Introduction
Halcion (triazolam) is a short-acting benzodiazepine derivative primarily used for the short-term treatment of insomnia. As a Schedule IV controlled substance, it has a high potential for dependence and abuse. First approved by the FDA in 1982, Halcion remains an important therapeutic option when used appropriately for brief periods under careful medical supervision.
Mechanism of Action
Triazolam enhances the effect of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. It binds to specific sites on the GABA-A receptor complex, increasing the frequency of chloride channel opening events. This hyperpolarizes neuronal membranes and reduces neuronal excitability, resulting in sedative, hypnotic, anxiolytic, and muscle relaxant effects.
Indications
- Short-term treatment of insomnia (typically 7-10 days)
- Difficulty falling asleep
- Frequent nocturnal awakenings
- Early morning awakenings
Note: Use should be limited to the lowest effective dose for the shortest duration necessary due to risks of dependence and tolerance.
Dosage and Administration
Adults: 0.125-0.25 mg orally before bedtime Geriatric/debilitated patients: 0.125 mg initially; may increase to 0.25 mg if needed Maximum dose: 0.5 mg daily Administration:- Take immediately before bedtime
- Ensure 7-8 hours dedicated to sleep after administration
- Do not crush or chew tablets
- Use shortest duration possible (typically not exceeding 2-3 weeks)
Pharmacokinetics
Absorption: Rapid and complete (oral bioavailability >90%) Onset: 15-30 minutes Peak concentration: 1-2 hours post-administration Distribution: Highly protein bound (90%), crosses blood-brain barrier and placenta Metabolism: Extensive hepatic metabolism via CYP3A4 to inactive metabolites Elimination: Primarily renal (80%) with some fecal excretion Half-life: 1.5-5.5 hours (significantly prolonged in hepatic impairment)Contraindications
- Hypersensitivity to triazolam or other benzodiazepines
- Acute narrow-angle glaucoma
- Concurrent use with strong CYP3A4 inhibitors (ketoconazole, itraconazole, nefazodone)
- Pregnancy (especially first trimester)
- Severe respiratory insufficiency
- Severe hepatic impairment
- Myasthenia gravis
- Sleep apnea syndrome
Warnings and Precautions
Boxed Warning: Risks of concomitant use with opioids (CNS depression, respiratory depression, coma, death)- Potential for abuse, dependence, and withdrawal symptoms
- Anterograde amnesia and paradoxical reactions (agitation, aggression)
- Impaired coordination and cognitive function
- Depression and suicidal ideation
- Next-day impairment (residual sedation)
- Elderly patients at increased risk of falls and cognitive impairment
- Respiratory depression in patients with compromised respiratory function
- Withdrawal symptoms after discontinuation (rebound insomnia, anxiety)
Drug Interactions
Major interactions:- CYP3A4 inhibitors: Significantly increased triazolam levels (avoid with strong inhibitors)
- CYP3A4 inducers: Reduced efficacy (carbamazepine, phenytoin, rifampin)
- CNS depressants: Additive effects (alcohol, opioids, other sedatives)
- Oral contraceptives: May increase triazolam levels
- Protease inhibitors: Variable effects on metabolism
- Antidepressants (SSRIs, TCAs)
- Antihistamines
- Muscle relaxants
- Anticonvulsants
Adverse Effects
Common (>10%):- Drowsiness
- Dizziness
- Lightheadedness
- Coordination impairment
- Headache
- Anterograde amnesia
- Confusion
- Nausea/vomiting
- Visual disturbances
- Fatigue
- Respiratory depression
- Paradoxical reactions (agitation, aggression)
- Depression/suicidal ideation
- Severe allergic reactions
- Complex sleep-related behaviors (sleep-driving, sleep-eating)
Monitoring Parameters
- Efficacy assessment (sleep latency, sleep duration, awakenings)
- CNS depression signs (sedation, coordination)
- Respiratory function (especially in at-risk patients)
- Mental status changes
- Signs of dependence or abuse
- Renal and hepatic function (periodically)
- Fall risk assessment in elderly
- Withdrawal symptoms upon discontinuation
Patient Education
- Take immediately before bedtime with 7-8 hours dedicated for sleep
- Avoid alcohol and other CNS depressants
- Do not drive or operate machinery until drug effects are known
- Report any unusual behaviors, memory problems, or mood changes
- Do not stop abruptly after prolonged use
- Use non-drug sleep hygiene measures concurrently
- Store securely to prevent misuse by others
- Inform all healthcare providers about Halcion use
- Understand risk of dependence with prolonged use
References
1. FDA Prescribing Information: Halcion (triazolam) tablets 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. Greenblatt DJ, et al. Clinical pharmacokinetics of triazolam. Clin Pharmacokinet. 1986;11(3):170-183. 4. Dündar Y, et al. Comparative efficacy of newer hypnotic drugs for the treatment of insomnia: a systematic review and meta-analysis. Hum Psychopharmacol. 2004;19(5):305-322. 5. American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2019 Updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2019;67(4):674-694. 6. Griffiths RR, et al. Abuse liability and clinical pharmacokinetics of triazolam in alcoholics. J Clin Psychopharmacol. 1991;11(3):196-202. 7. Kleykamp BA, et al. The clinical pharmacology of benzodiazepines. In: Schatzberg AF, Nemeroff CB, eds. The American Psychiatric Publishing Textbook of Psychopharmacology. 4th ed. American Psychiatric Publishing; 2009:459-478.