Liver enzyme elevations during statin-ezetimibe therapy in

Introduction: Statin-ezetimibe combination therapy is widely used and generally well tolerated; however, liver enzyme elevations may occur during treatment and can be difficult to interpret in patients with polypharmacy and other contributing factors. The potential role of drug-drug-gene interactions (DDGIs) in this context remains insufficiently explored. Materials and Methods: We present a series of 11 patients from the PGx-CardioDrug study, selected for documented liver enzyme elevations during statin-ezetimibe therapy that led to treatment modification and carriage of the Results: The series included six women and five men, aged 27-78 years. Muscle symptoms and/or creatine kinase (CK) elevations were observed in six patients, including two with rhabdomyolysis requiring hospitalization. Dose reduction, drug discontinuation, or switching to alternative lipid-lowering therapy resulted in improvement of laboratory parameters in several patients. In two patients, abnormalities persisted or increased during subsequent ezetimibe monotherapy. Follow-up laboratory results were not available for all patients. Eight patients had the Discussion: These cases illustrate the difficulty of interpreting liver enzyme elevations during statin-ezetimibe therapy in patients with concomitant medications and other contributing factors. The narrative review provides a pharmacokinetic rationale for considering DDGIs, but the case series does not establish their contribution to the observed abnormalities. Genotype-based selection, incomplete clinical data, and the small descriptive comparator group limit interpretation. These observations remain hypothesis-generating.