Effect of Klonopin on the Pharmacokinetics of Other Drugs: Klonopin does not appear to alter the
pharmacokinetics of phenytoin, carbamazepine, or phenobarbital. The effect of clonazepam on the metabolism of other
drugs has not been investigated.
Effect of Other Drugs on the Pharmacokinetics of Klonopin: Literature reports suggest that
ranitidine, an agent that decreases stomach acidity, does not greatly alter clonazepam pharmacokinetics.
In a study in which the 2 mg clonazepam orally disintegrating tablet was administered with and without
propantheline (an anticholinergic agent with multiple effects on the GI tract) to healthy volunteers, the AUC of
clonazepam was 10% lower and the Cmax of clonazepam was 20% lower when the orally disintegrating tablet
was given with propantheline compared to when it was given alone.
Fluoxetine does not affect the pharmacokinetics of clonazepam. Cytochrome P-450 inducers, such as phenytoin,
carbamazepine and phenobarbital, induce clonazepam metabolism, causing an approximately 30% decrease in plasma
clonazepam levels. Although clinical studies have not been performed, based on the involvement of the cytochrome
P-450 3A family in clonazepam metabolism, inhibitors of this enzyme system, notably oral antifungal agents, should be
used cautiously in patients receiving clonazepam.
Pharmacodynamic Interactions: The CNS-depressant action of the benzodiazepine class of drugs may be
potentiated by alcohol, narcotics, barbiturates, nonbarbiturate hypnotics, antianxiety agents, the phenothiazines,
thioxanthene and butyrophenone classes of antipsychotic agents, monoamine oxidase inhibitors and the tricyclic
antidepressants, and by other anticonvulsant drugs.