WASHINGTON — Data presented at the XIX International AIDS Conference indicate that there is little potential for interaction between pitavastatin and combination darunavir/ritonavir.
Pitavastatin (Livalo, Kowa Pharmaceuticals and Eli Lilly) is the most recent statin approved in the United States. According to Craig Sponseller, MD, vice president of medical affairs at Kowa Pharmaceuticals, statins pose a risk when given with protease inhibitors, including the combination darunavir (Prezista, Janssen) and ritonavir (Norvir, Abbott), because both drugs compete for the cytochrome P450 (CYP) metabolism.
“There is a risk that when you use protease inhibitor combinations and add certain statins on top of that, the drugs will compete for the CYP metabolism, and that the levels of the statin will go up or that the levels of the protease inhibitor will be compromised,” Sponseller told Infectious Disease News. “Pitavastatin does not use CYP metabolism.”
Researchers conducted a single-center, open-label, fixed-sequence, multiple-dose drug interaction study in healthy adult volunteers. The participants received 4 mg pitavastatin on days 1 to 5 and days 12 to 16. They received 800 mg darunavir and 100 mg ritonavir on days 6 to 16. The participants provided serum pharmacokinetics samples pre-dose and up to 24 hours after dose on days 5, 11 and 16.
The study included 28 participants. When administered with darunavir/ritonavir, pitavastatin peak exposure, measured by maximum plasma concentration (Cmax), decreased by 4%. The total exposure of pitavastatin, measured by AUC0-T, decreased by approximately 26%. When coadministered with pitavastatin, the maximum plasma concentration Cmax of darunavir increased by 6% and the AUC0-T of darunavir increased by 3%. The Cmax of ritonavir increased by 2% and AUC0-T of ritonavir increased by 8%.
The researchers also investigated the safety of pitavastatin and darunavir/ritonavir when each treatment was given alone or in combination. Most adverse events were mild. No serious or severe adverse events were reported. Nineteen of 28 patients reported at least one adverse event, 10 of whom were from the darunavir/ritonavir only group, seven were from the pitavastatin and darunavir/ritonavir group and two were from the pitavastatin only group.
Yu CY. #TUPE053. Presented at: XIX International AIDS Conference; July 22-27; Washington, D.C.
Dr. Sponseller is employed by Kowa Pharmaceuticals.