Zaleplon | Pharmacology Mentor

Generic Name

Zaleplon

Brand Names

*Sonata*) is a short‑acting hypnotic of the benzodiazepine receptor agonist class used for the acute treatment of insomnia.

Mechanism

Zaleplon acts as a positive allosteric modulator at the γ‑aminobutyric acid A (GABAA) receptor complex.
It preferentially binds to the benzodiazepine site, enhancing GABA‑mediated chloride influx and neuronal hyperpolarization.
Its action is receptor‑selective, favoring a rapid onset without significant sedative, muscle‑relaxant, or antispasmodic effects typical of longer‑acting benzodiazepines.

Pharmacokinetics

Rapid absorption (Cmax ≈ 4–5 min post‑oral); onset of action within 15 min.
Very short elimination half‑life (~1 hour), which limits accumulation and next‑day residual sedation.
Metabolism: Hepatic oxidation via CYP3A4 and glucuronidation to inactive metabolites.
Excretion: Renal (≈ 50 % unchanged parent drug) and hepatic.
Food effect: Minimal; may be taken with or without food.

Indications

FDA‑approved for the acute treatment of insomnia characterized by difficulty falling asleep (not for maintenance of sleep or short‑term sleep).
Indicated for short‑term use of ≤ 3 weeks in patients with moderate to severe insomnia symptoms requiring a safe, rapid onset hypnotic.

Contraindications

Contraindicated in:
Severe respiratory insufficiency or obstructive sleep apnea.
Severe hepatic impairment.
Known hypersensitivity to any component of the formulation.
Warnings:
Risk of tolerance, dependence, and withdrawal after prolonged use.
Potential for paradoxical reactions (agitation, hostility).
Use with caution in elderly; increased sensitivity to CNS side‑effects.
Avoid concomitant use of alcohol or other CNS depressants due to additive sedation.

Dosing

Initial dose: 7.5 mg orally, taken 30 min before bedtime.
Maximum recommended dose: 15 mg per night, if needed (rare).
Route: One 7.5‑mg gelatin capsule (0.5 g) or 15‑mg tablet.
If delayed: Take if bed‑time delay exceeds 30 min; if not needed, omit dose.
Elderly: Start at the lowest effective dose; avoid > 15 mg per night.

Adverse Effects

Common (≤ 5 % incidence): somnolence, dizziness, headache, vivid dreams, impaired coordination, dysgeusia.
Serious (≤ 1 % incidence): respiratory depression, severe hypotension, anaphylactic reactions, complex sleep‑related behaviors (sleep‑walking, sleep‑driving), memory impairment, suicidal ideation.
Rare: Paradoxical agitation, aggression, hallucinations, and mood changes.

Monitoring

CNS status: Assess for excessive sedation, respiratory depression, agitation, or paradoxical reactions.
Sleep studies: In patients with suspected sleep apnea; repeat polysomnography if respiratory events worsen.
Renal/hepatic function: Baseline and periodic monitoring if disease or concomitant hepatotoxic/renotoxic agents are used.
Drug‑interaction surveillance: Avoid concurrent CYP3A4 inhibitors/inducers (e.g., ketoconazole, rifampin) and CNS depressants.

Clinical Pearls

Short half‑life minimizes carry‑over sedation; ideal for patients who need to remain alert the following morning.
Avoid alcohol: Alcohol potentiates GABAergic effect, increasing risk of respiratory depression.
No tolerance after 3 weeks: If insomnia persists beyond 3 weeks, consider discontinuation or switch to a non‑benzodiazepine hypnotic (e.g., zolpidem, eszopiclone).
Elderly caution: Even at low doses, elderly patients are at higher risk for falls, delirium, and next‑day confusion.
Withdrawal guidance: For patients treated > 2 weeks, taper by reducing the dose by 2 mg every 2–3 days or switch to a medication with a longer half‑life and lower abuse potential.
Drug interactions: Patients on proton pump inhibitors or antacids may have altered absorption; administer at least 2 hours apart.

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• Key pharmacology terms: *Zaleplon*, *GABAA receptor*, *benzodiazepine receptor agonist*, *insomnia*, *half‑life*, *CYP3A4 metabolism*, *CNS depression*, *tolerance*, *paradoxical reactions*.

*For detailed prescribing information, consult the FDA label and institutional protocols.*