Version May 2024
Note: Formulations of niacin (regular release versus extended release) are not interchangeable.
Dietary supplement (OTC labeling): Oral: 50 mg twice daily or 100 to 250 mg once daily. Note: Many over-the-counter formulations exist.
Dyslipidemia: Oral:
Note: Niacin is no longer recommended, except in specific clinical situations (eg, high triglyceride levels [>500 mg/dL], if not able to achieve desired response, or intolerance to other therapies) (ACC [Lloyd-Jones 2017]; Boden 2014; Garg 2017; Landray 2014; Wierzbicki 2014).
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.
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.
Pellagra (off-label use): Oral: Regular release formulation: 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).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.
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.
Hepatic toxicity: Transaminases rise ≥3 times ULN, either persistent or if symptoms of nausea, fever, and/or malaise occur: Discontinue therapy.
Refer to adult dosing.
(For additional information see "Niacin (vitamin B3): Pediatric drug information")
Note: Formulations of niacin (regular release [crystalline] versus extended release) are not interchangeable.
Dyslipidemia: Very limited data available (Miller 2015): Note: Niacin (nicotinic acid) is rarely used in pediatric patients for treatment of dyslipidemias and is not considered a primary agent nor a routine secondary, adjunctive agent for dyslipidemia management in pediatric patients (AAP [Daniels 2008]; AHA [McCrindle 2007]; NHLBI 2011)
Children ≥10 years and Adolescents (Miller 2015; NHLBI 2011): Oral:
Regular release: Initial: 100 to 250 mg/day in 3 divided doses with meals; maximum initial daily dose: 10 mg/kg/day; increase weekly by 100 mg/day or increase every 2 to 3 weeks by 250 mg/day as tolerated; evaluate efficacy and adverse effects with laboratory tests at 20 mg/kg/day or 1,000 mg/day (whichever is less); continue to increase if needed and as tolerated; re-evaluate at each 500 mg increment; daily doses up to 2,250 mg/day have been used (Colletti 1993)
Sustained release: Reported range: 500 to 1,500 mg/day; initiate at a low dose administered once daily (based on experience in adults); reported initial daily dose has not exceeded 10 mg/kg/day; titrate every 3 to 4 weeks (in adults, doses are titrated every 4 weeks) (AHA [McCrindle 2007]; Colletti 1993)
Pellagra; treatment: Children and Adolescents: Oral: Regular release: 50 to 300 mg/day in divided doses 3 times daily; usual treatment duration is 3 to 4 weeks (Kliegman 2016; WHO 2000)
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity: Children ≥10 years and Adolescents: In a trial of pediatric patients, discontinuation of niacin therapy was reported for hepatotoxicity (eg, transaminases increases, either persistent or if symptoms of nausea, fever, and/or malaise), headache, abdominal pain and/or severe flushing (Colletti 1993)
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.
All patients: 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.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined:
Cardiovascular: Atrial fibrillation, cardiac arrhythmia, edema, flushing, hypotension, orthostatic hypotension, palpitations, tachycardia
Central nervous system: Chills, dizziness, headache, insomnia, migraine, myasthenia, nervousness, pain, paresthesia
Dermatologic: Acanthosis nigricans, burning sensation of skin, diaphoresis, hyperpigmentation, maculopapular rash, pruritus, skin discoloration, skin rash, urticaria, xeroderma
Endocrine & metabolic: Decreased glucose tolerance, decreased serum phosphate, gout, hyperuricemia, increased amylase, increased lactate dehydrogenase
Gastrointestinal: Abdominal pain, diarrhea, dyspepsia, eructation, flatulence, nausea, peptic ulcer, vomiting
Hematologic & oncologic: Decreased platelet count, prolonged prothrombin time
Hepatic: Hepatitis, increased serum bilirubin, increased serum transaminases (dose-related), jaundice,
Neuromuscular & skeletal: Increased creatine phosphokinase, leg cramps, myalgia, myopathy (with concurrent HMG-CoA reductase inhibitor), weakness
Ophthalmic: Blurred vision, cystoid macular edema, toxic amblyopia
Respiratory: Cough, dyspnea
<1%, postmarketing, and/or case reports: Hepatic necrosis, hypersensitivity reaction (includes anaphylaxis, angioedema, laryngismus, vesiculobullous rash), rhabdomyolysis (with concurrent HMG-CoA reductase inhibitor), syncope
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
Concerns related to adverse effects:
• Flushing/pruritus: Flushing and pruritus are common adverse effects of niacin; may be attenuated with a gradual increase in dose, administering with food, avoidance of concurrent ingestion of ethanol, hot or spicy foods/liquids, and/or by taking aspirin 30 minutes before dosing. 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 of flushing/pruritus. Consider discontinuation if persistent severe cutaneous symptoms occur during therapy.
• GI effects: May cause GI distress, vomiting, diarrhea, or aggravate peptic ulcer; GI 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. Consider discontinuation if unexplained abdominal pain/weight loss or other GI symptoms occur during therapy.
• 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. Discontinue use if hepatic transaminase levels rise, particularly to 3 x ULN and are persistent, or if they are associated with symptoms of nausea, fever, and/or malaise.
• 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 preexisting 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). Consider discontinuation if new-onset atrial fibrillation occurs during therapy.
• Diabetes: Use is associated with new-onset diabetes or worsening glucose tolerance in patients with preexisting diabetes (Garg 2017; Goldie 2016). Use with caution in patients with diabetes. Monitor glucose; adjustment of diet and/or hypoglycemic therapy may be necessary. Consider discontinuation if persistent hyperglycemia occurs during therapy.
• Gout: May be associated with hyperuricemia. Use with caution in patients predisposed to gout. Consider discontinuation if acute gout occurs during therapy.
• 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.
• Renal impairment: Use with caution in patients with renal impairment.
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.
In pediatric patients, a high incidence of reversible adverse effects has been observed; in a dyslipidemia trial (n=21, age range: 4 to 14 years), flushing was most common (71%); increased liver enzymes were observed in 29% of patients; in the trial, dosage form (crystalline or sustained release) did not affect adverse effect incidence (Colletti 1993).
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 [DSC], 500 mg [DSC]
Powder, Oral:
Generic: (100 g, 500 g, 1000 g)
Tablet, Oral:
Niacin-50: 50 mg [DSC] [starch free, sugar free, wheat free]
Niacor: 500 mg [scored]
True Vitamin B3: 50 mg, 100 mg, 250 mg, 500 mg
Generic: 50 mg, 100 mg, 250 mg, 500 mg
Tablet, Oral [preservative free]:
Generic: 100 mg [DSC], 500 mg
Tablet Extended Release, Oral:
Niaspan: 500 mg [DSC] [contains fd&c yellow #6(sunset yellow)alumin lake]
Niaspan: 750 mg [DSC]
Niaspan: 1000 mg [DSC] [contains fd&c yellow #6(sunset yellow)alumin lake]
Slo-Niacin: 250 mg [scored; contains fd&c red #40 (allura red ac dye)]
Slo-Niacin: 500 mg [contains fd&c red #40 (allura red ac dye)]
Slo-Niacin: 500 mg, 750 mg [scored; contains fd&c red #40 (allura red ac dye)]
Generic: 500 mg, 750 mg, 1000 mg
Tablet Extended Release, Oral [preservative free]:
Generic: 250 mg, 500 mg, 1000 mg
Yes
Capsule Extended Release (Niacin ER Oral)
250 mg (per each): $0.05 - $0.09
500 mg (per each): $0.06
Tablet, controlled release (Niacin ER (Antihyperlipidemic) Oral)
500 mg (per each): $2.50 - $5.22
750 mg (per each): $3.39 - $6.04
1000 mg (per each): $4.71 - $9.22
Tablet, controlled release (Niacin ER Oral)
250 mg (per each): $0.05
500 mg (per each): $0.06
1000 mg (per each): $0.07
Tablet, controlled release (Slo-Niacin Oral)
250 mg (per each): $0.11
500 mg (per each): $0.17
750 mg (per each): $0.20
Tablets (Niacin (Antihyperlipidemic) Oral)
500 mg (per each): $11.54 - $11.82
Tablets (Niacin Oral)
50 mg (per each): $0.03
100 mg (per each): $0.03
250 mg (per each): $0.05
500 mg (per each): $0.03 - $0.06
Tablets (Niacor Oral)
500 mg (per each): $4.73
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Injection:
Generic: 100 mg/mL ([DSC])
Administer with food. To attenuate flushing symptoms, may premedicate with aspirin 30 minutes before dose; avoid ingestion of alcohol, hot or spicy foods/liquids concurrently with niacin. May also use other nonsteroidal anti-inflammatory drugs 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 IR 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.
Bariatric surgery: Capsule and tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. ER formulations should be swallowed whole. Do not chew or crush. If safety and efficacy of niacin can be effectively monitored, no change in formulation or administration is required after bariatric surgery. Bariatric vitamin supplementation is recommended on a lifelong basis after surgery; consider integration of daily niacin regimen into the bariatric vitamin regimen.
Oral: Administer with food or milk to decrease GI upset; to minimize flushing: Administer dose at bedtime; premedicate with aspirin (adults: 325 mg) 30 minutes before niacin; and avoid alcohol, hot drinks, or spicy food around the time of administration. In adults, may also use other NSAIDs to prevent flushing according to the manufacturer.
Niaspan: Administer at bedtime with a low-fat snack (do not administer on an empty stomach). 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 regular/immediate release preparations.
Dietary supplement: Use as a dietary supplement.
Dyslipidemias: 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 adults at risk of pancreatitis
Note: Niacin is no longer considered a primary or secondary agent for dyslipidemias. Although niacin consistently affects surrogate markers, especially LDL-C, it has not been shown to reduce cardiovascular disease outcomes beyond that achieved with statin use and may be associated with harm (ACC [Lloyd-Jones 2017]; Garg 2017; Wierzbicki 2014). In two large clinical trials, the addition of niacin to patients receiving simvastatin did not reduce cardiovascular morbidity or mortality (Boden 2011; Landray 2014). May consider use in patients with very high triglyceride levels (>500 mg/dL) or in dyslipidemia for patients who do not achieve the desired response or have intolerance to a statin or other alternative therapy (Boden 2014; Flink 2015).
Pellagra
Niacin may be confused with Minocin, niacinamide, Niaspan
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alcohol (Ethyl): May enhance the adverse/toxic effect of Niacin. Management: Avoid alcohol around the time of niacin administration to minimize flushing. Use caution in patients who drink larger amounts of alcohol due to the potential for enhanced hepatotoxicity. Consider monitoring serum transaminases more frequently. Risk D: Consider therapy modification
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Niacin. Management: Consider separating the administration times of niacin and bile acid sequestrants by a few hours in order to reduce the potential for decreased efficacy of these agents. Risk D: Consider therapy modification
HMG-CoA Reductase Inhibitors (Statins): Niacin may enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Rosuvastatin: Niacin may enhance the myopathic (rhabdomyolysis) effect of Rosuvastatin. Risk C: Monitor therapy
Simvastatin: Niacin may enhance the myopathic (rhabdomyolysis) effect of Simvastatin. Niacin may increase the serum concentration of Simvastatin. Management: Avoid this combination in Chinese patients; some non-US labeling state this combination is not recommended in any Asian patients. If coadministered, consider simvastatin dose reductions and monitor closely for signs and symptoms of muscle toxicity. Risk D: Consider therapy modification
Water soluble vitamins cross the placenta (IOM 1998).
When used as a dietary supplement, the recommended dietary allowance of niacin is increased during pregnancy compared to nonpregnant patients (IOM 1998).
It is not known if niacin at lipid-lowering doses is harmful to the developing fetus. If a patient becomes pregnant while receiving niacin for primary hypercholesterolemia, niacin should be discontinued. If a patient becomes pregnant while receiving niacin for hypertriglyceridemia, the benefits and risks of continuing niacin should be assessed on an individual basis.
Niacin is present in breast milk.
Concentrations of niacin in breast milk increase with supplementation. When used as a dietary supplement, the recommended dietary allowance of niacin is increased in breastfeeding patients compared to nonbreastfeeding patients (IOM 1998). Doses of niacin for the treatment of dyslipidemias are greater than those used as a dietary supplement. Due to the potential for serious adverse reactions in the breastfed infant (including hepatoxicity), the manufacturer recommends that breastfeeding be discontinued when niacin is used for treatment of dyslipidemias
Should be taken with meal; low-fat meal if treating dyslipidemia. Avoid alcohol, hot or spicy foods/liquids around the time of niacin dose.
Dietary adequate intake (National Academy of Sciences, 1998):
0 to 5 months: 2 mg daily
6 to 11 months: 3 mg daily
Dietary recommended daily allowances (National Academy of Sciences, 1998):
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: Females: 14 mg daily; Males: 16 mg daily
Pregnancy (all ages): 18 mg daily
Lactation (all ages): 17 mg daily
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 to 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)
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; Sauve 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.
Protein binding: <20% bound to serum proteins
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.
Bioavailability: Single dose studies indicate that only certain Niaspan tablet strengths are interchangeable (ie, two 500 mg tablets are equivalent to one 1,000 mg tablet; however, three 500 mg tablets are not equivalent to two 750 mg tablets)
Half-life elimination: 20 to 48 minutes
Time to peak, serum: Immediate release formulation: 30 to 60 minutes; extended release formulation: 4 to 5 hours
Excretion: Urine 60% to 88% (unchanged drug [up to 12% recovered after multiple dosing] and metabolites)
Sex: Steady-state plasma concentrations and metabolites are generally higher in women.
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