What drugs can cause myositis?

Drugs That Can Cause Myositis

Several classes of medications can cause myositis, with statins being the most well-documented, followed by immune checkpoint inhibitors, fibrates, and other drugs that can trigger autoimmune muscle inflammation. 1, 2

Statin-Induced Myositis

Statins are the most common medication class associated with myositis:

• Statin therapy carries a definite risk of myopathy, with severe myopathy reported in approximately 0.08% of patients taking lovastatin and simvastatin 1
• Elevations of creatine kinase (CK) greater than 10 times the upper limit of normal have been reported in 0.09% of patients treated with pravastatin 1
• Statin-associated autoimmune myopathy (with anti-HMGCR antibodies) is a rare but serious condition that requires statin cessation and immunosuppressive therapy 1, 3
• This form of myositis can persist despite discontinuation of the statin, requiring immunosuppressive treatment 4, 5

Risk factors for statin-induced myositis:

• Advanced age (especially >80 years), female sex, small body frame, chronic renal insufficiency, and polypharmacy 1
• Drug interactions that affect statin metabolism, particularly those involving the cytochrome P-450 3A4 isozyme 1, 2

Drug Combinations That Increase Myositis Risk

The risk of myositis is significantly increased when statins are combined with:

• Fibrates, particularly gemfibrozil (contraindicated with simvastatin) 6, 2
• Cyclosporine and danazol (contraindicated with simvastatin) 2
• Amiodarone, dronedarone, ranolazine, and calcium channel blockers 2
• Macrolide antibiotics (erythromycin, clarithromycin) 2
• Azole antifungals (itraconazole, ketoconazole, posaconazole, voriconazole) 2
• HIV and HCV protease inhibitors 2
• Niacin at lipid-modifying doses (≥1 gram/day) 6, 2
• Daptomycin (consider temporarily suspending statin during treatment) 2

Immune Checkpoint Inhibitors (ICIs)

• Myositis is a rare but potentially severe and fatal complication of ICI therapy 6
• More common with PD-1/PD-L1 inhibitors (like pembrolizumab) than with CTLA-4 inhibitors 6, 7
• Can present as reactivation of pre-existing paraneoplastic polymyositis/dermatomyositis or as de novo myositis 6
• May have a fulminant necrotizing course with rhabdomyolysis and can involve vital skeletal muscle, including the myocardium 6
• Myositis occurred in 0.5% of patients treated with pembrolizumab in combination with enfortumab vedotin 7

Other Medications Associated with Myositis

• Proton pump inhibitors: Case reports suggest omeprazole may trigger polymyositis, particularly when combined with statins 8
• Fibrates when used alone can cause myopathy 6
• Corticosteroids: Paradoxically, long-term use can cause steroid myopathy 6

Clinical Presentation and Diagnosis

• Main symptoms include proximal muscle weakness, difficulties in standing up, lifting arms, and moving around 6
• In severe cases, patients may also experience myalgia 6
• Laboratory findings include markedly elevated CK levels and inflammatory markers 6
• Differential diagnosis includes polymyalgia rheumatica, fibromyalgia, and muscle dystrophies 6
• Diagnostic tests may include EMG (showing muscle fibrillations), MRI (showing increased intensity and edema in affected muscles), and muscle biopsy 6

Management Approach

• For statin-induced myopathy, discontinuation of the statin is the first step 1, 9
• For immune-mediated myositis (including statin-associated autoimmune myopathy and ICI-induced myositis), immunosuppressive therapy is required 6, 4
• High-dose corticosteroids are the cornerstone of initial treatment for severe cases 6
• For refractory cases, additional immunosuppressants, IVIG, or plasmapheresis may be necessary 6, 8

Important Pitfalls to Avoid

• Not all muscle symptoms in patients taking statins are drug-related; common non-specific muscle aches occur in approximately 5% of patients on statins, similar to placebo rates 1
• Failure to recognize statin-associated autoimmune myopathy, which persists despite statin discontinuation and requires immunosuppressive therapy 4, 5
• Missing myositis in patients with remote statin exposure, as symptoms can develop years after discontinuation 3
• Overlooking potential drug interactions that increase the risk of myositis 2