Management of Statin-Induced Myopathy

• A drug-induced myopathy can be defined as the acute or subacute manifestations of myopathic symptoms such as elevated creatinine kinase, muscle weakness, myalgia or myoglobinuria that can occur in patient without muscle disease when they are exposed to certain drugs.
• Statins, an HMG-CoA reductase inhibitors, are one of the many drugs that are well-recognized as myotoxic agents. It can cause toxicity in muscle tissue, leading to significant morbidity and disability.
• Up to 5% of users develop CK elevation, typically 2 to 10 times the upper limit of normal.
•  CK usually drops after stopping statins but may require weeks to months to normalize. Rarely, statin users develop a serious immune-mediated necrotizing myopathy  
• Mechanisms of CK elevation in response to statins include increased muscle membrane fragility due to decreased cholesterol content, inhibition of isoprenoid production (a necessary step in the synthesis of membrane proteins), and depletion of ubiquinone, leading to mitochondrial dysfunction

Management:

• When a patient on statin reports muscle pain, a detailed history should be obtained.
• Rule out other conditions unrelated to statin therapy e.g osteoarthritis, tendinitis, radiculopathy, muscle strain.
• Assess level of creatinine kinase (CK). The magnitude of elevation will impact on how the patient is managed.

Elevated CK>10x Upper Limit Normal

•  Considered as potential rhabdomyolysis case
•  Investigate urine myoglobin levels and deteriorating renal function
•  Stop statin therapy immediately
•  For such patient, continued use of statin therapy must be balanced against risk of further myotoxicity.
•  Alternative non-statin therapy could be used
•  If benefits outweigh the risks, reintroduce statin at a low dose with careful monitoring

Elevated CK<10x Upper Limit Normal

•  Statin therapy can be continued at the same or a lower dose, providing muscle symptoms are tolerable
•  Monitor closely to ensure CK levels are not continuing to rise and that symptoms remain the same
•  Stop statin if symptoms worsening, CK levels progressively rising, or noted intolerable muscle symptoms. Observe the patient until symptoms resolve and CK levels return to normal.

References:

1. Managing Statin-Induced Myopathy Vol 1 2009 retrieved at http://www.pharmaceutical-journal.com/files/rps-pjonline/pdf/cp200907_learninglight-319.pdf
2. Drug-related Myopathies of Which The Clinician Should Be Aware retrieved at  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3092639/
3. Approach To Asymptomatic Creatinine Kinase Elevation retrieved at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4871266/