Recommendations for coadministration of pravastatin with darunavir have been based on a small PK study that showed substantial intersubject variability in the impact of interactions between the two drugs. In that study, concurrent administration of pravastatin (40 mg, single dose) with darunavir/ritonavir 600 mg/100 mg BID resulted in an overall geometric mean increase in pravastatin AUC of 81% and Cmax of 63%, compared with levels when pravastatin was taken alone. Further, in a few study subjects, the pravastatin AUC and Cmax increases were even higher (for AUC, up to 6 times higher than baseline, for Cmax, up to 10 times higher).
A recently published study examined these same drug interactions. In that study, 40 mg of pravastatin was administered to 28 healthy volunteers before and after starting darunavir/ritonavir 600 mg/100 mg BID. In the overall study population, the geometric mean increase in pravastatin AUC was 21% and the increase in Cmax was 23%, when compared with baseline measures. As in the first study, though, some subjects had much larger increases in pravastatin levels (up to a 4-fold increase in AUC) when this statin was given concurrently with darunavir/ritonavir.
Clinical Bottom Line
Although the second study shows a lesser overall effect of darunavir/ritonavir on pravastatin levels, it confirms that some individuals experience a huge and potentially dangerous increase in levels of this statin. Based on these data, clinicians should continue to follow the recommendations presented in the darunavir package insert: When pravastatin is used with darunavir, it should be started at the lowest dosage with careful monitoring for toxicity. The darunavir package insert further states that atorvastatin dosage should not exceed 20 mg per day.