Published: September 2011

High dose simvastatin increases myopathy risk

Prescriber Update 32(3): 23
September 2011

Simvastatin data sheets are in the process of being updated to warn prescribers about the increased risk of myopathy in patients who receive high doses.

Prescribers are advised that high dose (80mg) simvastatin should only be considered in patients who have not achieved their treatment target with lower doses. This advice follows an analysis of the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) trial, which showed an increased risk of myopathy in patients taking 80 mg/day simvastatin compared with lower doses.1

The incidence of myopathy seen in the SEARCH trial increased with increasing dose. For patients taking 80 mg simvastatin daily, the incidence of myopathy was 0.9%, compared with 0.02% for patients taking 20 mg daily. In terms of efficacy, the trial found that treatment with 80 mg simvastatin did not provide clinically significant benefits over 20 mg or 40 mg daily.

The risk of myopathy also increases with age (≥ 65 years), female gender, uncontrolled hypothyroidism, and renal impairment.

Although myopathy is a well known adverse effect of simvastatin the risk increases with increasing dose. Prescribers are advised to consider this risk in light of the limited increase in benefit seen with high dose simvastatin therapy.

Updated contraindications

The findings of the SEARCH study have also led to changes to contraindications for simvastatin.

The use of simvastatin is now additionally contraindicated in patients who have experienced myopathy when treated with other lipid lowering agents. In addition the use of simvastatin is contraindicated when a patient is treated with either potent CYP3A4 inhibitors (e.g. itraconazole, ketoconazole, posaconazole, HIV protease inhibitors, erythromycin, clarithromycin, telithromycin and nefazodone), or gemfibrozil, cyclosporin or danazol.

A comprehensive list of medicines that interact with simvastatin, and recommendations about how to manage potential interactions is available in the medicine data sheet at: http://www.medsafe.govt. nz/Medicines/infoSearch.asp

Prescribers are reminded to advise patients about the risk of myopathy and to report unexplained muscle pain, tenderness or weakness to a healthcare professional promptly. This advice applies to patients either starting treatment, or following a dose increase.

Simvastatin therapy should be discontinued immediately if myopathy is suspected.

Key messages:

  • High dose (80mg) simvastatin should only be considered in patients who have not achieved their treatment target with lower doses or with alternative agents.
  • Do not use simvastatin in patients with a history of statin-induced myopathy.
  • Do not use simvastatin with potent CYP3A4 inhibitors, gemfibrozil, cyclosporin or danazol.
  • Inform patients about the risk of myopathy associated with simvastatin and to get in contact with a healthcare professional if they experience symptoms.
  • Discontinue simvastatin immediately if myopathy is suspected.
  1. US Food and Drug Administration. 8 June 2011. Safety Communication: New restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury. Accessed online: Drugs/DrugSafety/ucm256581.htm#Simvastatin_Dose_ Limitations