From the FDA Drug Label
The most common adverse reactions that led to discontinuation were: gastrointestinal disorders (0.5%), myalgia (0.1%), and arthralgia (0. 1%). Myopathy/Rhabdomyolysis In clinical studies with a median follow-up of at least 4 years, in which 24,747 patients received simvastatin, the incidence of myopathy (defined as unexplained muscle weakness, pain, or tenderness accompanied by CK increases greater than 10xULN) was approximately 0.03%, 0.08%, and 0. 61% for the simvastatin 20 mg, 40 mg, and 80 mg daily groups, respectively.
The patient symptom that will create the greatest concern for the provider is Muscle pain, as it can be a sign of myopathy or rhabdomyolysis, which are serious adverse reactions associated with simvastatin use 1.
From the Research
Muscle pain would create the greatest concern for the provider when a patient is taking both azithromycin and simvastatin. This combination increases the risk of statin-induced myopathy, which can range from mild muscle pain to severe rhabdomyolysis, a potentially life-threatening condition. Azithromycin can inhibit the metabolism of simvastatin by affecting the CYP3A4 enzyme system, leading to increased simvastatin levels in the blood, as reported in a case study published in 2021 2. While this interaction is less potent than with other macrolide antibiotics like erythromycin or clarithromycin, it still poses a significant risk, particularly in patients with genetic polymorphisms such as SLCO1B1, which can further increase the risk of myopathy 2.
Key Considerations
- The risk of statin-induced myopathy is dose-dependent and can be increased by drug interactions, such as the one between azithromycin and simvastatin 3.
- Patients with statin-induced myopathy may present with muscle pain, which can range from mild to severe, and may be accompanied by elevated creatine kinase levels 4.
- The combination of azithromycin and simvastatin has been reported to cause rhabdomyolysis, a life-threatening condition, in rare cases 5.
Management
If a patient reports muscle pain while on this combination, the provider should immediately evaluate the patient, consider checking creatine kinase levels, and potentially discontinue the simvastatin temporarily. The other symptoms listed (nausea, tiredness, and headache) are common side effects of either medication but don't specifically signal the dangerous drug interaction that muscle pain does. It is essential to weigh the benefits and risks of statin therapy and consider alternative treatments if necessary, as the benefit/risk ratio of statin therapy is generally positive 4.