Pharmacology Update: Niacin Extended-Release and Lovastatin Tablets (AdvicorTM)
June 15, 2002
Pharmacology Update
Niacin Extended-Release and Lovastatin Tablets (AdvicorTM)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
The FDA has approved a combination of niacin and lovastatin for the management of lipid disorders. Kos Pharmaceuticals has combined extended-release niacin with lovastatin in a once-a-day tablet to lower LDL-cholesterol, triglycerides, and raise HDL-cholesterol. The extended-release form of niacin is currently marketed by Kos as Niaspan®. The combination will be marketed under the trade name "Advicor."
Indications
Niacin/lovastatin is indicated for the treatment of primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Frederickson Types IIa and IIb) in patients on lovastatin who require further lowering of triglycerides or raising of HDL-cholesterol or patients on niacin who require further lowering of LDL-cholesterol.1
Dosage
It is recommended that patients be titrated to the desired dose of niacin (as Niaspan) and lovastatin before converting to the equivalent dose of Advicor.1 It should be taken at bedtime with a low-fat snack. Tablets should be taken whole and not broken, crushed, or chewed before swallowing. Should titration of niacin/lovastatin be required, it should not exceed 500 mg of niacin every 4 weeks. If the drug is discontinued for more than 7 days, reinstitution should begin with the lowest dose.1
Niacin/lovastatin is supplied as 500 mg/20 mg, 750 mg/20 mg, and 1000 mg/20 mg tablets.
Potential Advantages
Advicor provides the convenience of a once-daily formulation combining extended-release niacin and lovastatin in one tablet.
Potential Disadvantages
The fixed-combination allows for less flexibility in the titrating of each drug to the desired effect. Niacin increases the risk of statin-induced myopathy.1,9
Comments
Both niacin and lovastatin are effective drugs in reducing coronary heart disease (CHD) mortality in the role of primary or secondary prevention.2-4 While HMG-CoA reductase inhibitors (statins) are effective in lowering total cholesterol and LDL-cholesterol, they are less effective in lowering triglycerides or raising HDL-cholesterol and do not affect lipoproteins(a). In contrast, niacin is effective in lowering triglycerides, raising HDL-cholesterol, and lowering lipoprotein(a). The latter appears to be associated with CHD.7 In patients with mixed dyslipidemia, the combination of niacin and a statin combines the benefits of both drugs, and the combination is generally effective and well tolerated.5,10 Advicor is the first combination of niacin and lovastatin that has been approved by the FDA. It was studied in a 52-week study in patients with type IIa or IIb hyperlipemia (n = 814).6 The combination of extended-release niacin and lovastatin (titrated to 2000 mg of niacin and 40 mg of lovastatin) reduced mean LDL-cholesterol by 45% (195 mg/dL to 110 mg/dL), mean triglyceride by 42% (199 mg/dL to 111 mg/dL), and mean HDL-cholesterol was raised by 41% (48 mg/dL to 66 mg/dL). Mean non-HDL cholesterol was decreased by 46% (236 mg/dL to 132 mg/dL). The most common side effects were flushing, gastrointestinal symptoms, pruritus, and rash. Seven patients discontinued the study due to creatine kinase (CK) elevation although myopathy (myalgia and CK values > 10 times the upper limit of normal) was reported. Advicor at 2000 mg/40 mg cost about $3.00 per day and ranges from $1.20 to $1.60 per tablet.
Clinical Implications
The Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) maintained attention to intensive treatment of patients with CHD but also intensive LDL-cholesterol lowering as primary prevention in those with multiple risk factors.8 In patients with certain dyslipidemia, the combination of niacin or fibrate with a statin may be considered. Patients with high triglycerides (200-499 mg/dL), high triglyceride with low HDL-cholesterol, or diabetic dyslipidemia (elevated triglycerides, low HDL-C, and small dense LDL) non-HDL are the secondary targets for therapy. This can be accomplished with intensive LDL-lowering therapy or the addition of niacin or fibrate. Advicor, effective in lowering non-HDL cholesterol, provides a convenient regimen of niacin and lovastatin for these dyslipidemias after the patient has been titrated appropriately with individual agents.
References
1. Advicor Product Labeling. Kos Pharmaceuticals Inc., November 2001.
2. Downs JR, et al. JAMA. 1998;279(20):1615-1622.
3. Knatterud GL, et al. Circulation. 2000;102(2):157-165.
4. Coronary Drug Project Research Group. JAMA. 1975; 231:360-381.
5. Taher TH, et al. Am J Cardiol. 2002;89(4):390-394.
6. Kashyap ML, et al. Am J Cardiol. 2002;89(6):672-678.
7. Danesh J, et al. Circulation. 2000;102:1082-1085.
8. NCEP Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). National Heart, Lung, and Blood Institute. NIH. May 2001.
9. Maron DJ, et al. Circulation. 2000;101:207-213.
10. Stein EA, et al. J Cardiovasc Pharmacol Ther. 1996; 1(2):107-116.
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. Both are Associate Editors of Internal Medicine Alert.
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