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Drug Reference

diazepam

benzodiazepine· Brands: Valium, Diazemuls, Stesolid, AnsiolinIMIVPOPR

Mechanism of action
Diazepam is a benzodiazepine that enhances the effect of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) at the GABA-A receptor. It binds to the benzodiazepine site, increasing the frequency of chloride channel opening, leading to hyperpolarization of the neuronal membrane and central nervous system depression. This results in anxiolytic, sedative, muscle relaxant, and anticonvulsant effects.
Pharmacokinetics
Diazepam is well absorbed from the gastrointestinal tract after oral administration, with peak plasma concentrations occurring within 1 to 2 hours. It is highly lipophilic and rapidly distributes into the central nervous system, followed by redistribution to adipose tissue. Diazepam is metabolised in the liver by cytochrome P450 enzymes, mainly CYP2C19 and CYP3A4, to active metabolites such as nordazepam and temazepam. The elimination half-life of diazepam is about 20 to 70 hours, and that of its active metabolites is even longer, leading to accumulation with repeated dosing. Excretion is primarily via the kidneys, mostly as conjugated metabolites.
Indications & dosing

Anxiety (short-term)

Short-term use only; avoid in elderly.

  • adult · PO: 2–10 mg 2-4 times daily · Short-term use only; avoid in elderly.

Muscle spasm

May be used adjunctively.

  • adult · PO: 5–10 mg TDS · May be used adjunctively.

Status epilepticus

Repeat once after 5-10 min if seizures continue.

  • adult · IV: 10 mg ONCE · Repeat once after 5-10 min if seizures continue.

Alcohol withdrawal

Tapering regimen; monitor for respiratory depression.

  • adult · PO: 10–20 mg Q2-4H PRN · Tapering regimen; monitor for respiratory depression.

Preoperative sedation

Given 30-60 min before procedure.

  • adult · IV: 5–10 mg ONCE · Given 30-60 min before procedure.
Contraindications & precautions
  • Myasthenia gravis · Relaxant effect on skeletal muscle may exacerbate weakness.
  • Severe respiratory insufficiency · Risk of respiratory depression and worsening of hypoxia/hypercapnia.
  • Sleep apnoea · Central apnoea may be aggravated by respiratory depressant effect.
  • Severe hepatic impairment · Metabolism impaired, increased risk of accumulation and encephalopathy.
  • Acute narrow-angle glaucoma · May increase intraocular pressure in undiagnosed closed-angle disease.
  • Hypersensitivity to benzodiazepines · Risk of allergy or cross-sensitivity.
  • Avoid abrupt withdrawal; taper dose gradually to prevent rebound, seizures, and delirium.
  • Use with caution in the elderly due to increased risk of falls, confusion, and paradoxical reactions.
  • Caution in patients with history of drug or alcohol misuse, as dependence risk is higher.
  • Reduce dose in hepatic impairment or in the elderly; monitor for excessive sedation.
  • Advise patients about avoidance of alcohol and other CNS depressants, including opioids.
  • Warn patients about impairment of driving ability and operating machinery.
Adverse effects
  • Drowsiness
  • Ataxia
  • Fatigue
  • Muscle weakness
  • Amnesia
  • Confusion
  • Paradoxical excitementserious
  • Respiratory depressionserious
  • Dependenceserious
Interactions
  • morphinemajorAvoid concomitant use unless absolutely necessary. If co-prescribed, prescribe the lowest effective doses for the shortest duration, monitor vital signs and level of consciousness frequently, and ensure that naloxone and resuscitative equipment are immediately available. Dose reduction of one or both agents may be required. Warn patients and caregivers about the signs of respiratory depression and excessive sedation.
  • methadonemajorAvoid concurrent use if possible. If unavoidable, use the lowest effective doses, prescribe with extreme caution, and advise the patient to avoid alcohol and other CNS depressants. Monitor for excessive sedation, respiratory rate, and oxygen saturation, particularly during initiation and dose adjustments. Consider prescribing naloxone for emergency use.
Renal & hepatic adjustment
  • eGFR 0+: No dose adjustment usually required. Use caution in severe renal impairment (CrCl < 30 mL/min) due to accumulation of active metabolites; consider dose reduction or prolonged dosing interval.
  • Hepatic impairment (mild): Use with caution; consider dose reduction as clearance may be reduced. Monitor for excessive sedation.
  • Hepatic impairment (moderate): Use at reduced dose; may need to reduce by 50% or more. Monitor for hepatic encephalopathy. Consider alternative therapy.
  • Hepatic impairment (severe): Avoid; risk of precipitating hepatic encephalopathy. (avoid)
Monitoring, pregnancy & toxicity
  • Respiratory rate · During initial therapy and with dose changes
  • Level of sedation · Regularly, especially in elderly or debilitated patients
  • Blood pressure · Monitor for hypotension, particularly with IV administration
  • Liver function tests (LFTs) · For long-term use
  • Signs of dependence or withdrawal · For long-term use
  • Falls · In elderly patients
  • Pregnancy: Avoid use during pregnancy, especially in the first trimester and late pregnancy. If treatment is essential, use the lowest effective dose for the shortest possible duration. Third-trimester exposure may cause neonatal sedation, hypotonia, and withdrawal symptoms. Consider alternative therapy where possible.
  • Toxicity: CNS depression: drowsiness, confusion, ataxia, slurred speech · Supportive care; monitor airway, breathing, and circulation. Assess consciousness.
  • Toxicity: Respiratory depression and hypotension · Administer oxygen, IV fluids, and mechanical ventilation if needed. Consider flumazenil for severe respiratory depression.
  • Toxicity: Paradoxical agitation (rare) · Observe and calm patient; avoid further doses. Consider flumazenil if severe.
  • Toxicity: Coma and severe CNS depression · Supportive care; flumazenil may be considered but not routinely due to seizure risk, especially in mixed overdoses.
Antidotes & reversal
  • Flumazenil · Benzodiazepine antagonist; seizure risk in TCA co-ingestion or chronic use - rarely given in ED.
Clinical notes
Diazepam is used in the treatment of anxiety, acute alcohol withdrawal, muscle spasms, and as an adjunct for seizures, including status epilepticus. It is also used for sedation before procedures. Because of its long half-life, it may accumulate, especially in the elderly or those with hepatic impairment, causing prolonged sedation. Tolerance and dependence can develop with long-term use, and abrupt withdrawal may lead to rebound seizures or withdrawal delirium. It should be used with caution in patients with respiratory insufficiency, myasthenia gravis, or pre-existing dependence on CNS depressants. Caution is needed when used with alcohol, opioids, or other sedatives. Flumazenil is a specific antagonist.

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BNF; local formulary