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

From the Guidelines

Rhabdomyolysis can be caused by several medications, with statins being the most commonly associated drug class, particularly simvastatin, atorvastatin, and rosuvastatin, as well as fibrates like gemfibrozil, according to the most recent evidence from 2021 1. Medications that frequently cause rhabdomyolysis include:

• Statins (particularly simvastatin, atorvastatin, and rosuvastatin)
• Fibrates (gemfibrozil)
• Antipsychotics (haloperidol, risperidone)
• Certain antibiotics (daptomycin, trimethoprim-sulfamethoxazole)
• Antiretrovirals (particularly HIV protease inhibitors)
• Colchicine
• Drugs of abuse (cocaine, heroin, amphetamines) The risk increases significantly with drug interactions, such as combining statins with fibrates or certain antibiotics. Rhabdomyolysis occurs when these medications damage muscle cells, causing them to break down and release myoglobin into the bloodstream, which can lead to kidney damage. Risk factors include high medication doses, drug interactions, dehydration, and underlying medical conditions. Symptoms include muscle pain, weakness, dark urine, and kidney dysfunction. If these symptoms develop while taking any of these medications, immediate medical attention should be sought, as prompt discontinuation of the offending drug and supportive care are essential for preventing complications, as recommended by the American Heart Association in 2016 1 and the American College of Cardiology in 2014 1. It is also important to note that the combination of statins and fibrates, particularly gemfibrozil, increases the risk of rhabdomyolysis, as reported in the FDA Adverse Event Reporting System database 1. Therefore, it is crucial to carefully evaluate the benefits and risks of using these medications, especially in combination, and to monitor patients closely for signs of rhabdomyolysis, as suggested by the 2019 standards of medical care in diabetes 1.

From the FDA Drug Label

Simvastatin may cause myopathy and rhabdomyolysis. Acute kidney injury secondary to myoglobinuria and rare fatalities have occurred as a result of rhabdomyolysis in patients treated with statins, including simvastatin Atorvastatin plasma levels can be significantly increased with concomitant administration of inhibitors of CYP3A4 and transporters Cases of myopathy and rhabdomyolysis have been reported with concomitant use of ledipasvir plus sofosbuvir with atorvastatin calcium.

Medications that cause rhabdomyolysis include:

• Simvastatin, particularly when used concomitantly with certain other drugs, such as strong CYP3A4 inhibitors, cyclosporine, danazol, or gemfibrozil 2
• Atorvastatin, especially when used with drugs that increase its plasma levels, such as cyclosporine, gemfibrozil, or certain anti-viral medications 2 3

Key risk factors for myopathy and rhabdomyolysis include:

• Age 65 years or greater
• Uncontrolled hypothyroidism
• Renal impairment
• Concomitant use with certain other drugs
• Higher simvastatin dosage
• Chinese patients on simvastatin may be at higher risk for myopathy 2

From the Research

Medications that Cause Rhabdomyolysis

• Statins, particularly when combined with other medications such as gemfibrozil or macrolide antibiotics, can increase the risk of rhabdomyolysis 4, 5, 6, 7, 8
• The combination of cerivastatin and gemfibrozil has been reported to cause rhabdomyolysis in several cases 7, 8
• Other statins, such as simvastatin, can also cause rhabdomyolysis when used alone or in combination with other medications 4, 5

Risk Factors for Rhabdomyolysis

• Concurrent use of medications that inhibit cytochrome p450-3A4 (CYP3A4), such as macrolide antibiotics 5
• Higher doses of statins 7
• Renal insufficiency 7
• Use of diuretics 7
• Hypothyroidism 7

Clinical Features and Treatment

• Rhabdomyolysis is a life-threatening adverse effect that requires prompt recognition and treatment 4, 5
• Clinical features include generalized muscle pain or weakness, and elevated creatine phosphokinase (CPK) levels 4, 5
• Treatment involves discontinuation of the offending medication and supportive care, including hospitalization and dialysis in severe cases 4, 5, 6, 7, 8