Simvastatin 80mg dose and myopathy risk

• there is an increased risk of myopathy associated with high-dose (80 mg) simvastatin. The 80-mg dose should be considered only in patients with severe hypercholesterolaemia and high risk of cardiovascular complications who have not achieved their treatment goals on lower doses, when the benefits are expected to outweigh the potential risks
• simvastatin (Zocor) product information (Summary of Product Characteristics and Patient Information Leaflet) has been updated to include warnings about increased risk of myopathy in patients receiving the highest licensed dose (80 mg). Similar changes are being implemented to the product information for combination products that contain simvastatin, such as Inegy (simvastatin combined with ezetimibe)
  • the updated SPC follows a review of the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH)
    
    
    • SEARCH was a multicentre, double-blind, active-treatment, factorial-design study conducted at 88 sites in the UK, which evaluated the effect of treatment with Zocor 80 mg versus 20 mg on major vascular events (MVEs, defined as fatal coronary events, nonfatal myocardial infarction, coronary revascularisation procedure, non-fatal or fatal stroke, or peripheral revascularisation procedure) in 12 064 patients with a history of myocardial infarction, over a median follow-up of 6·7 years
    • results showed that treatment with simvastatin 80 mg did not provide any significant benefits over simvastatin 20 mg
      • incidence of MVEs was similar for 80 mg (1477, 24·5%) versus 20 mg (1553, 25·7%; risk ratio 0·94 [95% CI 0·88-1·01])
      • was no evidence of increased total or cause-specific mortality, vascular mortality, non-vascular mortality, or higher risk of cancer or haemorrhagic stroke with the high dose of simvastatin
      • however, myopathy occurred in 52 patients (0·9%) randomly assigned simvastatin 80 mg compared with one patient (0·02%) randomly assigned simvastatin 20 mg. An estimated 11 patients in the simvastatin 80-mg group developed rhabdomyolysis compared with none in the simvastatin 20-mg group
        
        
      • Advice for health professionals
        • there is an increased risk of myopathy associated with high-dose (80 mg) simvastatin
          
          
        • simvastatin 80 mg should be considered only in patients with severe hypercholesterolaemia and high risk of cardiovascular complications who have not achieved their treatment goals on lower doses, when the benefits are expected to outweigh the potential risks
          
          
        • prescribers treating patients who are taking simvastatin 80 mg or who are being considered for an up-titration to that dose may need to review their treatment during their next visit, to take into account the new evidence
          
          
        • patients who are currently taking simvastatin 80 mg should not stop taking their medicine. However, they should be advised to contact their doctor immediately if they experience unexplained muscle pain, tenderness, or weakness
          
          
        • please report suspected adverse reactions with medicines, including statins, to us via the Yellow Card Scheme (www.yellowcard.gov.uk)

Reference:

• MHRA. Simvastatin: increased risk of myopathy at high dose (80mg). Drug Safety Update. May 2010;3(10):7-8
• MHRA Drug Safety Update (August 2012). Simvastatin: increased risk of myopathy at high dose (80 mg)