Rhabdomyolysis requiring emergency dialysis as a consequence of simultaneous administration of simvastatin and clarithromycin

Rhabdomyolysis requiring emergency dialysis as a consequence of simultaneous administration of simvastatin and clarithromycin

Michael Toolis1, Iouri Banakh2, John Botha3

1Intensive Care Consultant, Frankston Hospital and Latrobe Regional Hospital, Victoria, Australia; 2Senior Pharmacist Critical Care and Surgery, Frankston Hospital, Victoria, Australia; 3Intensive Care Consultant, Frankston Hospital, Victoria, Australia

International-Journal-of-Case-Reports-2d code

Iatrogenic complications from polypharmacy have significantly increased over the past decade and clinicians and pharmacists must remain aware of potentially dangerous drug interactions 1–3. Our case is a reminder of the potential for significant patient harm from drug interactions when additional medication that is seemingly innocuous is prescribed in addition to a patient’s regular long-term medications. Our case also highlights the diagnosis and management of rhabdomyolysis and acute kidney injury.

A 75-year-old Caucasian male presented to the emergency department with nausea, bilateral calf tenderness and a reduced urine output. Creatinine Kinase (CK) levels demonstrated severe rhabdomyolysis and the patient’s creatinine was significantly elevated with a concurrent metabolic acidosis requiring urgent renal replacement therapy in the intensive care unit (ICU). He was recently prescribed clarithromycin 500mg twice daily as part of Helicobacter pylori eradication therapy in addition to his regular combination therapy of simvastatin 80 mg and ezetimibe 10 mg daily dose.

Statins may cause dose dependent Statin Associated Myopathies (SAMs) such as myositis and rhabdomyolysis and are metabolised by the hepatic cytochrome P450 (CYP450) 3A4 enzyme4,5. Clarithromycin is a potent CYP450 3A4 hepatic enzyme inhibitor that leads to significantly elevated plasma levels of statin medications, increasing the risk of SAMs4,6–8. Our patient responded to the cessation of the offending medications and initiation of continuous renal replacement therapy. This case demonstrates the dangerous  side effects and interactions of commonly prescribed medications.

Keywords: Drug interaction, statins, macrolides, clarithromycin, simvastatin, rhabdomyolysis, acute kidney injury, dialysis

Free Full-text PDF

How to cite this article:

Michael Toolis, Iouri Banakh, John Botha. Rhabdomyolysis requiring emergency dialysis as a consequence of simultaneous administration of simvastatin and clarithromycin. International Journal of Case Reports, 2020 4:147. DOI: 10.28933/ijcr-2020-06-1805


1. Hubbard RE, Peel NM, Scott IA, Martin JH, Smith A, Pillans PI, et al. Polypharmacy among inpatients aged 70 years or older in Australia. Med J Aust. 2015;
2. Samuel MJ. American Geriatrics Society 2015 updated beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;
3. Banakh I. Polypharmacy in very elderly hospitalised patients: a single centre study. J Pharm Ther. 2018;
4. Stroes ES, Thompson PD, Corsini A, Vladutiu GD, Raal FJ, Ray KK, et al. Statin-associated muscle symptoms: impact on statin therapy – European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. European Heart Journal. 2015.
5. Thompson PD, Panza G, Zaleski A, Taylor B. Statin-associated side effects. Journal of the American College of Cardiology. 2016.
6. Enzymes CYP, Substrate V, Enzymes SCYP, Classification I. Drug Development and Drug Interactions : Table of Substrates , Inhibitors and Inducers. In Vivo. 2009.
7. Hylton Gravatt LA, Flurie RW, Lajthia E, Dixon DL. Clinical Guidance for Managing Statin and Antimicrobial Drug-Drug Interactions. Current Atherosclerosis Reports. 2017.
8. Hougaard Christensen MM, Bruun Haastrup M, Øhlenschlæger T, Esbech P, Arnspang Pedersen S, Bach Dunvald AC, et al. Interaction potential between clarithromycin and individual statins—A systematic review. Basic and Clinical Pharmacology and Toxicology. 2020.
9. Kashani A, Sallam T, Bheemreddy S, Mann DL, Wang Y, Foody JAM. Review of Side-Effect Profile of Combination Ezetimibe and Statin Therapy in Randomized Clinical Trials. Am J Cardiol. 2008;
10. Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;
11. Torres PA, Helmstetter JA, Kaye AM, Kaye AD. Rhabdomyolysis: pathogenesis, diagnosis, and treatment. Ochsner J. 2015;15(1):58–69.
12. Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. European Heart Journal. 2018.
13. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2018;
14. Aboyans V, Ricco JB, Bartelink MLEL, Björck M, Brodmann M, Cohnert T, et al. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS). European Heart Journal. 2018.
15. Grundy SM, Stone NJ, Chair V, Bailey AL, Beam C, Birtcher KK, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/ AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol Circulation. Circulation. 2018;
16. Rowan C, Brinker AD, Nourjah P, Chang J, Mosholder A, Barrett JS, et al. Rhabdomyolysis reports show interaction between simvastatin and CYP3A4 inhibitors. Pharmacoepidemiol Drug Saf. 2009;
17. Mitchell H, Katelaris P. Epidemiology, clinical impacts and current clinical management of helicobacter pylori infection. Med J Aust. 2016;
18. Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. American Journal of Gastroenterology. 2017.
19. Pasqualetti G, Bini G, Tognini S, Polini A, Monzani F. Clarithromycin-induced rhabdomyolysis: a case report. Vol. 5, International journal of general medicine. 2012. p. 283–5.
20. Ezad S, Cheema H, Collins N. Statin-induced rhabdomyolysis: a complication of a commonly overlooked drug interaction. Oxford Med Case Reports [Internet]. 2018 Mar 14;2018(3). Available from: https://doi.org/10.1093/omcr/omx104
21. Werion A, Komuta M, Descamps OS, Henrion J. Statins and Clarithromycin : a dangerous combination. Case report and review of the literature. Acta Gastroenterol Belg. 2019;82(1):87–92.
22. Lee AJ, Maddix DS. Rhabdomyolysis secondary to a drug interaction between simvastatin and clarithromycin. Ann Pharmacother. 2001;
23. Mellal AA, Hussain N, Said ASA. The clinical significance of statins-macrolides interaction: Comprehensive review of in vivo studies, case reports, and population studies. Therapeutics and Clinical Risk Management. 2019.

Terms of Use/Privacy Policy/ Disclaimer/ Other Policies:
You agree that by using our site, you have read, understood, and agreed to be bound by all of our terms of use/privacy policy/ disclaimer/ other policies (click here for details).

This work and its PDF file(s) are licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.