Generic Name

Quazepam

Mechanism

• Positive allosteric modulator of the GABA‑A receptor – binds to the benzodiazepine ligand site, increasing the frequency of chloride channel opening triggered by endogenous GABA.
• Enhances inhibitory synaptic transmission in the limbic system and thalamus, lowering neuronal excitability and facilitating sleep onset.
• Lower intrinsic efficacy at the receptor accounts for its relatively mild anxiolytic and muscle‑relaxant effects.

Pharmacokinetics

• Absorption – rapidly absorbed; peak plasma concentration at 1–2 h after oral dosing. Bioavailability ~45 % due to first‑pass metabolism.
• Protein binding – ~95 %; mainly to albumin.
• Metabolism – Phase I oxidation (CYP3A4) → 1‑hydroxy‑Quazepam; Phase II glucuronidation. Minimal active metabolites are formed.
• Elimination – Renal excretion (≈35 %) and biliary excretion; elimination half‑life ~2–3 h (short‑acting).
• Drug interactions – CYP3A4 inhibitors (ketoconazole, clarithromycin) increase plasma levels; CYP3A4 inducers (rifampin, phenobarbital) decrease exposure.

Indications

• Acute insomnia – primarily for sleep initiation in adults; short‑term use (≤4 weeks).
• Anxiety disorders – occasional short‑term adjunct for severe agitation or panic episodes (off‑label).

Contraindications

• Contraindications – hypersensitivity to benzodiazepines; severe respiratory insufficiency; sleep apnea; acute narrow‑angle glaucoma; hepatic failure; age <18 years (safety not established).
• Warnings –
• Potential for tolerance, dependence, and withdrawal syndrome.
• Respiratory depression in opioid users or sedation with concomitant CNS depressants.
• Cognitive and psychomotor impairment – advise against operating machinery until the effect wears off.
• Elderly patients: increased sensitivity; higher risk of falls and delirium.

Dosing

• Begin with the lowest effective dose; shorten treatment duration if insomnia persists beyond 4 weeks.
• Discontinue gradually to avoid rebound insomnia.

Adverse Effects

• Common: drowsiness, dizziness, impaired coordination, transient memory impairment, dry mouth, constipation.
• Serious:
• Respiratory depression (especially with opioids or alcohol).
• Severe CNS depression, retrospective amnesia.
• Paradoxical agitation or hallucinations (rare).
• Dependence with prolonged use >4 weeks; withdrawal includes insomnia, tremor, seizures.

Monitoring

• Clinical – assess sleep onset latency, sleep quality, daytime alertness, mood, and depressive symptoms.
• Laboratory – routine liver function tests if long‑term therapy or concomitant hepatotoxic drugs.
• Safety – monitor for signs of abuse (e.g., requesting dose increases, early refill requests).
• Practical – advise patients to avoid driving or operating machinery for at least 6 h post-dose.

Clinical Pearls

• *Short‑acting advantage*: Quazepam’s rapid elimination makes it ideal for patients needing quick sleep onset without prolonged residual sedative effects.
• *Avoid “sleep‑in‑multiple‑dose” schedule*: A single bedtime dose limits accumulation; higher multiples precipitate retrograde amnesia.
• *Rebound insomnia*: Abrupt cessation often provokes rebound insomnia; taper 0.5 mg every 3–5 days to mitigate.
• *Drug‑driven sedation*: When prescribed with opioids or sedative‑hypnotics, concurrent respiratory depression risk doubles; monitor pulse oximetry if clinically indicated.
• *Pregnancy*: Category B; use only if benefits outweigh potential fetal risk; avoid during 3rd trimester if possible.
• *Legal status*: Quazepam is a Schedule IV controlled substance in the U.S.; prescription refills require physician’s approval and monitoring of patient adherence.

*Reference keywords integrated:* Quazepam, benzodiazepine, GABA-A receptor modulator, insomnia, short‑acting hypnotic, respiratory depression, withdrawal, dosage titration, clinical pearls.