What medications should be stopped or adjusted if creatine kinase (CK) levels are elevated?

Medications to Stop or Adjust When CK is Elevated

When creatine kinase (CK) levels are elevated, statins should be discontinued immediately if CK is greater than 10 times the upper limit of normal (ULN) with muscle symptoms, or if muscle symptoms are severe with any CK elevation. 1

Statins and CK Elevation

• Statins are the primary medications that should be stopped or adjusted with elevated CK levels, as they can cause myopathy, myositis, and rhabdomyolysis 1, 2
• Risk of statin-induced myopathy increases with higher doses, particularly with simvastatin 80mg daily (0.61% incidence) compared to 20mg daily (0.03% incidence) 2
• Simvastatin is associated with a higher likelihood of significant CK elevation (≥10x ULN) compared to lovastatin 3

Management Based on CK Levels and Symptoms

• Asymptomatic with CK >10x ULN: Strong consideration should be given to stopping statin therapy 1
• Muscle symptoms with CK >10x ULN: Discontinue statin therapy immediately 1, 2
• Muscle symptoms with CK 3-10x ULN: Follow symptoms and CK levels weekly; consider dose reduction or temporary discontinuation 1
• Muscle symptoms with normal or mildly elevated CK: Monitor symptoms and consider dose reduction if symptoms are bothersome 1

Other Medications to Consider Stopping or Adjusting

• Fibrates: Discontinue if used in combination with statins when CK is elevated, particularly gemfibrozil which increases statin-associated myopathy risk 1, 2
• Niacin: Consider discontinuing when used with statins if CK is elevated, as combination increases myopathy risk 1, 2
• Colchicine: May increase risk of myopathy when used with statins 4
• Amlodipine: Consider discontinuing when used with statins, particularly atorvastatin, as this combination has been associated with rhabdomyolysis 5
• Immune checkpoint inhibitors: If CK elevation occurs during treatment, consider holding therapy and initiating corticosteroids based on severity 1

Risk Factors for Medication-Induced CK Elevation

• Advanced age (especially >80 years), with women at higher risk than men 1, 2
• Small body frame and frailty 1
• Multisystem disease (e.g., chronic renal insufficiency, especially due to diabetes) 1
• Multiple medications (polypharmacy) 1
• Perioperative periods 1
• Hypothyroidism 1
• Asian ethnicity (particularly with rosuvastatin) 4
• Elevated serum creatinine 3

Monitoring Recommendations

• Obtain baseline CK measurement before initiating statin therapy 1
• Measure CK if patient reports muscle symptoms while on statins 1
• Check thyroid-stimulating hormone in patients with muscle symptoms, as hypothyroidism predisposes to myopathy 1
• For patients with moderate CK elevations (3-10x ULN), monitor more frequently with serial measurements 1
• If statins are discontinued due to CK elevation, wait for symptoms to resolve and CK levels to return to normal before considering reinitiating therapy at a lower dose 1

Common Pitfalls and Caveats

• Not all muscle pain in statin users is due to the medication; rule out common causes such as exercise or strenuous work 1
• Asymptomatic patients may have moderate CK elevations at baseline or during treatment; they can usually be treated with a statin but require careful monitoring 1
• Immune-mediated necrotizing myopathy is a rare but serious autoimmune condition associated with statin use that may persist despite discontinuation 2, 4
• Avoid restarting statins at the same dose after a myopathy episode; if reinitiation is necessary, use a lower dose or a different statin with lower myopathy risk 1, 2
• Consider holding statins during acute illness, major surgery, or other conditions that increase risk of renal failure secondary to rhabdomyolysis 2, 4

Remember that the only effective treatment for medication-induced myopathy is discontinuation of the offending agent, particularly when CK levels are significantly elevated or the patient is symptomatic 6.