What are the guidelines for using statins (HMG-CoA reductase inhibitors) in patients at risk for rhabdomyolysis?

From the Guidelines

Patients at risk for rhabdomyolysis should be prescribed statins with caution, using the lowest effective dose and careful monitoring, as recommended by the 2013 ACC/AHA guideline 1. Risk factors for rhabdomyolysis include advanced age, female gender, small body frame, kidney or liver disease, hypothyroidism, diabetes, and certain medications that interact with statins. When initiating statin therapy in high-risk patients, it is recommended to start with lower-potency statins like pravastatin or fluvastatin at reduced doses (10-20mg daily) 1. Some key points to consider when managing patients on statin therapy include:

• Avoiding simvastatin and lovastatin in patients taking CYP3A4 inhibitors such as erythromycin, clarithromycin, ketoconazole, and certain antivirals 1
• Using rosuvastatin and atorvastatin cautiously, as they are less affected by these interactions 1
• Monitoring patients closely with baseline and follow-up liver function tests, creatine kinase levels, and kidney function tests at initiation, after dose changes, and periodically during therapy 1
• Educating patients to report muscle pain, weakness, or dark urine immediately, and temporarily discontinuing the statin and checking creatine kinase levels if these symptoms occur 1
• Considering alternative statins or doses if muscle symptoms persist or worsen, as outlined in the management algorithm for muscle symptoms in statin-treated patients 1 It is essential to weigh the benefits of statin therapy against the potential risks, particularly in patients at high risk for rhabdomyolysis, and to individualize treatment decisions based on patient-specific factors, as recommended by the 2014 US Department of Veterans Affairs and US Department of Defense clinical practice guideline 1.

From the FDA Drug Label

Atorvastatin calcium may cause myopathy (muscle pain, tenderness, or weakness associated with elevated creatine kinase [CK]) and rhabdomyolysis. Risk Factors for Myopathy include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs (including other lipid-lowering therapies), and higher atorvastatin calcium dosage. Steps to Prevent or Reduce the Risk of Myopathy and Rhabdomyolysis include discontinuing atorvastatin calcium if markedly elevated CK levels occur or if myopathy is either diagnosed or suspected. Rosuvastatin may cause myopathy [muscle pain, tenderness, or weakness associated with elevated creatine kinase (CK)] and rhabdomyolysis. Risk factors for myopathy include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs (including other lipid-lowering therapies), and higher rosuvastatin dosage.

The guidelines for using statins in patients at risk for rhabdomyolysis include:

• Monitoring for muscle symptoms and elevated creatine kinase (CK) levels
• Discontinuing statin therapy if myopathy is diagnosed or suspected
• Avoiding concomitant use with certain other drugs that increase the risk of myopathy
• Reducing the statin dosage in patients with risk factors for myopathy
• Informing patients of the risk of myopathy and rhabdomyolysis when starting or increasing statin therapy
• Temporarily discontinuing statin therapy in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis 2 3 Key considerations:
• Age 65 years or greater
• Uncontrolled hypothyroidism
• Renal impairment
• Concomitant use with certain other drugs
• Higher statin dosage Recommendations:
• Use the lowest effective statin dosage
• Monitor patients closely for muscle symptoms and elevated CK levels
• Discontinue statin therapy if myopathy is diagnosed or suspected

From the Research

Guidelines for Using Statins in Patients at Risk for Rhabdomyolysis

• The use of statins, particularly rosuvastatin, has been associated with an increased risk of rhabdomyolysis, a rare but potentially serious adverse effect 4, 5, 6.
• Patients with certain risk factors, such as high dosage, old age, renal and hepatic impairment, and pharmacogenetic variants, are more susceptible to statin-induced myopathy 6.
• A proactive multifactorial risk assessment is recommended to guide and individualize statin therapy in high-risk patients 6.
• The co-administration of statins and antiplatelet therapies, such as ticagrelor, may increase the risk of rhabdomyolysis, particularly with atorvastatin and rosuvastatin 7.
• Clinicians should be aware of the common causes, diagnosis, and treatment options for rhabdomyolysis, and take steps to avoid acute kidney injury in patients at risk 8.

Risk Factors for Rhabdomyolysis

• High dosage of statins
• Old age
• Renal and hepatic impairment
• Pharmacogenetic variants, such as SLCO1B1*1 a/*5
• Co-administration of antiplatelet therapies, such as ticagrelor

Treatment and Management

• Immediate discontinuation of the offending statin
• Intravenous fluid administration to prevent acute kidney injury
• Cautious monitoring of serum electrolytes and creatine kinase levels
• Temporary dialysis may be required in severe cases 5
• Dietary therapy may be recommended as an alternative to statin therapy in patients at high risk for rhabdomyolysis 4