Introduction
Restoril (temazepam) is a benzodiazepine medication primarily used for the short-term treatment of insomnia. As a Schedule IV controlled substance, it acts as a central nervous system depressant with sedative-hypnotic properties. First approved by the FDA in 1981, temazepam remains a commonly prescribed sleep medication despite increased awareness of benzodiazepine-related risks.
Mechanism of Action
Temazepam exerts its therapeutic effects through potentiation of gamma-aminobutyric acid (GABA) neurotransmission. It binds to specific sites on GABA-A receptors, enhancing GABA's inhibitory effects by increasing chloride ion conductance through the receptor channel. This hyperpolarizes neuronal membranes and reduces neuronal excitability throughout the central nervous system, particularly in the limbic system and reticular formation, resulting in sedative, hypnotic, anxiolytic, and muscle relaxant properties.
Indications
- FDA-approved: Short-term treatment of insomnia (generally 7-10 days)
- Off-label uses: Preoperative sedation, anxiety disorders (limited use due to dependency risk)
Dosage and Administration
Adults: 7.5-30 mg orally at bedtime- Initiate with lowest effective dose (typically 7.5-15 mg)
- Maximum recommended dose: 30 mg daily
Pharmacokinetics
- Absorption: Well absorbed from GI tract; bioavailability >96%
- Onset: 30-60 minutes
- Peak concentration: 2-3 hours post-administration
- Distribution: Protein binding: 96%; crosses blood-brain barrier and placenta; excreted in breast milk
- Metabolism: Hepatic via conjugation (glucuronidation) with minimal CYP450 involvement
- Elimination: Half-life: 8-20 hours; excreted primarily in urine (80%) as inactive metabolites
- Duration of action: 6-8 hours
Contraindications
- Hypersensitivity to temazepam or other benzodiazepines
- Acute narrow-angle glaucoma
- Pregnancy (especially first trimester)
- Severe respiratory insufficiency
- Sleep apnea syndrome
- Severe hepatic impairment
Warnings and Precautions
Black Box Warning:- Risk of abuse, misuse, addiction, and dependence
- Concurrent use with opioids may result in profound sedation, respiratory depression, coma, and death
- Elderly patients: Increased risk of falls, cognitive impairment, and paradoxical reactions
- Depression: May worsen depressive symptoms; monitor for emergence of suicidal ideation
- Respiratory disease: Use with extreme caution in patients with COPD, sleep apnea, or other respiratory conditions
- Tolerance and dependence: Can develop rapidly with prolonged use
- Withdrawal: Abrupt discontinuation may cause rebound insomnia, anxiety, and withdrawal symptoms
- Complex sleep behaviors: Reports of sleepwalking, sleep driving, and other complex behaviors
- Impaired alertness: May impair cognitive and motor performance; caution regarding driving and operating machinery
Drug Interactions
Major interactions:- Opioids: Increased CNS depression, respiratory depression, and sedation
- Alcohol: Potentiates CNS depressant effects
- Other CNS depressants: Barbiturates, antipsychotics, antidepressants, anticonvulsants, sedative antihistamines
- CYP3A4 inhibitors: Although minimal metabolism via CYP450, potent inhibitors may affect clearance
- Theophylline: May reduce temazepam efficacy
- Oral contraceptives: May increase temazepam concentrations
- Protease inhibitors: Potential increased sedation
Adverse Effects
Common (≥1%):- Drowsiness (14%)
- Dizziness (7%)
- Lethargy (5%)
- Headache (4%)
- Fatigue (3%)
- Nervousness (3%)
- Hangover effect
- Respiratory depression
- Anterograde amnesia
- Paradoxical reactions (agitation, aggression, hallucinations)
- Depression, suicidal ideation
- Complex sleep behaviors
- Physical and psychological dependence
- Withdrawal symptoms (anxiety, insomnia, tremors, seizures)
Monitoring Parameters
- Sleep patterns and effectiveness
- CNS depression: Level of alertness, cognitive function
- Signs of misuse, abuse, or dependence
- Respiratory function in patients with pulmonary disease
- Mood changes, emergence of depression
- Fall risk in elderly patients
- Withdrawal symptoms during taper
- Renal and hepatic function with long-term use
Patient Education
- Take exactly as prescribed, immediately before bedtime
- Allow 7-8 hours for sleep after taking medication
- Avoid alcohol and other CNS depressants
- Do not drive or operate machinery until drug effects are known
- Report any unusual behaviors during sleep (sleepwalking, eating, driving)
- Do not stop abruptly; taper under medical supervision
- Use non-pharmacological sleep hygiene measures concurrently
- Store securely to prevent misuse by others
- Be aware of potential next-day impairment
- Report signs of allergic reaction, mood changes, or worsening sleep
References
1. FDA Prescribing Information: Restoril (temazepam) capsules. 2022 2. Schutte-Rodin S, et al. Clinical guideline for the evaluation and management of chronic insomnia in adults. J Clin Sleep Med. 2008;4(5):487-504 3. Lieberman JA. Update on the safety considerations in the management of insomnia with hypnotics. Nature and Science of Sleep. 2017;9:157-165 4. Holbrook AM, et al. Meta-analysis of benzodiazepine use in the treatment of insomnia. CMAJ. 2000;162(2):225-233 5. American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2023 Updated AGS Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2023;71(7):2052-2081 6. Greenblatt DJ, et al. Clinical pharmacokinetics of temazepam. J Clin Psychiatry. 1982;43(12 Pt 2):12-16 7. Substance Abuse and Mental Health Services Administration. Clinical Guidance for Treating Pregnant and Parenting Women With Opioid Use Disorder and Their Infants. 2018
This information is for educational purposes only and does not constitute medical advice. Always consult with a healthcare professional for personalized medical guidance.