Toxicology Review Newsletter
Volume 1 - Number 1
Over 2 million people in the U.S. are taking a drug product containing 80 mg. of simvastatin. Are any of those people your patients? On June 8, 2011, the FDA announced changes to prescribing simvastatin, recommending limiting the use of the highest approved dose of 80 mg. to those patients who have been taking this dose for 12 months or more without evidence of myopathy. Now 40 mg. of simvastatin daily is the dose not to exceed. DO NOT start new patients on simvastatin 80 mg. is the word from the FDA. This includes patients who are now on lower doses of simvastatin.
What if your patient who is on simvastatin 40 mg. and not meeting their LDL cholesterol goal:
The FDA recommendation is to choose alternative treatment .
Changes to the label include new contraindications and dose limitations with particular drugs. So, for your patients who are on simvastatin or one of the combination products, Simcor or Vytorin, review all their medications. Some drugs are known to increase the risk of myopathy when used with simvastatin.
Drugs that are contraindicated for use with simvastatin:
- strong CYP3A4 inhibitors- some of these drugs include itraconazole, clarithromycin, HIV protease inhibitors, ketoconazole, posaconazole, erythromycin, telithromycin, nefazodone, cyclosporine, danazol
*Caution should be used with other fibrates, niacin 1 g/day or more, and dronedarone
Certain drugs when used with simvastatin can raise the levels of simvastatin in the body and as a result increase the risk of myopathy. Therefore, the following recommendations should be followed and are included in the new labeling mandated by the FDA.
Do Not Exceed 10 mg. simvastatin daily with:
*Since Simcor is only available with 20 mg. or 40 mg. of simvastatin, then the above mentioned drugs are contraindicated with use of Simcor
Do Not Exceed 20 mg. simvastatin daily with:
- 80 mg. of simvastatin lowers LDL cholesterol by an additional 6% over 40 mg. of simvastatin
- Rhabdomyolysis is rare but hospitalized rhabdomyolysis cases do occur in 4.9 out of every 100,000 people exposed to simvastatin for one full year and was highest in the first 12 months of therapy
- Older age or being female increase the risk of myopathy
- Approximately 60% of the cases of myopathy are associated with a genetic variant which affects the coding of the transporter responsible for simvastatin uptake in the liver, thereby increasing the plasma concentration of simvastatin and thus increasing the risk of myopathy
*Antihypercholesterolemic and antihyperlipidemic drugs are not recommended for use in women who are pregnant or nursing
The FDA has been conducting an ongoing safety review of simvastatin. These new changes are based on the review of the seven-year Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine trial (SEARCH). The findings from the SEARCH trial are supported by analyses of the FDA’s Adverse Event Reporting System (AERS) database. For a complete data summary follow this link: http://www.fda.gov/Drugs/Drugsafety/ucm25658.htm
- FDA Drug Safety Communications: New restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury Safety announcement 06-08-2011
- Pharmacist’s Letter 2011; 27(7):270712
Editor: Nonna Barton
URMC Therapeutics Committee: This is a joint committee of Strong and Highland Hospitals. Each month, this newsletter will include a report of topics brought before the committee.
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