Ex) Article Title, Author, Keywords
Ex) Article Title, Author, Keywords
Pharmacoepidemiology and Risk Management 2023; 15(1): 81-93
Published online March 31, 2023 https://doi.org/10.56142/perm.23.0009
Copyright © Korean Society for Pharmacoepidemiology and Risk Management.
Junhyuk Chang1,2, Eunjung Choo1, Rae Woong Park2,4, Sukhyang Lee1,3
장준혁1,2, 추은정1, 박래웅2,4, 이숙향1,3
Correspondence to:Sukhyang Lee
College of Pharmacy, Ajou University, 206 Worldcup-ro, Suwon 16499, Korea
Tel: +82-31-219-3443
Fax: +82-31-219-3435
E-mail: suklee@ajou.ac.kr
This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Objective: Drug-induced rhabdomyolysis can cause acute kidney injury and rate of polypharmacy is high in the elderly. This study aimed to assess the incidence of rhabdomyolysis with combination therapy of CYP3A4 substrates (S) and inhibitors (I) in the elderly in Korea. Methods: Patients were selected from the 2017 elderly patient data (the Korean Health Insurance Review and Assessment Service - Aged Population Sample). The list of CYP3A4 S and I was taken from the Indiana university of pharmacy and converted to Korean ATC codes. Further selection criteria were a medication possession ratio greater than 80%, duration of medication 7 days or longer, and duration of follow-up 3 months or longer. The incidence and odds ratio of rhabdomyolysis with top 50 pairs of the combination of drugs were assessed. Comparative analysis of the association of rhabdomyolysis with patient characteristics and comorbidities was analyzed using Chi-square test. Logistic regression models were used to analyze the association with rhabdomyolysis for each variable. Results: Rhabdomyolysis was identified in 78 cases in 24,240 patients with 7 days or longer use (DC7), and 19 cases in 3,444 patients with 30 days or longer use (DC30) of CYP3A4 S and I. The comorbidities of severe liver disease and rheumatoid disease had a significant association. Among patients with DC7, the drug pairs (S,I) with significant adjusted odds ratio (aOR) were [clopidogrel, cimetidine] (0.32; 95% CI, 0.10–0.96). Among patients with DC30, the drug pairs with significant aOR were [atorvastatin and fluconazole] (16.13; 95% CI, 2.40–108.36), [alprazolam and amiodarone] (10.74; 95% CI, 1.62–71.38), [zolpidem tartrate and ciprofloxacin] (9.61; 95% CI, 1.38–66.83), [lansoprazole and amiodarone] (7.51; 95% CI, 1.04–54.23). Conclusion: In the elderly, the combination uses of CYP3A4 substrate and inhibitor with 30 days or longer use of atorvastatin and fluconazole had the highest risk of rhabdomyolysis with risk factors of comorbidities of liver disease or rheumatoid disease.
KeywordsRhabdomyolysis, Drug interaction, CYP3A4 substrate, CYP3A4 inhibitor
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