Does HMG-CoA reductase inhibitor (statin) cause muscle spasms?

From the Guidelines

Statin use can lead to muscle spasms, although this is less common than muscle pain or weakness, with an estimated frequency of 5-10% in statin users. According to the most recent and highest quality study 1, statin-associated muscle symptoms (SAMS) are the most commonly encountered side effect in clinical practice, occurring in approximately 5% to 20% of patients. These symptoms may include muscle spasms, myalgias, or weakness, and are more likely to be statin-associated if they are bilateral, involve proximal muscles, and have their onset within weeks to months after initiation of statins.

Some key points to consider when evaluating muscle symptoms in statin users include:

• The symptoms tend to be symmetric myalgias or weakness in large proximal muscle groups
• Other causes of muscle symptoms, such as hypothyroidism or vitamin D deficiency, must be ruled out
• Drug-drug interactions that can increase systemic statin exposure must be considered
• Certain patient populations, such as women, individuals of Asian descent, and the elderly, may be at increased risk for statin-associated muscle symptoms

If a patient experiences muscle spasms while taking a statin, the recommended approach is to discontinue statin therapy until resolution of symptoms and subsequent rechallenge to verify recurrence of muscle-related symptoms 1. Alternative statin regimens, such as alternate-day dosing or de-escalation dosing, may also be considered. Nonstatin therapies, such as ezetimibe or PCSK9 inhibitors, may be considered in patients who have failed at least two statins and have not achieved adequate reduction in LDL-C or non-HDL-C on maximally tolerated statin therapy.

It is essential to note that true complete statin intolerance is uncommon, and most patients who experience statin-associated muscle symptoms are able to tolerate statin rechallenge with an alternative statin or dose reduction 1. Therefore, a systematic approach to evaluating statin-associated side effects is crucial to encourage adherence to evidence-based statin treatment and minimize the risk of muscle symptoms.

From the FDA Drug Label

Atorvastatin calcium may cause myopathy (muscle pain, tenderness, or weakness associated with elevated creatine kinase [CK]) and rhabdomyolysis.

Myopathy/Rhabdomyolysis: ... 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

Musculoskeletal: myopathy, rhabdomyolysis, tendon disorder, polymyositis, immune-mediated necrotizing myopathy associated with statin use.

Statin and Muscle Spasm:

• Myopathy and Rhabdomyolysis are potential side effects of statin use, including atorvastatin and pravastatin.
• Muscle symptoms such as pain, tenderness, or weakness may occur, and patients should be instructed to promptly report any unexplained muscle pain, tenderness, or weakness.
• Risk factors for myopathy include age, uncontrolled hypothyroidism, renal impairment, and concomitant use with certain other drugs.
• The FDA drug label for atorvastatin and pravastatin does not directly mention "muscle spasm" as a side effect, but it does mention myopathy and rhabdomyolysis, which can cause muscle symptoms.
• Therefore, it can be inferred that statins may cause muscle spasm as part of the myopathy syndrome, but this is not explicitly stated in the label. 2 3

From the Research

Statin-Associated Muscle Symptoms

• Statin therapy has been shown to cause a small excess of mostly mild muscle pain, with most (>90%) of all reports of muscle symptoms by participants allocated statin therapy not due to the statin 4.
• The incidence of statin-associated muscle symptoms (SAMS) in clinical practice is 5-10%, with clinical manifestations ranging from mild weakness, cramps, and muscle pains to the very rare and severe rhabdomyolysis 5.
• The evidence in support of muscle pain caused by statins is in some cases equivocal and not particularly strong, with reported symptoms difficult to quantify and rarely a causal link between statins and muscle pain established 6.

Management of Statin-Associated Muscle Symptoms

• A strategic approach involving clinical assessment, patients' reassurance regarding statin safety, and reintroduction of low statin dose (daily or alternate scheme) combined with nonstatins (ezetimibe first and if required, the addition of alirocumab or evolocumab) will allow the majority of patients with SAMS to achieve meaningful low-density lipoprotein-cholesterol reductions 5.
• Exchange of statin may be beneficial, although all statins have been associated with muscle pain, and reduction of dose is worth trying, especially in primary prevention 6.
• Timely intervention with modified statin or non-statins is beneficial in patients with true statin-associated side effects (SASE) 7.

Prevalence of Statin-Associated Muscle Symptoms

• Statin-associated muscle symptoms are the most common reason for a patient to not be on statin therapy, with the data on the true prevalence of these symptoms mixed and continued studies showing that the symptoms may be less prevalent than previously believed 8.
• In randomized controlled trials, statins are well tolerated, and muscle-pain related side-effects are similar to placebo, with nocebo effects of statins also present 6.