TRIAZOLAM
Clinical safety rating: avoid
Positive evidence of fetus risks but benefits may outweigh risks in some cases
Triazolam is a benzodiazepine that binds to GABA-A receptors at the alpha-1 subunit, potentiating the inhibitory effects of GABA and increasing chloride ion influx, leading to neuronal hyperpolarization and sedation.
| Metabolism | Primarily metabolized by CYP3A4 to alpha-hydroxytriazolam (active) and 4-hydroxytriazolam (inactive), further conjugated to glucuronides. |
| Excretion | Primarily renal: approximately 80% as metabolites, less than 2% unchanged; biliary/fecal: minor (about 8-10%). |
| Half-life | 1.5-5.5 hours (mean 2-4 hours) in healthy adults; prolonged in hepatic cirrhosis and elderly. |
| Protein binding | 85-90%, primarily to serum albumin. |
| Volume of Distribution | 0.8-1.3 L/kg; indicates extensive tissue distribution and rapid redistribution from CNS. |
| Bioavailability | Oral: approximately 44% (range 25-65%) due to extensive first-pass metabolism. |
| Onset of Action | Oral: 15-30 minutes (full sedative effect). |
| Duration of Action | 1.5-3 hours for hypnotic effect; clinical duration short due to rapid redistribution and elimination. Avoid repeat dosing within same night. |
| Molecular Weight | 343.2 |
0.125-0.25 mg orally once daily at bedtime; maximum 0.5 mg/day.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment required; use with caution in severe impairment. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated. |
| Pediatric use | Not recommended for pediatric patients (safety and efficacy not established in children). |
| Geriatric use | Initial dose 0.125 mg orally at bedtime; may increase to 0.25 mg if needed. Avoid use due to increased risk of falls and cognitive impairment; limit to short-term use. |
| 1st trimester | Avoid due to potential teratogenic effects; studies suggest possible association with oral clefts. |
| 2nd trimester | Avoid as benzodiazepines may cause hypotonia, hypothermia, and respiratory depression in the neonate. |
| 3rd trimester | Avoid during labor; can lead to floppy infant syndrome, withdrawal symptoms, and respiratory depression. |
Clinical note
Strong CYP3A4 inhibitors are contraindicated due to risk of profound sedation Can cause anterograde amnesia and severe sedation.
| Placental transfer | Triazolam crosses the placenta; fetal levels may approach maternal levels. |
| Breastfeeding | Triazolam is excreted into breast milk in small amounts; however, long-acting metabolites may accumulate. Avoid breastfeeding due to risks of neonatal sedation, poor feeding, and withdrawal. |
■ FDA Black Box Warning
Triazolam has a boxed warning for concomitant use with opioids due to risk of profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for patients without alternative treatment options.
| Common Effects | Sedation |
| Serious Effects |
Hypersensitivity to triazolam or other benzodiazepinesAcute narrow-angle glaucomaSevere hepatic impairmentConcurrent use with itraconazole, ketoconazole, or nefazodonePregnancy
| Precautions | Risk of CNS depression, impaired motor function, and amnesia, Anterograde amnesia may occur, Worsening of depression or suicidal thoughts, Respiratory depression in patients with compromised respiratory function, Dependence and withdrawal syndrome with prolonged use, Paradoxical reactions (e.g., agitation, hallucinations), Elderly patients at increased risk of falls and cognitive impairment |
| Food/Dietary |
Loading safety data…
| Lactation Rating |
| L4 (Hazardous) - Avoid |
| Teratogenic Risk | Triazolam is a benzodiazepine classified as Pregnancy Category X. In the first trimester, there is evidence of increased risk of congenital malformations, particularly cleft lip and palate, when used during early pregnancy. Use during the second and third trimesters may lead to fetal exposure and potential neonatal withdrawal symptoms, including hypotonia, respiratory depression, and floppy infant syndrome. There is also risk of neonatal sedation and withdrawal if used near term or during labor. Avoid use in pregnancy unless absolutely necessary for seizure disorders. |
| Fetal Monitoring | Maternal: Monitor for excessive sedation, dizziness, ataxia, and cognitive impairment. Assess for signs of dependence or withdrawal. Fetal: If exposure occurs during pregnancy, monitor fetal growth and development; consider detailed ultrasound for structural anomalies if first trimester exposure. Neonatal: Observe for symptoms of hypotonia, respiratory depression, and withdrawal (e.g., irritability, tremors, hypertonia) at birth. |
| Fertility Effects | Triazolam may affect fertility in males and females. In animal studies, high doses caused decreased fertility and impaired reproductive performance. In humans, benzodiazepines may disrupt menstrual cyclicity and spermatogenesis, but clinical data are limited. Use may interfere with hormonal balance and ovulation. |
| Grapefruit and grapefruit juice may increase triazolam levels; avoid concurrent intake. High-fat meals may delay absorption but do not significantly affect overall exposure. No specific dietary restrictions other than limiting caffeine if insomnia persists. |
| Clinical Pearls | Triazolam is a short-acting benzodiazepine with rapid onset (15-30 min) and elimination half-life of 1.5-5.5 hours. Use lowest effective dose for shortest duration (≤7-10 days) to minimize tolerance and dependence. Avoid in elderly due to increased fall risk and cognitive impairment. Contraindicated in severe hepatic impairment, myasthenia gravis, narrow-angle glaucoma, and concurrent use with CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, nefazodone, and some HIV protease inhibitors). Rebound insomnia may occur upon discontinuation; taper gradually. Not recommended for children under 18 years. |
| Patient Advice | Take exactly as prescribed; do not increase dose or duration without consulting your doctor. · Do not consume alcohol or other central nervous system depressants (e.g., opioids, other sedatives) while taking this medication. · Do not drive or operate heavy machinery until you know how triazolam affects you; drowsiness and dizziness are common. · You may experience amnesia or unusual behaviors (e.g., sleep-driving, making phone calls) if you do not get enough sleep after taking the medication. · Do not stop abruptly; withdrawal symptoms including anxiety, irritability, and insomnia may occur. Follow your doctor's tapering schedule. · Store in a secure place away from children; misuse can cause severe harm or death. · Inform your doctor of all medications you take, including over-the-counter drugs and herbal supplements, to avoid interactions. |