Drug Interactions between imipramine and posaconazole

Consumer information for this interaction is not currently available.

MONITOR: The coadministration with azole antifungal agents may increase the plasma concentrations of some tricyclic antidepressants (TCAs). Elevated TCA levels may result in CNS toxicity, anticholinergic symptoms, and QT interval prolongation. The mechanism is decreased TCA clearance due to azole-related inhibition of the CYP450 3A4 isoenzyme, which is partially responsible for the metabolism of TCAs like amitriptyline, clomipramine, imipramine, and possibly others. Fluconazole additionally inhibits CYP450 2C19, which is another secondary route of metabolism for several TCAs. The effect of a single dose of fluconazole on TCA pharmacokinetics has not been reported. In a pharmacokinetic study involving six healthy subjects, ketoconazole (200 mg/day for 14 days) increased the half-life and area under the plasma concentration-time curve (AUC) of a single dose of imipramine (100 mg) by 15% and 20%, respectively, but did not affect the pharmacokinetics of desipramine or its metabolite.

MANAGEMENT: During concomitant therapy with azole antifungal agents, patients stabilized on their TCA regimen should be observed for increased pharmacologic response to the TCA, and the dosage adjusted accordingly if necessary. Serum TCA levels should be monitored following initiation or discontinuation of azole antifungal therapy. Patients should be advised to notify their caregiver if they experience excessive dry mouth, visual disturbances, urinary retention, dizziness, syncope, fast or irregular heartbeat, constipation, or seizures.