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Pronunciation
(NYE a sin)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of dyslipidemias (Fredrickson types IIa and IIb or primary hypercholesterolemia) as mono- or adjunctive therapy; to lower the risk of recurrent MI in patients with a history of MI and hyperlipidemia; to slow progression or promote regression of coronary artery disease; treatment of hypertriglyceridemia in patients at risk of pancreatitis
Use: Unlabeled
Treatment of pellagra; dietary supplement
Pregnancy Risk Factor
A/C (dose exceeding RDA recommendation)
Pregnancy Considerations
Animal reproduction studies have not been conducted. It is unknown whether or not niacin at lipid-lowering doses is harmful to the developing fetus. If a woman becomes pregnant while receiving niacin for primary hypercholesterolemia, niacin should be discontinued. If a woman becomes pregnant while receiving niacin for hypertriglyceridemia, the benefits and risks of continuing niacin should be assessed on an individual basis.
Lactation
Enters breast milk/consider risk:benefit
Breast-Feeding Considerations
Niacin is excreted in human breast milk. Because lipid-lowering doses of niacin may cause serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Contraindications
Hypersensitivity to niacin, niacinamide, or any component of the formulation; active hepatic disease or significant or unexplained persistent elevations in hepatic transaminases; active peptic ulcer; arterial hemorrhage
Warnings/Precautions
Concerns related to adverse effects:
• Flushing/pruritus: Flushing and pruritus, common adverse effects of niacin, may be attenuated with a gradual increase in dose, and/or by taking aspirin (adults: 325 mg) or an NSAID 30-60 minutes before dosing. Compliance is enhanced with twice-daily dosing (extended-release product excluded).
• Hepatotoxicity: Cases of severe hepatotoxicity, including fulminant hepatic necrosis, have occurred when immediate release (crystalline) niacin products have been substituted with sustained-release (modified release, timed-release) niacin products at equivalent doses. Patients should be initiated with low doses (eg, 500 mg at bedtime) with titration to achieve desired response. Liver function tests should be monitored in all patients receiving lipid-lowering doses of niacin.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with unstable angina or MI.
• Diabetes: Use niacin with caution in patients with diabetes mellitus; niacin may increase fasting blood glucose, although clinical data suggest increases are generally modest (<5%). Monitor glucose; adjustment of hypoglycemic therapy may be necessary.
• Gallbladder disease: Use with caution in patients with active gallbladder disease; can exacerbate.
• Gout: Use may be associated with hyperuricemia. Use with caution in patients with gout.
• Hepatic impairment and/or heavy ethanol users: Use with caution in patients with a past history of hepatic impairment and/or who consume substantial amounts of ethanol; monitor liver function tests. Contraindicated with active liver disease or unexplained persistent transaminase elevation.
• Renal impairment: Use with caution in patients with renal impairment.
Concurrent drug therapy issues:
• Anticoagulants: Use with caution in patients taking anticoagulants; may slightly increase prothrombin time.
• HMG-CoA reductase inhibitors: Rare cases of rhabdomyolysis have occurred during concomitant use with HMG-CoA reductase inhibitors; with concurrent use or if symptoms suggestive of myopathy occur, monitor creatine phosphokinase (CPK) and potassium. Use with caution in patients with renal impairment, inadequately treated hypothyroidism, patients with diabetes or the elderly; risk for myopathy and rhabdomyolysis may be increased.
Dosage form specific issues:
• Product interchangeability: Note: Formulations of niacin (regular release versus extended release) are not interchangeable; bioavailability varies.
Other warnings/precautions:
• Appropriate use: Prior to initiation, secondary causes for hypercholesterolemia (eg, poorly controlled diabetes mellitus, hypothyroidism) should be excluded; management with diet and other nonpharmacologic measures (eg, exercise or weight reduction) should be attempted prior to initiation. Use has not been evaluated in Fredrickson type I or III dyslipidemias.
Adverse Reactions
Frequency not defined.
Cardiovascular: Arrhythmias, atrial fibrillation, edema, flushing, hypotension, orthostasis, palpitation, syncope (rare), tachycardia
Central nervous system: Chills, dizziness, headache, insomnia, migraine, nervousness, pain
Dermatologic: Acanthosis nigricans, burning skin, dry skin, hyperpigmentation, maculopapular rash, pruritus, rash, skin discoloration, urticaria
Endocrine & metabolic: Glucose tolerance decreased, gout, phosphorous levels decreased, hyperuricemia
Gastrointestinal: Abdominal pain, amylase increased, diarrhea, dyspepsia, eructation, flatulence, nausea, peptic ulcers, vomiting
Hematologic: Platelet counts decreased
Hepatic: Hepatic necrosis (rare), hepatitis, jaundice, transaminases increased (dose-related), prothrombin time increased, total bilirubin increased
Neuromuscular & skeletal: CPK increased, leg cramps, myalgia, myasthenia, myopathy (with concurrent HMG-CoA reductase inhibitor), paresthesia, rhabdomyolysis (with concurrent HMG-CoA reductase inhibitor; rare), weakness
Ocular: Blurred vision, cystoid macular edema, toxic amblyopia
Respiratory: Cough, dyspnea
Miscellaneous: Diaphoresis, hypersensitivity reactions (rare; includes anaphylaxis, angioedema, laryngismus, vesiculobullous rash), LDH increased
Metabolism/Transport Effects
None known.
Drug Interactions
Bile Acid Sequestrants: May decrease the absorption of Niacin. Risk D: Consider therapy modification
HMG-CoA Reductase Inhibitors: Niacin may enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Management: This is of greatest concern with niacin doses of 1 g or greater daily. Avoid simvastatin 80 mg in combination with niacin 1 g or greater in Chinese patients. Canadian labeling contraindicates use of niacin with rosuvastatin 40 mg. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid heavy use; avoid use around niacin dose.
Storage
Niaspan®: Store at room temperature of 20°C to 25°C (68°F to 77°F).
Niacor®: Store at controlled room temperature of 15°C to 30°C (59°F to 86°F).
Mechanism of Action
Component of two coenzymes which is necessary for tissue respiration, lipid metabolism, and glycogenolysis; inhibits the synthesis of very low density lipoproteins (VLDL) and low density lipoproteins (LDL); may also increase the rate of chylomicron triglyceride removal from plasma.
Pharmacodynamics/Kinetics
Absorption: Rapid and extensive (60% to 76%)
Distribution: Mainly to hepatic, renal, and adipose tissue
Metabolism: Extensive first-pass effects; converted to nicotinamide adenine dinucleotide, nicotinuric acid, and other metabolites
Half-life elimination: 20-45 minutes
Time to peak, serum: Immediate release formulation: 30-60 minutes; extended release formulation: 4-5 hours
Excretion: Urine 60% to 88% (unchanged drug [up to 12% recovered after multiple dosing] and metabolites)
Dosage
Oral: Note: Formulations of niacin (regular release versus extended release) are not interchangeable.
Children:
Pellagra (unlabeled use): 50-100 mg/dose 3 times/day (some experts prefer niacinamide for treatment due to more favorable side effect profile)
Adequate intake (National Academy of Sciences, 1998):
0-5 months: 2 mg/day
6-11 months: 3 mg/day
Recommended daily allowances (National Academy of Sciences, 1998):
1-3 years: 6 mg/day
4-8 years: 8 mg/day
9-13 years: 12 mg/day
14-18 years: Females: 14 mg/day; Males: 16 mg/day
≥19 years: Refer to adult dosing
Adults:
Recommended daily allowances (National Academy of Sciences, 1998):
≥19 years: Females: 14 mg/day; Males: 16 mg/day
Pregnancy (all ages): 18 mg/day
Lactation (all ages): 17 mg/day
Dietary supplement (OTC labeling): 50 mg twice daily or 100 mg once daily. Note: Many over-the-counter formulations exist.
Hyperlipidemia:
Regular release formulation (Niacor®): Initial: 250 mg once daily (with evening meal); increase frequency and/or dose every 4-7 days to desired response or first-level therapeutic dose (1.5-2 g/day in 2-3 divided doses); after 2 months, may increase at 2- to 4-week intervals to 3 g/day in 3 divided doses (maximum dose: 6 g/day [NCEP recommends 4.5 g/day] in 3 divided doses). Usual daily dose after titration (NCEP, 2002): 1.5-3 g/day. Note: Many over-the-counter formulations exist.
Sustained release (or controlled release) formulations: Note: Several over-the-counter formulations exist. Usual daily dose after titration (NCEP, 2002): 1-2 g/day
Extended release formulation (Niaspan®): Initial: 500 mg at bedtime for 4 weeks, then 1 g at bedtime for 4 weeks; adjust dose to response and tolerance; may increase dose every 4 weeks by 500 mg/day to a maximum of 2 g/day. Usual daily dose after titration (NCEP, 2002): 1-2 g once daily
If additional LDL-lowering is necessary with lovastatin or simvastatin: Recommended initial lovastatin or simvastatin dose: 20 mg/day (maximum lovastatin or simvastatin dose: 40 mg/day); Note: Lovastatin prescribing information recommends a maximum dose of 20 mg/day with concurrent use of niacin (>1 g/day).
Pellagra (unlabeled use): 50-100 mg 3-4 times/day; maximum: 500 mg/day (some experts prefer niacinamide for treatment due to more favorable side effect profile)
Dosage adjustment in renal impairment: No dosage adjustment recommended; use with caution
Dosage adjustment in hepatic impairment: Contraindicated in patients with significant or unexplained hepatic dysfunction, active liver disease or unexplained persistent transaminase elevations.
Dosage adjustment for hepatic toxicity: Transaminases rise ≥3 times ULN, either persistent or if symptoms of nausea, fever, and/or malaise occur: Discontinue therapy.
Administration: Oral
Administer with food.
Niaspan®: Administer at bedtime. Tablet strengths are not interchangeable. When switching from immediate release tablet, initiate Niaspan® at lower dose and titrate. If therapy is interrupted for an extended period, dose should be retitrated. Long-acting forms should not be crushed, broken, or chewed. Do not substitute long-acting forms for immediate release ones.
Monitoring Parameters
Blood glucose (in diabetic patients); CPK and serum potassium (if on concurrent HMG-CoA reductase inhibitor); liver function tests pretreatment, every 6-12 weeks for first year, then periodically (approximately every 6 months), monitor liver function more frequently if history of transaminase elevation with prior use; lipid profile; platelets; PT (if on anticoagulants); uric acid (if predisposed to gout); phosphorus (if predisposed to hypophosphatemia)
Test Interactions
False elevations in some fluorometric determinations of plasma or urinary catecholamines; false-positive urine glucose (Benedict's reagent)
Dietary Considerations
Should be taken with meal; low-fat meal if treating hyperlipidemia. Avoid hot drinks around the time of niacin dose.
Patient Education
Take with food to reduce incidence of GI upset. Do not crush sustained release capsules. You may experience flushing, sensation of heat, or headache; these reactions may be decreased by increasing dose slowly or by taking aspirin 30-60 minutes prior to taking niacin. Avoid alcohol to minimize flushing. Taking at bedtime, after a low-fat snack, is also recommended. You may experience dizziness or lightheadedness. Report persistent GI disturbance or changes in color of urine or stool.
Geriatric Considerations
The definition of and, therefore, when to treat hyperlipidemia in the elderly is a controversial issue. The National Cholesterol Education Program recommends that all adults maintain a plasma cholesterol <160 mg/dL. Elderly with one additional risk factor, goal LDL would be <130 mg/dL. It is the authors' belief that pharmacologic treatment be reserved for those who are unable to obtain a desirable plasma cholesterol concentration by diet alone and for whom the benefits of treatment are believed to outweigh the potential adverse effects, drug interactions, and cost of treatment.
Cardiovascular Considerations
Niacin lowers LDL-cholesterol (LDL-C) and triglycerides (TGs) and increases HDL-cholesterol (HDL-C). It causes a shift from small, dense to large, buoyant LDL particles that are less atherogenic. Niacin also significantly lowers lipoprotein A levels. Immediate-release niacin may cause itching, flushing, headache and requires frequent daily dosing. Adverse effects may be attenuated by increasing the dose slowly and/or by taking aspirin 30-60 minutes before dosing. Compliance is enhanced with twice daily dosing. Extended release niacin may offer lipoprotein benefits similar to immediate-release dosage forms with less flushing and once daily dosing. Sustained release products may be less efficacious and cause an increased incidence of hepatotoxicity.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause dizziness, insomnia, or nervousness
Mental Health: Effects on Psychiatric Treatment
None reported
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Caplet, timed release, oral: 500 mg
Capsule, oral: 50 mg, 250 mg
Capsule, extended release, oral: 250 mg, 500 mg
Capsule, timed release, oral: 250 mg, 400 mg, 500 mg
Tablet, oral: 50 mg, 100 mg, 250 mg, 500 mg
Niacor®: 500 mg [scored]
Tablet, controlled release, oral:
Slo-Niacin®: 250 mg, 500 mg, 750 mg [scored]
Tablet, extended release, oral:
Niaspan®: 500 mg, 750 mg, 1000 mg
Tablet, timed release, oral: 250 mg, 500 mg, 750 mg, 1000 mg
Niacin-Time®: 500 mg
Pricing: U.S. (www.drugstore.com)
Tablet, controlled release (Niacin CR)
1000 mg (100): $15.99
Tablet, controlled release (Niaspan)
500 mg (30): $89.99
750 mg (30): $124.99
1000 mg (30): $153.99
Tablet, controlled release (Slo-Niacin)
500 mg (100): $25.99
Tablets (Niacin)
500 mg (100): $11.99
References
Carlson LA and Rosenhamer G, “Reduction of Mortality in the Stockholm Ischaemic Heart Disease Secondary Prevention Study by Combined Treatment With Clofibrate and Nicotinic Acid,” Acta Med Scand, 1988, 223(5):405-18.
“Clofibrate and Niacin in Coronary Heart Disease,” JAMA, 1975, 231(4):360-81.
“Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin and Choline. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board, Institute of Medicine,” National Academy of Sciences, Washington, DC: National Academy Press, 1998. Available at http://www.nap.edu
Elam MB, Hunninghake DB, Davis KB, et al, “Effect of Niacin on Lipid and Lipoprotein Levels and Glycemic Control in Patients With Diabetes and Peripheral Arterial Disease - Study: A Randomized Trial. Arterial Disease Multiple Intervention Trial,” JAMA, 2000, 284(10):1263-70.
“Executive Summary of 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),” JAMA, 2001, 285(19):2486-97.
Hegyi J, Schwartz RA, and Hegyi V, “Pellagra: Dermatitis, Dementia, and Diarrhea,” Int J Dermatol, 2004, 43(1):1-5.
Knopp RH, Ginsberg J, Albers JJ, et al, “Contrasting Effects of Unmodified and Time-Release Forms of Niacin on Lipoproteins in Hyperlipidemic Subjects: Clues to Mechanism of Action of Niacin,” Metabolism, 1985, 34(7):642-50.
Mahley RW and Bersot TP, “Drug Therapy for Hypercholesterolemia and Dyslipidemia,” Goodman and Gilman's The Pharmacological Basis of Therapeutics, 10th ed, Hardman JE and Limbird LE, eds, New York, NY: McGraw-Hill, 2001, 993-5.
McPherson R, Frohlich J, Fodor G, et al, “Canadian Cardiovascular Society Position Statement--Recommendations for the Diagnosis and Treatment of Dyslipidemia and Prevention of Cardiovascular Disease,” Can J Cardiol, 2006, 22(11):913-27; published erratum appears in Can J Cardiol, 2006, 22(12):1077.
McKenney JM, Proctor JD, Harris S, et al, “A Comparison of the Efficacy and Toxic Effects of Sustained- vs Immediate-Release Niacin in Hypercholesterolemic Patients,” JAMA, 1994, 271(9):672-7.
Mills E, Prousky J, Raskin G, et al, “The Safety of Over-the-counter Niacin. A Randomized Placebo-Controlled Trial [ISRCTNI8054903],” BMC Clin Pharmacol, 2003, 3:4-11.
Smith SC Jr, Benjamin EJ, Bonow RO, et al, “AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients With Coronary and Other Atherosclerotic Vascular Disease: 2011 Update: A Guideline From the American Heart Association and American College of Cardiology Foundation,” Circulation, 2011, 124(22):2458-73.
Taylor AJ, Sullenberger LE, Lee JH, et al, “Arterial Biology for the Investigation of the Treatment Effects of Reducing cholesterol (ARBITER) 2: A Double-blind, Placebo-Controlled Study of Extended-Release Niacin on Atherosclerosis Progression in Secondary Prevention Patients Treated With Statins,” Circulation, 2004, 110(23):3512-17.
“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), Final Report,” Circulation, 2002, 106(25):3143-421.
International Brand Names
Lexi-Comp.com
Last full review/revision January 2012
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