Clonazepaminteractions

Effect of Concomitant Use of Benzodiazepines and Opioids: The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration. Benzodiazepines interact at GABAA sites, and opioids interact primarily at mu receptors. When benzodiazepines and opioids are combined, the potential for benzodiazepines to significantly worsen opioid-related respiratory depression exists. Limit dosage and duration of concomitant use of benzodiazepines and opioids, and follow patients closely for respiratory depression and sedation. Effect of Clonazepam on the Pharmacokinetics of Other Drugs: Clonazepam does not appear to alter the pharmacokinetics of carbamazepine or phenobarbital. Clonazepam has the potential to influence concentrations of phenytoin. Monitoring of phenytoin concentration is recommended when clonazepam is co-administrated with phenytoin. The effect of clonazepam on the metabolism of other drugs has not been investigated. Effect of Other Drugs on the Pharmacokinetics of Clonazepam: 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 C max of clonazepam was 20% lower when the orally disintegrating tablet was given with propantheline compared to when it was given alone. The selective serotonin reuptake inhibitors sertraline (weak CYP3A4 inducer) and fluoxetine (CYP2D6 inhibitor), and the anti-epileptic drug felbamate (CYP2C19 inhibitor and CYP3A4 inducer) do not affect the pharmacokinetics of clonazepam. Cytochrome P450 inducers, such as phenytoin, carbamazepine, lamotrigine, and phenobarbital induce clonazepam metabolism, causing an approximately 38% 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 (e.g., fluconazole), should be used cautiously in patients receiving clonazepam because they may impair the metabolism of clonazepam leading to exaggerated concentrations and effects.

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.