HALCION
Clinical safety rating: caution
Comprehensive clinical and safety monograph for HALCION (HALCION).
Triazolam is a benzodiazepine that enhances the effect of GABA at the GABA-A receptor, increasing chloride ion conductance and causing neuronal hyperpolarization, leading to CNS depression.
| Metabolism | Primarily metabolized by CYP3A4 to alpha-hydroxytriazolam and 4-hydroxytriazolam, which are further conjugated and excreted renally. |
| Excretion | Primarily renal (80%) as conjugated metabolites; fecal (8%); unchanged drug <1%. |
| Half-life | Terminal elimination half-life is 1.5–5.5 hours (mean 2.5 hours). Short half-life minimizes next-day sedation. |
| Protein binding | 85–90% bound to albumin. |
| Volume of Distribution | 0.9–1.5 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral: 70–100% (mean 80%). |
| Onset of Action | Oral: 15–30 minutes to sleep induction. |
| Duration of Action | Duration of hypnotic effect is 4–6 hours (short-acting), suitable for sleep maintenance with minimal hangover. |
| Molecular Weight | 343.2 |
0.25 mg orally once daily at bedtime, maximum 0.5 mg per day.
| Dosage form | TABLET |
| Renal impairment | No specific adjustment recommended; use with caution in severe renal impairment (CrCl <10 mL/min) due to potential accumulation. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). In mild to moderate impairment (Child-Pugh A or B), reduce dose by 50% and monitor closely. |
| Pediatric use | Not recommended for use in pediatric patients under 18 years of age due to lack of safety and efficacy data. |
| Geriatric use | Initial dose 0.125 mg orally at bedtime; maximum 0.25 mg per day due to increased sensitivity and risk of falls, cognitive impairment, and residual sedation. |
| 1st trimester | Avoid; benzodiazepines are associated with increased risk of congenital malformations, particularly oral clefts, when used in first trimester. |
| 2nd trimester | Use only if clearly needed; may cause fetal sedation and withdrawal symptoms. |
| 3rd trimester | Avoid; use near delivery may cause floppy infant syndrome, respiratory depression, and withdrawal in neonates. |
Clinical note
Comprehensive clinical and safety monograph for HALCION (HALCION).
| Placental transfer | Crosses placenta; detected in fetal plasma at concentrations similar to maternal plasma. |
| Breastfeeding | Triazolam is excreted into breast milk in small amounts; however, due to risk of infant sedation and withdrawal, breastfeeding is not recommended. If necessary, use the lowest dose for the shortest duration. |
■ FDA Black Box Warning
Concomitant use with opioids may result in profound sedation, respiratory depression, coma, and death. Avoid use in patients with severe hepatic impairment.
| Serious Effects |
Known hypersensitivity to triazolam or other benzodiazepinesAcute narrow-angle glaucomaSevere hepatic impairmentConcurrent use with ketoconazole, itraconazole, or other potent CYP3A4 inhibitorsPregnancy (especially first and third trimesters)
| Precautions | Risk of dependence, tolerance, withdrawal reactions, amnesia, CNS depression, and impaired psychomotor function. Elderly patients at increased risk for falls and cognitive impairment. |
| Food/Dietary | Avoid grapefruit and grapefruit juice, as they inhibit CYP3A4 and increase triazolam levels. Limit caffeine intake, as it may counteract the hypnotic effect. Take on an empty stomach for faster onset, but with food if gastrointestinal upset occurs. |
Loading safety data…
| Lactation Rating |
| L3 (Moderately Safe) - limited data suggest risk but may be acceptable with caution. |
| Teratogenic Risk | Triazolam (Halcion) is a benzodiazepine classified as FDA Pregnancy Category X. First-trimester exposure is associated with an increased risk of congenital malformations, particularly cleft lip and palate. Second and third trimester exposure may cause fetal benzodiazepine syndrome, including hypotonia, lethargy, respiratory depression, and withdrawal symptoms in the neonate. Use is contraindicated during pregnancy. |
| Fetal Monitoring | Regular monitoring of maternal vital signs, sedation level, and respiratory status is advised. In neonates exposed in utero, monitor for signs of respiratory depression, hypotonia, poor feeding, and withdrawal symptoms such as irritability and tremors. |
| Fertility Effects | Benzodiazepines may affect reproductive function by altering hypothalamic-pituitary-adrenal axis and gonadal hormone secretion. In males, there have been reports of decreased libido and erectile dysfunction. In females, menstrual irregularities may occur. Effects on fertility in humans are not well established, but caution is warranted. |
| Clinical Pearls | Halcion (triazolam) is a short-acting benzodiazepine for insomnia. Avoid in patients with history of complex sleep behaviors (e.g., sleep-driving). Use lowest effective dose due to high potency and risk of anterograde amnesia. Contraindicated with concurrent CYP3A4 inhibitors (e.g., ketoconazole, ritonavir). Taper to discontinue to prevent rebound insomnia. |
| Patient Advice | Take exactly as prescribed; do not increase dose or duration. · Do not consume alcohol or other CNS depressants while taking this medication. · Avoid driving or operating machinery until you know how the drug affects you. · Report any unusual behaviors during sleep (e.g., eating, driving, making phone calls). · Do not stop abruptly; risk of withdrawal or rebound insomnia. |