Class: Antilipemic Agents, Miscellaneous
ATC Class: A11HA01
VA Class: VT103
CAS Number: 59-67-6
Brands: Niacor, Niaspan, Slo-Niacin

Medically reviewed by Drugs.com on Jul 26, 2021. Written by ASHP.

Introduction

Water-soluble, B complex vitamin. Prescription-only preparations are FDA-labeled for use as antilipemic agents.

Do not use dietary supplement preparations and prescription-only preparations interchangeably. (See Substitution of Different Niacin Preparations under Cautions.)

Uses for Niacin

Prevention of Cardiovascular Events

Adjunct to dietary therapy in patients with a history of MI and hyperlipidemia to reduce the risk of recurrent nonfatal MI.

Adjunct to bile acid sequestrant therapy in patients with CHD and hyperlipidemia to slow progression or promote regression of atherosclerosis.

AHA/ACC cholesterol management guideline states that lifestyle modification is the foundation of cardiovascular risk reduction. If pharmacologic therapy is needed, statins are first-line drugs of choice because of their demonstrated benefits in reducing risk of atherosclerotic cardiovascular disease (ASCVD). Nonstatin drugs may be considered as adjunctive therapy in certain high-risk patients, but other drugs (e.g., ezetimibe) are generally recommended. Although niacin has mild LDL-lowering effects, randomized controlled studies do not support its use as add-on therapy to statins.

Studies have shown that addition of niacin to statin therapy does not provide incremental benefit on cardiovascular morbidity and mortality, but may increase risk of adverse effects.

Dyslipidemias

Adjunct to dietary therapy to decrease elevated serum total cholesterol, LDL-cholesterol, apolipoprotein B (apo B), and triglyceride concentrations, and to increase HDL-cholesterol concentrations in the management of primary hypercholesterolemia and mixed dyslipidemia, including heterozygous familial hypercholesterolemia and other causes of hypercholesterolemia (e.g., polygenic hypercholesterolemia).

Adjunctive therapy in the management of severe hypertriglyceridemia in patients at risk of developing pancreatitis (typically those with serum triglyceride concentrations >2000 mg/dL and elevated concentrations of VLDL-cholesterol and fasting chylomicrons) who do not respond adequately to dietary management.

Also may be used in patients with triglyceride concentrations of 1000–2000 mg/dL who have a history of pancreatitis or of recurrent abdominal pain typical of pancreatitis.

Efficacy in patients with type IV hyperlipoproteinemia and triglyceride concentrations <1000 mg/dL who exhibit type V patterns subsequent to dietary or alcoholic indiscretion not adequately studied.

Not indicated for use in patients with type I hyperlipoproteinemia who have elevated triglyceride and chylomicron concentrations but normal VLDL-cholesterol concentrations.

Dietary Requirements

Adequate intake of niacin needed to prevent niacin deficiency and pellagra.

In the US, niacin is principally obtained from fish, meat, or poultry, and niacin-enriched or niacin-fortified food (e.g., enriched and whole grain breads and bread products). Conversion of dietary tryptophan to niacin also contributes to niacin intake.

Niacin Deficiency and Pellagra

Prevention of niacin deficiency.

Treatment of pellagra. Niacinamide preferred by some clinicians due to its lack of vasodilating effects.

Niacin Dosage and Administration

General

• Dietary supplements containing niacin are not FDA-labeled for prevention of cardiovascular events or management of dyslipidemias; use prescription-only preparations for these indications.

• Do not use different formulations (i.e., immediate-release, extended-release) interchangeably since pharmacokinetics (e.g., metabolism) may vary. (See Substitution of Different Niacin Preparations under Cautions.)

• Minimize flushing, pruritus, and GI distress by initiating therapy at low dosages, increasing dosage gradually, and avoiding administration on an empty stomach. May also administer a prostaglandin-synthesis inhibitor (e.g., aspirin up to the recommended dose of 325 mg) approximately 30 minutes prior to administration of niacin to reduce flushing.

Administration

Oral Administration

Immediate-release niacin (e.g., Niacor): Administer orally with meals.

Extended-release niacin (Niaspan): Administer orally at bedtime following a low-fat snack. Administer tablets whole; do not break, crush, or chew.

To minimize risk of flushing or pruritus, avoid administering concomitantly with alcohol, hot drinks, or spicy foods.

Dosage

Commercially available as dietary supplements and as prescription-only preparations. Do not use these preparations interchangeably. (See Substitution of Different Niacin Preparations under Cautions.)

Pediatric Patients

Dietary Requirements

Recommended Daily Allowance (RDA) generally expressed in terms of niacin equivalents (NE). NE is calculated as follows: 1 mg of NE = 1 mg of niacin = 60 mg of tryptophan.

Oral

Recommended Dietary Allowance (RDA) is nutrient recommendation from National Academy of Sciences (NAS) for children and adults. The RDA for a given nutrient is the goal for dietary intake in individuals.

Adequate Intake (AI) is nutrient recommendation from NAS for infants ≤12 months of age; used when data are insufficient or too controversial to establish an RDA. AI set for infants ≤6 months of age is based on the observed mean niacin intake of infants fed principally human milk. AI set for infants 6–12 months of age is based on the AI for younger infants and data from adults.

Niacin Deficiency

Pellagra

Oral

Niacin or niacinamide: 100–300 mg daily in divided doses.

Adults

Prevention of Cardiovascular Events

Extended-release Tablets (Niaspan)

Oral

Initially, 500 mg once daily at bedtime. If response is inadequate, increase dosage by no more than 500 mg at 4-week intervals until desired effect is observed or maximum daily dosage of 2 g is reached.

Usual maintenance dosage is 1–2 g once daily at bedtime.

In patients previously treated with immediate-release preparations or in those who have discontinued extended-release niacin (Niaspan) therapy for an extended period, titrate dosage as with initial therapy.

Dyslipidemias

Immediate-release Preparations

Oral

Initially, 100–500 mg 3 times daily. Increase dosage gradually (e.g., 300 mg daily at 4- to 7-day intervals) until desired effect is achieved.

Initial dosage of 250 mg daily following the evening meal recommended by manufacturer of Niacor (immediate-release preparation). Increase dosage of Niacor at 4- to 7-day intervals until desired effect is achieved or dosage of 1.5–2 g daily is reached. If adequate response is not achieved after 2 months, may then increase dosage at 2- to 4-week intervals to 3 g daily (1 g 3 times daily). Manufacturer of Niacor states that higher doses (up to 6 g daily) occasionally may be required in patients with marked lipid abnormalities. Usual maintenance dosage recommended by manufacturer of Niacor is 1–2 g daily given in 2 or 3 divided doses.

Extended-release Tablets (Niaspan)

Oral

Initially, 500 mg once daily at bedtime. If adequate response is not achieved after 4 weeks, increase dosage by no more than 500 mg at 4-week intervals until desired effect is observed.

Usual maintenance dosage is 1–2 g once daily at bedtime.

Titrate Niaspan dosage as with initial therapy in patients previously treated with immediate-release niacin preparations or in those in whom therapy with extended-release niacin (Niaspan) has been discontinued for a prolonged period.

Dietary Requirements

RDA generally expressed in terms of NE. NE is calculated as follows: 1 mg of NE = 1 mg of niacin = 60 mg of tryptophan.

Oral

RDA for healthy men: 16 mg of NE daily.

RDA for healthy women: 14 mg of NE daily.

RDA for pregnant women: 18 mg of NE daily. Higher dosages required in women pregnant with >1 fetus.

RDA for lactating women: 17 mg of NE daily. Higher dosages required in mothers nursing >1 infant.

Higher dosages required in patients with Hartnup disease, liver cirrhosis, carcinoid syndrome, malabsorption syndrome, or in individuals receiving long-term isoniazid therapy or undergoing hemodialysis or peritoneal dialysis.

Niacin Deficiency

Pellagra

Oral

Niacin or niacinamide: 300–500 mg daily in divided doses.

Hartnup Disease

Oral

Niacin: 50–200 mg daily.

Prescribing Limits

Adults

Prevention of Cardiovascular Events

Oral

Extended-release niacin (Niaspan): Maximum 2 g daily.

Dyslipidemias

Oral

Immediate-release preparations: Maximum 4.5 g daily; manufacturer of Niacor states that maximum of 6 g daily generally should not be exceeded.

Extended-release niacin (Niaspan): Maximum 2 g daily. When used in combination with lovastatin, maximum 2 g of Niaspan and 40 mg of lovastatin daily.

Cautions for Niacin

Contraindications

• Known hypersensitivity to niacin or any ingredient in the formulation.

• Active liver disease or unexplained persistent elevations of serum transaminases, active peptic ulcer disease, or arterial bleeding.

Warnings/Precautions

Warnings

Substitution of Different Niacin Preparations

Do not use dietary supplement preparations and prescription-only preparations interchangeably. Do not use different formulations (i.e., immediate-release, extended-release) interchangeably. Severe hepatic toxicity (e.g., fulminant hepatic necrosis) reported in some individuals who substituted certain sustained-release niacin preparations for immediate-release niacin at equivalent dosages.

Hepatic Effects

Abnormal liver function test results (e.g., increased serum bilirubin, AST, ALT, and LDH concentrations), hypoalbuminemia, cholelithiasis, jaundice, hepatitis, chronic liver damage, and hepatic failure reported.

Perform liver function tests before initiation of therapy, every 6–12 weeks during the first year, and periodically thereafter (e.g., semiannually).

If increased serum AST/ALT concentrations or manifestations of liver disease occur, perform second liver function evaluation to confirm findings and continue monitoring liver function until abnormalities return to normal. If increases in AST or ALT concentrations of ≥2–3 times the ULN occur or persist, or if associated with nausea, fever, and/or malaise, discontinue therapy. Consider performing liver biopsy if elevations persist after discontinuance of therapy.

Musculoskeletal Effects

Elevations in serum creatine kinase (CK, creatine phosphokinase, CPK), myalgia, myopathy, and rhabdomyolysis reported with niacin alone or in combination with other antilipemic agents (e.g., gemfibrozil, various statins).

Carefully monitor patients for signs and symptoms of muscle pain, tenderness, or weakness, especially early in the course of therapy or during upward titration. Consider periodic monitoring of serum CK and potassium concentrations in patients exhibiting such symptoms; no assurance that such monitoring will prevent occurrence of severe myopathy.

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, flushing, dyspnea, tongue edema, laryngeal edema, facial edema, peripheral edema, laryngismus, vesiculobullous rash) reported rarely.

Major Toxicities

Effects on Glucose Tolerance

Decreased glucose tolerance, hyperglycemia, and glycosuria reported.

Closely observe patients with (or those at risk of developing) diabetes mellitus.

If used in diabetic or potentially diabetic patients, adjust dosages of niacin and/or antidiabetic agents as appropriate.

Hematologic Effects

Increased PT and decreased platelet count reported. Use with caution in patients undergoing surgery. Closely monitor PT and platelet count in patients receiving niacin concomitantly with anticoagulants.

Metabolic Effects

Hyperuricemia reported; use with caution in patients predisposed to gout.

Reductions in phosphorus concentrations reported; monitor phosphorus concentrations periodically in patients at risk for developing hypophosphatemia.

General Precautions

Role as Adjunct Therapy

Prior to institution of antilipemic therapy, vigorously attempt to control serum cholesterol by appropriate dietary regimens, weight reduction, exercise, and treatment of any underlying disorder that might be the cause of lipid abnormality.

Concomitant Illnesses

Use with caution in patients with unstable angina, AMI, or CHD, particularly when these patients also are receiving vasoactive drugs such as nitrates, calcium-channel blockers, or adrenergic-blocking agents.

Use with caution and closely observe patients with history of jaundice, hepatobiliary disease, or peptic ulcer disease.

Use with caution in patients with renal or hepatic impairment; lack of data in such patients. (See Specific Populations under Cautions.)

Specific Populations

Pregnancy

Category C. If used for primary hypercholesterolemia, discontinue therapy when patient becomes pregnant. If used for hypertriglyceridemia, assess benefits and risks of continued therapy.

Lactation

Distributed into milk. Discontinue nursing or the drug.

Pediatric Use

Safety and efficacy not established in children or adolescents ≤16 years of age.

Extended-release niacin (Niaspan): Safety and efficacy not evaluated in patients <21 years of age.

Geriatric Use

Extended-release niacin (Niaspan): No overall differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.

Hepatic Impairment

Use with caution in patients who consume substantial amounts of alcohol and/or have a history of liver disease.

Contraindicated in patients with active liver disease or unexplained, persistent elevations of serum transaminases.

Renal Impairment

Use with caution.

Common Adverse Effects

Flushing (e.g., warmth, redness, itching and/or tingling), headache, pain, abdominal pain, diarrhea, dyspepsia, nausea, vomiting, rhinitis, pruritus, rash.

Interactions for Niacin

Ganglionic Blocking and Vasoactive Drugs

Potentiation of hypotensive effects, resulting in postural hypotension.

Specific Drugs and Laboratory Tests

Niacin Pharmacokinetics

Absorption

Bioavailability

Rapidly and extensively (60–76% of dose) absorbed following oral administration.

Peak plasma concentrations attained within 30–60 minutes or 4–5 hours following oral administration of immediate-release niacin (Niacor) or extended-release niacin (Niaspan), respectively.

Onset

Reductions in triglyceride concentrations apparent within 1–4 days. Reductions in LDL-cholesterol concentrations achieved within 3–5 weeks.

In the treatment of pellagra, redness and swelling of the tongue disappear within 24–72 hours, mental symptoms and infections of the mouth and other mucous membranes clear rapidly, and GI symptoms disappear within 24 hours.

Special Populations

Peak plasma concentrations following oral administration of Niaspan appear to be slightly higher in women than in men, possibly because of differences in metabolism.

Distribution

Extent

Distributed mainly to the liver, kidney, and adipose tissue.

Distributed into milk.

Elimination

Metabolism

Rapidly metabolized; undergoes extensive first-pass metabolism.

Converted to several metabolites, including nicotinuric acid (NUA), nicotinamide, and nicotinamide adenine dinucleotide (NAD). Nicotinamide does not appear to exert antilipemic effects; the activity of other metabolites on lipoprotein fractions currently unknown.

Elimination Route

Niacin and metabolites are rapidly excreted in urine.

Immediate-release niacin (e.g., Niacor): Approximately 88% of oral dose excreted in urine as unchanged drug and inactive metabolites.

Extended-release niacin (Niaspan): Approximately 60–76% of oral dose excreted in urine as unchanged drug and inactive metabolites.

Half-life

20–60 minutes.

Stability

Storage

Oral

Tablets

Niaspan: 20–25°C.

Niacor: 15–30°C.

Actions

• Niacinamide (formed from conversion of niacin) required for lipid metabolism, tissue respiration, and glycogenolysis.

• At daily dosages ≥1 g, niacin decreases serum total cholesterol, LDL-cholesterol, VLDL-cholesterol, and triglyceride concentrations, and increases serum HDL-cholesterol concentrations in patients with type II, III, IV, or V hyperlipoproteinemia. Mechanism of antilipemic effects independent of role as vitamin. Has no effect on cholesterol synthesis or fecal excretion of fats, sterols, or bile acids. Refractoriness to antilipemic effects of large niacin doses reported.

• Slows progression and promotes regression of coronary atherosclerotic lesions.

• Causes only cutaneous vasodilation at daily dosages of 300–800 mg. May cause histamine release (resulting in increased gastric motility and acid secretion) and activate fibrinolytic system.

Advice to Patients

• Risk of flushing; may vary in severity, last for several hours, and likely occur during sleep if niacin taken at bedtime. Pretreatment with aspirin or other NSAIA (e.g., taken 30 minutes prior to extended-release niacin [Niaspan] dose) may minimize flushing. If awakened by flushing at night, patient should get up slowly, especially if flushing is accompanied by a feeling of dizziness or fainting, or if patient is receiving antihypertensive therapy.

• Importance of informing clinician if dizziness occurs.

• In patients with diabetes mellitus, importance of informing clinician of changes in blood glucose values.

• Importance of informing clinician if niacin therapy has been discontinued for an extended period of time (retitration of dosage is recommended in such cases).

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements (especially those containing niacin or nicotinamide), as well as any concomitant illnesses.

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed; necessity for clinicians to advise women to avoid pregnancy during therapy, advise pregnant women of risk to the fetus, and advise males to use effective contraception during therapy.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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Frequently asked questions

• How long does niacin stay in the human system?

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