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No significant drug interactions found between tenofovir DF and indinavir, lopinavir/r, lamivudine, or efavirenz

Brian Boyle, MD for HIVandhepatitis.com

Tenofovir disoproxil fumarate (VireadTM), a nucleotide analogue reverse transcriptase inhibitor (NtRTI), was recently approved in the United States and Europe. A study presented at the 8th ECCATH explored potential drug-drug interactions between tenofovir DF indinavir, lopinavir/r, lamivudine and efavirenz.

In the study, pharmacokinetic profiles for each of the drugs, alone as well as in combination with tenofovir DF, was determined in healthy subjects. All drugs were administered pursuant to their labelling requirement.

Tenofovir DF pharmacokinetics were unaffected by lamivudine and efavirenz, while indinavir increased the Cmax (14%) of Tenofovir DF without affecting the area under the curve (AUC), and lopinavir/r moderately increased both the Cmax (30%) and AUC of Tenofovir DF. None of these changes were considered clinically significant.

Tenofovir DF was not found to have any interaction with efavirenz; however, it was found to cause (1) a slight delay in the time to maximal concentration of lamivudine and a decrease (24%) in the Cmax of lamivudine without altering the AUC; (2) a lowered Cmax of indinavir (11%) without a change in AUC; and (3) a lowered Cmax and AUC (15%) for lopinavir while maintaining the lopinavir Cmin and inhibitory quotient.

There were no significant adverse events associated with the combination of Tenofovir DF with indinavir, lopinavir/r, lamivudine or efavirenz. The authors reported that “all adverse events were mild-moderate severity and did not differ substantially for drugs given alone versus together.”

Based upon these data, the authors conclude that the “coadministration of tenofovir with 3TC, IDV, LPV/r or EFV does not result in clinically relevant drug-drug interactions [and] adverse events reported are known to be common for the antiretrovirals evaluated.”

Reference:

B Kearney B and others. Lack of clinically relevant drug-drug interactions between tenofovir DF and efavirenz, indinavir, lamivudine and lopinavir/ritonavir in healthy subjects. 8th ECCATH, Athens, Greece, October 2001. Abstract P171.

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