Drug interactions between Selzentry and st. john's wort

GENERALLY AVOID: Coadministration with St. John's wort may significantly reduce the plasma concentrations of certain antiretroviral agents such as protease inhibitors, nonnucleoside reverse transcriptase inhibitors (NNRTIs), and CCR5 coreceptor antagonists. The mechanism is induction of CYP450 3A4 metabolism by constituents of St. John's wort. In eight healthy volunteers, St. John's wort (300 mg, standardized to 0.3% hypericin, three times a day for 14 days) decreased the 8-hour area under the plasma concentration-time curve (AUC) and extrapolated 8-hour trough of indinavir (800 mg every 8 hours for 4 doses) by a mean of 57% and 81%, respectively, compared to administration of indinavir alone. All participants showed a reduction in the indinavir 8-hour postdose concentration ranging from 49% to 99%. The interaction was also suspected as the cause of low nevirapine plasma levels in five HIV patients who used St. John's wort while being treated with nevirapine and two nucleoside reverse transcriptase inhibitors. MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, patients treated with antiretroviral agents should avoid using St. John's wort. Concomitant use of St. John's wort is specifically contraindicated according to the product labeling for fosamprenavir, lopinavir-ritonavir, and tipranavir. Patients should be advised to consult with their caregivers before using any herbal or alternative medicines.