Monotherapy with erythromycin results in severe rhabdomyolysis

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1 CASE REPORT PEER REVIEWED OPEN ACCESS Monotherapy with erythromycin results in severe rhabdomyolysis Lukas Birkner, Dimitri Zolotov, Mario Iasevoli ABSTRACT Introduction: Rhabdomyolysis is a potentially life-threatening condition caused by muscle necrosis and extravasation of intracellular muscle contents into the blood circulation. An elevation in serum creatine kinease is most confirmatory laboratory test. Erythromycin is an inhibitor of the CYP3A4 enzyme system which is responsible for the metabolism of several drugs, particularly some statins. Although rhabdomyolysis asssociated with macrolid-statin interaction has been previously described, we report the first case of erythromycin-induced rhabdomyolysis. Case Report: In our case, a 38-year-old male admitted with pneumonia developed rhabdomyolysis associated with erythromycin administration. Conclusion: Clinicians need to be aware of the risks this potential adverse drug reaction poses. International Journal of Case Reports and Images (IJCRI) International Journal of Case Reports and Images (IJCRI) is an international, peer reviewed, monthly, open access, online journal, publishing high-quality, articles in all areas of basic medical sciences and clinical specialties. Aim of IJCRI is to encourage the publication of new information by providing a platform for reporting of unique, unusual and rare cases which enhance understanding of disease process, its diagnosis, management and clinico-pathologic correlations. IJCRI publishes Review Articles, Case Series, Case Reports, Case in Images, Clinical Images and Letters to Editor. Website: (This page in not part of the published article.)

2 Birkner et al. 551 CASE case REPORT report Peer Reviewed OPEN ACCESS Monotherapy with erythromycin results in severe rhabdomyolysis Lukas Birkner, Dimitri Zolotov, Mario Iasevoli Abstract Introduction: Rhabdomyolysis is a potentially life-threatening condition caused by muscle necrosis and extravasation of intracellular muscle contents into the blood circulation. An elevation in serum creatine kinease is most confirmatory laboratory test. Erythromycin is an inhibitor of the CYP3A4 enzyme system which is responsible for the metabolism of several drugs, particularly some statins. Although rhabdomyolysis asssociated with macrolid-statin interaction has been previously described, we report the first case of erythromycin-induced rhabdomyolysis. Case Report: In our case, a 38-year-old male admitted with pneumonia developed rhabdomyolysis associated with erythromycin administration. Conclusion: Clinicians need to be aware of the risks this potential adverse drug reaction poses. Keywords: Erythromycin, Penicillin intolerance, Pneumonia, Rhabdomyolysis Lukas Birkner 1, Dimitri Zolotov 1, 2, Mario Iasevoli 1 Affiliations: 1 MD, Department of Internal Medicine, Ev, Krankenhaus Witten ggmbh, University of Witten/Herdecke, Pferdebachstr, 27, Witten, Germany; 2 MD, Dialysis Practice of Internal and nephrology Medicine, Pferdebachstr. 11, Witten, Germany. Corresponding Author: Dr. Med. Lukas Birkner, Department of Internal Medicine Ev Krankenhaus Witten ggmbh, University of Witten/Herdecke, Pferdebachstr 27, Witten, Germany; lukasbirkner@freenet.de Received: 07 March 2016 Accepted: 26 May 2016 Published: 01 August 2016 How to cite this article Birkner L, Zolotov D, Iasevoli M. Monotherapy with erythromycin results in severe rhabdomyolysis. Int J Case Rep Images 2016;7(8): Article ID: Z CR10686LB ********* doi: /ijcri cr INTRODUCTION Rhabdomyolysis is a potentially life-threatening condition characterized by the leaking of creatine kinease and other intracellular proteins and electrolytes into the blood circulation [1]. The most common symptoms of rhabdomyolysis include muscle weakness, brown urine, electrolyte imbalances, acute renal failure and disseminated intravascular coagulation. An elevation in serum creatine kinase (CK) and myoglobin is the most confirmatory laboratory test for rhabdomyolysis since all cases are associated with it [2, 3]. Although there are multiple physical and nonphysical causes of rhabdomyolysis the most common cause is medication [4]. Especially, rhabdomyolysis related to macrolide-statin interaction, such as clarithromycin or ketoconazole interacting with simvastatin, has been previously described in literature [5]. CASE REPORT We report a case of 38-year-old male presented with a clinical diagnosis of common acquired pneumonia.

3 He was treated with erythromycin (500 mg two times a day) for one and a half days due to a known penicillin intolerance. The patient subsequently developed joint and muscle pain after the first day of administration and an anuria with growing nausea after the second day without a documented source of infection. Consequently, the patient was admitted to our inpatient hospital complaining of an anuria. An extremely elevated creatine kinase concentration of U/L (normal <200) was discovered after the first day of hospitalization and reached U/L the following day. The estimated glomerular filtration rate (GFR) was reduced to <10 ml/min (normal 120 ml/min per 1.73 m 2 ). Other parameters indicating rhabdomyolysis were serum aspartate aminotransferase (AST) 5789 U/l (normal 5 34), serum alanine aminotransferase (ALT) 1093 U/l (normal < 55) and serum lactate dehydrogenase (LDH) increased to a maximum of 10,100 U/l (normal ). Rhabdomyolysis associated with acute renal failure and hepatopathy was diagnosed. Erythromycin was immediately stopped and the patient received dialysis treatment as required over the course of two and a half weeks. The serum CK gradually decreased. Two weeks later creatine kinase returned to 2927 U/L. During the course of the dialysis treatment the micturition gradually increased and muscle pain subdued. No further laboratory tests were ordered. Erythromycin was thought to be the precipitating factor for rhabdomyolysis because the patient was neither taking other medication nor had a conspicious anamnesis or relevant pre-existing conditions. Additionally, using the Naranjo adverse drug reactions probability scale a score of 6 was determined. Thus erythromycin can be considered a probable cause of rhabdomyolysis [6]. DISCUSSION Rhabdomyolysis associated with macrolid-statin interaction has been previously described, however, rhabdomyolisis related to erythromycin has not been reported until now [7]. Erythromycin is an inhibitor of the CYP3A4 enzyme system, which is responsible for the metabolism of several drugs, particularly some statins as simvastatin or atorvastatin. Any documented cases of erythromycin induced rhabdomyolysis involved drug interactions with statins through inhibition of CYP3A4 enzyme system. It has a similar spectrum of activity as clarithromycin [8]. Of interest, clarithromycin induced rhabdomyolysis has been previously reported in a few cases. A five-year-old Asian-American girl was admitted with 102ºF fever and a five-day history of productive cough. The patient was prescribed clarithromycin 125 mg twice a day. After five days a creatine kinase concentration of 949 U/L (normal <177) was discovered. Clarithromycin was immediately stopped and the child recovered [9, 10]. Undoubtedly, Birkner et al. 552 both cases show parallels, such as the elevation of serum CK associated with the respective drug and the course of recovery, although differences in the severity must be noted. In our case, there was a definite connection between erythromycin exposure-withdrawal and the gradual recovery of the patient. Considering the sequence of events we ruled out infection as the possible cause of rhabdomyolysis. As a matter of fact the patients symptoms were inconspicious, while serum CK drastically increased one day after the start of treatment with erythromycin. Thus, the chronological relationship between the appearance of myalgia and the start of erythromycin suggest the conclusion that erythromycin is the responsible agent in our case. CONCLUSION We reported a probable case of erythromycin-induced rhabdomyolysis. The mechanism behind this adverse drug reaction is not understood, although there have been a few cases of rhabdomyolysis associated with macrolides. Clinicians need to be aware of the risks this potential adverse drug reaction poses, espeacially concerning patients at risk for rhabdomyolysis. ********* Author Contributions Lukas Birkner Substantial contributions to Dimitri Zolotov Substantial contributions to Mario Iasevoli Substantial contributions to Guarantor The corresponding author is the guarantor of submission. Conflict of Interest Authors declare no conflict of interest. Copyright 2016 Lukas Birkner et al. This article is distributed under the terms of Creative Commons Attribution

4 License which permits unrestricted use, distribution and reproduction in any medium provided the original author(s) and original publisher are properly credited. Please see the copyright policy on the journal website for more information. REFERENCES 1. Miller ML. Clinical manifestations and diagnosis of Rhabdomyolysis. UpToDate, [Available at: clinical-manifestations-and-diagnosis-ofrhabdomyolysis#h ] 2. Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury. N Engl J Med 2009 Jul 2;361(1): Khan FY. Rhabdomyolysis: a review of the literature. Neth J Med 2009 Oct;67(9): Mannix R, Tan ML, Wright R, Baskin M. Acute pediatric rhabdomyolysis: causes and rates of renal failure. Pediatrics 2006 Nov;118(5): Spach DH, Bauwens JE, Clark CD, Burke WG. Rhabdomyolysis associated with lovastatin and Birkner et al. 553 erythromycin use. West J Med 1991 Feb;154(2): Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981 Aug;30(2): Campbell G, Jayakumar U, McCracken S, Bene J. A cautionary tale: delayed onset rhabdomyolysis due to erythromycin/simvastatin interaction. Age Ageing 2007 Sep;36(5): Westphal JF. Macrolide - induced clinically relevant drug interactions with cytochrome P-450A (CYP) 3A4: an update focused on clarithromycin, azithromycin and dirithromycin. Br J Clin Pharmacol 2000 Oct;50(4): Schor AM, Hellerstein A. Rhabdomyolysis following a short course of clarythromycin. J Pediatr Pharmacol Ther 2011 Jul;16(3): Pasqualetti G, Bini G, Tognini S, Polini A, Monzani F. Clarithromycin-induced rhabdomyolysis: a case report. Int J Gen Med 2012;5: Access full text article on other devices Access PDF of article on other devices

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