Drug Interactions between amprenavir and Desyrel

ADJUST DOSE: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations and pharmacologic effects of trazodone, which is primarily metabolized by the isoenzyme. In ten healthy volunteers, administration of a single 50 mg dose of trazodone in combination with the potent CYP450 3A4 inhibitor ritonavir (200 mg orally for 4 doses) increased mean trazodone peak plasma concentration (Cmax) by 34% and systemic exposure (AUC) by 137% compared to administration with placebo. Trazodone elimination half-life was prolonged 122% by ritonavir, while apparent oral clearance decreased 52%. Sedation, fatigue, and performance impairment were also increased during coadministration with ritonavir, and three subjects experienced nausea, dizziness, and hypotension. Although not reported in the study, the potential for increased risk of QT interval prolongation and ventricular arrhythmias including torsade de pointes should also be considered. There have been postmarketing reports of torsade de pointes associated with immediate-release trazodone following overdose and in the presence of multiple confounding factors, even at dosages of 100 mg/day or less. Moreover, some of the potent CYP450 3A4 inhibitors such as clarithromycin, erythromycin, telithromycin, lopinavir-ritonavir, saquinavir, and azole antifungal agents have also been reported to prolong the QT interval, thus additive effects may occur when used with trazodone.

MANAGEMENT: If concomitant use cannot be avoided, a lower dosage of trazodone should be considered during coadministration with a potent CYP450 3A4 inhibitor. Pharmacologic response to trazodone should be monitored more closely whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy, and the trazodone dosage adjusted as necessary. Patients should seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitations, irregular heartbeat, shortness of breath, or syncope.