indication

Used as an anticonvulsant in the treatment of the Lennox-Gastaut syndrome (petit mal variant), akinetic and myoclonic seizures.

pharmacology

Clonazepam, a benzodiazepine, is used primarily as an anticonvulsant in the treatment of absence seizures, petit mal variant seizures (Lennox-Gastaut syndrome), akinetic and myoclonic seizures, and nocturnal myoclonus.

mechanism of action

Allosteric interactions between central benzodiazepine receptors and gamma-aminobutyric acid (GABA) receptors potentiate the effects of GABA. As GABA is an inhibitory neurotransmitter, this results in increased inhibition of the ascending reticular activating system. Benzodiazepines, in this way, block the cortical and limbic arousal that occurs following stimulation of the reticular pathways.

toxicity

Somnolence, confusion, coma, and diminished reflexes

biotransformation

Hepatic (cytochrome P450, including CYP3A). Biotransformation occurs mainly by reduction of the 7-nitro group to the 4-amino derivative. This derivative can be acetylated, hydroxylated, and glucuronidated.

absorption

Clonazepam is rapidly and completely absorbed after oral administration. The absolute bioavailability of clonazepam is about 90%.

half life

30-40 hours

route of elimination

Clonazepam is highly metabolized, with less than 2% unchanged clonazepam being excreted in the urine. Metabolites of Klonopin are excreted by the kidneys

drug interactions

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

Clozapine: Increased risk of toxicity

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

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

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

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

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

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

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

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

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

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

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

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

Triprolidine: The CNS depressants, Triprolidine and Clonazepam, 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 clonazepam by decreasing its metabolism. Monitor for clonazepam toxicity if voriconazole is initiated or dose increased.