Correspondence |
Worsening myopathy associated with ezetimibe in a patient with McArdle disease
Sir,McArdle disease (MD) is the most common disorder of muscle carbohydrate metabolism, caused by mutations in the gene that encodes myophosphorylase.1 Only striated muscles are involved, hence the clinical picture of exercise intolerance, muscle cramps and myoglobinuria secondary to rhabdomyolysis. This predisposition to rhabdomyolysis may exclude the use of certain drugs in MD patients. Ezetimibe, an inhibitor of intestinal cholesterol absorption, is well tolerated, and no adverse muscular effects have been reported to date.2
An overweight 45-year-old White man, diagnosed with MD by biochemical profile and muscular biopsy, with essential hypertension, type 2 diabetes mellitus, hypercholesterolemia and hypertryglyceridemia suffered a non-Q-wave myocardial infarction. Treatment with low fat and low calorie diet, insulin, ramipril, bisoprolol and aspirin was started. His lipid profile slightly improved (Table 1) but remained above recommended levels according to his estimated cardiovascular risk score. Given the absence of muscular symptoms and the low level of creatine kinase (CK), we added ezetimibe 10 mg/day to his therapy. For the first three months it was well tolerated. CK levels slightly increased, with no weakness or muscular cramps. The patient remained stable for 20 weeks, when he started to complain of fatigue, with impairment of exercise tolerance. Four weeks later, CK levels dramatically increased, and the patient eventually reported slight myoglobinuria and severe weakness. No drugs other than those scheduled had been taken, and he had carefully avoided physical exertion during this period. Ezetimibe was discontinued, and the patient recovered uneventfully. CK levels returned to previous values after 4 weeks, and the patient remains stable 6 months later.
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Myotoxicity is a well known side-effect of statins, with a reported incidence of 1–7%.3 No cases of rhabdomyolysis due to monotherapy with ezetimibe have been described. However, myopathy triggered by ezetimibe in patients taking statins has been documented in two patients.4 Although MD is a known cause of rhabdomyolysis, the present case strongly suggests that myotoxicity may be elicited by ezetimibe, and poses the question of whether ezetimibe may trigger muscular damage by mechanisms that are presently unknown.
Servicio de Medicina Interna Hospital Clinico Universitario "Lozana Blesa" Zaragoza Spain e-mail: mibh-jperez{at}hcu-lblesa.es
Hospital Universitario ‘Miguel Servet’ Zaragoza Spain
Departamento de Anatomía Patológica Hospital Universitario ‘12 de Octubre’ Madrid Spain
References
1. Lebo RV, Gorin F, Fletterick RJ, Kao FT, Cheung MC, Bruce BD, et al. High-resolution chromosome sorting and DNA spot-blot analysis assign McArdle's syndrome in chromosome 11. Science 1984; 225:57–9.
2. Bays HE, Moore PB, Drehobl MA, Rosenblatt S, Coth PD, Dujovne CA, et al. Effectiveness and tolerability of ezetimibe in patients with primary hypercholesterolemia: pooled analysis of two phase studies. Clin Ther 2001; 23:1209–30.[CrossRef][Web of Science][Medline]
3. Evans M, Rees A. The myotoxicity of statins. Curr Opin Lipidol 2002; 13:415–20.[CrossRef][Web of Science][Medline]
4. Fux R, Mörike K, Gundel UF, Hartmann R, Gleiter CH. Ezetimibe and statin associated myopathy. Ann Intern Med 2004; 40:671–2.
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