Pharmacology Update

Niacin/simvastatin Extended-Release Tablets (Simcor®)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationship to this field of study.

The FDA has approved extended release niacin plus simvastatin as a combination product. Along with niacin/lovastatin that was approved in 2001, this represents the second niacin/statin combination for the treatment of hyperlipidemia. The new product combines two widely used drugs, simvastatin and extended-release niacin (Niaspan ). It is marketed by Abbott Laboratories, Inc. as Simcor.

Indications

Niacin/simvastatin is indicated to reduce elevated total cholesterol, LDL-cholesterol, Apo B, non-HDL cholesterol and triglycerides (TG) or to increase HDL-cholesterol in patients with primary hypercholesterolemia and mixed dyslipidemia when monotherapy with simvastatin or niacin extended-release is considered inadequate. It is also indicated to treat hypertriglyceridemia (Fredrickson type IV hyperlipidemia) when simvastatin or niacin alone is inadequate.1

Dosage

The recommended starting dose for either naïve patients or those switching from extended-release niacin is 500 mg of niacin and 20 mg of simvastatin once daily. Maintenance dose ranges from 1000/20 mg to 2000/40 mg. The dose may be titrated by increments not exceeding 500 mg of niacin every 4 weeks. Doses above 2000/40 mg are not recommended. The tablets should be taken at bedtime with a low-fat snack. Aspirin or ibuprofen taken 30 minutes before dosing may minimize flushing.1

Niacin/simvastatin is available as 500/20 mg, 750/20 mg, and 1000/20 mg tablets.

Potential Advantages

Niacin/simvastatin 1000/20 mg and 2000/40 mg combinations are more effective in reducing non-HDL-C than simvastatin 20 mg alone. Niacin/simvastatin is more effective, in general, than simvastatin in reducing TG and increasing HDL-C.1 Niaspan has been associated with less flushing than the immediate-release niacin formulations and may be associated with less hepatotoxicity than other sustained-release niacin preparations such as Slo-Niacin and Nicobid.2 The combination offers a more potent statin than the previously available combination (lovastatin/niacin).

Potential Disadvantages

Flushing is a common adverse event associated with niacin occurring in 59% of subjects in a controlled clinical study. This is often accompanied with dizziness, syncope, tachycardia, palpitations, shortness of breath, sweating, chills, and/or edema. Niacin is contraindicated in patients with active liver disease or peptic ulcer disease. Niacin can increase blood glucose, uric acid levels, prothrombin time and decrease platelet counts. Glucose levels should be closely monitored in diabetic or potentially diabetic patients particularly during the first few months. Myopathy and/or rhabdomyolysis have been reported with the combination of simvastatin and niacin (³1 gram). Patients should be monitored for muscle-related symptoms (eg, pain, tenderness, weakness) after initiation of therapy or dose increase. Periodic assessment of creatine kinase levels may be appropriate. Additional benefit of niacin over simvastatin alone on cardiovascular mortality or morbidity has not been established.1

Comments

The combination of a statin with niacin results in significant reduction in TG and elevation of HDL-C not achieved with a statin alone. The addition of niacin (1000 mg or 2000 mg daily) to simvastatin 20 mg compared to simvastatin 20 mg alone resulted in the following changes at 24-weeks; non-HDL-C (-13.6% and -19.5% vs -5%), LDL-C (-11.9% and -14.3% vs -6.7%), total-C (-8.8% and -11.1% vs -4.5%), TG (-26.5% and -38.0% vs -15.3%), ApoB (-13.2% and -18.5% vs -5.6%), HDL-C (+20.7% and +29.0% vs +7.8%). Niacin/simvastatin (1000/40 mg and 2000/40 mg) only showed significant changes in TG and HDL-C compared to simvastatin 80 mg. Overall, niacin/simvastatin was superior to simvastatin alone in lowering TG and raising HDL-C. Flushing is the most annoying adverse event of niacin affecting about 60% of patients. The cost of niacin/simvastatin is about 11% higher than niacin/lovastatin at equal milligram doses (eg, 1000 mg/20 mg), $3.36 compared to $3.03 per tablet respectively. At roughly equipotent doses (ie, 1000/20 mg niacin/simvastatin and 1000/40 mg niacin/lovastatin) niacin/simvastatin is about a 4% less costly, $3.36 compared to $3.52.

Clinical Implications

In comparison with the previously available niacin/statin product, niacin/simvastatin provides a product with the identical niacin formulation but with twice the statin potency. The maximum recommended dose of both niacin/lovastatin and niacin/simvastatin are 2000/40 mg. While the benefit of combination therapy in terms of cardiovascular mortality and morbidity has not been established, the addition of extended-release niacin to background statin therapy has been reported to induce atherosclerosis regression as measured by carotid intima-media thickness (CIMT) and slowed the progression of atherosclerosis among individuals with known coronary heart disease and moderately low HDL-C.3,4

References

1. Simcor Product Information. Abbott Laboratories, Inc. February 2008.

2. Alsheikh-Ali AA, Karas RH. Am J Cardiol. 2007;99:379-381.

3. Taylor AJ, et al. Curr Med Res Opin. 2006;22(11):2243-2250.

4. Taylor AJ, et al. Circulation. 2004;110(23):3512-3517