ritonavir and Desipramine Interactions

Interactions between ritonavir and Desipramine (desipramine)

desipramine and ritonavir (Moderate Drug-Drug)

ADJUST DOSE: Coadministration with ritonavir may increase the plasma concentrations of desipramine. The mechanism is ritonavir inhibition of CYP450 2D6, the isoenzyme responsible for the metabolic clearance of desipramine. In an open label study consisting of 14 healthy volunteers, ritonavir (500 mg orally every 12 hours) increased the mean area under the plasma concentration-time curve (AUC) and half-life of desipramine (100 mg single dose) by approximately 145% and 100%, respectively. It is not known to what extent, if any, the interaction may occur when ritonavir is used in lower dosages as a pharmacokinetic booster. No interaction was observed when desipramine was given with lopinavir-ritonavir in drug interaction studies.

MANAGEMENT: A reduction in desipramine dosage should be considered in patients treated with antiretroviral dosages of ritonavir. In patients stabilized on desipramine, clinical and laboratory monitoring of antidepressant response is recommended whenever ritonavir is added to or withdrawn from therapy, and the dosage adjusted accordingly. Patients should be advised to notify their physician if they experience excessive tricyclic antidepressant effects such as dry mouth, blurry vision, irregular or fast heartbeat, constipation, urinary retention, dizziness, or orthostatic hypotension.