex with C, amphotericin B cholesteryl sulfate complex, atracurium, cefepime, linezolid, meropenem, pancuronium. Syringe incompatibility: Hydromorphone, nalbuphine, sufentanil, doxapram, glycopyrrolate, heparin. Admixture incompatibility: Furosemide, floxacillin, dobutamine, bleomycin, buprenorphine, doxorubicin, fluorouracil.
Contraindications
 Hypersensitivity; myasthenia gravis, preexisting CNS depression or coma, respiratory depression; acute pulmonary insufficiency or sleep apnoea syndrome; severe hepatic impairment; acute narrow angle glaucoma; children <6 mth (oral); pregnancy and lactation.
Warnings / Precautions
 Impaired renal and hepatic function, respiratory disease, organic cerebral changes, elderly, psychotic patients, epileptics, history of alcohol or drug addiction, impaired gag reflux, obese patients. May cause CNS depression. Discontinue treatment if patient develops psychiatric and paradoxical reactions. Caution when used in patients with depression or anxiety associated with depression, especially if patient has suicidal risk. May increase risk of falls. Safety and efficacy of the inj have not been established in children <1 mth of age. Safety and efficacy of oral use have not been established in children <6 mth of age. Safety and efficacy of rectal gel have not been established in children <2 yr of age. Abrupt withdrawal or large dose reduction may cause rebound or withdrawal symptoms.
Adverse Reactions
 Psychological and physical dependence with withdrawal syndrome, fatigue, drowsiness, sedation, ataxia, vertigo, confusion, depression, GI disturbances, changes in salivation, amnesia, jaundice, paradoxical excitation, elevated liver enzyme values; muscle weakness, visual disturbances, headache, slurring of speech and dysarthria, mental changes, incontinence, constipation, hypotension, tachycardia, changes in libido, pain and thrombophlebitis at inj site (IV).
Potentially Fatal: Respiratory and CNS depression, coma.
Overdose Reactions
 Symptoms: Somnolence, confusion, coma, diminished reflexes. Management: treatment is supportive and symptomatic. Gastric lavage may help to reduce absorption. As with the management of intentional overdosage with any drug, it should be borne in mind that multiple agents may have been ingested. Flumazenil may be used for the complete or partial reversal of the sedative effects of benzodiazepines. However, the prescriber should be aware of the risk of seizure associated with flumazenil treatment, especially in long-term benzodiazepine users and in cyclic antidepressant overdose. Refer to flumazenil full package insert before use. Dialysis is of limited value.
Drug Interactions
 Increased clearance of diazepam when used with phenytoin, carbamazepine and phenobarbital. Reversible deterioration of parkinsonism may occur when given together with levodopa. Combination with lithium may produce hypothermia. May need to reduce dose of narcotics when used concurrently.
Potentially Fatal: Phenothiazines, barbiturates, MAOIs potentiate action of diazepam. Additive CNS depressant effects with alcohol and CNS depressants or psychoactive medications. Mutual potentiation of action with analgesics, anaesthetics and some anticonvulsants.
See Below for More diazepam Drug Interactions
Lab Interactions
 False-positive urinary glucose determinations.
Food Interactions
 Grapefruit juice may increase serum levels and toxicity of diazepam. Levels may be reduced by St John's wort. Avoid valerian, kava kava, gotu kola and St John's wort.
Mechanism of Actions
 Diazepam is a long-acting benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant and amnestic properties. It increases neuronal membrane permeability to chloride ions by binding to stereospecific benzodiazepine receptors on the postsynaptic GABA neuron within the CNS and enhancing the GABA inhibitory effects resulting in hyperpolarisation and stabilisation.
Absorption: Readily and completely absorbed from the GI tract, peak plasma concentrations after 30-90 min (oral). Rapidly absorbed, peak plasma concentrations after 10-30 min (rectal).
Distribution: Readily crosses the blood-brain barrier; redistributed into fat depots and tissues. Protein-binding: 98-99%.
Metabolism: Extensively hepatic; converted to desmethyldiazepam, oxazepam and temazepam.
Excretion: Urine (as free or conjugated metabolites). Elimination half-life: Rapid (initial), 1-2 days (terminal), 2-5 days (desmethyldiazepam).
Administration
 May be taken with or without food.
Storage Conditions
 Intravenous: Store at 20-25°C. Oral: Store at 15-30°C. Parenteral: Store at 20-25°C. Rectal: Store below 25°C.
ATC Classification
 N05BA01 - diazepam ; Belongs to the class of benzodiazepine derivatives anxiolytics. Used in the management of anxiety, agitation or tension.
Storage
 Intravenous: Store at 20-25°C. Oral: Store at 15-30°C. Parenteral: Store at 20-25°C. Rectal: Store below 25°C.
Available As
  • Diazepam 10 mg
  • Diazepam 15 mg
  • Diazepam 2 mg
  • Diazepam 2.5 mg
  • Diazepam 25 mg
  • Diazepam 5 mg

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