Kowa Pharmaceuticals America, Inc., a pharmaceutical company specializing primarily in the area of cardiometabolic diseases, and Eli Lilly and Company has released results from a pharmacokinetic (PK) study exploring potential drug interaction between the cholesterol medication pitavastatin (LIVALO) four mg and the protease inhibitor (PI) combination darunavir/ritonavir (Prezista/Norvir) 800mg/100mg in healthy volunteers.

The study is presented at the 19th International AIDS Conference in Washington, DC, found that when co-administered, the blood levels for LIVALO and each of the PIs were not significantly affected. In February 2012, the PK data darunavir/ritonavir were added to the LIVALO label.

“Examining drug interactions has been an ongoing part of product development, and  we are pleased that results show no clinically significant drug interaction between pitavastatin and the protease inhibitor combination darunavir/ritonavir,” said Dr Craig Sponseller, vice president of Medical Affairs, Kowa Pharmaceuticals America, Inc.

The current study was designed to assess the changes in pharmacokinetic parameters when pitavastatin four mg and darunavir/ritonavir 800mg/100mg were administered alone or in combination.  Pitavastatin and darunavir/ritonavir were co-administered in 28 healthy, adult volunteers over a 16-day period. When co-administered with darunavir/ritonavir, pitavastatin peak exposure, as measured by Cmax, decreased by four per cent, while total exposure of pitavastatin, as measured by AUC0-t, decreased by approximately 26 per cent. When co-administered with pitavastatin, the Cmax and AUC0-t of darunavir increased by six per cent and three per cent respectively, and the Cmax and AUC0-t of ritonavir increased by two per cent and eight per cent, respectively. These effects were not considered to be clinically significant.

A secondary objective of the study was to investigate the safety of pitavastatin and darunavir/ritonavir when each treatment was given alone or in combination. The majority of treatment emergent adverse events (TEAEs) were mild in severity, and no serious or severe adverse events were reported. Nineteen of 28 patients reported at least one TEAE, of which 10 were from the darunavir/ritonavir only group; seven from the pitavastatin and darunavir/ritonavir group; two from the pitavastatin only group.

For TEAEs occurring in  > /= 2 subjects in any treatment group, the most frequently reported drug-related TEAEs were diarrhea (7.1 per cent darunavir/ ritonavir only group; 7.4 per cent pitavastatin and darunavir/ritonavir; 3.6 per cent pitavastatin only), headache, (10.7 per cent darunavir/ritonavir only group; 0 per cent pitavastatin and darunavir/ritonavir; 0 per cent from the pitavastatin only group) and myalgia (7.1 per cent darunavir/ritonavir only; 3.7 per cent pitavastatin and darunavir/ritonavir group; 3.6 per cent pitavastatin only). One subject was discontinued from the study due to maculopapular rash during treatment with darunavir/ritonavir only.

LIVALO is a HMG-CoA reductase inhibitor indicated for patients with primary hyperlipidemia and mixed dyslipidemia as an adjunctive therapy to diet to reduce elevated total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), triglycerides (TG), and to increase high-density lipoprotein cholesterol (HDL-C).

Doses of LIVALO greater than four mg once daily were associated with an increased risk for severe myopathy in pre-marketing clinical studies. Do not exceed four mg once daily dosing of LIVALO. The effect of LIVALO on cardiovascular morbidity and mortality has not been determined. LIVALO has not been studied in Fredrickson Type I, III, and V dyslipidemias.

In addition to being launched in the US in June 2010, LIVALO is also approved in Japan (2003), South Korea (2005), Thailand (2007), China (2008), European Union (2010), Taiwan (2011), Mexico (2009) and Australia (2010).

Primary hyperlipidemia is defined as an elevation of cholesterol, particularly "bad" cholesterol (LDL-C), triglycerides (TG), or both. Mixed dyslipidemia is usually characterized by an elevation of LDL-C, TG, and a decrease in the "good" cholesterol (HDL-C) in the blood.

Kowa Company, Ltd. (KCL) is a privately held multinational company. The company is actively engaged in various manufacturing and commercial activities in the fields of pharmaceutical, life science, information technology, textiles, machinery and various consumer products.