Drug Interactions between Ambien CR and isoniazid

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with isoniazid (INH) may increase the plasma concentrations and therapeutic effects of benzodiazepines and related drugs that are primarily metabolized by CYP450 3A4 (e.g., diazepam, flurazepam, triazolam, midazolam, zopiclone, eszopiclone) and to a lesser extent, 2C9, 2C19, and/or 2E1. Isoniazid has been shown to be an inhibitor of these isoenzymes, although some data is limited to in vitro studies. Inhibition of the relevant CYP450 isoenzyme by INH may decrease the clearance and prolong the half-life of the benzodiazepine, leading to an elevated risk of benzodiazepine CNS side effects (e.g., sedation, respiratory depression). According to triazolam product labeling, coadministration of INH increased the peak plasma concentration (Cmax) of triazolam by 20%, decreased the clearance by 42%, and increased the half-life by 31%. Clinical data are not available for all benzodiazepines. In addition, the net effect on benzodiazepines when coadministered with other anti-tuberculosis agents that have additional CYP450 drug interactions (i.e. CYP450 3A4 induction by rifampin) have not been evaluated.

MANAGEMENT: Caution and clinical monitoring are advised when isoniazid is coadministered with benzodiazepines and related drugs that are substrates of CYP450 3A4, 2C9, 2C19, and/or 2E1. If coadministration is required, close clinical monitoring for adverse effects (e.g., sedation, respiratory depression) is advised and benzodiazepine dose adjustments may be required, particularly when isoniazid is initiated or withdrawn from concomitant therapy. Individual product labeling for the coadministered benzodiazepine should be consulted. Additional caution and clinical monitoring may be advised if isoniazid is being used in conjunction with, or immediately following treatment with other anti-tuberculosis agents that have additional CYP450 drug interactions (i.e. CYP450 3A4 induction by rifampin), as this may change the nature and/or severity of this drug interaction.