Introduction
Temazepam is a benzodiazepine derivative primarily used for the short-term treatment of insomnia. Marketed under brand names including Restoril, it belongs to the class of central nervous system depressants and is classified as a Schedule IV controlled substance in the United States due to its potential for abuse and dependence.
Mechanism of Action
Temazepam exerts its therapeutic effects through potentiation of the gamma-aminobutyric acid (GABA) neurotransmitter system. It binds to specific sites on the GABA-A receptor complex, enhancing GABAergic inhibition throughout the central nervous system. This binding increases the frequency of chloride channel opening, resulting in hyperpolarization of neuronal membranes and reduced neuronal excitability, producing sedative, hypnotic, anxiolytic, and muscle relaxant effects.
Indications
- Short-term treatment of insomnia (generally 7-10 days)
- Difficulty falling asleep
- Frequent nocturnal awakenings
- Early morning awakenings
Dosage and Administration
Adults: 7.5-30 mg orally at bedtime Geriatric patients or debilitated patients: Initial dose of 7.5 mg until response determined Duration: Treatment should not exceed 2-3 weeks for insomnia Special Populations:- Hepatic impairment: Reduce dose and monitor closely
- Renal impairment: Use with caution
- Pediatrics: Safety and efficacy not established
Pharmacokinetics
Absorption: Well absorbed from GI tract, peak plasma concentrations reached in 2-3 hours Distribution: 96% protein-bound, crosses blood-brain barrier and placenta Metabolism: Hepatic metabolism via glucuronide conjugation (CYP450 independent) Elimination: Primarily renal excretion (80%) as inactive metabolites, elimination half-life 8-20 hoursContraindications
- Hypersensitivity to temazepam or other benzodiazepines
- Acute narrow-angle glaucoma
- Pregnancy (especially first trimester)
- Severe respiratory insufficiency
- Severe hepatic impairment
- Myasthenia gravis
- Sleep apnea syndrome
Warnings and Precautions
Boxed Warning: Risk of abuse, misuse, addiction, physical dependence, and withdrawal reactions- Paradoxical reactions (excitation, agitation) may occur
- Impaired coordination and cognitive function
- Depression and suicidal ideation
- Respiratory depression, especially in patients with pulmonary disease
- Next-day impairment of psychomotor performance
- Complex sleep behaviors (sleep-walking, sleep-driving)
- Elderly patients at increased risk of falls and cognitive impairment
Drug Interactions
Contraindicated combinations:- Opioids (increased risk of respiratory depression, sedation, death)
- Alcohol (additive CNS depression)
- Other CNS depressants (barbiturates, antipsychotics, antidepressants)
- CYP3A4 inhibitors (ketoconazole, clarithromycin) - may increase levels
- CYP3A4 inducers (rifampin, carbamazepine) - may decrease levels
- Oral contraceptives may decrease clearance
Adverse Effects
Common (≥1%):- Drowsiness
- Dizziness
- Lethargy
- Headache
- Fatigue
- Respiratory depression
- Anterograde amnesia
- Depression
- Suicidal ideation
- Physical and psychological dependence
- Withdrawal syndrome upon discontinuation
- Complex sleep behaviors
Monitoring Parameters
- Efficacy: Sleep latency, total sleep time, awakenings
- Safety: Respiratory rate, oxygen saturation (in at-risk patients)
- Cognitive and psychomotor function
- Signs of misuse, abuse, or dependence
- Withdrawal symptoms upon discontinuation
- Fall risk assessment in elderly patients
- Periodic liver function tests with long-term use
Patient Education
- Take exactly as prescribed, do not increase dose without consultation
- Avoid alcohol and other CNS depressants
- May cause drowsiness - do not drive or operate machinery until effects known
- Do not discontinue abruptly - follow taper schedule
- Report any unusual thoughts or behaviors, especially suicidal ideation
- Use non-pharmacological sleep hygiene measures concurrently
- Not recommended for long-term use
- Store securely to prevent misuse by others
- Inform all healthcare providers of temazepam use
References
1. FDA Prescribing Information: Restoril (temazepam) capsules 2. Schatzberg AF, Nemeroff CB. The American Psychiatric Association Publishing Textbook of Psychopharmacology. 5th ed. American Psychiatric Association Publishing; 2017. 3. Brunton LL, Hilal-Dandan R, Knollmann BC. Goodman & Gilman's: The Pharmacological Basis of Therapeutics. 13th ed. McGraw-Hill Education; 2017. 4. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Insomnia. 2022. 5. Sateia MJ, Buysse DJ, Krystal AD, et al. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med. 2017;13(2):307-349. 6. Greenblatt DJ, Harmatz JS, Shapiro L, et al. Pharmacokinetics and pharmacodynamics of benzodiazepines. In: Benzodiazepines in Clinical Practice. Raven Press; 1993.