indication

For the management of anxiety disorder or the short-term relief of symptoms of anxiety and for the treatment of panic disorder, with or without agoraphobia.

pharmacology

Alprazolam, a benzodiazepine, is used to treat panic disorder and anxiety disorder. Unlike chlordiazepoxide, clorazepate, and prazepam, alprazolam has a shorter half-life and metabolites with minimal activity. Like other triazolo benzodiazepines such as triazolam, alprazolam may have significant drug interactions involving the hepatic cytochrome P-450 3A4 isoenzyme. Clinically, all benzodiazepines cause a dose-related central nervous system depressant activity varying from mild impairment of task performance to hypnosis. Unlike other benzodiazepines, alprazolam may also have some antidepressant activity, although clinical evidence of this is lacking.

mechanism of action

Benzodiazepines bind nonspecifically to benzodiazepine receptors BNZ1, which mediates sleep, and BNZ2, which 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 the inhibitory neurotransmitter GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell.

toxicity

Oral, mouse: LD₅₀=1020 mg/kg. Symptoms of overdose include confusion, coma, impaired coordination, sleepiness, and slowed reaction time.

biotransformation

Hepatic. Hydroxylated in the liver to α-hydroxyalprazolam, which is also active. This and other metabolites are later excreted in urine as glucuronides.

absorption

Readily absorbed from the gastrointestinal tract. Bioavailability is 80-90%.

half life

6.3-26.9 hours

route of elimination

Alprazolam and its metabolites are excreted primarily in the urine.

drug interactions

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

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

Carbamazepine: Carbamazepine may decrease the effect of the benzodiazepine, alprazolam.

Cimetidine: Cimetidine may increase the effect of the benzodiazepine, alprazolam.

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

Clozapine: Increased risk of toxicity

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

Digoxin: The benzodiazepine, alprazolam, may increase the effect of digoxin.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Tipranavir: Tipranavir may decrease the metabolism and clearance of Alprazolam. Consider alternate therapy or monitor for Alprazolam toxic effects if Tipranavir is initiated or dose increased.

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

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