Generic Name

Halcion

Mechanism

• Enhances GABAA receptor activity: Binds to the benzodiazepine site on GABAA receptors, increasing chloride influx and hyperpolarizing neuronal membranes.
• Rapid onset and short half‑life: Peak plasma concentrations within 10–30 min; terminal half‑life ~1–2 h, accounting for its effectiveness for sleep onset but limited duration, minimizing next‑day sedation.
• High affinity for α1 subunit: Confers strong hypnotic effect with relatively less anxiolytic or anticonvulsant activity compared to longer‑acting benzodiazepines.

Pharmacokinetics

• Absorption: Oral bioavailability ~70%; first‑pass metabolism in the liver.
• Distribution: Highly protein‑bound (≈97%); crosses placenta and blood‑brain barrier.
• Metabolism: Oxidative hepatic CYP3A4 predominantly; minor glucuronidation.
• Elimination: Renal excretion of metabolites; total body clearance ≈5 L/h.
• Duration of action: 4–6 h; sedative effect usually lasts 2–4 h.
• Drug interactions: Strong CYP3A4 inhibitors (ketoconazole, clarithromycin) ↑ plasma levels; inducers (rifampin, carbamazepine) ↓ efficacy.

Indications

• Short‑term treatment of insomnia (2–4 weeks) characterized by difficulty falling asleep.
• Pre‑operative anxiolysis as adjunct to general anesthesia.
• Management of severe agitation in psychiatric or neurological emergencies (off‑label).

Contraindications

• Absolute contraindications:
• Allergy to benzodiazepines or any ingredient.
• Severe respiratory insufficiency or COPD exacerbations.
• Acute intoxication or overdose.
• Advanced hepatic disease (Child‑Pugh B/C).
• Relative contraindications:
• Elderly patients, pregnancy (especially 1st trimester), lactation.
• History of substance abuse or dependence.
• Severe myasthenia gravis, neuromuscular disorders.
• Warnings:
• Risk of sleep‑related breathing disorders (apnea, hypoventilation).
• Potential for cognitive impairment, impaired coordination, or paradoxical agitation.
• Use caution with bupropion or other serotonergic agents due to seizure risk.

Dosing

• Administration: Oral tablets; may be swallowed whole.
• Duration of therapy: ≤4 weeks; longer use risks tolerance, dependence, and rebound insomnia.
• Discontinuation: Gradual taper over 1–2 weeks to avoid withdrawal symptoms.

Adverse Effects

Common (≤10%)
• Somnolence, dizziness, impaired concentration
• Tinnitus, transient memory loss (anterograde amnesia)
• Dry mouth, blurred vision

Serious (≤1%)
• Paradoxical agitation, aggression, or disinhibition
• Severe respiratory depression (especially with concomitant opioids, alcohol)
• Hypersensitivity reactions (rash, urticaria, anaphylaxis)
• Dependence or withdrawal syndrome—spasms, insomnia, anxiety, seizures

Monitoring

• Sleep latency and quality: Sleep diaries or actigraphy.
• Cognitive function in elderly: MMSE or MoCA periodically.
• Breathing: Pulse oximetry if underlying sleep apnea.
• Drug levels/interactions: Consider checking CYP3A4 inhibitors or inducers.
• Dependence assessment: Regular evaluation of withdrawal potential, especially after >2 weeks therapy.

Clinical Pearls

• “No Residual Sedation”: Triazolam’s short half‑life makes it ideal for patients who need rapid sleep onset but must remain alert the next day (e.g., night‑shift workers).
• Avoid “Triazolam + Alcohol”: Even modest doses of alcohol precipitate severe respiratory depression; counsel patients strictly.
• Use a “Sleep Hygiene” toolkit: Pair Halcion with non‑pharmacologic interventions (dark, cool room, CBT‑I) to reduce total dose and duration needed.
• Taper is Key: Withdraw by reducing the dose by 25–50 % weekly to minimize rebound insomnia and withdrawal.
• Elderly Precautions: Start at half the adult dose; monitor for orthostatic hypotension and falls.
• Pregnancy‑safe Alternatives: If treatment is needed during pregnancy, consider zolpidem (if short‑acting) or non‑benzodiazepine hypnotics with better safety profiles.

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• *For the most current dosing recommendations and safety data, refer to the approved prescribing information and your institution’s formularies.*