Drug interactions between Adapin and emtricitabine/lopinavir/ritonavir/tenofovir

doxepin ↔ ritonavir

Applies to:Adapin (doxepin) and emtricitabine/lopinavir/ritonavir/tenofovir

MONITOR: Coadministration with ritonavir may increase the plasma concentrations of drugs that are substrates of the CYP450 2D6 isoenzyme. The mechanism is decreased clearance due to competitive inhibition of CYP450 2D6 activity by ritonavir. The systemic exposure (AUC) of some coadministered drugs has been reported to increase by up to twofold.

MANAGEMENT: Caution is advised if ritonavir must be used concurrently with medications that undergo metabolism by CYP450 2D6, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever ritonavir is added to or withdrawn from therapy.

doxepin ↔ lopinavir

Applies to:Adapin (doxepin) and emtricitabine/lopinavir/ritonavir/tenofovir

GENERALLY AVOID: Lopinavir in combination with ritonavir may cause dose-related prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In a study of 39 healthy adults who were administered lopinavir-ritonavir at a therapeutic dosage of 400 mg-100 mg twice daily and a supratherapeutic dosage of 800 mg-200 mg twice daily, the maximum mean time-matched difference in QTcF interval from placebo (after baseline correction) was 5.3 msec for the lower dosage and 15.2 msec for the supratherapeutic dosage in the 12 hours postdose on treatment day 3 when exposures were approximately 1.5 and 3-fold higher, respectively, than those observed with recommended once-daily or twice-daily dosages of lopinavir-ritonavir at steady state. No subject experienced an increase in QTcF greater than 60 msec from baseline or a QTcF interval exceeding the potentially clinically relevant threshold of 500 msec. There have been cases of QT interval prolongation and torsade de pointes arrhythmia during postmarketing use of lopinavir-ritonavir, although causality could not be established. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: The use of lopinavir-ritonavir in combination with other drugs that may prolong the QT interval should generally be avoided. Patients treated with any medication that can cause QT prolongation should be advised to seek 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.