Introduction
Quazepam is a benzodiazepine derivative with hypnotic properties, approved by the FDA in 1985 for the treatment of insomnia. It is classified as a Schedule IV controlled substance due to its potential for dependence and abuse. As a fluorinated benzodiazepine, quazepam exhibits unique pharmacokinetic properties that distinguish it from other medications in its class.
Mechanism of Action
Quazepam exerts its therapeutic effects through potentiation of gamma-aminobutyric acid (GABA) neurotransmission. It binds selectively to benzodiazepine receptor sites on the GABA-A receptor complex, enhancing GABA's inhibitory effects by increasing chloride ion conductance through neuronal membranes. This hyperpolarizes neurons and reduces neuronal excitability, resulting in sedative, hypnotic, anxiolytic, and muscle relaxant properties.
Indications
- Short-term treatment of insomnia characterized by difficulty falling asleep, frequent nocturnal awakenings, and/or early morning awakenings
- Not indicated for chronic use (generally limited to 7-10 days of continuous therapy)
Dosage and Administration
Adults: 15 mg orally at bedtime Elderly/debilitated patients: Initial dose of 7.5 mg at bedtime Maximum duration: 7-10 days of continuous therapy Administration: Should be taken immediately before bedtime due to rapid onset of actionPharmacokinetics
Absorption: Well absorbed from GI tract, peak plasma concentrations reached in approximately 2 hours Distribution: Highly protein-bound (95%), crosses blood-brain barrier and placenta Metabolism: Extensively metabolized in liver via oxidative pathways (CYP3A4) to active metabolites including 2-oxoquazepam and N-desalkyl-2-oxoquazepam Elimination: Primarily renal excretion (62%) with some fecal elimination; elimination half-life of parent drug is 25-41 hours, while active metabolites have half-lives up to 73 hours Special populations: Reduced clearance in elderly patients and those with hepatic impairmentContraindications
- Hypersensitivity to quazepam or other benzodiazepines
- Pregnancy (especially first trimester)
- Severe respiratory insufficiency
- Sleep apnea syndrome
- Severe hepatic impairment
- Concurrent use with strong CYP3A4 inhibitors
Warnings and Precautions
Boxed Warning: Risk of dependence, withdrawal symptoms, and abuse potential- May cause daytime drowsiness and impair cognitive function
- Risk of complex sleep behaviors including sleep-walking, sleep-driving, and other complex behaviors
- Potential for additive CNS depression with alcohol and other CNS depressants
- Withdrawal symptoms may occur after discontinuing treatment, especially with prolonged use
- Paradoxical reactions including excitement, agitation, and aggression may occur
- Caution in patients with depression, history of drug abuse, or respiratory disorders
Drug Interactions
Major interactions:- Alcohol: Additive CNS depression
- Opioids: Increased risk of respiratory depression
- Other CNS depressants: Enhanced sedative effects
- CYP3A4 inhibitors (ketoconazole, itraconazole): Increased quazepam levels
- CYP3A4 inducers (rifampin, carbamazepine): Decreased quazepam levels
- Antipsychotics, antidepressants: Enhanced sedative effects
- Anticonvulsants: Potential additive effects
Adverse Effects
Common (≥1%):- Somnolence
- Headache
- Fatigue
- Dizziness
- Dry mouth
- Gastrointestinal disturbances
- Respiratory depression
- Complex sleep behaviors
- Anterograde amnesia
- Dependence and withdrawal syndrome
- Paradoxical reactions
- Severe allergic reactions
Monitoring Parameters
- Sleep patterns and effectiveness
- Daytime alertness and cognitive function
- Signs of dependence or abuse
- Respiratory function in susceptible patients
- Hepatic and renal function with long-term use
- Mental status changes
- Withdrawal symptoms upon discontinuation
Patient Education
- Take immediately before bedtime
- Avoid alcohol and other CNS depressants
- Do not operate machinery or drive until effects are known
- Report any unusual behaviors during sleep
- Do not discontinue abruptly without medical supervision
- Use only as prescribed due to risk of dependence
- Inform healthcare providers of all medications being taken
- Not recommended during pregnancy or breastfeeding
References
1. FDA Prescribing Information: Quazepam (Doral) 2. American Academy of Sleep Medicine. (2017). Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults. Journal of Clinical Sleep Medicine. 3. Greenblatt DJ, et al. (1989). Clinical pharmacokinetics of quazepam. Journal of Clinical Pharmacology. 4. Scharf MB, et al. (1990). A multicenter, placebo-controlled study evaluating quazepam in the treatment of chronic insomnia. Journal of Clinical Psychiatry. 5. Ashton H. (2005). The diagnosis and management of benzodiazepine dependence. Current Opinion in Psychiatry. 6. Griffiths RR, et al. (1990). Relative abuse liability of benzodiazepines in humans. Drug and Alcohol Dependence.
Note: This information is for educational purposes only and should not replace professional medical advice. Always consult with a healthcare provider for personalized medical guidance.