Class: Antilipemic Agents, Miscellaneous
ATC Class: A11HA01
VA Class: VT103
CAS Number: 59-67-6
Brands: Advicor, Niacor, Niaspan, Nicotinex, Nico-400, Slo-Niacin

Introduction

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

Do not use dietary supplement preparations and prescription-only preparations interchangeably.^{178 191} (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 hypercholesterolemia to reduce the risk of recurrent nonfatal MI.¹⁶⁰

Adjunct to bile acid sequestrant therapy in patients with CHD and hypercholesterolemia to slow progression or promote regression of atherosclerosis.^{134 157 158 160}

May use extended-release niacin in fixed combination with lovastatin when treatment with both extended-release niacin (for prevention of cardiovascular events) and lovastatin (for dyslipidemias and/or prevention of cardiovascular events) is appropriate.¹⁹²

ACC/AHA cholesterol management guideline states that nonstatin drugs (e.g., niacin) do not provide acceptable ASCVD risk reduction benefits compared to their potential for adverse effects in the routine prevention of ASCVD.³⁵⁰ May be useful as adjuncts to statin therapy in certain high-risk patients (e.g., patients with ASCVD, LDL-cholesterol concentrations ≥190 mg/dL, or diabetes mellitus) who have a less-than-anticipated response to statins, are unable to tolerate even a less-than-recommended intensity of a statin, or are completely intolerant to statin therapy.³⁵⁰ However, use of niacin in combination with simvastatin-based therapy not shown to further reduce incidence of major cardiovascular events but reportedly increased risk of severe adverse effects (see Interactions).³⁶⁹ Current recommendations from ACC/AHA regarding prevention of ASCVD and lifestyle modifications to reduce cardiovascular risk are available at or ³⁵²

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).^{107 120 121 122 124 156 160 161 163 181}

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.^{160 161}

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.^{160 161}

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.¹⁶⁰

Not indicated for use in patients with type I hyperlipoproteinemia who have elevated triglyceride and chylomicron concentrations but normal VLDL-cholesterol concentrations.^{160 161}

May use extended-release niacin in fixed combination with lovastatin when treatment with both extended-release niacin (for dyslipidemias) and lovastatin (for dyslipidemias and/or prevention of cardiovascular events) is appropriate.¹⁹²

Dietary Requirements

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

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.^a

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

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.¹⁹¹

• Do not use different formulations (i.e., immediate-release, extended-release) interchangeably since pharmacokinetics (e.g., metabolism) may vary.^{160 161} (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.^{160 161 186 188} 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.^{104 105 106 107 118 124 151 160 161 186 192}

Administration

Oral Administration

Immediate-release niacin (e.g., Niacor): Administer orally with meals.¹⁶¹

Extended-release niacin (Niaspan) or extended-release niacin/lovastatin fixed combination (Advicor): Administer orally at bedtime following a low-fat snack.^{160 188} Take tablets whole; do not break, crush, or chew.^{160 188}

To minimize risk of flushing or pruritus, avoid administering concomitantly with alcohol, hot drinks, or spicy foods.^{160 161 192}

Dosage

Commercially available as dietary supplements and as prescription-only preparations.^{160 161 188} Do not use these preparations interchangeably.^{190 191} (See Substitution of Different Niacin Preparations under Cautions.)

Pediatric Patients

Dietary Requirements

Recommended Daily Allowance (RDA) generally expressed in terms of niacin equivalents (NE).^a 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.

Age	RDA	AI
0–6 months		2 mg of preformed niacin (0.3 mg/kg) daily
6–12 months		4 mg of NE (0.4 mg/kg) daily
1–3 years	6 mg of NE daily
4–8 years	8 mg of NE daily
9–13 years	12 mg of NE daily
14–18 years	Boys: 16 mg of NE daily

Niacin Deficiency

Pellagra

Oral

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

Adults

Prevention of Cardiovascular Events

Extended-release Tablets (Niaspan)

Oral

Initially, 500 mg once daily at bedtime.¹⁶⁰ 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.¹⁶⁰

Usual maintenance dosage is 1–2 g once daily at bedtime.¹⁶⁰

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.¹⁶⁰

Extended-release Niacin/Lovastatin Fixed-combination Tablets (Advicor)

Oral

Patients not currently receiving extended-release niacin (as Niaspan): Must start therapy with the fixed combination at the lowest available dosage (extended-release niacin 500 mg and lovastatin 20 mg as a single tablet once daily).¹⁹² Increase dosage by no more than 500 mg daily (of niacin component) at 4-week intervals.¹⁹² Adjust dosage according to individual requirements (i.e., target cholesterol and triglyceride goals) and response.¹⁹² Dosages >2 g of extended-release niacin and 40 mg of lovastatin daily not recommended.¹⁹² If fixed-combination therapy has been discontinued for >7 days, reinstitute at the lowest available dosage.¹⁹²

Advicor may be substituted for equivalent dosages of Niaspan only; do not substitute for other modified- or immediate-release niacin preparations.¹⁹²

Patients already receiving a stable niacin dosage as Niaspan: May switch directly to a niacin-equivalent dosage of Advicor.¹⁹²

Patients receiving niacin preparations other than Niaspan: Switch from existing niacin therapy to Niaspan at the recommended dosage titration schedule, then adjust niacin dosage according to individual response before switching to Advicor.¹⁹²

Because of differences in bioavailability, do not substitute 1 tablet of Advicor 1 g/40 mg for 2 tablets of Advicor 500 mg/20 mg, or vice versa.¹⁹²

Dyslipidemias

Immediate-release Preparations

Oral

Initially, 100–500 mg 3 times daily.^b Increase dosage gradually (e.g., 300 mg daily at 4- to 7-day intervals) until desired effect is achieved.^b Usual maintenance dosage is 1.5–3 g daily given in 2 or 3 divided doses.¹⁸⁷

Initial dosage of 250 mg daily following the evening meal recommended by manufacturer of Niacor (immediate-release preparation).¹⁶¹ 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.¹⁶¹ 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).¹⁶¹ Manufacturer of Niacor states that higher doses (up to 6 g daily) occasionally may be required in patients with marked lipid abnormalities.¹⁶¹ Usual maintenance dosage recommended by manufacturer of Niacor is 1–2 g daily given in 2 or 3 divided doses.¹⁶¹

Extended-release Tablets (Niaspan)

Oral

Initially, 500 mg once daily at bedtime.¹⁶⁰ 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.¹⁶⁰

Usual maintenance dosage is 1–2 g once daily at bedtime.¹⁶⁰

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.¹⁶⁰

Extended-release Niacin (Niaspan) and Lovastatin Combination Therapy

Oral

In patients already receiving a stable dosage of lovastatin, add Niaspan (using recommended titration schedule).¹⁶⁰

In patients already receiving a stable dosage of Niaspan, add lovastatin (at initial dosage of 20 mg once daily).¹⁶⁰ Adjust dosage at 4-week intervals.¹⁶⁰

Extended-release Niacin/Lovastatin Fixed-combination Tablets (Advicor)

Oral

Patients not currently receiving extended-release niacin (as Niaspan): Must start therapy with the fixed combination at the lowest available dosage (extended-release niacin 500 mg and lovastatin 20 mg as a single tablet once daily).¹⁹² Increase dosage by no more than 500 mg daily (of niacin component) at 4-week intervals.¹⁹² Adjust dosage according to individual requirements (i.e., target cholesterol and triglyceride goals) and response.¹⁹² Dosages >2 g of extended-release niacin and 40 mg of lovastatin daily not recommended.¹⁹² If fixed-combination therapy has been discontinued for >7 days, reinstitute at the lowest available dosage.¹⁹²

Advicor may be substituted for equivalent dosages of Niaspan only; do not substitute for other modified- or immediate-release niacin preparations.¹⁹²

Patients already receiving a stable niacin dosage as Niaspan: May switch directly to a niacin-equivalent dosage of Advicor.¹⁹²

Patients receiving niacin preparations other than Niaspan: Switch from existing niacin therapy to Niaspan at the recommended dosage titration schedule, then adjust niacin dosage according to individual response before switching to Advicor.¹⁹²

Because of differences in bioavailability, do not substitute 1 tablet of Advicor 1 g/40 mg for 2 tablets of Advicor 500 mg/20 mg, or vice versa.¹⁹²

Dietary Requirements

RDA generally expressed in terms of NE.^a 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.^a

Hartnup Disease

Oral

Niacin: 50–200 mg daily.^a

Prescribing Limits

Adults

Prevention of Cardiovascular Events

Oral

Extended-release niacin (Niaspan): Maximum 2 g daily.¹⁶⁰

Extended-release niacin/lovastatin fixed combination (Advicor): Maximum 2 g of extended-release niacin and 40 mg of lovastatin daily.¹⁹²

Dyslipidemias

Oral

Immediate-release preparations: Maximum 4.5 g daily;¹⁸⁷ manufacturer of Niacor states that maximum of 6 g daily generally should not be exceeded.¹⁶¹

Extended-release niacin (Niaspan): Maximum 2 g daily.¹⁶⁰ When used in combination with lovastatin, maximum 2 g of Niaspan and 40 mg of lovastatin daily.¹⁶⁰

Extended-release niacin/lovastatin fixed combination (Advicor): Maximum 2 g of extended-release niacin and 40 mg of lovastatin daily.¹⁸⁸

Cautions for Niacin

Contraindications

• Known hypersensitivity to niacin or any ingredient in the formulation.^{160 161 188}

• Active liver disease or unexplained persistent elevations of serum transaminases, active peptic ulcer disease, or arterial bleeding.^{160 161 188}

Warnings/Precautions

Warnings

Substitution of Different Niacin Preparations

Do not use dietary supplement preparations and prescription-only preparations interchangeably.^{178 191} Do not use different formulations (i.e., immediate-release, extended-release) interchangeably.^{141 160 161 178} 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.^{140 143 160 161 178 c d}

Hepatic Effects

Abnormal liver function test results^{160 161 162 163 188} (e.g., increased serum bilirubin, AST, ALT, and LDH concentrations), hypoalbuminemia, cholelithiasis, jaundice,^{160 161 162 188} hepatitis,^{181 188 e} chronic liver damage,^{160 161} and hepatic failure^{140 143 162} reported.

Perform liver function tests before initiation of therapy, every 6–12 weeks during the first year, and periodically thereafter (e.g., semiannually).^{160 161}

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.^{160 161} 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.^{160 161 350} Consider performing liver biopsy if elevations persist after discontinuance of therapy.¹⁶¹

Musculoskeletal Effects

Elevations in serum creatine kinase (CK, creatine phosphokinase, CPK),¹⁶³ myalgia,¹⁸⁸ myopathy,^{160 163 188} and rhabdomyolysis reported with niacin alone¹⁵² or in combination with other antilipemic agents (e.g., gemfibrozil,¹⁵² various statins).^{134 135 136 137 147 160 192}

Carefully monitor patients for signs and symptoms of muscle pain, tenderness, or weakness, especially early in the course of therapy or during upward titration.^{160 161 188} Consider periodic monitoring of serum CK and potassium concentrations in patients exhibiting such symptoms;^{160 161} no assurance that such monitoring will prevent occurrence of severe myopathy.^{160 161 188}

Fixed-combination Preparation

When using the fixed-combination preparation containing lovastatin, consider the cautions, precautions, and contraindications associated with lovastatin.¹⁸⁸

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.¹⁶⁰

Major Toxicities

Effects on Glucose Tolerance

Decreased glucose tolerance, hyperglycemia, and glycosuria reported.^{160 161 a}

Closely observe patients with (or those at risk of developing) diabetes mellitus.¹⁶⁰

ACC/AHA cholesterol management guideline recommends obtaining fasting blood glucose concentrations or glycosylated hemoglobin (hemoglobin A_1c, HbA_1c) before initiation of therapy, following an increase in dosage, and periodically (e.g., every 6 months) thereafter.³⁵⁰

If used in diabetic or potentially diabetic patients, adjust dosages of niacin and/or antidiabetic agents as appropriate.^{160 167 188}

Discontinue therapy if hyperglycemia persists.³⁵⁰

Hematologic Effects

Increased PT and decreased platelet count reported.^{160 188} Use with caution in patients undergoing surgery.^{160 188} Closely monitor PT and platelet count in patients receiving niacin concomitantly with anticoagulants.¹⁶⁰

Metabolic Effects

Hyperuricemia reported; use with caution in patients predisposed to gout.^{160 161 188} ACC/AHA cholesterol management guideline recommends obtaining uric acid concentrations before initiation of therapy, following an increase in dosage, and periodically (e.g., every 6 months) thereafter.³⁵⁰ Discontinue therapy if acute gout occurs.³⁵⁰

Reductions in phosphorus concentrations reported;¹⁶⁰ monitor phosphorus concentrations periodically in patients at risk for developing hypophosphatemia.^{160 188}

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.^{160 161}

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.^{160 161 188}

Use with caution and closely observe patients with history of jaundice, hepatobiliary disease, or peptic ulcer disease.¹⁶⁰

Use with caution in patients with renal or hepatic impairment; lack of data in such patients.¹⁶⁰ (See Specific Populations under Cautions.)

Specific Populations

Pregnancy

Category C.¹⁶⁰ If used for primary hypercholesterolemia, discontinue therapy when patient becomes pregnant.^{160 161 188} If used for hypertriglyceridemia, assess benefits and risks of continued therapy.^{160 161 188}

Fixed combination of extended-release niacin and lovastatin (Advicor): Category X (due to lovastatin component).¹⁸⁸

Lactation

Distributed into milk.^{160 188} Discontinue nursing or the drug.^{160 161}

Advicor should not be used in nursing women.¹⁸⁸

Pediatric Use

Safety and efficacy not established in children or adolescents¹⁶¹ ≤16 years of age.¹⁶⁰

Extended-release niacin (Niaspan): Safety and efficacy not evaluated in patients <21 years of age.¹⁶⁰

Fixed combination of extended-release niacin and lovastatin (Advicor): Safety and efficacy not evaluated in patients <18 years of age.¹⁸⁸ Manufacturer states that use of Advicor not currently recommended in patients <18 years of age.¹⁸⁸

Geriatric Use

Extended-release niacin (Niaspan): No overall differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.¹⁶⁰

Fixed combination of extended-release niacin and lovastatin (Advicor): No substantial differences in safety and efficacy relative to younger adults; however, higher serum amylase concentrations observed in geriatric patients.¹⁸⁸

Hepatic Impairment

Use with caution in patients who consume substantial amounts of alcohol and/or have a history of liver disease.¹⁶⁰

Contraindicated in patients with active liver disease or unexplained, persistent elevations of serum transaminases.^{160 161 188}

Renal Impairment

Use with caution.^{160 188}

Common Adverse Effects

Flushing (e.g., warmth, redness, itching and/or tingling), headache, pain, abdominal pain, diarrhea, dyspepsia, nausea, vomiting, rhinitis, pruritus, rash.^{160 161 188}

Interactions for Niacin

When used in fixed combination with lovastatin, consider interactions associated with lovastatin.¹⁹²

Ganglionic Blocking and Vasoactive Drugs

Potentiation of hypotensive effects, resulting in postural hypotension.^{160 161 188}

Specific Drugs and Laboratory Tests

Drug or Test	Interaction	Comments
Anticoagulants, coumarin	Potential additive anticoagulant effect (increased PT and decreased platelet count reported)160	Closely monitor PT and platelet count160
Antihypertensive agents (e.g., ganglionic blocking drugs, vasoactive agents)	Possible potentiation of hypotensive effects160 161 188
Aspirin	Decreased niacin metabolic clearance160 161 188	Clinical relevance not fully elucidated160 188
Bile acid sequestrants (cholestyramine, colestipol)	Decreased niacin bioavailability due to binding of niacin to bile acid sequestrant160 188	Administer niacin and bile acid sequestrant at least 4–6 hours apart160 188
HMG-CoA reductase inhibitors (statins)	Increased risk of myopathy and rhabdomyolysis with antilipemic dosages (>1 g daily) of niacin135 136 137 160 161 193 194 195 196 197 198 199 Simvastatin: Increased risk of myopathy observed in Chinese versus non-Chinese patients receiving simvastatin 40 mg daily with antilipemic dosages of niacin193 Simvastatin: Increased risk of severe adverse effects (disturbances in glycemic control requiring hospitalization, development of diabetes mellitus, adverse GI effects, myopathy, gout, rash, skin ulceration, infection, bleeding) with concomitant use of niacin (1.5–2 g daily) and simvastatin (40–80 mg daily, with or without ezetimibe)369 371	Carefully weigh potential benefits and risks of combined therapy;160 161 193 196 198 use concomitantly with caution193 194 195 196 197 198 199 Atorvastatin: Consider using lower initial and maintenance dosages of atorvastatin; carefully monitor for muscle pain, tenderness, or weakness, particularly during initial months of atorvastatin therapy or following an increase in dosage of either drug196 Fluvastatin, pitavastatin, or pravastatin: If used concomitantly with antilipemic dosages of niacin, consider reducing statin dosage195 197 199 Simvastatin: In patients of Chinese descent, caution when using simvastatin dosages >20 mg daily concomitantly with antilipemic dosages of niacin; avoid concomitant use of simvastatin 80 mg daily with antilipemic dosages of niacin193
Isoniazid, long-term therapy	Possible interference with conversion of dietary tryptophan to niacin. Possible increased niacin requirement
Vitamins or nutritional supplements containing large doses of niacin or nicotinamide	Potentiation of niacin adverse effects160
Tests for catecholamines	Possible false elevations in some fluorometric determinations of plasma or urinary catecholamines160
Tests for urine glucose	Possible false-positive reactions with cupric sulfate solution (Benedict’s reagent)160

Niacin Pharmacokinetics

Absorption

Bioavailability

Rapidly and extensively (60–76% of dose) absorbed following oral administration.^{160 161 166}

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.^{160 161 162 163 166}

Bioavailability of 1 tablet containing 1 g of extended-release niacin in fixed combination with 40 mg of lovastatin (Advicor 1 g/40 mg) differs from that of 2 tablets each containing 500 mg of extended-release niacin in fixed combination with 20 mg of lovastatin (Advicor 500 mg/20 mg).¹⁸⁸ (See Adults under Dosage and Administration.)

Onset

Reductions in triglyceride concentrations apparent within 1–4 days.¹⁶² Reductions in LDL-cholesterol concentrations achieved within 3–5 weeks.¹⁶²

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.^a

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.^{160 166}

Distribution

Extent

Distributed mainly to the liver, kidney, and adipose tissue.¹⁶⁰

Distributed into milk.¹⁶⁰

Elimination

Metabolism

Rapidly metabolized; undergoes extensive first-pass metabolism.¹⁶⁰

Converted to several metabolites, including nicotinuric acid (NUA), nicotinamide, and nicotinamide adenine dinucleotide (NAD).^{160 164 166} Nicotinamide does not appear to exert antilipemic effects;¹⁶⁰ the activity of other metabolites on lipoprotein fractions currently unknown.¹⁶⁰

Elimination Route

Niacin and metabolites are rapidly excreted in urine.^{160 161 162 163}

Immediate-release niacin (e.g., Niacor): Approximately 88% of oral dose excreted in urine as unchanged drug and inactive metabolites.¹⁶¹

Extended-release niacin (Niaspan): Approximately 60–76% of oral dose excreted in urine as unchanged drug and inactive metabolites.^{160 166}

Half-life

20–60 minutes.^{161 162 163}

Stability

Storage

Oral

Tablets

Advicor or Niaspan: 20–25°C.^{160 188}

Niacor: 15–30°C.¹⁶¹

Actions

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

• 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.^{151 160 161 162 163 165} Mechanism of antilipemic effects independent of role as vitamin.^{160 161 162} Has no effect on cholesterol synthesis or fecal excretion of fats, sterols, or bile acids.¹⁶² Refractoriness to antilipemic effects of large niacin doses reported.^b

• Slows progression and promotes regression of coronary atherosclerotic lesions.^{160 161 129 157}

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

Advice to Patients

• Risk of flushing; may vary in severity, last for several hours, and likely occur during sleep if niacin taken at bedtime.^{160 161} Pretreatment with aspirin or other NSAIA (e.g., taken 30 minutes prior to extended-release niacin [Niaspan] dose) may minimize flushing.^{160 161} 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.¹⁶⁰

• Importance of informing clinician if dizziness occurs.¹⁶⁰

• In patients with diabetes mellitus, importance of informing clinician of changes in blood glucose values.¹⁶⁰

• Importance of informing clinician if niacin therapy has been discontinued for an extended period of time (retitration of dosage is recommended in such cases).¹⁶⁰

• 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.¹⁶⁰

• 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

Niacin

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Bulk	Powder*
Oral	Capsules, extended-release	125 mg*
		250 mg*
		400 mg*	Nico-400	King
		500 mg*
	Elixir	50 mg/5 mL	Nicotinex (with alcohol 14%)	Fleming
	Tablets	50 mg*
		100 mg*
		250 mg*
		500 mg*	Niacor (scored)	Upsher-Smith
	Tablets, extended-release	250 mg*	Slo-Niacin	Upsher-Smith
		500 mg*	Niaspan	Kos
			Slo-Niacin	Upsher-Smith
		750 mg*	Niaspan	Kos
			Slo-Niacin	Upsher-Smith
		1000 mg	Niaspan	Kos

Niacin Combinations

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, extended-release	500 mg with Lovastatin 20 mg	Advicor	Abbott
		750 mg with Lovastatin 20 mg	Advicor	Abbott
		1 g with Lovastatin 20 mg	Advicor	Abbott
		1 g with Lovastatin 40 mg	Advicor	Abbott

Niacin and niacinamide are also commercially available in combination with other vitamins, minerals, cerebral stimulants, sedatives, antacids, amino acids, hormones, infant formulas, vasodilators, antihistamines, local anesthetics, expectorants, enzymes, and laxatives.^a For IV infusion, niacinamide is commercially available in combination with other vitamins in caloric and electrolyte solutions.^a