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Pronunciation

(NYE a sin)

Index Terms

  • Nicotinic Acid
  • Vitamin B3

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule Extended Release, Oral:

Generic: 250 mg, 500 mg

Capsule Extended Release, Oral [preservative free]:

Generic: 250 mg, 500 mg

Powder, Oral:

Generic: (100 g, 1000 g)

Tablet, Oral:

Niacin-50: 50 mg [starch free, sugar free, wheat free]

Niacor: 500 mg [scored]

Generic: 50 mg, 100 mg, 250 mg, 500 mg

Tablet, Oral [preservative free]:

Generic: 50 mg [DSC], 100 mg, 500 mg

Tablet Extended Release, Oral:

Niaspan: 500 mg, 750 mg, 1000 mg [contains fd&c yellow #6 aluminum lake]

Slo-Niacin: 250 mg [scored]

Slo-Niacin: 500 mg, 750 mg [scored; contains fd&c red #40]

Generic: 500 mg, 750 mg, 1000 mg

Tablet Extended Release, Oral [preservative free]:

Generic: 250 mg, 500 mg, 1000 mg

Brand Names: U.S.

  • Niacin-50 [OTC]
  • Niacor
  • Niaspan
  • Slo-Niacin [OTC]

Pharmacologic Category

  • Antilipemic Agent, Miscellaneous
  • Vitamin, Water Soluble

Pharmacology

Niacin (nicotinic acid) is bioconverted to nicotinamide which is further converted to nicotinamide adenine dinucleotide (NAD+) and the hydride equivalent (NADH) which are coenzymes necessary for tissue metabolism, lipid metabolism, and glycogenolysis (Belenky, 2006; Suave, 2008). The mechanism by which niacin (in lipid-lowering doses) affects plasma lipoproteins is not fully understood. It may involve several actions including partial inhibition of release of free fatty acids from adipose tissue, and increased lipoprotein lipase activity, which may increase the rate of chylomicron triglyceride removal from plasma. Ultimately, niacin reduces total cholesterol, apolipoprotein (apo) B, triglycerides, VLDL, LDL, lipoprotein (a), and increases HDL and other important components and subfractions (eg, LPA-I) (Kamanna, 2000)

Absorption

Immediate release formulation: Rapid and extensive. Extent of niacin ER absorption from niacin ER/lovastatin is increased (22% to 30%) with food.

Distribution

Mainly to hepatic, renal, and adipose tissue

Metabolism

Extensive first-pass metabolism; converted to nicotinamide adenine dinucleotide, nicotinuric acid (after conjugation with glycine), and other metabolites. At doses used to treat hyperlipidemia, metabolic pathways are saturable.

Excretion

Urine 60% to 88% (unchanged drug [up to 12% recovered after multiple dosing] and metabolites)

Time to Peak

Serum: Immediate release formulation: 30 to 60 minutes; extended release formulation: 4 to 5 hours

Half-Life Elimination

25 to 48 minutes

Protein Binding

<20% bound to serum proteins

Special Populations: Gender

Steady-state plasma concentrations and metabolites are generally higher in women.

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; adjunctive therapy for severe hypertriglyceridemia in adult patients at risk of pancreatitis; dietary supplement

Use: Unlabeled

Treatment of pellagra

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

Dosing: Adult

Note: Formulations of niacin (regular release versus extended release) are not interchangeable.

Recommended daily allowances (National Academy of Sciences, 1998): Oral:

≥19 years: Females: 14 mg daily; Males: 16 mg daily

Pregnancy (all ages): 18 mg daily

Lactation (all ages): 17 mg daily

Dietary supplement (OTC labeling): Oral: 50 mg twice daily or 100 mg once daily. Note: Many over-the-counter formulations exist.

Hyperlipidemia: Oral:

Regular release formulation (Niacor): Initial: 250 mg once daily (with evening meal); increase frequency and/or dose every 4 to 7 days to desired response or first-level therapeutic dose (1.5 to 2 g daily in 2 to 3 divided doses); after 2 months, may increase at 2- to 4-week intervals to 3 g daily in 3 divided doses (maximum dose: 6 g daily in 3 divided doses). Note: Many over-the-counter formulations exist.

ACC/AHA Blood Cholesterol Guideline recommendations: Initial: 100 mg administered 3 times daily; increase dose gradually as tolerated to 3 g daily divided in 2 to 3 doses (Stone, 2013)

Sustained release (or controlled release) formulations: Note: Several over-the-counter formulations exist. Slo-Niacin: Usual dosage is 250 to 750 mg once daily, taken morning or evening, or as directed. Before using more than 500 mg daily, patient should consult health care provider.

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 daily dose every 4 weeks by not more than 500 mg daily to a maximum of 2 g daily. Recommended maintenance dose: 1,000 to 2,000 mg at bedtime.

ACC/AHA Blood Cholesterol Guideline recommendations: Initial: 500 mg once daily; increase dose gradually (ie, no sooner than at weekly intervals) over 4 to 8 weeks as tolerated to a maximum dose of 2 g once daily (Stone, 2013)

Pellagra (off-label use): Oral: 50 to 100 mg 3 to 4 times daily; maximum: 500 mg daily (Prousky 2003; Delgado-Sanchez 2008; DesGroseilliers 1976; Oldham 2012). Some experts prefer niacinamide for treatment due to more favorable side effect profile (Hegyi 2004; Jen 2010).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Formulations of niacin (regular release versus extended release) are not interchangeable.

Adequate intake (National Academy of Sciences, 1998): Oral:

0 to 5 months: 2 mg daily

6 to 11 months: 3 mg daily

Recommended daily allowances (National Academy of Sciences, 1998): Oral:

1 to 3 years: 6 mg daily

4 to 8 years: 8 mg daily

9 to 13 years: 12 mg daily

14 to 18 years: Females: 14 mg daily; Males: 16 mg daily

≥19 years: Refer to adult dosing.

Pellagra (off-label use) Oral: 50 to 100 mg 3 times daily. Some experts prefer niacinamide for treatment due to more favorable side effect profile (Hegyi 2004; Jen 2010).

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use with caution.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). Contraindicated in patients with significant or unexplained hepatic dysfunction, active liver disease or unexplained persistent transaminase elevations.

Dosing: Adjustment for Toxicity

Hepatic toxicity: Transaminases rise ≥3 times ULN, either persistent or if symptoms of nausea, fever, and/or malaise occur: Discontinue therapy.

Administration

Administer with food. To attenuate flushing symptoms, may premedicate with aspirin 325 mg administered 30 minutes before dose; avoid ingestion of hot liquids, alcohol, or spicy foods concurrently with niacin (Stone, 2013). May also use other NSAIDs to prevent flushing according to the manufacturer.

Niaspan: Administer at bedtime after a low-fat snack. Two of the 500 mg and one of the 1,000 mg tablet strengths are interchangeable, but three of the 500 mg and two of the 750 mg tablet strengths are not interchangeable. When switching from immediate-release tablet, initiate Niaspan with the recommended titration schedule. If therapy is interrupted for an extended period, dose should be retitrated.

Long-acting forms should not be crushed, broken, or chewed. Slo-Niacin may be broken along the score line. Do not substitute long-acting forms for immediate release ones.

Dietary Considerations

Should be taken with meal; low-fat meal if treating hyperlipidemia. Avoid alcohol, hot drinks, and spicy foods around the time of niacin dose.

Storage

Niaspan: Store at 20°C to 25°C (68°F to 77°F).

Niacor: Store at 15°C to 30°C (59°F to 86°F).

Drug Interactions

Alcohol (Ethyl): May enhance the adverse/toxic effect of Niacin. Consider therapy modification

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Bile Acid Sequestrants: May decrease the absorption of Niacin. Consider therapy modification

HMG-CoA Reductase Inhibitors: Niacin may enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Monitor therapy

Rosuvastatin: Niacin may enhance the myopathic (rhabdomyolysis) effect of Rosuvastatin. Monitor therapy

Simvastatin: Niacin may enhance the myopathic (rhabdomyolysis) effect of Simvastatin. Niacin may increase the serum concentration of Simvastatin. Management: Use of simvastatin 80 mg with niacin should be avoided and simvastatin doses over 20 mg/day should be used cautiously in Chinese patients; some non-US labeling state this combination is not recommended in any Asian patients. Consider therapy modification

Test Interactions

False elevations in some fluorometric determinations of plasma or urinary catecholamines; false-positive urine glucose (Benedict's reagent)

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

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, administering with food, avoidance of concurrent ingestion of ethanol or hot liquids, and/or by taking aspirin (adults: 325 mg) 30 minutes before dosing (Stone, 2013). May also use other NSAIDs according to the manufacturer. Flushing associated with extended release preparation is significantly reduced (Guyton, 2007). For immediate release preparations, may administer in 2 to 3 divided doses to reduce the frequency and severity. Niacin should not be used if patient experiences persistent severe cutaneous symptoms during therapy (Stone, 2013).

• Gastrointestinal effects: May cause gastrointestinal distress, vomiting, diarrhea, or aggravate peptic ulcer; gastrointestinal distress may be attenuated with a gradual increase in dose and administration with food. Use is contraindicated in patients with active peptic ulcer disease; use with caution in patients with a past history of peptic ulcer. Niacin should not be used if patient experiences unexplained abdominal pain or gastrointestinal symptoms or unexplained weight loss during therapy (Stone, 2013).

• Hematologic effects: Dose-related reductions in platelet count and increases of prothrombin time may occur.

• 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, niacin extended-release 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. Niacin should not be used if hepatic transaminase elevations >2 to 3 times upper limit of normal occur during therapy (Stone, 2013).

• Hypophosphatemia: Has been associated with small but statistically significant dose-related reductions in phosphorus levels. Monitor phosphorus levels periodically in patients at risk for hypophosphatemia.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with unstable angina or in the acute phase of an MI. In patients with pre-existing coronary artery disease, the incidence of atrial fibrillation was observed more frequently in those receiving immediate release (crystalline) niacin as compared to placebo (Coronary Drug Project Research Group, 1975). Niacin should not be used if patient experiences new-onset atrial fibrillation during therapy (Stone, 2013).

• Diabetes: Niacin may increase fasting blood glucose, although clinical data suggest increases are generally modest (<5%) (Guyton, 2007). Use niacin with caution in patients with diabetes. Monitor glucose; adjustment of diet and/or hypoglycemic therapy may be necessary. Niacin should not be used if patient experiences persistent hyperglycemia during therapy (Stone, 2013).

• Gout: May be associated with hyperuricemia. Use with caution in patients predisposed to gout. Niacin should not be used if patient experiences acute gout during therapy (Stone, 2013).

• Hepatic impairment: Use with caution in patients with a past history of hepatic impairment; monitor liver function tests. Contraindicated with active liver disease or unexplained persistent transaminase elevation. Niacin should not be used if hepatic transaminase elevations >2 to 3 times upper limit of normal occur during therapy (Stone, 2013).

• Renal impairment: Use with caution in patients with renal impairment.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• Product interchangeability: Formulations of niacin (immediate release versus extended release) are not interchangeable (bioavailability varies): cases of severe hepatotoxicity, including fulminant hepatic necrosis, have occurred in patients who have substituted niacin products at equivalent doses.

Other warnings/precautions:

• Alcohol use: Use with caution in patients who consume large amounts of ethanol due to the increased risk of liver dysfunction.

• 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.

Monitoring Parameters

2013 ACC/AHA Blood Cholesterol Guideline recommendations (Stone, 2013): Baseline hepatic transaminases, fasting blood glucose or hemoglobin A1c, and uric acid before initiation and repeat during uptitration to maintenance dose and every 6 months thereafter.

Manufacturer recommendations: Blood glucose (in diabetic patients); if on concurrent HMG-CoA reductase inhibitor, may periodically check CPK and serum potassium; 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 (if on anticoagulants); PT (if on anticoagulants); uric acid (if predisposed to gout); phosphorus (if predisposed to hypophosphatemia)

Pregnancy Risk Factor

C

Pregnancy Considerations

Animal reproduction studies have not been conducted. Water soluble vitamins cross the placenta. When used as a dietary supplement, niacin requirements may be increased in pregnant women compared to nonpregnant women (IOM, 1998). It is not known if 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.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience flushing, itching, diarrhea, cough, or nausea. Have patient report immediately to prescriber signs of high blood sugar (confusion, feeling sleepy, more thirst, hunger, passing urine more often, flushing, fast breathing, or breath that smells like fruit), signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), muscle pain, muscle weakness, angina, severe dizziness, passing out, shortness of breath, or sweating a lot (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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