TEMAZEPAM
Clinical safety rating: avoid
Positive evidence of fetus risks but benefits may outweigh risks in some cases
Positive allosteric modulator of GABA-A receptors, enhancing the effect of GABA by increasing chloride ion influx, leading to neuronal hyperpolarization and sedation.
| Metabolism | Hepatic via CYP3A4 and glucuronidation; major metabolites include oxazepam and temazepam glucuronide. |
| Excretion | Renal excretion of conjugated metabolites (primarily as glucuronide) accounts for approximately 80% of an oral dose; fecal excretion accounts for about 12%; less than 1% is excreted unchanged in urine. |
| Half-life | Terminal elimination half-life is 8–20 hours in healthy adults (mean ~15 hours); may be prolonged in elderly (up to 50 hours) and in hepatic impairment (up to 40 hours); clinical context: typical dosing interval is 12–24 hours. |
| Protein binding | 96–98% bound to albumin; binding is concentration-dependent within therapeutic range. |
| Volume of Distribution | 0.8–1.5 L/kg (mean ~1.0 L/kg); clinical meaning: moderate distribution into tissues, including brain; higher in elderly. |
| Bioavailability | Oral: 91–98% (well absorbed, minimal first-pass metabolism); Intramuscular: 50–70% (erratic, not recommended). |
| Onset of Action | Oral: 30–60 minutes (subjective sedation); Intramuscular: erratic absorption, not recommended; Intravenous: 1–3 minutes (not available in US). |
| Duration of Action | Oral: 3–8 hours (hypnotic effect); clinical notes: residual sedation may last longer, especially in elderly; accumulation with repeated dosing leads to prolonged effect. |
| Molecular Weight | 300.35 |
10-20 mg orally at bedtime, up to 30 mg in severe insomnia.
| Dosage form | CAPSULE |
| Renal impairment | No adjustment required; temazepam is not significantly renally eliminated. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use. |
| Pediatric use | Not recommended for use in children <18 years due to lack of safety and efficacy data. |
| Geriatric use | Initiate at 5 mg orally at bedtime; maximum 15 mg. Use with caution due to increased risk of falls, cognitive impairment, and prolonged half-life. |
| 1st trimester | Human data suggest risk of cleft palate and malformations; avoid use unless absolutely necessary. |
| 2nd trimester | Use only if benefit outweighs risk; monitor for maternal and fetal effects. |
| 3rd trimester | Avoid due to risk of neonatal withdrawal, respiratory depression, hypotonia, and floppy infant syndrome. |
Clinical note
CNS depressants including alcohol and opioids increase sedation risk Abrupt discontinuation can cause withdrawal symptoms.
| Placental transfer | Temazepam crosses the placenta; degree of transfer is approximately 50% of maternal plasma levels in cord blood. |
| Breastfeeding | Temazepam is excreted into breast milk in small amounts; repeated exposure could lead to infant sedation or feeding difficulties. Use with caution, especially in preterm infants or with prolonged use. |
■ FDA Black Box Warning
Concomitant use of benzodiazepines with opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for patients for whom alternative treatment options are inadequate.
| Common Effects | Sedation |
| Serious Effects |
Hypersensitivity to temazepam or any benzodiazepineSevere hepatic impairmentMyasthenia gravisSevere respiratory insufficiencySleep apnea syndrome
| Precautions | Risk of respiratory depression, especially with other CNS depressants, Potential for abuse and dependence; may cause withdrawal symptoms upon discontinuation, May impair cognitive and motor function; caution in elderly and debilitated patients, Concomitant use with opioids increases risk of sedation and respiratory depression |
| Food/Dietary |
Loading safety data…
| Lactation Rating |
| L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Limited data; possible increased risk of oral clefts (odds ratio ~1.5). Second and third trimesters: Risk of floppy infant syndrome (hypotonia, respiratory depression) and neonatal withdrawal if used near term. Avoid use in pregnancy unless benefit clearly outweighs risk. |
| Fetal Monitoring | Monitor maternal sedation, respiratory rate (risk of respiratory depression). For prolonged use in late pregnancy, monitor neonatal adaptation (respiratory effort, tone, feeding) post-delivery. Assess for withdrawal symptoms in newborn if chronic maternal use. |
| Fertility Effects | No specific human studies; animal data show no significant impairment of fertility at clinically relevant doses. Potential for effects based on CNS depressant properties are theoretical. |
| Avoid consumption of grapefruit or grapefruit juice as it may increase temazepam levels and risk of excessive sedation. Alcohol is contraindicated due to additive CNS depressant effects. High-fat meals may delay absorption but do not significantly alter clinical effect. St. John's Wort may reduce temazepam efficacy by inducing glucuronidation. No other significant food interactions documented. |
| Clinical Pearls | Temazepam is a short-to-intermediate acting benzodiazepine with a half-life of 8-20 hours, making it suitable for sleep onset and maintenance insomnia without significant next-day sedation. Due to its low lipophilicity, it has minimal hepatic first-pass metabolism and is primarily conjugated by glucuronidation, reducing drug-drug interaction potential. Onset of action occurs within 30-60 minutes; advise patients to take immediately before bedtime. Avoid in severe hepatic impairment, narrow-angle glaucoma, and myasthenia gravis. Tolerance develops within 2-4 weeks; taper slowly to prevent withdrawal seizures. Use with caution in elderly due to fall risk and cognitive impairment. Co-administration with CNS depressants increases sedation; avoid alcohol. |
| Patient Advice | Take temazepam exactly 30-60 minutes before bedtime only when you have a full night (7-8 hours) to sleep. · Do not take with alcohol or other sedating medications as it can cause severe drowsiness, breathing problems, or overdose. · Temazepam may cause next-day drowsiness, dizziness, or impaired coordination; avoid driving or operating machinery until you know how it affects you. · Use the lowest effective dose for the shortest duration necessary (generally ≤4 weeks) to avoid dependence and tolerance. · Do not stop taking abruptly; a gradual dose reduction under medical supervision is required to prevent withdrawal symptoms (anxiety, insomnia, seizures). · Notify your doctor if you become pregnant, are planning pregnancy, or are breastfeeding; temazepam may harm a fetus or pass into breast milk. · Store in a secure place to prevent misuse or accidental ingestion by others. Dispose of unused tablets via medication take-back programs. |