Myopathy is defined as any abnormal condition or disease of the muscle tissues, commonly involving skeletal tissue. Associated with strenuous muscular exercise, myopathy also has other causes, including alcoholism and idiopathic muscle destruction. Influenza and other viral illnesses also are considered causative.1 (TABLE 1) lists factors that have been associated with myopathy.) Many drugs have been implicated as causes of myopathy (TABLE 2), including antimalarials, colchicine, corticosteroids, lipid-lowering agents (particularly hydroxymethylglutaryl coenzyme A [HMG-CoA] reductase inhibitors), penicillamine, zidovudine, and drugs associated with abuse, such as alcohol and cocaine.
Drug-induced myopathy usually develops insidiously. The onset of clinical manifestations can occur from days to months after exposure to the causative agent.1,2 Commonly, patients present with nonspecific complaints of progressive, generalized muscle weakness, muscle pain (myalgia), or fatigue. Proximal muscle weakness of the arms and legs is the hallmark symptom. The weakness may range from mild to moderate, with or without myalgia, to debilitating quadriplegic weakness with severe myalgia and lethargy. In its most severe presentation, drug-induced myopathy may lead to rhabdomyolysis, a condition of acute massive muscle injury, which may lead to myoglobinuric acute renal failure. Despite its severity, it is usually reversible when treated promptly.3,4 Although the exact incidence of drug-induced myopathy is unknown, clinicians must be aware of agents known to cause the condition.
Fibric acids derivatives (clofibrate,
Certain HMG-CoA reductase inhibitors
(lovastatin, fluvastatin, simvastatin)
Drugs may cause muscle injury by direct, indirect, or immunologically mediated mechanisms.2,5,6 A drug need not be injected locally into a muscle to cause direct myotoxic effects. The majority of causative agents, such as antimalarials, colchicine, corticosteroids, fibric acid derivatives, HMG-CoA reductase inhibitors, and zidovudine, may invoke direct effects on muscle in a diffuse or generalized manner when administered systemically. Indirect myotoxic effects secondary to drug-induced coma (and subsequent ischemic muscle compression, seizures, and rhabdomyolysis) have been described with acute ingestion of alcohol or cocaine.7,8 Muscle injury may also be caused by a drug-induced immunological action directed at the muscle, also known as immune complex-mediated myositis.9,10 This type of inflammatory myotoxicity is associated with penicillamine.
Among the many factors considered in the differential diagnosis of myopathy, drugs are the usual suspects but are frequently overlooked because symptoms are often mild and nonspecific. Muscle strength is measured in both the proximal and distal limbs and typically reveals inability to overcome resistance with the affected limbs. Deep-tendon reflexes may be hypoactive or diminished. When neuropathy is present, sensations to pinprick are absent or reduced.1,2,11
In suspected cases of drug-induced myopathy, the plasma concentrations of cellular contents released from damaged muscle are assessed. These laboratory parameters include creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), aldolase myoglobin, and potassium and phosphorus, both of which increase with muscle injury. Serum CK is considered to be the most sensitive indicator, but its lack of specificity is a major limitation. In the presence of drug-induced myopathy, serum CK may be normal, slightly elevated, or as high as 10–20 times the upper normal limit.1,4
Although drug-induced myopathy may be responsible for the increase in the serum CK concentration, other causes should be considered in the differential diagnosis (TABLE 3).
Amyotrophic lateral sclerosis
Neuroleptic malignant syndrome
Diagnostic electromyography (EMG) is useful to detect myopathic changes consistent with drug-induced myopathies.1,2,11 EMG findings may reveal a reduction in myoelectrical activity or abnormal spontaneous activity, such as fibrillation potentials, positive sharp waves, or complex repetitive discharges of the affected muscle. Nerve conduction studies may be used to determine the presence of coexistent neuropathy of the axonal junction. Findings consistent with drug-induced axonal neuropathy include reduced amplitudes of motor and sensory responses with normal or borderline-slow conduction velocities.
A muscle biopsy, although not customarily performed, confirms the diagnosis of drug-induced myopathy.1,2 Histopathogical and histochemical markers found in the specimen should support the diagnosis of drug-induced myopathy. The muscle biopsy report is used to identify the type of affected muscle fibers (type I or II) and the extent of muscle damage (variability in size and atrophy). Morphological assessment may determine the presence of vacuoles, inflammation or necrosis, which are characteristic findings of muscle injury associated with drug-induced myopathies and polymyositis. Viral-induced polymyositis, a chronic myopathy, may be clinically and histopathologically indistinguishable from drug-induced myopathy, a self-limiting, reversible process. Viral cultures are routinely performed to rule out the presence of Guillain-Barré infection, a leading cause of chronic polymyositis.
Diagnostic findings associated with specific drugs are listed in TABLE 4. Although a muscle biopsy and drug rechallenge would allow a definite diagnosis, a probable diagnosis of drug-induced myopathy is often made when resolution of the myopathy occurs after the suspected offending agent is discontinued.
||normal or mildly elevated||+ / –||–||–||–|
|normal or mildly elevated||–||+||–||+|
|Corticosteroids||normal or mildly elevated||+ / –||–||–||–|
|Fibric acid derivatives||markedly elevated||+||–||+||–|
|normal to moderately elevated||+||–||–||–|
|Zidovudined||normal to moderately elevated||–||+||–||–|
|aCurvilinear and myeloid
inclusion bodies present on muscle biopsy
bLysosomes present on muscle biopsy
cInflammatory process with myositis or dermatomyositis
dMitochondrial abnormalities on muscle biopsy
+ = present; – = absent
The onset of drug-induced myopathy is usually insidious in the outpatient setting, but can be acute in the inpatient setting, where patients may develop drug-induced myopathy superimposed on comorbidities.11 Drug-induced myopathy is associated with a high incidence of morbidity. Prompt diagnosis and withdrawal of the offending agent is essential to curtail the duration and severity of symptoms.
Patients should be informed of the signs of rhabdomyolysis and be asked to report them to their physician immediately. Although the clinical presentation of drug-induced rhabdomyolysis is extremely varied, the presence of myalgias, weakness and dark urine may suggest this type of muscle injury. (When muscle tissue breaks down, myoglobin is released from muscle cells and may impart a red or red-brown color to the urine.) The condition is often dose-related, self-limiting, and completely reversible after the offending agent is withdrawn. Before a diagnosis of drug-induced rhabdomyolysis is made, all other causes of markedly increased serum CK levels should be ruled out. Myoglobinuric renal failure, a serious complication of rhabdomyolysis, is best managed with supportive treatment in an acute care setting.
Drug-Induced Myopathy Fact Sheet
Drug-induced myopathies are rare adverse events associated with drug therapy and are
usually completely reversible.
• Drug-induced myopathy is usually related to dose and/or duration of treatment, except with immune-complex mediated myopathy.
• Hepatic or renal failure, metabolic enzyme inhibition, comorbidities and concomitant use of myotoxic drugs increase the risk of drug-induced myopathy.
• Proximal weakness of the arms and legs is the hallmark clinical sign associated with drug-induced myopathy and may be present with or without myalgia.
• The signs and symptoms of drug-induced myopathy usually occur insidiously.
• Electromyography (EMG) and muscle biopsy confirm the diagnosis of drug-induced myopathy.
• Rhabdomyolysis and myoglobinuric renal failure are complications of drug-induced myopathy.
• Clinicians should recognize offending agents that are potentially myotoxic and educate prescribers and counsel patients.
• Drug-induced myopathy is primarily treated by discontinuing the offending agent or reducing the dose.
The clinical symptoms of muscle weakness and myalgia may take several weeks or months
to resolve after laboratory parameters such as muscle enzymes return to baseline.11
Patients should be counseled appropriately and alternative drug therapy attempted. If
necessary, a drug rechallenge with a lower dose may be indicated after laboratory
abnormalities resolve. The dose may be gradually titrated while the patient is carefully
Drugs Linked to Myopathy
Corticosteroids: Corticosteroids most commonly have been reported to cause drug-induced myopathy. Chronic administration of doses >10 mg prednisone (or its equivalent) per day may predispose patients to muscle injury. The underlying pathogenesis of steroid-induced myopathy associated with chronic use is a non-necrotic atrophic myopathy resulting in proximal muscle weakness without muscle pain or tenderness.12-14
Unlike with other drug-induced myopathies, serum CK concentration does not markedly increase with steroid myopathy. EMG is normal or may show low amplitude myopathic motor unit potentials and no signs of neuropathy. Muscle biopsy usually reveals an increased variation in the diameter of fibers and type IIb muscle fiber atrophy without muscle fiber inflammation or necrosis. However, a necrotizing steroid myopathy has also been reported to occur.15 Proximal muscle weakness of the lower and upper extremities is significantly related to the cumulative dose of steroid. An increase in muscle strength occurring 3–4 weeks after dose reduction usually indicates steroid-induced myopathy. However, chronic myopathy may persist after prolonged treatment with high doses of corticosteroids.
Acute myopathy is a cause of weakness in a variety of critically ill patients, including transplant recipients. In these patients, steroid-induced myopathy may lead to additional morbidity.16-18 Myopathy and the concurrent administration of corticosteroids and neuromuscular blockers are well described in the intensive care unit (ICU) setting.11 (In fact, the combined use of these drugs carries a greater risk for myopathy than does each drug separately.) Patients with myopathy remained in the ICU longer than unaffected patients or controls. Patients with steroid-induced myopathy may also experience a significant decline in respiratory function, leading to symptomatic dyspnea. The clinical course is usually reversible, with either improvement or resolution of weakness and respiratory impairment.
Malnutrition and negative nitrogen balance are risk factors for respiratory compromise to occur with steroids.19 In the presence of malignancy, respiratory function may be compromised even when proximal limb muscles remain strong. The need for close monitoring of dosage and signs and symptoms of muscle weakness in patients receiving steroids is essential.
Steroid myopathy may be reversible with a reduction of dose or discontinuation of the steroid. The effect of reducing exposure to corticosteroids in high-risk patients warrants further investigation.
Lipid-Lowering Agents: Lipid-lowering agents such as HMG-CoA reductase inhibitors (also known as statin drugs), are generally well tolerated. Side effects, mainly hepatic and muscular disorders, are rare. Myopathy in the presence of hepatic dysfunction may be severe, disabling, and lead to rhabdomyolysis.20 Risk factors associated with statin-induced myopathy include hepatic failure or renal insufficiency, metabolic enzyme inhibition, and concomitant use of other myotoxic agents.
Myopathy occurs less frequently (<0.5%) than myalgia (1%–7%) with HMG-CoA reductase inhibitors and is characterized by a >10-fold increase in serum CK concentration.21,22 Lovastatin, fluvastatin, pravastatin, and simvastatin all have been reported to cause myopathy. The pathogenesis of muscle injury with the statins has not been fully elucidated. It has been postulated that reductase inhibitors may disrupt muscle energy production by reducing ubiquinone, or coenzyme Q10, production.5 Although little data exist on the newer HMG-CoA reductase inhibitors, such as atorvastatin and cerivastatin, regarding myopathy, caution is necessary when the agents are given with other myotoxic drugs.21
Other lipid-lowering agents, such as the fibric acid derivatives (clofibrate, gemfibrozil) and niacin, also have low myotoxic potential.20,22,23 However, when used in combination with a statin, the incidence of myopathy and rhabdomyolysis increases. Lovastatin or gemfibrozil when used alone rarely lead to myopathy or rhabdomyolysis. Combined with gemfibrozil, lovastatin has been associated with a higher prevalence of both disorders.24 The incidence of lovastatin-induced myopathy when used alone is <0.5%. Combined with gemfibrozil, the incidence of myopathy with lovastatin is 5%–8%.
Furthermore, combined with enzyme inhibitors such as cyclosporine, lovastatin has been associated with a high incidence (30%) of rhabdomyolysis with myoglobinuria and renal failure.25 It is believed that cyclosporine inhibits cytochrome (CYP)3A3/4, the primary pathway in the metabolism of lovastatin, and may increase serum levels of lovastatin. Patients who are taking high therapeutic doses of lovastatin concomitantly with cyclosporine or other CYP3A3/4 enzyme inhibitors may be at increased risk for lovastatin-induced myopathy. Such toxicity is uncommon at low serum statin concentrations, but may occur when enzyme inhibition leads to elevated serum levels. The lowest therapeutic dose of lovastatin should be administered to avoid clinically significant drug interactions. Other CYP3A3/4 enzyme inhibitors, itraconazole, ketoconazole, and erythromycin, are also known to significantly increase lovastatin serum levels and lead to myopathy and rhabdomyolysis.21,26 In contrast, pravastatin is not metabolized by CYP3A3/4 to a clinically significant extent, and may have less propensity than lovastatin for drug interactions.
Serum CK levels are markedly elevated, and EMG findings reveal myopathic changes in cases of myopathy induced by lipid-lowering agents. When available, muscle biopsy characteristically shows widespread necrosis of type I and II muscle fibers.20,24 Initially, necrotizing myopathy manifests as severely painful muscle weakness and may lead to rhabdomyolysis.
Non-lipid-lowering properties of statin drugs, such as antiproliferative and immunosuppressive effects, are currently being investigated for prevention of restenosis following angioplasty, prevention of glomerular injury in renal disease, treatment of malignant disease, and the prevention of rejection in organ transplantation.27 Broadening the therapeutic applications of these drugs may lead to a greater likelihood of adverse effects due to more widespread use in patient populations at risk.
Colchicine: Chronic administration of colchicine is used in the treatment of gouty arthritis, familial Mediterranean fever, amyloidosis, Behçet’s disease, and dermatoses.1,21 Colchicine causes both muscle and peripheral nerve toxicity, or myoneuropathy, in a dose-dependent manner.28 Drug-induced myoneuropathy should be considered in the differential diagnosis of progressive, disabling weakness in patients receiving chronic colchicine therapy.29 The typical clinical presentation is characterized by marked proximal muscle weakness of the arms and legs (usually painless) and elevations in the serum CK concentration up to 10–20 times the upper normal limit. Both features usually remit within three to four weeks after the drug is discontinued or the dose is reduced.30 In most cases of colchicine myoneuropathy, EMG and nerve conduction studies show myopathic changes and motor axonal neuropathy. Resolution of the myopathy after withdrawal of colchicine strongly supports the diagnosis. However, the accompanying sensimotor features that usually manifest as mild sensory symptoms and diminished deep tendon reflexes resolve more slowly. When available, muscle biopsy reveals non-necrotizing, morphologically disrupted muscle fibers characterized by the presence of vacuoles and the inclusion of lysosomes.
The pathogenesis of colchicine myopathy is related to a direct toxic effect on muscle cells. Such toxicity is unusual at low serum concentrations of colchicine but may be present when elimination of the drug is impaired by hepatic or renal failure.28 Colchicine is eliminated predominantly by secretion into bile and partly by renal secretion. Impairment at either site will increase the serum concentration of colchicine.
Colchicine-induced myoneuropathy in the presence of renal insufficiency and concomitant cyclosporine administration have been described.31 Patients are often treated with colchicine for cyclosporine-induced gout. Transplant patients who are receiving cyclosporine often have some degree of renal insufficiency. Concomitant renal insufficiency and increased serum cyclosporine levels are risk factors associated with colchicine-induced myoneuropathy, because cyclosporine significantly inhibits colchicine secretion into urine in the presence of renal insufficiency. Patients with underlying renal failure are prone to colchicine-induced myoneuropathy if dose adjustments are not made according to renal function. Colchicine myoneuropathy may occur in patients who receive customary doses of the drug but have elevated serum colchicine levels because of impaired renal function.
In one report,32 five out of 10 renal transplant patients receiving cyclosporine and colchicine were found to have myopathy. Because transplant recipients receiving colchicine may be at increased risk of developing colchicine-induced myoneuropathy, especially in the presence of renal insufficiency, other modalities should be used to treat post-transplant gouty arthritis. If necessary, post-transplant patients with renal insufficiency should receive reduced doses of colchicine. Serum cyclosporine and CK concentrations, renal function and liver function tests and signs of neuromuscular toxicity should be monitored closely.
Zidovudine: The nucleoside reverse transcriptase inhibitor (NRTI), zidovudine (ZDV), widely used in combination antiretroviral therapy (ART), in the treatment of human immunodeficiency virus (HIV) disease, has been associated with myopathy. Nearly 20% of patients taking zidovudine complain of muscle weakness.21,33,34 Oftentimes, the initial clinical presentation of muscle weakness associated with HIV infection is difficult to distinguish from zidovudine-induced myopathy.
A complete medical and drug history, physical and neurological exam, and EMG are helpful. A muscle biopsy is essential in the diagnosis of ZDV-induced myopathy. Diagnostic histological findings reveal vacuolization and mitochondrial abnormalities with lipid accumulation, also classified as mitochondrial myopathy, consistent with ZDV-induced myopathy. Molecular studies by Masanes et al.,35 revealed the depletion of mitochondrial DNA in ZDV-treated patients which was reversible after the drug was discontinued. Usually, clinical complaints disappear within 3 months after discontinuation of treatment.
The risks of developing ZDV-induced myopathy must be weighed against the expected therapeutic benefits.36 Patient adherence to medical therapy is essential. Frequently missed doses or a reduction in the daily dose of ZDV due to adverse effects will render the therapy ineffective. When possible, suspected ZDV-induced myopathy should be proven with muscle biopsy before drug cessation. Discontinuing ZDV in a compliant patient with durable HIV suppression on optimal combination (dose and selection of agent) may result in HIV resistance and treatment failure because effective antiviral drugs are limited in number and mechanisms of action. Also, cross-resistance between specific agents are well documented.
Penicillamine: More than 10% of patients who receive penicillamine, a heavy metal chelating agent, complain of arthralgia and weakness. Penicillamine is used in the treatment of Wilson’s disease, cystinuria, and rheumatoid arthritis.21,37 The drug is known to cause life-threatening aplastic anemia and agranulocytosis. The drug has also been implicated in several autoimmune disorders, such as drug-induced systemic lupus erythematosus, Goodpasture’s syndrome, and myasthenia gravis as well as inflammatory myopathy (myositis) that is clinically and morphologically similar to polymyositis.10,38 Because the drug can cause serious adverse reactions, its use in rheumatoid arthritis is restricted to patients who have failed conventional treatment and have debilitating, active disease. The risks of penicillamine treatment must be weighed against the expected therapeutic benefits.
The underlying pathogenesis of penicillamine-induced myositis is an immune complex-mediated toxicity that results in inflammation and necrosis of muscle fiber. The clinical presentation consists of proximal muscle weakness with or without dermatomyositis that typically manifests as rashes over the knuckles and joints.9
Laboratory findings reveal elevated serum CK levels, and diagnostic findings include myopathic changes on EMG. Muscle biopsy reveals a necrotizing inflammatory process. Within a few weeks after discontinuing penicillamine treatment, muscle weakness resolves and laboratory parameters return to baseline.37,38 In cases of severe, debilitating muscle weakness associated with penicillamine-induced myositis, high-dose corticosteroid treatment may be instituted and tapered down when muscle strength improves.
Penicillamine-induced myositis, unlike other drug-induced myopathies of nonimmunological etiology, bears no relationship to either the daily dose or the length of therapy. The drug must be permanently discontinued when myopathy occurs. There are no known risk factors that predispose patients to penicillamine-induced myopathy. However, contraindications to the drug’s use include a previous hypersensitivity reaction to penicillin or penicillamine, renal insufficiency, or penicillamine-related aplastic anemia or agranulocytosis.
Antimalarials: Antimalarials, such as chloroquine and hydroxychloroquine, have been successfully used as steroid-sparing agents in the symptomatic management of systemic lupus erythematosus and rheumatoid arthritis. Although myopathy has been reported rarely with these agents,39,40 clinicians should be aware that both may lead to neuromyopathy as well as irreversible retinopathy with chronic use. Myopathy has been reported to develop over a range of one to 10 years of chronic administration. Chloroquine and hydroxychloroquine should be used with extreme caution in patients with liver disease, glucose-6-phosphate dehydrogenase (G-6-PD) enzyme deficiency, alcoholism, and with concomitant hepatotoxic agents.
Usually patients complain of muscle weakness with or without muscle pain. Peripheral sensory abnormalities, such as lack of deep tendon reflexes, may be present on examination. Muscle enzymes are normal or slightly elevated. Both myopathic and neuropathic changes are detected on EMG. The pathogenesis of the myopathy is a necrotizing, vacuolization process with characteristic inclusion bodies. When available, muscle biopsy reveals the presence of vacuoles with curvilinear bodies and myeloid bodies.
Irreversible retinopathy and myopathy have occurred with prolonged and high-dose therapy. Both chloroquine and hydroxychloroquine should be permanently discontinued when visual field disturbances or muscle weakness occur.1,21 Because of the risk of irreversible retinopathy, reintroduction of either agent in lower doses is not recommended when myopathy occurs.
Alcohol: Alcohol-induced myopathy is divided into two categories, and management differs depending on which category manifests. Acute alcohol-induced myopathy is marked by myalgia, muscle swelling, and profound weakness after “binge” drinking. Chronic alcohol-induced myopathy with myalgia is marked by slowly progressive proximal weakness and is associated with a steady intake of alcohol. In acute alcoholic myopathy there is usually a sudden onset of pain and swelling in the muscles.2,41 This normally involves the thigh muscles, but other large muscle groups may be involved. The muscle is tense, swollen and unbearably tender. Muscle destruction from prolonged obtundation, seizures, hypokalemia and hypophosphatemia cause a marked increase in the serum CK concentration and lead to a necrotizing process. Rhabdomyolysis with myoglobinuric renal failure may develop with excess alcohol intake and is managed with supportive care. It is usually reversible; however, residual weakness may persist.
Chronic alcoholic myopathy is also associated with profound leg weakness. Muscle pain and tenderness are usually absent. Occasionally, the onset of weakness is gradual—over a period of weeks to months. Unlike acute alcohol-induced myopathy, chronic alcohol-induced myopathy is usually described as a non-necrotizing process associated with normal or mildly elevated serum CK levels. Myoglobinuric renal failure does not occur in chronic alcoholic myopathy.
A 1996 survey42 revealed that approximately 15.5% or 32 million people were binge drinkers, and 5.4% or 11 million people were heavy drinkers. The prevalence of alcohol abuse underscores the importance of an accurate account of medication or drug intake in the evaluation of myopathy, especially a history of alcohol intake.
Cocaine: Renal failure, cardiac and respiratory arrest, malignant hyperthermia and seizures are life-threatening complications of cocaine overdose and are treated emergently. Both direct and indirect muscle destruction are responsible for myotoxic complications, particularly, rhabdomyolysis.43,44 Massive muscle tissue destruction from cocaine overdose is characterized by markedly elevated serum CK concentrations and a necrotizing muscle process on muscle biopsy.
Clinicians should be aware of drugs known to cause myopathy. Early recognition and drug cessation are essential in the management of patients with drug-induced myopathy and may shorten the length and severity of morbidity. Although the clinical and diagnostic features may vary depending on the causative agent, they are reversible after discontinuation or a reduction in dose. Risk factors and comorbidties are associated with greater disability and complications, such as rhabdomyolysis and myoglobinuric renal failure. Risk factors associated with drug-induced myopathy include hepatic and renal insufficiency, enzyme inhibition, and concomitant use of myotoxic drugs.
Pharmacists should be able to recognize drugs with a myotoxic potential and identify risk factors in the development of drug-induced myopathy. Morbidity may be prevented in both the ambulatory and inpatient setting by counseling and monitoring patients who receive myotoxic drugs. As new agents become available and therapeutic indications of currently available agents are expanded, it is important for pharmacists to recognize cases of drug-induced myopathy and report them to the FDA’s MedWatch program.45 Because most of the literature on drug-induced myopathy is based on case reports or series, postmarketing drug surveillance is essential to determine the condition’s prevalence.
1. Zuckner J. Drug-related myopathies. Rheum Dis Clin North Am. 1994;20:1017-1032.
2. Mastaglia FL. Adverse effects of drugs on muscle. Drugs. 1982;24:304-321.
3. Prendergast BD, George CF. Drug-induced rhabdomyolysis:
mechanism and management. Postgrad Med J. 1993;69:33-36.
4. Curry SC, Chang D, Connor D. Drug- and toxin-induced rhabdomyolysis. Ann Emerg Med. 1989;18:1068-1084.
5. Ghirlanda G, Oradei A, Manto A. Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study. J Clin Pharmacol. 1993;33:226-229.
6. Mhiri C, Baudrimont M, Geny C et al. Zidovudine myopathy:
a distinctive disorder associated with mitochondrial dysfunction.
Ann Neurol. 1991;29:606-614.
7. Roth D, Alcaron FJ, Fernandez JA, et al. Acute rhabdomyolysis associated with cocaine intoxication. New Engl J Med. 1988;319:673-677.
8. Singhal PC, Rubin RB, Peters A, et al. Rhabdomyolysis and acute renal failure associated with cocaine abuse. J Toxicol Clin Toxicol. 1990;28:321-330.
9. Carroll GJ, Will RK, Peter JB, et al. Penicillamine induced polymyositis and dermatomyositis. J Rheum. 1987;14:995-1001.
10. Chappel R and Willems J. D-penicillamine-induced myositis in rheumatoid arthritis. Clin Rheumatol. 1996;15:86-87.
11. Fisher JR, Baer RK. Acute myopathy associated with combined
use of corticosteroids and neuromuscular blocking agents. Ann
12. Decramer M and Stas KJ. Corticosteroid-induced myopathy
involving respiratory muscles in patients with chronic obstructuve pulmonary disease or asthma. Am Rev Respir Dis. 1992;146:800-802.
13. Decramer M, de Bock V, Dom R. Functional and histologic picture of steroid-induced myopathy in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1996;153:1958-1964.
14. Janssens S and Decramer M. Corticosteroid-induced myopathy
and the respiratory muscles. Report of two cases. Chest. 1989;95:1160-1162.
15. Hanson P, Dive A, Brucher JM et al. Acute corticosteroid myopathy in intensive care patients. Muscle Nerve. 1997;20:1371-1380.
16. Behbehani NA, Al-Mane F, D’yachkova Y et al. Myopathy following mechanical ventilation for acute severe asthma: the role of muscle relaxants and corticosteroids. Chest. 1999;115:1627-1631.
17. Hirano M, Ott BR, Raps et al. Acute quadriplegic myopathy: a complication of treatment with steroids, nondepolarizing blocking agents or both. Neurology. 1992;42:2002-2007.
18. Lacomis D, Giuliani MJ, Van Cott A, Kramer DJ. Acute myopathy of intensive care: clinical, electromyographic, and pathological aspects. Ann Neurol. 1996;40:645-654.
19. Batchelor TT, Taylor LP, Thaler HT, et al. Steroid myopathy in cancer patients. Neurology. 1997;48:1234-1238.
20. London SF, Gross KF, Ringel SP. Cholesterol-lowering agent myopathy (CLAM). Neurology. 1991;41:1159-1160.
21. Drug Information Handbook 1999-2000 7th ed. Lacy CF, Armstrong LL, Goldman MP, Lance LL (eds). Hudson, OH: Lexi-Comp, Inc., 1999.
22. Magarian GJ, Lucas LM, Colley C. Gemfibrozil-induced myopathy. Arch Intern Med. 1991;151:1873-1874.
23. Chucrallah A, DeGirolami U, Freeman R, Federman M. Lovastain/gemfibrozil myopathy: a clinical, histochemical, and ultrastructural study. Eur Neurol. 1992;32:293-296.
24. Pierce LR, Wysowski DK, Gross TP. Myopathy and rhabdomyolysis associated with lovastatin-gemfibrozil combination therapy. JAMA. 1990;264:71-75.
25. Henwood JM, Heel RC. Lovastatin. A preliminary review of its pharmacodynamic properties and therapeutic use in hyperlipidemia. Drugs. 1988;36:429-454.
26. Bottorff MB, Behrens DH, Gross A, Markel M. Differences in the metabolism of lovastatin and pravastatin as assessed by CYP3A4 inhibition with erythromycin. Pharmacotherapy. 1997;17:184.
27. Wheeler DC. Are there potential non-lipid-lowering uses of statins? Drugs. 1998;56(4):517-522.
28. 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;18:264-269.
29. De Deyn PP, Ceuterick C, Saxena V et al. Chronic colchicine-induced myopathy and neuropathy. Acta Neurol Belg. 1995;95:29-32.
30. Kuncl RW, Duncan G, Watson D, et al: Colchicine myopathy and neuropathy. N Engl J Med. 1987;316:1562-1568.
31. Rana SS, Giuliani MJ, Oddis CV, Lacomis D. Acute onset of colchicine myoneuropathy in cardiac transplant recipients: case studies of three patients. Clin Neurol Neurosurg. 1997;99:266-270.
32. Dulcloux D, Schuller V, Bresson-Vautrin C, Chalopin JM. Colchicine myopathy in renal transplant recipients on cyclosporin. Nephrol Dial Transplant. 1997;12:2389-2392.
33. Paradis J and Calis KA. Zidovudine-associated myopathy. Am J Hosp Pharm. 1994;51:3026-3028.
34. Strauss DK, Simberkoff MS, Leaf HL. Zidovudine (ZDV)-associated myopathy in a large clinic population. Int Conf AIDS. 1990;6(3):198.
35. Masanes F, Barrientos A, Cebrian M et al. Clinical, histological
and moleular reversibility of zidovudine myopathy. J Neurol Sci. 1998;159:226-228.
36. Fletcher CV, Kakuda TN, Collier AC. Human Immunodeficiency Virus Infection (chapter 114). In: Pharmacotherapy: a pathophysiologic approach 4th ed. DiPiro JT et al (eds.), Stamford: Appleton & Lange 1999.
37. Munro R, Capell HA. Penicillamine. Br J Rheumatol. 1997;36:104-109.
38. Aydintug AD, Cervera R, D’Cruz D et al. Polymyositis complicating D-penicillamine treatment. Postgrad Med J. 1991;67:1018-1020.
39. Wassay M, Wolfe GI, Herrold JM et al. Chloroquine myopathy and neuropathy with elevated CSF protein. Neurology. 1998;51:1226-27.
40. Richards AJ. Hydroxychloroquine myopathy. J Rheumatol. 1998;25:1642-43.
41. Haller RG, Knochel JP. Skeletal muscle disease in alcoholism.
Med Clin North Am. 1984;68:91-93.
42. National Household Survey on Drug Abuse. Rockville, MD, U.S. Department of Health and Human Services, Substance Abuse and Mental Health Services Administration, 1996.
43. Roth D, Alarcon FJ, Fernandez JA et al. Acute rhabdomyolysis associated with cocaine intoxication. N Engl J Med. 1988;319:673-677.
44. Singhal PC, Rubin RB, Peters A et al. Rhabdomyolysis and acute renal failure associated with cocaine abuse. J Toxicol Clin Toxicol. 1990;28:321-330.