Interaction Checker

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Tipranavir now available on the Interaction Charts

Tuesday 07 November 2006

Tipranavir (Aptivus), a non-peptidic protease inhibitor, was recently licensed in Europe (FDA approval was granted earlier this summer). We have now completed our evaluation of the literature and have added tipranavir interactions to the Interaction Charts.

Please note that as tipranavir (a powerful CYP3A and P-gp inducer) is coadministered with ritonavir (a potent inhibitor), predicting interactions was difficult for drugs where no study data were available. There is the potential for TPV/r to affect the pharmacokinetics of other drugs and also the potential of other drugs to affect TPV PK.

Although tipranavir is a CYP3A inducer, the in vivo net effect of tipranavir/ritonavir (500/200 mg) is likely to be inhibition of CYP3A (ritonavir inhibits CYP3A), induction of P-gp, and inhibition of CYP2D6 (ritonavir inhibits CYP2D6). The net effect of tipranavir/ritonavir on other CYPs is not clearly known. Based on available data, we can expect increases in concentrations of drugs extensively metabolised by CYP3A (but possibly not such good substrates for P-gp) and decreases in concentrations of drugs that are good substrates for P-gp. For drugs metabolised by CYP3A and transported by P-gp, the net effect will depend on the affinity for proteins and the role of the liver and gut in the first pass metabolism/efflux of the particular drug.

We are in the processes of reviewing the other protease inhibitors. The PDA (HIV-Charts2go) and printable versions of the charts will be updated to include tipranavir once these reviews have been completed.

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