From the Guidelines
Muscle pain from statins should be evaluated carefully to distinguish between common side effects and serious complications, with red flags including severe pain, sudden onset, fever, unusual fatigue, or dark urine, which may indicate rhabdomyolysis, a rare but serious condition where muscle breakdown can damage kidneys. To differentiate normal statin-related muscle discomfort from concerning symptoms, note that typical statin muscle pain is usually mild to moderate, symmetrical, affects large muscle groups, and may worsen with exercise 1. The pain typically begins within weeks to months of starting therapy or increasing dosage.
Key Considerations
- If symptoms are mild, your doctor might recommend continuing the medication while monitoring symptoms, trying a different statin (like switching from atorvastatin to rosuvastatin), reducing the dose, or implementing an alternate-day dosing schedule 1.
- Coenzyme Q10 supplements are not recommended for routine use in patients treated with statins or for the treatment of statin-associated muscle symptoms (SAMS), as evidence for their effectiveness is mixed and not supported by recent guidelines 1.
- The mechanism behind statin-induced muscle pain involves decreased production of substances needed for muscle function and increased muscle cell breakdown.
- Routine measurements of creatine kinase and transaminase levels are not useful in patients treated with statins, unless there are symptoms suggesting hepatotoxicity or severe statin-associated muscle symptoms 1.
Monitoring and Management
- In patients with statin-associated side effects that are not severe, it is recommended to reassess and to rechallenge to achieve a maximal LDL-C lowering by modified dosing regimen, an alternate statin or in combination with nonstatin therapy 1.
- In patients with increased diabetes mellitus risk or new-onset diabetes mellitus, it is recommended to continue statin therapy, with added emphasis on adherence, net clinical benefit, and the core principles of regular moderate-intensity physical activity, maintaining a healthy dietary pattern, and sustaining modest weight loss 1.
- Most patients can find a statin regimen that manages their cholesterol while minimizing muscle discomfort through proper medical guidance.
From the FDA Drug Label
Pitavastatin tablets may cause myopathy (muscle pain, tenderness, or weakness associated with elevated creatine kinase [CK]) and rhabdomyolysis. Risk Factors for Myopathy Risk factors for myopathy include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use of certain drugs (including other lipid-lowering therapies), and higher pitavastatin tablets dosage Discontinue pitavastatin tablets if markedly elevated CK levels occur or if myopathy is either diagnosed or suspected Muscle symptoms and CK elevations may resolve if pitavastatin tablets is discontinued. Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing the pitavastatin tablets dosage. Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever.
Red flags for muscle pain from statins:
- Unexplained muscle pain, tenderness, or weakness
- Muscle symptoms accompanied by malaise or fever
- Markedly elevated CK levels
- Age 65 years or greater
- Uncontrolled hypothyroidism
- Renal impairment
- Concomitant use of certain drugs (including other lipid-lowering therapies)
- Higher statin dosage
How to differentiate muscle pain complaints:
- Evaluate for risk factors for myopathy
- Check CK levels
- Assess for symptoms of myopathy or rhabdomyolysis
- Consider alternative causes of muscle pain
- Discontinue statin if myopathy is diagnosed or suspected 2 2
- Consider immune-mediated necrotizing myopathy (IMNM) if muscle symptoms persist despite discontinuation of statin treatment 2 2
From the Research
Statin-Associated Muscle Pain
- Statin-associated muscle symptoms are frequently reported by patients, but the evidence in support of muscle pain caused by statins is often equivocal and not particularly strong 3.
- The mechanisms leading to statin-associated skeletal muscle-associated symptoms (SAMS) are not completely clarified, but may involve mitochondrial dysfunction and impairment of the Akt/mTOR pathway 4.
- Statin-associated muscle symptoms can range from mild muscle pain to more severe conditions such as rhabdomyolysis, a potentially fatal condition 4.
Red Flags for Statin-Associated Muscle Pain
- Elevated creatine kinase (CK) levels, with or without muscle discomfort or weakness, may indicate statin-associated myotoxicity 5.
- Proximal muscle weakness, elevated CK levels, and autoantibodies recognizing hydroxy-methyl-glutaryl coenzyme A reductase may indicate statin-associated autoimmune myopathy, a rare but serious condition 5.
- A history of muscle symptoms or myopathy with previous statin use may be a red flag for increased risk of statin-associated muscle pain 6.
Differentiating Muscle Pain Complaints
- Careful clinical judgment is necessary to differentiate between statin-associated muscle pain and other causes of muscle pain 3.
- A thorough medical history, physical examination, and laboratory tests (such as CK levels) may be necessary to diagnose and manage statin-associated muscle symptoms 5.
- Patient-reported symptoms and provider advice can vary widely, and a patient-centric approach to managing statin-associated muscle symptoms is necessary 6.
Management of Statin-Associated Muscle Pain
- Exchange of statin, reduction of dose, or addition of other therapies (such as vitamin D or coenzyme Q10) may be beneficial in managing statin-associated muscle symptoms 3, 6.
- Non-pharmacological strategies, such as patient education and involvement in treatment decisions, may also be effective in reducing the nocebo effect and improving treatment adherence 7.
- Alternative therapeutic strategies, such as bempedoic acid or anti-PCSK9 antibodies, may be considered for patients who are intolerant to statins 7.