Which statins (HMG-CoA reductase inhibitors) are less prone to causing rhabdomyolysis?

From the Guidelines

Pravastatin and fluvastatin are the statins least prone to causing rhabdomyolysis, with a lower risk profile due to their lipophilicity and metabolic pathways. These medications have different metabolic pathways compared to other statins, with pravastatin not being extensively metabolized by the cytochrome P450 system, and fluvastatin being primarily metabolized by CYP2C9 rather than CYP3A4, which is involved in many drug interactions 1. In contrast, simvastatin, lovastatin, and atorvastatin have higher risks of muscle toxicity, particularly at higher doses.

When prescribing statins to patients with risk factors for rhabdomyolysis, such as advanced age, renal impairment, hypothyroidism, or those taking medications that interact with statins, consider starting with pravastatin or fluvastatin at lower doses. Some key points to consider when prescribing statins include:

• Regular monitoring for muscle symptoms, including unexplained muscle pain, tenderness, or weakness, especially when accompanied by malaise or fever
• Patients should be instructed to report these symptoms promptly and have their creatine kinase levels checked if they develop concerning symptoms
• The risk of rhabdomyolysis increases with higher statin doses and when combined with certain medications like fibrates, particularly gemfibrozil 1.

It is essential to note that while the risk of rhabdomyolysis is lower with pravastatin and fluvastatin, it is still crucial to monitor patients closely for any signs of muscle toxicity, as the risk can never be completely eliminated. By prioritizing the use of these statins and carefully monitoring patients, clinicians can minimize the risk of rhabdomyolysis and ensure the best possible outcomes for their patients.

From the FDA Drug Label

Pravastatin may cause myopathy and rhabdomyolysis. Acute kidney injury secondary to myoglobinuria and rare fatalities have occurred as a result of rhabdomyolysis in patients treated with statins, including pravastatin Myopathy, defined as muscle aching or muscle weakness in conjunction with increases in creatine phosphokinase (CK) to greater than 10 times the upper limit of normal (ULN), occurred <0. 1% in pravastatin-treated patients in clinical trials. Simvastatin may cause myopathy and rhabdomyolysis. Acute kidney injury secondary to myoglobinuria and rare fatalities have occurred as a result of rhabdomyolysis in patients treated with statins, including simvastatin In clinical studies of 24,747 simvastatin -treated patients with a median follow-up of 4 years, the incidence of myopathy, defined as unexplained muscle weakness, pain, or tenderness accompanied by creatinine kinase (CK) increases greater than ten times the upper limit of normal (10xULN), were approximately 0.03%, 0.08%, and 0. 61% in patients treated with simvastatin 20 mg, 40 mg, and 80 mg daily, respectively.

Statins less prone to rhabdomyolysis:

• Pravastatin has a lower incidence of myopathy (<0.1%) compared to simvastatin (0.03% to 0.61%).
• The risk of myopathy is increased by elevated plasma levels of simvastatin and simvastatin acid.
• Pravastatin may be considered less prone to rhabdomyolysis compared to simvastatin, especially at higher doses 2 3.

From the Research

Statins and Rhabdomyolysis

• Rhabdomyolysis is a serious adverse drug reaction of statins, with simvastatin having the highest risk in comparison to other statins, as shown in a pharmacovigilance comparative study 4.
• The risk of rhabdomyolysis is higher in men, older than 74 years, and in cases of drug interactions 4.
• A narrative review of statin-induced rhabdomyolysis found that the primary mechanism is believed to be a decrease in ubiquinone (coenzyme Q) produced by the HMG-CoA pathway, and that different types of lipophilic and hydrophilic statins play a role in causing rhabdomyolysis 5.

Comparison of Statins

• A study comparing the lipid-lowering effects of pitavastatin and pravastatin found that pitavastatin 4 mg demonstrated superior LDL-C reductions compared with pravastatin 40 mg after 12 weeks of therapy in adults with primary hyperlipidemia or mixed dyslipidemia, with no reports of myositis or rhabdomyolysis 6.
• A pharmacokinetic comparison of simvastatin, lovastatin, fluvastatin, and pravastatin found that fluvastatin and pravastatin may be better choices than simvastatin or lovastatin for an over-the-counter statin due to their pharmacokinetic profiles 7.
• A comparison of rosuvastatin with atorvastatin, simvastatin, and pravastatin found that rosuvastatin 10 mg was more effective in allowing patients to reach LDL-C goals and produced greater reductions in LDL-C, total cholesterol, and non-HDL-C compared to the other treatments 8.

Statins Less Prone to Rhabdomyolysis

• Based on the available evidence, fluvastatin and pravastatin may be less prone to rhabdomyolysis due to their pharmacokinetic profiles and lower risk of myotoxicity 7.
• Pitavastatin and rosuvastatin also appear to have a lower risk of rhabdomyolysis, with no reports of myositis or rhabdomyolysis in the study comparing pitavastatin and pravastatin 6, and rosuvastatin being more effective in allowing patients to reach LDL-C goals with a lower risk of myotoxicity 8.