(AA) Adverse Events of Myopathy After Comedication of Statin-Contraindicated Drugs: Case/Noncase Study Using Korea Adverse Event Reporting System (KAERS) Database, 2016-2020

Publication Number: 672

Background: Statin-associated muscle symptoms range from potentially life-threatening rhabdomyolysis and necrotizing autoimmune myopathy and vary considerably in frequency and severity. The risk of muscle-related adverse events may be significantly increased when an interactive drug is added to the treatment of patients taking statins. Previous studies have reported that potential Drug-drug interactions (DDIs) may increase the risk of statin-related myopathy, and several drug are included as contraindicated to prescribed with statins in Korean national drug utilization review (DUR) system. However, there have been no studies focusing on contraindication conducted using the Korea Institute of Drug Safety & Risk Management-Korea adverse event reporting system database (KIDS-KD).

Objectives: To assess patterns of spontaneous reporting of myopathy following combined use of statin-contraindicated drugs, compared with reports of non-myopathy.

Methods: Among the individual cases safety reports (ICSRs) reported to the KIDS-KD from 2016 to 2020, the drug of interest was a statin and the selection criteria were statin classified as C10AA HMG CoA reductase inhibitors according to the Anatomical Therapeutic Chemical (ATC) Classification System code (out of 8 types of detailed component name classification, 7 types of domestically marketed drugs). The combinations of statin and contraindicated drug were extracted from DUR criteria in Korea. We defined myopathy cases using ‘Myopathy’ and ‘Rhabdomyolysis’ among MedDRA SMQ terms, and matched appropriate WHO-ART code in which AE terms are recorded in the database. Non-cases were defined as all reports with other AEs. In statistical analysis, a logistic regression model was used to calculate the reported odds ratios (RORs) and 95% confidence intervals (CI) for case/non-case.

Results: Among total of 1,011,234 spontaneous reported ICSRs in KIDS-KD, the number of ICSRs of included myopathy was 18,886 (reports with statin, n=2,109; reports without statin, n=16,777). The most reported contraindicated drug with a statin was ‘Cyclosporine’, with 114 reported cases. The ROR of myopathy associated with statins with contraindicated drugs was 7.71 (95% CI,4.63–12.83), and statins without contraindicated drugs was 3.43 (95% CI,1.96-6.00).

Conclusions: Although we identified signals of increased reports of myopathy associated with ‘contraindicated concomitant drugs with statins’, ‘concomitant drugs with statins’ also showed significant ROR. Further pharmacoepidemiological studies on the use of Statin-contraindicated drugs are needed.