Pitavastatin therapy in polymedicated patients is associated with a low risk of drug-drug interactions: analysis of real-world and phase 3 clinical trial data

Abstract

Objectives: Medications that interact with the pathways responsible for statin metabolism may increase the risk of statin-associated myalgia. Pharmacokinetic studies show that pitavastatin is carried into the liver by a range of transporters and is minimally metabolized by cytochrome P450 in healthy volunteers, indicating a reduced potential for drug-drug interactions (DDIs). This post hoc analysis investigates the incidence of adverse events in patients receiving pitavastatin with concomitant medication in two large data sets.

Methods: The largest pitavastatin patient data sets are the LIVALO Effectiveness and Safety (LIVES) postmarketing surveillance study in Japan (n = 19,925) and the European phase 3 clinical trial program (n = 2,396). Adverse events were classified according to the Medical Dictionary for Regulatory Activities (Med-DRA) and whether they occurred in patients taking medications that interact with hepatocyte organic anion-transporting polypeptide or cytochrome P450 (CYP) isoenzyme pathways.

Results: Concomitant administration of pitavastatin with other medications was not associated with clinically significant increases in the incidence of adverse drug reactions (ADRs), even when given with medications that interact with CYP2C9, responsible for the minimal CYP metabolism of pitavastatin. There was a significant interaction with biguanides in LIVES, but this was associated with a reduced risk of muscle ADRs.

Conclusion: In clinical trials, pitavastatin is associated with a low incidence of adverse events related to DDIs, consistent with data from healthy volunteers. Prescribing a metabolically stable statin, such as pitavastatin, may improve patient adherence to medication, thus facilitating the attainment of lipid targets and reducing cardiovascular risk.