Coadministration has not been studied. Naproxen is mainly glucuronidated by UGT2B7 (major) and demethylated to desmethylnaproxen by CYP2C9 (major) and CYP1A. Emtricitabine and tenofovir are eliminated renally. A clinically significant interaction with emtricitabine is unlikely. In vitro data suggest that naproxen is a weak inhibitor of OCT2, and also inhibits the renal transporters OAT1 and OAT3 (which are involved in tenofovir excretion). Renal elimination of tenofovir-DF could potentially decrease, thereby increasing the risk of nephrotoxicity. The risk is also increased if an NSAID is used for a long duration, if the patient has a pre-existing renal dysfunction, has a low body weight, or receives other drugs that may increase tenofovir exposure. Cases of acute renal failure after initiation of high dose or multiple NSAIDs have been reported in patients treated with tenofovir-DF and with risk factors for renal dysfunction. Alternatives to NSAIDs should be considered in patients at risk for renal dysfunction. If emtricitabine/tenofovir-DF is co-administered with an NSAID, renal function should be monitored adequately.