Combination of LIVALO and itraconazole drugs shows no adverse reactions

Sep 2 2009

BARCELONA, Spain, Sept. 2 /PRNewswire/ -- LIVALO (pitavastatin) may have the potential for fewer drug-drug interactions, versus other statins, as evidenced by a new study that evaluated the effects of itraconazole, an antifungal medication, on the pharmacokinetics of LIVALO in healthy volunteers. The data were presented by Kowa at the European Society of Cardiology (ESC) Congress in Barcelona, Spain.

Many statins currently prescribed in the United States, such as atorvastatin and simvastatin, are metabolized by the cytochrome P450 system, particularly through the 3A4 pathway. Strong inhibitors of this pathway, such as itraconazole and grapefruit juice, can influence drug exposure levels that may result in other clinical complications, such as hospitalizations due to severe muscle problems.(1)

"Many patients taking statins require additional medications to address other cardiovascular risk factors or comorbid diagnoses, which can result in drug-drug interactions and subsequent noncompliance," said Peter P. Toth, M.D., Ph.D., Director of Preventive Cardiology, Sterling Rock Falls Clinic, Ltd. "While statins are the mainstay of dyslipidemia management, there is still an unmet need among these patients who take multiple medications. These data suggest that LIVALO is a clinically effective and well-tolerated statin that has less potential for these types of interactions."

The open-label study was conducted to determine the potential pharmacokinetic interaction of itraconazole (200 mg), an antifungal agent that strongly inhibits CYP3A4, on the pharmacokinetics of LIVALO (4 mg). The secondary objective assessed the safety of LIVALO 4 mg with the addition of itraconazole. Eighteen healthy males (aged 18 to 55 years) received LIVALO 4 mg once daily on days 1 and 8, and itraconazole 200 mg once daily on days 5 to 9. The results of this study showed that itraconazole did not increase plasma concentrations of LIVALO or its main metabolite pitavastatin lactone, potentially reducing the incidence of adverse events.

Additionally, LIVALO was shown to be well tolerated both as monotherapy and when combined with itraconazole and was not associated with any moderate or severe adverse events or clinically relevant changes in laboratory, vital or physical signs or ECG. No subjects withdrew from the study.

"This study suggests that, compared with other commonly prescribed statins, LIVALO's metabolic route may offer a favorable tolerability profile when administered with drugs that inhibit CYP3A4," said Roger E. Morgan, M.D., Chief Medical Officer, Kowa Research Institute. "Combined with LIVALO's safety and efficacy profile, the low incidence of drug-drug interactions represents a benefit in the long-term treatment of patients with dyslipidemia."

These results support previous LIVALO studies showing that grapefruit juice did not have a significant effect on plasma concentrations (<15%).( )