- Marc L Miller, MD
Marc L Miller, MD
- Clinical Assistant Professor of Medicine
- Tufts University School of Medicine
- Section Editors
- Ira N Targoff, MD
Ira N Targoff, MD
- Section Editor — Muscle Disease
- Professor of Medicine, Section of Rheumatology
- University of Oklahoma Health Sciences Center
- Jeremy M Shefner, MD, PhD
Jeremy M Shefner, MD, PhD
- Section Editor — Neuromuscular Disease
- Professor and Chair of Neurology, Barrow Neurological Institute
- Professor of Neurology, University of Arizona, Phoenix
- Clinical Professor of Neurology, Creighton University
Although the precise incidence is unknown, drug-induced myopathy is among the most common causes of muscle disease. Drug-induced myopathy ranges from mild myalgias with or without mild weakness to chronic myopathy with severe weakness and to massive rhabdomyolysis with acute renal failure [1,2]. Over 150 agents have been associated with rhabdomyolysis . This topic will review drug-induced myopathies. Rhabdomyolysis and statin myopathy are discussed in detail separately. (See "Causes of rhabdomyolysis" and "Clinical manifestations and diagnosis of rhabdomyolysis" and "Statin myopathy".)
Drug-induced myopathy may result from several different mechanisms [4,5]:
●Direct myotoxicity – Examples include alcohol, cocaine, glucocorticoids, lipid-lowering drugs, antimalarials (which are associated with vacuolar myopathies), colchicine (which is associated with vacuolar myopathies), and zidovudine (which causes a mitochondrial myopathy).
●Immunologically induced inflammatory myopathy – The myopathy associated with D-penicillamine is an example of this mechanism.
●Indirect muscle damage – This problem can occur by a variety of mechanisms including drug-induced coma with subsequent ischemic muscle compression, drug-induced hypokalemia (eg, diuretics), drug-induced hyperkinetic states (eg, delirium tremens or seizures secondary to alcohol), dystonic states associated with phenothiazines, hyperthermia related to cocaine use, and the neuroleptic malignant syndrome.
- Zuckner J. Drug-related myopathies. Rheum Dis Clin North Am 1994; 20:1017.
- Prendergast BD, George CF. Drug-induced rhabdomyolysis--mechanisms and management. Postgrad Med J 1993; 69:333.
- Curry SC, Chang D, Connor D. Drug- and toxin-induced rhabdomyolysis. Ann Emerg Med 1989; 18:1068.
- Lane RJ, Mastaglia FL. Drug-induced myopathies in man. Lancet 1978; 2:562.
- Sieb JP, Gillessen T. Iatrogenic and toxic myopathies. Muscle Nerve 2003; 27:142.
- von Kemp K, Herregodts P, Duynslaeger L, et al. Muscular fibrosis due to chronic intramuscular administration of narcotic analgesics. Acta Clin Belg 1989; 44:383.
- Stricker BH, van Kasteren BJ. Diclofenac-induced isolated myonecrosis and the Nicolau syndrome. Ann Intern Med 1992; 117:1058.
- Haller RG, Knochel JP. Skeletal muscle disease in alcoholism. Med Clin North Am 1984; 68:91.
- Gabow PA, Kaehny WD, Kelleher SP. The spectrum of rhabdomyolysis. Medicine (Baltimore) 1982; 61:141.
- Song SK, Rubin E. Ethanol produces muscle damage in human volunteers. Science 1972; 175:327.
- Lafair JS, Myerson RM. Alcoholic myopathy. With special reference to the significance of creatine phosphokinase. Arch Intern Med 1968; 122:417.
- Martin F, Ward K, Slavin G, et al. Alcoholic skeletal myopathy, a clinical and pathological study. Q J Med 1985; 55:233.
- Urbano-Márquez A, Estruch R, Fernández-Solá J, et al. The greater risk of alcoholic cardiomyopathy and myopathy in women compared with men. JAMA 1995; 274:149.
- Urbano-Marquez A, Estruch R, Navarro-Lopez F, et al. The effects of alcoholism on skeletal and cardiac muscle. N Engl J Med 1989; 320:409.
- Eisner V, Lenaers G, Hajnóczky G. Mitochondrial fusion is frequent in skeletal muscle and supports excitation-contraction coupling. J Cell Biol 2014; 205:179.
- Fernandez-Sola J, Estruch R, Grau JM, et al. The relation of alcoholic myopathy to cardiomyopathy. Ann Intern Med 1994; 120:529.
- Roth D, Alarcón FJ, Fernandez JA, et al. Acute rhabdomyolysis associated with cocaine intoxication. N Engl J Med 1988; 319:673.
- Herzlich BC, Arsura EL, Pagala M, Grob D. Rhabdomyolysis related to cocaine abuse. Ann Intern Med 1988; 109:335.
- Pogue VA, Nurse HM. Cocaine-associated acute myoglobinuric renal failure. Am J Med 1989; 86:183.
- Singhal PC, Rubin RB, Peters A, et al. Rhabdomyolysis and acute renal failure associated with cocaine abuse. J Toxicol Clin Toxicol 1990; 28:321.
- Brody SL, Wrenn KD, Wilber MM, Slovis CM. Predicting the severity of cocaine-associated rhabdomyolysis. Ann Emerg Med 1990; 19:1137.
- Zamora-Quezada JC, Dinerman H, Stadecker MJ, Kelly JJ. Muscle and skin infarction after free-basing cocaine (crack). Ann Intern Med 1988; 108:564.
- Parks JM, Reed G, Knochel JP. Cocaine-associated rhabdomyolysis. Am J Med Sci 1989; 297:334.
- Estes ML, Ewing-Wilson D, Chou SM, et al. Chloroquine neuromyotoxicity. Clinical and pathologic perspective. Am J Med 1987; 82:447.
- Wittes R. Neuromyopathy associated with amodiaquine hydrochloride. CMAJ 1987; 137:635.
- Avina-Zubieta JA, Johnson ES, Suarez-Almazor ME, Russell AS. Incidence of myopathy in patients treated with antimalarials. A report of three cases and a review of the literature. Br J Rheumatol 1995; 34:166.
- Stein M, Bell MJ, Ang LC. Hydroxychloroquine neuromyotoxicity. J Rheumatol 2000; 27:2927.
- Newton-Cheh C, Lin AE, Baggish AL, Wang H. Case records of the Massachusetts General Hospital. Case 11-2011. A 47-year-old man with systemic lupus erythematosus and heart failure. N Engl J Med 2011; 364:1450.
- Iglesias Cubero G, Rodriguez Reguero JJ, Rojo Ortega JM. Restrictive cardiomyopathy caused by chloroquine. Br Heart J 1993; 69:451.
- Ratliff NB, Estes ML, Myles JL, et al. Diagnosis of chloroquine cardiomyopathy by endomyocardial biopsy. N Engl J Med 1987; 316:191.
- Cotroneo J, Sleik KM, Rene Rodriguez E, Klein AL. Hydroxychloroquine-induced restrictive cardiomyopathy. Eur J Echocardiogr 2007; 8:247.
- Kuncl RW, Duncan G, Watson D, et al. Colchicine myopathy and neuropathy. N Engl J Med 1987; 316:1562.
- Uri DS, Biavis M. Colchicine neuromyopathy. J Clin Rheumatol 1996; 2:163.
- Schiff D, Drislane FW. Rapid-onset colchicine myoneuropathy. Arthritis Rheum 1992; 35:1535.
- Wallace SL, Singer JZ, Duncan GJ, et al. Renal function predicts colchicine toxicity: guidelines for the prophylactic use of colchicine in gout. J Rheumatol 1991; 18:264.
- van der Velden W, Huussen J, Ter Laak H, de Sévaux R. Colchicine-induced neuromyopathy in a patient with chronic renal failure: the role of clarithromycin. Neth J Med 2008; 66:204.
- Rutkove SB, De Girolami U, Preston DC, et al. Myotonia in colchicine myoneuropathy. Muscle Nerve 1996; 19:870.
- Duarte J, Cabezas C, Rodríguez F, et al. Colchicine-induced myopathy with myotonia. Muscle Nerve 1998; 21:550.
- Vanin JR. Ipecac abuse--danger. J Am Coll Health 1992; 40:237.
- Spielmann L, Messer L, Moreau P, et al. Gemcitabine-induced myopathy. Semin Arthritis Rheum 2014; 43:784.
- Burris HA 3rd, Hurtig J. Radiation recall with anticancer agents. Oncologist 2010; 15:1227.
- Ardavanis AS, Ioannidis GN, Rigatos GA. Acute myopathy in a patient with lung adenocarcinoma treated with gemcitabine and docetaxel. Anticancer Res 2005; 25:523.
- Brunasso AM, Aberer W, Massone C. New onset of dermatomyositis/polymyositis during anti-TNF-α therapies: a systematic literature review. ScientificWorldJournal 2014; 2014:179180.
- Cirigliano G, Della Rossa A, Tavoni A, et al. Polymyositis occurring during alpha-interferon treatment for malignant melanoma: a case report and review of the literature. Rheumatol Int 1999; 19:65.
- Dietrich LL, Bridges AJ, Albertini MR. Dermatomyositis after interferon alpha treatment. Med Oncol 2000; 17:64.
- Hengstman GJ, Vogels OJ, ter Laak HJ, et al. Myositis during long-term interferon-alpha treatment. Neurology 2000; 54:2186.
- Kälkner KM, Rönnblom L, Karlsson Parra AK, et al. Antibodies against double-stranded DNA and development of polymyositis during treatment with interferon. QJM 1998; 91:393.
- Sheik Ali S, Goddard AL, Luke JJ, et al. Drug-associated dermatomyositis following ipilimumab therapy: a novel immune-mediated adverse event associated with cytotoxic T-lymphocyte antigen 4 blockade. JAMA Dermatol 2015; 151:195.
- Halla JT, Fallahi S, Koopman WJ. Penicillamine-induced myositis. Observations and unique features in two patients and review of the literature. Am J Med 1984; 77:719.
- Carroll GJ, Will RK, Peter JB, et al. Penicillamine induced polymyositis and dermatomyositis. J Rheumatol 1987; 14:995.
- Takahashi K, Ogita T, Okudaira H, et al. D-penicillamine-induced polymyositis in patients with rheumatoid arthritis. Arthritis Rheum 1986; 29:560.
- DRUGS CAUSING DIRECT MYOTOXICITY
- - Acute myopathy
- - Chronic myopathy
- Lipid-lowering drugs
- Antimalarial drugs
- Antipsychotic drugs
- Antiretroviral drugs
- Chemotherapeutic agents
- DRUGS CAUSING AN IMMUNOLOGICALLY MEDIATED MYOPATHY
- Tumor necrosis factor inhibitors
- Interferon alfa