Drug Interactions between Rescriptor and Viekira XR

MONITOR: Coadministration with delavirdine may increase the plasma concentrations of ritonavir. The mechanism is delavirdine inhibition of ritonavir metabolism via CYP450 3A4. In 12 HIV-infected patients stabilized on antiretroviral therapy that included ritonavir 600 mg twice a day as the sole protease inhibitor, addition of delavirdine (400 mg three times a day for 21 days) increased the mean peak plasma concentration (Cmax), area under the concentration-time curve (AUC) and trough plasma concentration (Cmin) of ritonavir by 66%, 64% and 81%, respectively, compared to baseline. Ritonavir did not significantly affect the steady-state concentrations of delavirdine when compared to those from a reference database for delavirdine administered with food. The combination was well tolerated in the study, and no serious adverse event occurred. With respect to lower dosages of the combination, no significant interaction occurred when delavirdine 400 mg was administered with ritonavir 300 mg twice a day in healthy volunteers. However, it is uncertain whether these data are applicable to HIV-infected patients, as altered patterns of drug metabolism have been observed in this population.

MANAGEMENT: Appropriate dosages for the combination of ritonavir and delavirdine with respect to safety and efficacy have not been established. Patients given the combination should be advised to notify their physician if they experience potential signs of ritonavir intolerance such as severe nausea, vomiting, anorexia, abdominal pain, taste perversion, and circumoral and peripheral paresthesias. The effect of delavirdine on lower dosages of ritonavir (e.g., 100 or 200 mg twice a day as a pharmacokinetic booster of other protease inhibitors) in HIV-infected patients is unknown.

Switch to consumer interaction data

MONITOR: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations of paritaprevir, which is primarily metabolized by the isoenzyme. In 12 study subjects, ketoconazole 400 mg given once daily increased single-dose paritaprevir peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 37% and 98%, respectively. The risk of hyperbilirubinemia may be increased, as paritaprevir can cause elevations in indirect (unconjugated) bilirubin via inhibition of OATP1B1/1B3.

MANAGEMENT: Caution is advised if paritaprevir is prescribed in combination with potent CYP450 3A4 inhibitors. Patients should be monitored for signs and symptoms of hepatotoxicity (i.e., ALT and bilirubin elevations).

Switch to consumer interaction data