Altered therapeutic effect or adverse reaction profile w/ drugs that induce or inhibit CYP3A, CYP2C9 & CYP2C19. Altered therapeutic effect or adverse reaction profile of drugs that are substrates of CYP3A, CYP2C9 & CYP2C19 or are transported by P-glycoprotein. Reduced plasma conc w/ dolutegravir (mitigated when co-administered w/ atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir). Should not be co-administered w/ other NNRTIs; fosamprenavir/ritonavir. Should not be co-administered w/o low-dose ritonavir: indinavir, nelfinavir. Decreased plasma conc & loss of therapeutic effect w/ nevirapine or efavirenz; ritonavir (600 mg bd); tipranavir/ritonavir; CYP450 inducers (eg, carbamazepine, phenobarb, or phenytoin, rifampin, rifapentine); systemic dexamethasone (CYP3A inducer); St. John's wort. When initiating a combination w/ digoxin, start w/ the lowest dose. Decreased conc of maraviroc [w/o a potent CYP3A inhibitor (eg, ritonavir-boosted PI)]; antiarrhythmics (eg, amiodarone, bepiridil, disopyramide, flecainide, lidocaine (systemic), mexiletine, propafenone, quinidine); itraconazole or ketoconazole; lovastatin & simvastatin. Increased conc of warfarin; diazepam; fluvastatin & pitavastatin. Increased plasma conc w/ posaconazole, itraconazole, ketoconazole, fluconazole, voriconazole. Decreased exposure of clarithromycin but increased conc of 14-hydroxy-clarithromycin leading to altered overall activity against Mycobacterium avium
complex (MAC). Potential decreased antimalarial efficacy of artemether/lumefantrine. Potential for significant reductions in etravirine exposure w/ rifabutin + darunavir/ritonavir, lopinavir/ritonavir or saquinavir/ritonavir. Co-administration w/ boceprevir in the presence of other drugs which may further decrease etravirine exposure is not recommended. Dose of atorvastatin may need to be altered based on clinical response. Possible effect on plasma conc of cyclosporine, sirolimus or tacrolimus. Clinical monitoring of w/drawal symptoms is recommended as buprenorphine (or buprenorphine/naloxone) or methadone maintenance therapy may need to be adjusted in some patients. Dose of sildenafil may need to be altered based on clinical effect. Decreased activation of clopidogrel to its active metabolite.