FDA black box warning on the use of 80 mg simvastatin

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Phone:617-632-7753; Associate Editor(s)-In-Chief: Kashish Goel, M.D.

Overview

Simvastatin 80 mg is the highest approved dose for this drug and it is estimated that approximately 2.1 million patients in the U.S. were prescribed this dose in the year 2010. In March 2010, FDA revised the simvastatin label and recommended that patients of Chinese descent should not receive simvastatin 80 mg with cholesterol-modifying doses of niacin-containing product. This review was based on the interim results of Heart Protection Study. On 8th June 2011, FDA added another black box warning to the use of high dose simvastatin. Based on the review of randomized clinical trial, Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH)[1], FDA recommended limiting the use of high-dose simvastatin[2]. This trial showed a significantly increased risk of myopathic complications (0.9% in intensive statin arm vs. 0.03% in standard dose arm) in the patients treated with simvastatin 80 mg as compared to 20 mg dose[1].

Recommendations

  • Simvastatin 80 mg should not be started in new patients, including those who are taking lower doses.
  • This dose should be used only in those who have taken this medication for more than 12 months without any evidence of myopathy.
  • New contraindications and dose limitations added to the label for use with other medications.


Change in Simvastatin label
Previous Simvastatin label New Simvastatin label
Avoid simvastatin with:
Itraconazole
Ketoconazole
Erythromcyin
Clarithromycin
Telithrromcyin
HIV protease inhibitors
Nefazodone
Contraindicated with simvastatin:
Itraconazole
Ketoconazole
Posaconazole (new)
Erythromcyin
Clarithromycin
Telithrromcyin
HIV protease inhibitors
Nefazodone
Gemfibrozil
Cyclosporine
Danazol
Do not exceed 10 mg simvastatin daily with:
Gemfibrozil
Cyclosporine
Danazol
Do not exceed 10 mg simvastatin daily with:
Amiodarone
Verapamil
Diltiazem
Do not exceed 20 mg simvastatin daily with:
Amiodarone
Verapamil
Do not exceed 20 mg simvastatin daily with:
Amlodipine
Ranolazine
Do not exceed 40 mg simvastatin daily with:
Diltiazem
Avoid large quantities of grapefruit juice (>1 quart daily) 'Avoid large quantities of grapefruit juice (>1 quart daily)

References

  1. 1.0 1.1 Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group. Armitage J, Bowman L, Wallendszus K, Bulbulia R, Rahimi K; et al. (2010). "Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial". Lancet. 376 (9753): 1658–69. doi:10.1016/S0140-6736(10)60310-8. PMC 2988223. PMID 21067805.
  2. http://www.fda.gov/Drugs/DrugSafety/ucm256581.htm

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