Significant interactions between tipranavir/ritonavir and statins

Data from lopinavir/ritonavir and rosuvastatin have shown that it is difficult to predict interactions between boosted protease inhibitors and statins.

Since tipranavir/ritonavir has a net inhibitory effect on CYP3A4, it has the potential to increase atorvastatin concentrations. However, rosuvastatin is considered unlikely to interact with tipranavir/ritonavir since it is not a CYP3A4 substrate and is not extensively metabolised.

Two open-label, prospective, single-arm, two-period studies, were performed in HIV-negative volunteers. These studies looked to identify interactions between tipranavir/ritonavir (500/200 mg twice daily) and either rosuvastatin (10 mg single dose) or atorvastatin (40 mg single dose),

Coadministration increased rosuvastatin AUC by 37% and increased Cmax by 2.23-fold. Atorvastatin AUC was increased by 9.36-fold and Cmax increased by 8.61-fold, when coadministered. Tipranavir pharmacokinetic parameters were not affected by single-dose rosuvastatin or atorvastatin. The atorvastatin data are consistent with marked inhibition of CYP3A4 and some transport proteins. The rosuvastatin data are consistent with previous findings evaluating this interaction with lopinavir/ritonavir and most likely due to inhibition of OATP1B1 and BCRP.

Based on these interactions, the authors recommend low initial doses of rosuvastatin (5 mg) and atorvastatin (10 mg), with careful clinical monitoring of rosuvastatin- or atorvastatin-related adverse events when combined with tipranavir/ritonavir.

Although these studies have shown the nature and magnitude of the pharmacokinetic interaction, they do not give any information on the pharmacodynamic interaction (i.e. the cholesterol-lowering efficacy of each statin) when given with tipranavir/ritonavir.

Data from rosuvastatin/lopinavir/ritonavir have shown that although plasma concentrations of rosuvastatin were increased, the cholesterol lowering efficacy was decreased when given in combination.

Ref: Pham PA et al. Differential effects of tipranavir plus ritonavir on atorvastatin or rosuvastatin pharmacokinetics in healthy volunteers. Antimicrob Agents Chemother, 2009, 53(10): 4385-4392.
http://www.ncbi.nlm.nih.gov/pubmed/19667285