What medications exacerbate rhabdomyolysis (rapid breakdown of skeletal muscle tissue)?

From the Guidelines

Medications that worsen rhabdomyolysis include statins, particularly when used at high doses or in combination with other medications, as well as fibrates like gemfibrozil, which has a higher risk of rhabdomyolysis compared to fenofibrate when combined with statins, as evident from the study published in Circulation in 2016 1. The risk of rhabdomyolysis is more common with higher doses of statins and renal insufficiency, and appears to be higher when statins are combined with gemfibrozil compared to fenofibrate, as reported in the study published in Diabetes Care in 2019 1 and 2021 1. Some key medications that can exacerbate rhabdomyolysis include:

• Statins: atorvastatin, simvastatin, and rosuvastatin
• Fibrates: gemfibrozil and fenofibrate, especially when combined with statins
• Antibiotics: daptomycin, fluoroquinolones, and trimethoprim-sulfamethoxazole
• Antipsychotics: haloperidol, risperidone
• Antiretrovirals: particularly protease inhibitors
• Immunosuppressants: cyclosporine, tacrolimus
• Recreational drugs and substances of abuse: cocaine, heroin, amphetamines, and alcohol These medications typically cause rhabdomyolysis through direct myotoxicity, altered muscle metabolism, or by increasing the blood levels of other myotoxic drugs through pharmacokinetic interactions, as described in the European Heart Journal in 2012 1. Patients with underlying risk factors such as renal impairment, advanced age, hypothyroidism, or genetic myopathies are particularly vulnerable, and careful monitoring of creatine kinase levels and renal function is essential when prescribing these medications, especially during the initial treatment period.

From the FDA Drug Label

Rare reports of rhabdomyolysis have been reported in patients taking these drugs concomitantly. Myopathy rhabdomyolysis was reported and in some of the reports, clarithromycin was administered concomitantly with statins, fibrates, colchicine or allopurinol

Medications that worsen rhabdomyolysis include:

• Statins: when administered concomitantly with erythromycin or clarithromycin 2 3
• Fibrates: when administered concomitantly with clarithromycin 3
• Colchicine: when administered concomitantly with erythromycin or clarithromycin 2 3
• Allopurinol: when administered concomitantly with clarithromycin 3
• Erythromycin: may increase the risk of rhabdomyolysis when administered concomitantly with HMG-CoA reductase inhibitors (e.g., lovastatin and simvastatin) 2
• Clarithromycin: may increase the risk of rhabdomyolysis when administered concomitantly with statins, fibrates, colchicine or allopurinol 3

From the Research

Medications that Worsen Rhabdomyolysis

• Statins, particularly simvastatin, have been associated with an increased risk of rhabdomyolysis 4, 5, 6, 7
• The risk of rhabdomyolysis is higher when statins are used in combination with certain medications, such as:
  • Macrolide antibiotics, like clarithromycin, which inhibit cytochrome p450-3A4 (CYP3A4) 4
  • Gemfibrozil, a fibric acid derivative 6, 8
• The use of fenofibrate in combination with statins may result in fewer reports of rhabdomyolysis compared to gemfibrozil 8
• Simvastatin has been found to have the highest risk of rhabdomyolysis among statins, with a reporting odds ratio (ROR) of 2.20 (2.11-2.29) 7

Factors that Increase the Risk of Rhabdomyolysis

• Concurrent use of medications that inhibit CYP3A4 4
• Age, with a higher risk in individuals older than 74 years 7
• Drug interactions, particularly with gemfibrozil and macrolide antibiotics 4, 6, 8
• Male sex, with a higher risk of rhabdomyolysis reported in men 7