RESTORIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RESTORIL (RESTORIL).
Temazepam is a benzodiazepine that enhances the effect of gamma-aminobutyric acid (GABA) at the GABA-A receptor, leading to increased chloride ion influx and hyperpolarization of the postsynaptic neuron, resulting in sedation and anxiolysis.
| Metabolism | Primarily hepatic via CYP3A4, glucuronidation; active metabolite (temazepam glucuronide) is renally excreted |
| Excretion | Renal (approximately 80% as conjugated metabolites, less than 2% unchanged); fecal (approximately 20%). |
| Half-life | Terminal elimination half-life is approximately 10-15 hours in healthy adults. Clinical context: Half-life may be prolonged in elderly patients and those with hepatic impairment; accumulation may occur with repeated dosing, leading to prolonged sedation. |
| Protein binding | Approximately 96% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Vd is approximately 0.8-1.3 L/kg. Clinical meaning: Indicates moderate tissue distribution; the drug is not extensively sequestered in tissues. |
| Bioavailability | Oral: 80-90% absorbed, with extensive first-pass metabolism; absolute bioavailability is approximately 80%. |
| Onset of Action | Oral: 20-30 minutes for hypnotic effect; 30-60 minutes for full sedative effect. |
| Duration of Action | 6-8 hours following a single oral dose. Clinical notes: Duration may be shorter in patients with rapid clearance; residual sedation may occur on awakening, especially with higher doses or in elderly. |
| Molecular Weight | 300.39 |
Oral: 15-30 mg once daily at bedtime, as needed for insomnia. Maximum dose: 30 mg/day.
| Dosage form | CAPSULE |
| Renal impairment | No specific dose adjustment recommended for renal impairment. Use with caution in severe renal impairment due to increased sensitivity. |
| Liver impairment | For mild to moderate hepatic impairment (Child-Pugh A/B): initial dose 15 mg at bedtime; titrate cautiously. Contraindicated in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Not recommended for pediatric patients due to lack of safety and efficacy data. |
| Geriatric use | Initial dose: 15 mg at bedtime. Use lowest effective dose due to increased risk of falls, cognitive impairment, and next-day sedation. |
| 1st trimester | Limited data; benzodiazepines are associated with increased risk of congenital malformations, particularly cleft lip/palate, when used in first trimester. Use only if clearly needed. |
| 2nd trimester | Use with caution; may cause fetal CNS depression and withdrawal. Avoid chronic use. |
| 3rd trimester | Avoid near term; risk of neonatal withdrawal syndrome, hypotonia, and respiratory depression. |
Clinical note
Comprehensive clinical and safety monograph for RESTORIL (RESTORIL).
| Placental transfer | Temazepam crosses the placenta with measurable fetal serum concentrations; transfer is rapid and accumulates in fetal tissue. |
| Breastfeeding | Temazepam is excreted into breast milk in low levels. Monitor infant for sedation, poor feeding, and weight gain. Chronic use may lead to accumulation. Consider alternative therapy, especially in neonates or preterm infants. |
■ FDA Black Box Warning
Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required.
| Serious Effects |
Hypersensitivity to temazepam or other benzodiazepinesSevere respiratory insufficiencySleep apnea syndromeMyasthenia gravisSevere hepatic impairment
| Precautions | Risk of respiratory depression, especially with concomitant CNS depressants; dependence and withdrawal; amnesia; complex sleep behaviors; worsening of depression or suicidal ideation; anaphylaxis/angioedema; avoid abrupt discontinuation |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase temazepam levels. Limit caffeine intake as it may reduce sedative effect. Alcohol should be avoided due to additive CNS depression. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Limited data; increased risk of oral clefts (RR 1.3-2.0) from case-control studies. Second trimester: Possible increased risk of congenital anomalies; avoid chronic use. Third trimester: Known risk of neonatal withdrawal syndrome (hypotonia, respiratory depression, feeding difficulties) and floppy infant syndrome. Chronic use may lead to neonatal sedation. |
| Fetal Monitoring | Maternal: Liver function, renal function, CBC. Fetal: Ultrasound for growth and anomalies if chronic use; neonatal assessment for withdrawal if used near term. |
| Fertility Effects | Menstrual irregularities and anovulation reported at high doses. No definitive evidence of impaired fertility in humans; animal studies show prolonged estrous cycle at doses 5x human therapeutic dose. |
| Clinical Pearls | RESTORIL (temazepam) is a benzodiazepine used for short-term insomnia. Due to its long half-life (8-20 hours), it may cause residual daytime sedation. Avoid in patients with severe hepatic impairment. Tolerance and dependence can develop; limit use to 7-10 days. Use with caution in elderly due to fall risk. |
| Patient Advice | Take exactly as prescribed; do not increase dose or duration. · Avoid alcohol and other CNS depressants. · May cause drowsiness; do not drive or operate machinery until you know how you react. · Do not stop abruptly; withdrawal seizures may occur. · Inform your doctor if you become pregnant or plan to breastfeed. |