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New Simvistatin (Zocor) Dosing Guidelines

Thursday, August 18, 2011 // Uncategorized

The following is the latest edition of The Medical Letter which describes the changes in dosing guidelines for the most potent statin available in generic.

New Simvastatin Dosing Recommendations

 
The Medical Letter on Drugs and Therapeutics • August 8, 2011 (Issue 1370) p. 61

The FDA has announced changes in the labeling of simvastatin to reduce the risk of myopathy.(MUSCLE INFLAMMATION). These changes include limiting the use of the 80-mg maximum dose to patients who have been taking it for 12 months or more without evidence of myopathy and new recommendations for use of simvastatin with other drugs.1 Simvastatin is available alone (Zocor, and others) and in combination with ezetimibe (Vytorin) and with niacin (Simcor).

MYOPATHY — The risk of myopathy with simvastatin is closely related to the dose of the drug and even more closely to its concentration in serum.2 In a 7-year randomized trial (SEARCH) in 12,064 patients, the incidence of myopathy (unexplained muscle pain or weakness and a CK >10 times the upper limit of normal) was 0.9% in patients taking 80 mg of simvastatin daily and 0.03% in those taking 20 mg daily. The risk of myopathy was highest in the first year after randomization.3

DRUG INTERACTIONS — Simvastatin is metabolized by CYP3A4. Concomitant use of drugs that inhibit CYP3A4 can increase simvastatin plasma concentrations and the risk of myopathy.2 The new simvastatin label states that its use is contraindicated with strong CYP3A4 inhibitors and with other drugs shown to increase the risk of myopathy when taken with simvastatin. In addition, the label now specifies a maximum simvastatin dose of 10 mg/day when taken with amiodarone, diltiazem or verapamil and 20 mg/day with amlodipine or ranolazine; these drugs have also been shown to increase simvastatin serum concentrations.

CHOICE OF A STATIN — All of the statins available in the US are listed in Table 2. Lovastatin, pravastatin and simvastatin are available generically. High-dose simvastatin (80 mg/d) lowers LDL-C by only about 6% more than 40 mg/d.1 Atorvastatin is more effective in lowering LDL-C, has a well-documented beneficial effect on clinical outcomes, and is expected to become available generically before the end of 2011; in clinical trials, the risk of myopathy with atorvastatin did not appear to be dose-related. Rosuvastatin may be even more effective than atorvastatin in lowering LDL-C, and now has also been shown to improve clinical outcomes; the risk of myopathy with rosuvastatin has been low. Pitavastatin has not been shown to offer any advantage in cholesterol-lowering over statins that are available generically, and clinical outcome studies are lacking.4

CONCLUSION — There is no need to take 80 mg of simvastatin. Patients who fail to achieve their LDL-C goal on 40 mg/day of simvastatin could take atorvastatin or rosuvastatin instead.

1. FDA drug safety communication: new restrictions, contraindications and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury. Available at www.fda.gov/drugsafety/ucm/htm. Accessed July 29, 2011.

2. Drug interactions with simvastatin. Med Lett Drugs Ther 2008; 50:83.

3. SEARCH Collaborative Group. 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 2010; 376:1658.

4. Drugs for lipids. Treat Guidel Med Lett 2011; 9:13

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