NIACOR

Niacin or nicotinic acid, a water-soluble B-complex vitamin and antihyperlipidemic agent, is 3-pyridinecarboxylic acid. It is a white, crystalline powder, sparingly soluble in water. It has the following structural formula: MW=123.11 C 6 H 5 NO 2 Each NIACOR ® Tablet, for oral administration, contains 500 mg of nicotinic acid. In addition, each tablet contains the following inactive ingredients: croscarmellose sodium, hydrogenated vegetable oil, magnesium stearate and microcrystalline cellulose. Chemical Structure

I. Therapy with lipid-altering agents should be only one component of multiple risk factor intervention in those individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Nicotinic acid, alone or in combination with a bile-acid binding resin, is indicated as an adjunct to diet for the reduction of elevated total and LDL cholesterol levels in patients with primary hypercholesterolemia (Types IIa and IIb) † , when the response to a diet restricted in saturated fat and cholesterol and other nonpharmacologic measures alone has been inadequate (see also the NCEP treatment guidelines 6 ). Prior to initiating therapy with nicotinic acid, secondary causes for hypercholesterolemia (e.g., poorly controlled diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinemias, obstructive liver disease, other drug therapy, alcoholism) should be excluded, and a lipid profile performed to measure total cholesterol, HDL cholesterol, and triglycerides. II. Nicotinic acid is also indicated as adjunctive therapy for the treatment of adult patients with very high serum triglyceride levels (Types IV and V hyperlipidemia) † who present a risk of pancreatitis and who do not respond adequately to a determined dietary effort to control them. Such patients typically have serum triglyceride levels over 2,000 mg/dL and have elevations of VLDL cholesterol as well as fasting chylomicrons (Type V hyperlipidemia) † . Subjects who consistently have total serum or plasma triglycerides below 1,000 mg/dL are unlikely to develop pancreatitis. Therapy with nicotinic acid may be considered for those subjects with triglyceride elevations between 1,000 and 2,000 mg/dL who have a history of pancreatitis or of recurrent abdominal pain typical of pancreatitis. Some Type IV patients with triglycerides under 1,000 mg/dL may, through dietary or alcoholic indiscretion, convert to a Type V pattern with massive triglyceride elevations accompanying fasting chylomicronemia, but the influence of nicotinic acid therapy on the risk of pancreatitis in such situations has not been adequately studied. Drug therapy is not indicated for patients with Type I hyperlipoproteinemia, who have elevations of chylomicrons and plasma triglycerides, but who have normal levels of VLDL. Inspection of plasma refrigerated for 14 hours is helpful in distinguishing Types I, IV, and V hyperlipoproteinemia 7 . † Classification of Hyperlipoproteinemias Lipoproteins Lipid Elevations Type Elevated Major Minor C = cholesterol, TG = triglycerides LDL = low-density lipoprotein VLDL = very low-density lipoprotein IDL = intermediate-density lipoprotein I (rare) Chylomicrons TG ↑→ C IIa LDL C ..... IIb LDL, VLDL C TG III (rare) IDL C/TG ..... IV VLDL TG ↑→ C V (rare) Chylomicrons, VLDL TG ↑→ C

The usual adult dosage of nicotinic acid is 1 to 2 grams two or three times a day. Doses should be individualized according to the patient's response. Start with one-half tablet (250 mg) as a single daily dose following the evening meal. The frequency of dosing and total daily dose can be increased every four to seven days until the desired LDL cholesterol and/or triglyceride level is achieved or the first-level therapeutic dose of 1.5 to 2 grams/day is reached. If the patient's hyperlipidemia is not adequately controlled after 2 months at this level, the dosage can then be increased at two to four week intervals to 3 grams/day (1 gram three times per day). In patients with marked lipid abnormalities, a higher dose is occasionally required, but generally should not exceed 6 grams/day. Flushing of the skin appears frequently and can be minimized by pretreatment with aspirin or non-steroidal anti-inflammatory drugs. Tolerance to this flushing develops rapidly over the course of several weeks. Flushing, pruritus, and gastrointestinal distress are also greatly reduced by slowly increasing the dose of nicotinic acid and avoiding administration on an empty stomach. Sustained-release (modified-release, timed-release) nicotinic acid preparations should not be substituted for equivalent doses of immediate-release (crystalline) nicotinic acid.

Nicotinic acid is contraindicated in patients with a known hypersensitivity to any component of this medication; significant or unexplained hepatic dysfunction; active peptic ulcer disease; or arterial bleeding.

Cardiovascular: Atrial fibrillation and other cardiac arrhythmias, orthostasis, hypotension. Gastrointestinal: Dyspepsia, vomiting, diarrhea, peptic ulceration, jaundice, abnormal liver function tests. Skin: Mild to severe cutaneous flushing, pruritus, hyperpigmentation, acanthosis nigricans, dry skin. Metabolic: Decreased glucose tolerance, hyperuricemia, gout. Eye: Toxic amblyopia, cystoid macular edema. Nervous System / Psychiatric: Headache.

HMG‑CoA Reductase Inhibitors See WARNINGS, Skeletal Muscle . Antihypertensive Therapy Nicotinic acid may potentiate the effects of ganglionic blocking agents and vasoactive drugs resulting in postural hypotension. Aspirin Concomitant aspirin may decrease the metabolic clearance of nicotinic acid. The clinical relevance of this finding is unclear. Other Concomitant alcohol or hot drinks may increase the side effects of flushing and pruritus and should be avoided at the time of drug ingestion.

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature].