Generic Name

Ambien (Zolpidem)

Mechanism

• Selective GABA‑A α1 subunit agonist: binds the benzodiazepine site on the GABA‑A receptor, enhancing chloride influx.
• Rapid onset (≈30 min) and moderate duration (~1–2 h) favor brief hypnotic effect without residual sedation.
• Minimal affinity for α2–α4 subunits → reduced anxiolytic, muscle‑relaxant, or anticonvulsant actions compared with non‑selective benzodiazepines.

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Pharmacokinetics

• Absorption: Peak plasma concentrations within 1 h post‑dose.
• Distribution: 25–30 % protein‑bound; large volume of distribution (~22 L/kg).
• Metabolism: Primarily hepatic via CYP3A4/3A5 → N‑oxide, glucuronide, and other minor pathways.
• Elimination: ~75 % renal excretion of metabolites; terminal half‑life 2–3 h (shorter in older adults).
• Drug interactions: Strong CYP3A4 inhibitors (ketoconazole, clarithromycin) ↑ concentration; CYP3A4 inducers (rifampin, carbamazepine) ↓ levels.

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Indications

• Short‑term treatment (≤4 weeks) of insomnia characterized by difficulty falling asleep.
• Off‑label: Sedation for procedural anxiolysis, acute agitation (rare).

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Contraindications

• Contraindicated in severe hepatic insufficiency (Child‑Pugh C) and uncontrolled respiratory disorders (COPD, severe OSA).
• Warnings:
• Abuse, dependence—particularly in patients with substance‑use disorders.
• Risk of next‑day impairment (impaired driving, complex tasks).
• Paradoxical reactions (aggression, hallucinations) in elderly or patients on serotonergic agents.
• Supine position may precipitate REM‑behavior disorder.

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Dosing

• Initial dose:
• Men: 5 mg (oral).
• Women: 2.5 mg (oral).
• Maximum: 10 mg once nightly.
• Timing: 30 min before sleep, avoid alcohol and concomitant CNS depressants.
• Re‑titration: Increase by 2.5–5 mg *only under close supervision* (dose‑related insomnia).

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Adverse Effects

• Common
• Somnolence, dizziness, headache, nausea, dry mouth.
• Serious
• Memory loss or transient amnesia.
• Complex sleep behaviors (sleep‑walking, driving while asleep).
• Respiratory depression in OP‑independent patients.
• Severe allergic reactions (rare).

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Monitoring

• Sleep diaries and polysomnography if REM‑behavior disorder suspected.
• Liver function tests at baseline and every 3–4 weeks if hepatic function is borderline.
• Cognitive/Alertness: assess driving/operating‑equipment safety.
• Screen for substance‑abuse history at each visit.

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Clinical Pearls

• Administer with a full breakfast to color the gastrointestinal tract; a full stomach delays absorption in a predictable manner, useful in managing delayed‑sleep phase.
• Use the lowest effective dose for the shortest duration to limit insomnia‑induced rebound and tolerance.
• Avoid using the same generic formula overnight; formulations containing “sublingual” may produce faster onset and higher peak levels, increasing the risk of hangover effects.
• Elderly patients: consider 1.25–2.5 mg (men) and 0.5–1.25 mg (women) to accommodate increased half‑life and sensitivity.
• Drug–Drug Interaction tip: a moderate CYP3A4 inhibitor can increase plasma levels by up to 4‑fold, necessitating a 50 % dose reduction or postponement.

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