indication

For short-term and intermittent use in patients with recurring insomnia and poor sleeping habits

pharmacology

Flurazepam, a benzodiazepine derivative, is a hypnotic agent which does not appear to decrease dream time as measured by rapid eye movements (REM). Furthermore, it decreases sleep latency and number of awakenings for a consequent increase in total sleep time.

mechanism of action

Flurazepam binds to an allosteric site on GABA-A receptors. Binding potentiates the action of GABA on GABA-A receptors by opening the chloride channel within the receptor, causing chloride influx and hyperpolarization.

toxicity

Coma, confusion, low blood pressure, sleepiness

biotransformation

Flurazepam is rapidly metabolized and is excreted primarily in the urine. Both hydroxyethyl flurazepam (the major metabolite) and N-desalkyl flurazepam are active. The N-desalkyl metabolite is slowly excreted in the urine as the conjugated form

absorption

Flurazepam hydrochloride is rapidly (30 minutes) absorbed from the gastrointestinal tract

half life

The mean apparent half-life of flurazepam is 2.3 hours. The half life of elimination of N1-des-alkyl- flurazepam ranged from 47 to 100 hours

route of elimination

Flurazepam is rapidly metabolized and is excreted primarily in the urine. Less than 1% of the dose is excreted in the urine as N1-desalkyl-flurazepam.

drug interactions

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

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

Clozapine: Increased risk of toxicity

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Telithromycin: Telithromycin may reduce clearance of Flurazepam. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Flurazepam if Telithromycin is initiated, discontinued or dose changed.

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

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

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of flurazepam by decreasing its metabolism. Monitor for flurazepam toxicity if voriconazole is initiated or dose increased.