Generic Name

Temazepam

Mechanism

Temazepam is a short‑acting benzodiazepine that binds to the γ‑aminobutyric acid‑A (GABA‑A) receptor complex as a positive allosteric modulator. By enhancing GABA‑mediated chloride influx, it increases neuronal membrane hyperpolarization, producing rapid onset of anxiolytic, hypnotic, anticonvulsant, and muscle‐relaxant effects[^1]. The drug’s affinity is highest for receptors containing the α1 subunit, accounting for its predominance as a hypnotic agent.

Pharmacokinetics

• Absorption: Rapid oral absorption; peak plasma concentrations occur 2–3 h post‑dose.
• Bioavailability: ~70 % (food can delay absorption by ~30 min).
• Distribution: Widely distributed; 70–80 % protein‑bound; crosses the blood‑brain barrier readily.
• Metabolism: Hepatic oxidative metabolism via cytochrome P450 (primarily CYP3A4 and CYP2C19) to inactive N‐hydroxy and N‑acetyl metabolites.
• Excretion: Renal elimination of metabolites; unchanged drug excreted minimally.
• Half‑life: 8–20 h (average 9–11 h); variable in elderly and patients with hepatic impairment.
• Drug Interactions: Concomitant use with CYP3A4 inhibitors (ketoconazole) or inducers (rifampin) alters plasma levels; CNS depressants (opioids, alcohol) potentiate sedative effects.

Indications

• Primary: Short‑term treatment of insomnia characterized by difficulty initiating sleep.
• Secondary: Brief management of withdrawal delirium secondary to benzodiazepine discontinuation (under specialist supervision).

Contraindications

• Contraindicated in:
• Severe respiratory insufficiency (COPD, sleep apnea).
• Porphyria.
• History of hypersensitivity to benzodiazepines.
• Warnings:
• Dependence and tolerance can develop after >4 weeks; recommend discontinuation plan.
• Elderly: increased risk of falls, psychomotor impairment, paradoxical agitation; dose reduction usually warranted.
• Pregnancy: Category C; use only when benefits outweigh potential risks.
• Hepatic dysfunction: prolonged half‑life; use lowest effective dose.

Dosing

• Administration route: Oral (tablet, oral solution). Take 30 min before bedtime.
• Use limitations: Limit to 2–4 weeks; consider tapering with gradual dose reduction to prevent rebound insomnia.

Adverse Effects

Common
• Somnolence, drowsiness, dizziness
• Dry mouth, blurred vision
• Muscular weakness, ataxia
• Cognitive blurring, memory impairment

Serious
• Hypersensitivity reactions (rash, anaphylaxis)
• Respiratory depression (especially with concurrent CNS depressants)
• Paradoxical agitation, aggression in elderly
• Delirium or psychotic symptoms
• Withdrawal syndrome (irritability, insomnia, tremor) if abruptly discontinued after prolonged use

Monitoring

• Sleep quality: Patient sleep diary or actigraphy.
• Cognitive/functional status: Mini‑Cog or Montreal Cognitive Assessment (MCA) in elderly.
• Adverse reactions: Check for signs of dependence, tolerance, or paradoxical agitation.
• Laboratory: Routine liver panels when hepatic impairment suspected; blood alcohol level if concurrent alcohol use.
• Drug interactions: Review concurrent medications for CYP3A4 modulators or CNS depressants.

Clinical Pearls

• Use a “short‑acting” benzodiazepine like temazepam** for insomnia to avoid next‑day accumulation; its half‑life limits daytime sedation.
• Start at the lowest effective dose: 10 mg for most adults reduces risk of oversedation while maintaining hypnotic efficacy.
• Avoid abrupt cessation: Even after 2–3 weeks, tapering (e.g., 5 mg every 2–4 days) minimizes rebound insomnia and withdrawal symptoms.
• Elderly safety check: Involve a fall‑prevention protocol; consider “night‑time” dosing with a “sleep‑on-the‑first” approach (dose prior to bedtime).
• Drug‑interaction primer: A patient taking a strong CYP3A4 inducer may need a *lower dose* until the inducer is discontinued.
• Behavioral cue: If a patient complains of “foggy” memory or slowed reaction, consider switching to a non‑benzodiazepine hypnotic or CBT‑I.

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