indication

For the short-term treatment of insomnia.

pharmacology

A short-acting benzodiazepine used as a hypnotic agent in the treatment of insomnia. Some countries temporarily withdrew triazolam from the market because of concerns about adverse reactions, mostly psychological, associated with higher dose ranges. Its use at lower doses with appropriate care and labeling has been reaffirmed by the FDA and most other countries. Triazolam has a shorter half-life than chlordiazepoxide, flurazepam, and prazepam and does not generate active metabolites.

mechanism of action

Benzodiazepines bind nonspecifically to bezodiazepine receptors BNZ1, which mediates sleep, and BNZ2, which affects affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. As benzodiazepine receptors are thought to be coupled to gamma-aminobutyric acid-A (GABA_A) receptors, this enhances the effects of GABA by increasing GABA affinity for the GABA receptor. Binding of GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell.

toxicity

Symptoms of overdose include drowsiness, slurred speech, motor inco-ordination, coma, and respiratory depression.

biotransformation

Hepatic. Small amounts of unmetabolized triazolam appear in the urine.

absorption

Bioavailability is 44% (oral) and 53% (sublingual).

half life

1.5-5.5 hours

route of elimination

Triazolam and its metabolites, principally as conjugated glucuronides, which are presumably inactive, are excreted primarily in the urine. Only small amounts of unmetabolized triazolam appear in the urine. The two primary metabolites accounted for 79.9% of urinary excretion.

drug interactions

Amprenavir: Amprenavir may increase the effect and toxicity of the benzodiazepine, triazolam.

Aprepitant: Aprepitant may increase the effect and toxicity of the benzodiazepine, triazolam.

Atazanavir: Atazanavir may increase the effect and toxicity of the benzodiazepine, triazolam.

Cimetidine: Cimetidine may increase the serum concentration of triazolam by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of triazolam if cimetidine is initiated, discontinued or dose changed.

Clarithromycin: The macrolide, clarithromycin, may increase the effect of the benzodiazepine, triazolam.

Clozapine: Increased risk of toxicity

Delavirdine: The antiviral agent, delavirdine, may increase the effect and toxicity of the benzodiazepine, triazolam.

Diltiazem: The calcium channel blocker, diltiazem, may increase the effect and toxicity of the benzodiazepine, triazolam.

Efavirenz: The antiviral agent, efavirenz, may increase the effect and toxicity of the benzodiazepine, triazolam.

Erythromycin: The macrolide, erythromycin, may increase the effect of the benzodiazepine, triazolam.

Ethotoin: Ethotoin may increase the metabolism of triazolam via CYP3A4.

Fluconazole: Fluconazole may increase the effect of the benzodiazepine, triazolam.

Fosamprenavir: Fosamprenavir may increase the effect and toxicity of the benzodiazepine, triazolam.

Fosphenytoin: Fosphenytoin may increase the metabolism of triazolam via CYP3A4.

Indinavir: The protease inhibitor, indinavir, may increase the effect of the benzodiazepine, triazolam.

Itraconazole: Itraconazole may increase the effect of the benzodiazepine, triazolam.

Josamycin: The macrolide, josamycin, may increase the effect of the benzodiazepine, triazolam.

Kava: Kava may increase the effect of the benzodiazepine, triazolam.

Ketoconazole: Ketoconazole may increase the effect of the benzodiazepine, triazolam.

Mephenytoin: Mephenytoin may increase the metabolism of triazolam via CYP3A4.

Modafinil: Modafinil decreases the effect of triazolam

Nefazodone: Nefazodone increases the effect of triazolam

Nelfinavir: The protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, triazolam.

Omeprazole: Omeprazole may increase the effect of the benzodiazepine, triazolam.

Phenytoin: Phenytoin may increase the metabolism of triazolam via CYP3A4.

Rifampin: Rifampin may decrease the effect of the benzodiazepine, triazolam.

Ritonavir: The protease inhibitor, ritonavir, may increase the effect of the benzodiazepine, triazolam.

Saquinavir: The protease inhibitor, saquinavir, may increase the effect of the benzodiazepine, triazolam.

St. John's Wort: St. John's Wort may decrease the effect of the benzodiazepine, triazolam.

Telithromycin: Telithromycin may increase the effect and toxicity of the benzodiazepine, triazolam.

Tipranavir: Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Triazolam. Concomitant therapy is contraindicated.

Triprolidine: The CNS depressants, Triprolidine and Triazolam, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.

Verapamil: Verapamil may increase the serum concentration of Triazolam by decreasing its metabolism. Avoid concomitant therapy if possible or consider a dose reduction in the initial dose of Triazolam.

Voriconazole: Voriconazole may increase the serum concentration of triazolam by decreasing its metabolism. Monitor for triazolam toxicity if voriconazole is initiated or dose increased.