What medications should be held in a patient with rhabdomyolysis (muscle breakdown)?

From the Guidelines

In cases of rhabdomyolysis, it is crucial to temporarily discontinue medications that can exacerbate muscle breakdown, nephrotoxicity, or hyperkalemia to prevent further kidney damage and complications. The medications to be held include nephrotoxic agents such as NSAIDs (ibuprofen, naproxen, ketorolac), ACE inhibitors (lisinopril, enalapril), ARBs (losartan, valsartan), and diuretics (furosemide, hydrochlorothiazide) as they can worsen kidney function 1. Additionally, statins (atorvastatin, simvastatin, rosuvastatin) should be suspended because they can worsen muscle breakdown, as evidenced by their association with myopathy and rhabdomyolysis 1. Metformin should also be held due to the increased risk of lactic acidosis in the setting of acute kidney injury 1. Medications that can cause hyperkalemia should be held as rhabdomyolysis often leads to potassium release from damaged muscle cells. Furthermore, consider temporarily discontinuing any medications primarily eliminated by the kidneys, as they may accumulate to toxic levels during impaired renal function 1. These medications should only be resumed once kidney function has improved and creatine kinase levels are trending downward. The rationale for holding these medications is to prevent additional kidney stress while the body clears myoglobin released from damaged muscle tissue, which can precipitate in renal tubules causing acute tubular necrosis and kidney failure. It is also important to note that the combination of statins with certain medications, such as fibrates, cyclosporine, or macrolide antibiotics, can increase the risk of myopathy and rhabdomyolysis 1. Therefore, careful monitoring and adjustment of medications are necessary to prevent these adverse interactions. Overall, the management of rhabdomyolysis requires a careful assessment of the patient's medication regimen and the potential risks and benefits of continuing or discontinuing certain medications.

From the FDA Drug Label

Atorvastatin calcium may cause myopathy (muscle pain, tenderness, or weakness associated with elevated creatine kinase [CK]) and rhabdomyolysis. Discontinue atorvastatin calcium tablets if markedly elevated CK levels occur or if myopathy is either diagnosed or suspected. Temporarily discontinue atorvastatin calcium tablets in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis (e.g., sepsis; shock; severe hypovolemia; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; or uncontrolled epilepsy). Concomitant use of cyclosporine, gemfibrozil, tipranavir plus ritonavir, or glecaprevir plus pibrentasvir with atorvastatin is not recommended Cases of myopathy/rhabdomyolysis have been reported with atorvastatin co-administered with lipid modifying doses (>1 gram/day) of niacin, fibrates, colchicine, and ledipasvir plus sofosbuvir

The following medications should be held in a patient with rhabdomyolysis:

• Atorvastatin: Discontinue if markedly elevated CK levels occur or if myopathy is diagnosed or suspected
• Cyclosporine: Concomitant use with atorvastatin is not recommended
• Gemfibrozil: Concomitant use with atorvastatin is not recommended
• Tipranavir plus ritonavir: Concomitant use with atorvastatin is not recommended
• Glecaprevir plus pibrentasvir: Concomitant use with atorvastatin is not recommended
• Niacin: Hold if patient is taking lipid modifying doses (>1 gram/day)
• Fibrates: Hold if patient is taking lipid modifying doses
• Colchicine: Hold if patient is taking with atorvastatin
• Ledipasvir plus sofosbuvir: Hold if patient is taking with atorvastatin 2 2 2

From the Research

Medications to be Held in Rhabdomyolysis

The following medications should be held in a patient with rhabdomyolysis:

• Statins, such as atorvastatin 3, 4, 5 and simvastatin 4, 5, as they can cause muscle damage and increase the risk of rhabdomyolysis
• Antibiotics, such as amoxicillin clavulanic acid 3, roxithromycin 4, and fusidic acid 5, as they can interact with statins and increase the risk of rhabdomyolysis
• Amlodipine 4, as it can contribute to the development of myopathy and rhabdomyolysis when used with statins
• Other medications that can cause muscle damage or interact with statins, as identified by the patient's medical history and current medications 6, 7

Considerations for Medication Management

When managing a patient with rhabdomyolysis, it is essential to:

• Discontinue any medications that may be contributing to the condition 3, 4, 5
• Monitor the patient's clinical and laboratory findings, including creatine kinase levels and liver function tests 3, 5
• Provide aggressive intravenous fluid resuscitation to prevent acute renal failure and improve outcomes 6, 7
• Avoid the use of bicarbonate and mannitol, as their effectiveness in treating rhabdomyolysis is not supported by high-quality evidence 6, 7