(254) Incidence of Rhabdomyolysis in The Elderly Patients in Combination Therapy of Cytochrome 3A4 Substrate and Inhibitor with the Korean Elderly Claims Data

Publication Number: 928

Background: Drug-induced rhabdomyolysis can cause acute kidney injury. Polypharmacy is high in the elderly.

Objectives: This study aimed to examine the incidence of rhabdomyolysis with combination therapy of CYP3A4 substrates and CYP3A4 inhibitors in the elderly in Korea

Methods: Patients using CYP3A4 substrates and inhibitors were selected from the 2017 elderly patient data (the Korean Health Insurance Review and Assessment Service - Aged Population Sample, HIRA-APS). Further selection criteria were patients with a medication possession ratio greater than 80%, duration of medication 7 days or longer, and duration of follow-up 3 months or longer patients.
The basic demographic information was collected for age, gender, type of health insurance, comorbidity, and drug pairs taken. The top 50 drug pairs and odds ratio of incidence rhabdomyolysis were extracted. The incidence of rhabdomyolysis due to basic characteristics and coexistence of diseases was analyzed.

Results: Rhabdomyolysis was identified in 78 in 24,240 patients with 7 days or longer use, and 19 in 3,444 patients with 30 days or longer use of drug pairs combined. Among comorbidities, severe liver disease and rheumatoid disease had a significant association with the incidence of rhabdomyolysis.
Among patients with 7 days or longer use, the drug pairs [substrate, inhibitor] with significant adjusted odds ratio (aOR) were [clopidogrel, cimetidine] (aOR, 0.32; 95% CI, 0.10-0.96), [esomeprazole, cimetidine] (aOR, 3.76; 95% CI, 1.61-8.77), [lidocaine, cimetidine] (aOR, 3.00; 95% CI, 1.35-6.68). Among patients with 30 days or longer use, the drug pairs with significant aOR were [atorvastatin, fluconazole] (aOR, 16.13; 95% CI, 2.40-108.36), [alprazolam, amiodarone] (aOR, 10.74; 95% CI, 1.62-71.38), [zolpidem tartrate, ciprofloxacin] (aOR, 9.61; 95% CI, 1.38-66.83), [lansoprazole, amiodarone] (aOR, 7.51; 95% CI,1.04-54.23).

Conclusions: In the elderly patients, the combination uses of drug pairs with CYP3A4 substrate and inhibitor had shown a higher risk of rhabdomyolysis. Among patients with 30 days or longer use of drug pairs, the combination of atorvastatin and fluconazole had the highest risk of rhabdomyolysis. The comorbidities of liver disease or rheumatoid disease were the risk factor for rhabdomyolysis.