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
Article date: May 2010
The 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).
Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine data
This update 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, non-fatal 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.
The results showed that treatment with simvastatin 80 mg did not provide any significant benefits over simvastatin 20 mg. The 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]). There 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 (for some suspected rhabdomyolysis cases there were no detailed data to confirm 100% diagnosis according to the criteria used).
For interim details of SEARCH, see: SEARCH Study Collaborative Group. Am Heart J 2007; 154: 815–23.e6.
Myopathy is a known side effect of all statins, including simvastatin, and the risk increases with higher doses. However, its most serious form, rhabdomyolysis, is a very rare side effect. The risk of myopathy is greater in: elderly patients (>65 years); women; patients with renal impairment or hypothyroidism; patients who consume large quantities of alcohol; those with a history of previous muscle problems during treatment with statins or other lipid-lowering drugs; or those with family history of muscle disorders. Concomitant use of some medicines may also increase the risk of muscle damage.
Advice for healthcare professionals
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.
Report suspected adverse reactions with medicines, including statins, to us via the Yellow Card Scheme.
Article citation: Drug Safety Update May 2010, vol 3 issue 10: 7.