What medications can cause myopathy?

Medications That Can Cause Myopathy

Statins are the most commonly implicated medications causing myopathy, with all statins carrying similar risk as a class effect, though certain drug interactions and patient factors dramatically increase this risk. 1

Primary Offenders: Statins

All Statins Carry Similar Myopathy Risk

• The FDA analysis demonstrates that all currently available statins (atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin) have clinically equivalent rates of severe myopathy and fatal rhabdomyolysis (less than 1 death per million prescriptions). 1
• Severe myopathy occurs in approximately 0.08-0.09% of patients in clinical trials, though real-world observational studies suggest 5-15% of patients develop muscle-related symptoms. 1, 2, 3
• Myopathy risk is dose-dependent across all statins—higher doses carry greater risk. 1, 4

High-Risk Drug Combinations with Statins

Avoid these combinations entirely:

• Cyclosporine + any statin (contraindicated due to severe myopathy risk) 4
• Gemfibrozil + any statin (contraindicated—gemfibrozil itself causes myopathy and dramatically increases statin levels) 4
• Tipranavir plus ritonavir + any statin (contraindicated) 4
• Glecaprevir plus pibrentasvir + any statin (contraindicated) 4

Require statin dose limitation (≤20 mg atorvastatin):

• Clarithromycin, itraconazole, saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, elbasvir plus grazoprevir, or letermovir 4

Require careful monitoring:

• Lipid-modifying doses of niacin (≥1 gram/day) increase myopathy risk 4
• Other fibrates (fenofibrate) increase risk but less than gemfibrozil 4
• Colchicine has documented cases of myopathy when combined with statins 4
• Ledipasvir plus sofosbuvir has reported myopathy cases 4

Patient-Specific Risk Factors for Statin Myopathy

The American College of Cardiology identifies these high-risk populations: 1

• Advanced age, especially >80 years (women > men)
• Small body frame and frailty
• Chronic renal insufficiency, particularly from diabetes
• Uncontrolled hypothyroidism 4
• Multiple concomitant medications
• Perioperative periods 1

Other Medications Causing Myopathy

Fibrates (Independent of Statins)

• Fibrates cause myopathy when used alone, with gemfibrozil carrying particularly high risk. 1, 5
• Clofibrate is specifically associated with painful myopathy. 5

Antimalarials

• Chloroquine and hydroxychloroquine cause painless myopathy with associated neuropathy. 5
• These produce vacuolar myopathy on histology. 5

Immunosuppressants

• Cyclosporin causes myopathy independently and dramatically increases statin myopathy risk through CYP3A4 inhibition. 4, 5
• Cyclosporin can induce vacuolar myopathy. 5

Colchicine

• Colchicine causes painless myopathy with neuropathy, particularly in patients with renal impairment. 4, 5
• Produces vacuolar myopathy histologically. 5
• Risk increases substantially when combined with statins. 4

Corticosteroids

• Corticosteroids cause painless myopathy without neuropathy, typically presenting as proximal muscle weakness. 5

Antiretroviral Agents

• Zidovudine causes mitochondrial myopathy with painful symptoms and polymyositis-like presentation. 5
• Multiple HIV protease inhibitors increase statin levels and myopathy risk. 4

Antimicrobials

• Macrolide antibiotics (erythromycin, clarithromycin) inhibit CYP3A4 and increase statin myopathy risk. 4
• Azole antifungals (itraconazole, ketoconazole, posaconazole, voriconazole) similarly increase statin exposure. 4

Other Agents

• D-penicillamine causes both myasthenic syndromes and polymyositis. 5
• Cimetidine can cause polymyositis. 5
• Amiodarone produces vacuolar myopathy. 5
• Vincristine causes necrotizing myopathy. 5
• Drugs causing hypokalemia (diuretics, laxatives) can induce vacuolar myopathy. 5
• L-tryptophan is associated with eosinophilia-myalgia syndrome. 5

Clinical Recognition and Monitoring

When to Suspect Drug-Induced Myopathy

Instruct all patients starting myopathy-risk medications to immediately report: 1

• Unexplained muscle pain, tenderness, or weakness
• Brown urine (suggesting myoglobinuria)
• Symptoms particularly affecting proximal muscles symmetrically 2

Laboratory Evaluation

• Measure creatine kinase (CK) when symptoms occur—routine monitoring in asymptomatic patients is not recommended. 1
• Discontinue the offending medication if CK >10 times upper limit of normal with muscle symptoms. 1
• For CK 3-10 times normal with symptoms, follow weekly and consider dose reduction or temporary discontinuation. 1
• Rule out hypothyroidism (check TSH), recent strenuous exercise, or other causes before attributing to medication. 6

Critical Pitfall

Grapefruit juice consumption >1.2 liters daily significantly increases statin levels and myopathy risk—counsel patients to avoid excessive intake. 4