Drug Interactions between lopinavir / ritonavir and oritavancin

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with drugs that are inducers of CYP450 3A4 may decrease the plasma concentrations of protease inhibitors (PIs), which are primarily metabolized by the isoenzyme.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, protease inhibitors should be used cautiously with agents that induce CYP450 3A4, particularly if only one PI is used in the antiretroviral regimen. Coadministration of atazanavir without ritonavir and carbamazepine, phenobarbital, or phenytoin is not recommended. Antiretroviral response should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the antiretroviral regimen adjusted as necessary.

Consumer information for this interaction is not currently available.

MONITOR: Coadministration of lopinavir-ritonavir with inducers of CYP450 3A4 may decrease the plasma concentrations of lopinavir, which is primarily metabolized by the isoenzyme. Clinical studies have shown that potent CYP450 3A4 inducers such as rifampin and phenytoin can significantly alter the plasma concentrations of lopinavir, possibly by overriding some of the inhibiting effects of ritonavir and enhancing the clearance of both lopinavir and ritonavir. In 22 healthy, HIV-negative subjects, administration of lopinavir-ritonavir (400 mg-100 mg twice daily for 20 days) with rifampin (600 mg once daily for 10 days) decreased lopinavir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) by 55%, 75% and 99%, respectively. In another study of 12 healthy volunteers, coadministration of lopinavir-ritonavir (400 mg-100 mg twice daily for 22 days) and phenytoin (300 mg once daily on days 11 through 22) resulted in decreases in Cmax, AUC and Cmin of lopinavir by 24%, 33% and 46%, respectively. Ritonavir Cmax, AUC and Cmin were also reduced by 20%, 28% and 47%, respectively, although only the change in Cmin was statistically significant. The extent to which other, less potent inducers of CYP450 3A4 may interact with lopinavir-ritonavir is unknown. In addition, when two or more medications with similar adverse effect profiles are given concurrently, the likelihood of experiencing these adverse reactions may be increased. For example, coadministration with other agents that can prolong the QT interval (e.g., apalutamide, encorafenib, enzalutamide) may result in additive effects and an increased risk of ventricular arrhythmias like torsade de pointes.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, caution is advised if lopinavir-ritonavir is prescribed with CYP450 3A4 inducers. Close clinical and laboratory monitoring of antiretroviral response is recommended. If the CYP450 3A4 inducer also carries a risk of prolonging the QT interval, then obtaining more frequent electrocardiograms (ECGs) to monitor the QT interval may be advisable. Patients should be counseled to seek immediate medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, syncope, palpitations, irregular heartbeat, and/or shortness of breath. The prescribing information for the concomitant CYP450 3A4 inducers should be consulted for specific recommendations.