NPC Archive Item: FDA restricts the use of simvastatin 80 mg because of an increased risk of myopathy

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24 August 2011

Following a review of safety data, the US FDA has restricted the use of simvastatin▼* 80 mg to reduce the risk of muscle damage (myopathy). The FDA recommend that patients should not be started on simvastatin 80mg and only be maintained on simvastatin 80 mg if they have been taking this dose for 12 months or more without evidence of myopathy. Additional FDA warnings are given regarding the coprescribing of drugs that can interact to raise the levels of simvastatin in the body. Health professionals in the UK should continue to follow NICE and MHRA guidance when prescribing simvastatin.

Health professionals should continue to follow NICE guidance on lipid modification and use simvastatin▼* 40 mg for most people. NICE lipid guidance explicitly sets no lipid targets that patients are expected to achieve, for either primary or secondary prevention (including those with acute coronary syndrome). Intensive statin therapy should not be automatic but may be considered in certain circumstances, taking into account the patient’s informed preference, including the benefits and risks of treatment.

Any possible incremental benefit of using intensive statin therapy over standard doses (e.g. 40 mg/day simvastatin) must be considered in the context of an increased risk of adverse events. Health professionals should also note guidance from the MHRA on the use of simvastatin 80 mg, which was published in 2010, and is entirely consistent with NICE guidance:

  • 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, via the Yellow Card Scheme.

Health professionals should refer to the Summaries of Product Characteristics for specific information on dosing recommendations, contraindications and precautions for use, including measures to reduce the risk of myopathy caused by medicinal product interactions.

*Note: The MHRA has advised that the black triangle (▼) refers to intensive monitoring being requested only when simvastatin is used in children and adolescents (10–17 years), in line with the recently licensed paediatric dosing recommendation.

Further information
The FDA recommends that simvastatin 80 mg should be used only in patients who have been taking this dose for 12 months or more without evidence of muscle damage (myopathy). Simvastatin 80 mg should not be started in new patients, including patients already taking lower doses of the drug. In addition to these new limitations, FDA is requiring changes to the simvastatin label in the US to add new contraindications and dose limitations for using simvastatin with certain medicines. The changes recommended by the FDA followed a review of the SEARCH trial and data from other sources. More details and background to the recommendations can be found in the FDA safety communication and in an NEJM Perspectives Article.

The increased risk of myopathy with simvastatin 80 mg was reviewed by the MHRA in the May 2010 edition of Drug Safety Update.

For more information and a discussion on the limitations of the evidence regarding benefits for intensive statin therapy over normal statin dosing, please refer to MeReC Rapid Review No. 2835 and references contained therein.

Further information on statins can be found on NHS Evidence and in the cardiovascular disease – lipids e-learning section of NPC.

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