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  • CLASSES

    Antilipemic Nicotinic Acid and Derivatives
    Niacin/Vitamin B3 Supplements
    Other Nonsteroidals For Inflammatory Skin Disorders

    DEA CLASS

    OTC, Rx

    DESCRIPTION

    B-complex vitamin available in two chemical forms
    Only nicotinic acid is used for hyperlipoproteinemia or peripheral vascular disease; both nicotinic acid and nicotinamide (niacinamide) are used for nutritional supplementation or pellagra
    Contraindicated for use in patients with severe hepatic impairment

    COMMON BRAND NAMES

    Niacor, Niaspan, Slo-Niacin

    HOW SUPPLIED

    Niacin (Vitamin B3) Oral Cap ER: 250mg, 500mg
    Niacin (Vitamin B3)/Niacin (Vitamin B3), Inositol Oral Cap: 500mg, 400-100mg, 500-141mg, 750-211.5mg
    Niacin (Vitamin B3)/Niacor Oral Tab: 50mg, 100mg, 250mg, 500mg
    Niacin (Vitamin B3)/Niaspan/Slo-Niacin Oral Tab ER: 250mg, 500mg, 750mg, 1000mg

    DOSAGE & INDICATIONS

    For the treatment of clinical manifestations of pellagra.
    Oral dosage (nicotinic acid or nicotinamide/niacinamide)
    Adults

    Up to 500 mg/day PO, depending on the severity of niacin deficiency.

    Intravenous or Intramuscular dosage
    Adults

    50 to 100 mg IM 5 times daily, or 25 to 100 mg given by slow IV infusion twice daily, depending on the severity of niacin deficiency. Max: 500 mg/day.

    Children

    Up to 300 mg/day given by slow IV infusion, depending on the severity of niacin deficiency.

    For nutritional supplementation to meet the recommended dietary allowance (RDA).
    Oral dosage (as nicotinic acid or nicotinamide/niacinamide)
    Adult and Adolescent pregnant females

    18 mg PO per day.

    Adult and Adolescent lactating females

    17 mg PO per day while breastfeeding.

    Adult females

    14 mg PO per day.

    Adult males

    16 mg PO per day.

    Adolescent females 14 years and older

    14 mg PO per day.

    Adolescent males 14 years and older

    16 mg PO per day.

    Children 9 to 13 years

    12 mg PO per day.

    Children 4 to 8 years

    8 mg PO per day.

    Children 1 to 3 years

    6 mg PO per day.

    Infants 7 to 12 months

    4 mg PO per day is the Adequate Intake (AI). No RDA has been established.

    Infants younger than 6 months

    2 mg PO per day is the Adequate Intake (AI). No RDA has been established.

    For use as adjunctive therapy to diet to reduce elevated total cholesterol (TC), LDL-cholesterol (LDL-C), apolipoprotein B (Apo B), and triglyceride (TG) concentrations, and to increase HDL-cholesterol (HDL-C) in patients with primary hyperlipoproteinemia and mixed dyslipidemia; in combination with a bile acid binding resin to reduce elevated TC and LDL-C concentrations in adult patients with primary hyperlipoproteinemia; as adjunctive therapy for treatment of adult patients with severe hypertriglyceridemia who present a risk of pancreatitis with inadequate response to diet.
    NOTE: Nicotinic acid is active as a hypolipidemic agent but nicotinamide (niacinamide) is not. Do not use nicotinamide to treat hyperlipidemias.
    Oral dosage (regular-release niacin as nicotinic acid only, e.g., Niacor)
    Adults

    Initially, 250 mg PO once daily after the evening meal. The total daily dose may be increased every 4 to 7 days as needed until the desired LDL-cholesterol and/or triglyceride concentration is achieved per the National Cholesterol Education Program (NCEP) guidelines or to the first-level therapeutic dose of 1.52 g/day PO is reached. If the patient's hyperlipidemia is not adequately controlled after 2 months at this level, the dosage can be gradually increased at 2 to 4 week intervals up to 3 g/day (1 g PO 3 times daily) if needed. The usual maintenance dosage is 1.5 to 3 g/day PO, given in 2 to 3 divided doses, with or after meals. In patients with marked lipid abnormalities, a higher dose may be required. Do not exceed 6 g/day.

    Children 4 years and older and Adolescents

    Safety and efficacy have not been established; however, limited data from a study including children and adolescents aged 4 to 14 years suggest initial doses of 100 to 250 mg/day PO in 3 divided doses (with meals). Increase weekly by 100 mg/day PO, or every 2 to 3 weeks by 250 mg/day PO if tolerated. Efficacy should be evaluated when doses reach 20 mg/kg/day or 1000 mg/day (whichever is less). Doses can continue to increase, with reevaluations at each 500 mg increment. Doses up to 3 g/day PO have been used, but doses greater than 1.5 g/day PO may not be tolerated. Although niacin treatment is effective in children, adverse reactions are common.

    Oral dosage (Niaspan)
    Adults and Adolescents older than 16 years

    500 mg PO at bedtime for weeks 1 thru 4, then 1000 mg PO at bedtime for weeks 5 thru 8. After week 8, titrate to patient response and tolerance. If response to 1000 mg/day is inadequate, increase dose to 1500 mg/day PO at bedtime. If response to 1500 mg/day is inadequate, may subsequently increase dose to 2000 mg/day PO. The usual maintenance dosage is 1000 to 2000 mg PO once daily at bedtime. The daily dose should not be increased more than 500 mg in any 4-week period. Maximum dosage is 2000 mg/day. Women may respond at lower doses than men.

    Oral dosage (niacin sustained-release preparations)
    Adults

    Carefully titrate to 1 to 2 g/day PO administered in 2 to 3 divided doses. When switching from an immediate-release formulation, smaller doses should be used to reduce the risk of hepatotoxicity. Rare cases of fulminant hepatitis have been reported with sustained-release preparations. The risk of hepatotoxicity appears to be greater with the sustained-release preparations of nicotinic acid than with immediate-release formulations. If there is a dramatic reduction in plasma lipids, impending hepatotoxicity should be considered. Advise patients not to switch from 1 preparation to another because of considerable variation among different preparations.

    To slow progression or promote regression of atherosclerosis.
    For patients with a history of coronary artery disease (CAD) and hyperlipidemia, in combination with a bile acid binding resin, to slow progression or promote regression of atherosclerosis.
    Oral dosage (Niaspan)
    Adults and Adolescents older than 16 years

    500 mg PO at bedtime for weeks 1 thru 4, then 1000 mg PO at bedtime for weeks 5 thru 8. After week 8, titrate to patient response and tolerance. If response to 1000 mg/day is inadequate, increase dose to 1500 mg/day PO at bedtime. If response to 1500 mg/day is inadequate, increase dose to 2000 mg/day PO. The usual maintenance dosage is 1000 to 2000 mg PO once daily at bedtime. The daily dose should not be increased more than 500 mg in any 4-week period. Maximum dosage is 2000 mg/day. Women may respond at lower doses than men.

    For use in combination with an HMG-CoA reductase inhibitor (statin) for the regression of atherosclerosis†.
    Oral dosage (Niaspan)
    Adults

    Titrate extended-release niacin to a target dose of 2000 mg per day PO. The Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6-HDL and LDL Treatment Strategies (ARBITER 6-HALTS) trial randomized 363 patients (208 completed the trial at the time of termination) on established statin therapy with coronary heart disease (CHD) or CHD risk equivalent, LDL cholesterol (LDL-C) less than 100 mg/dL, and HDL less than 50 (men) or 55 mg/dL (women) to ezetimibe 10 mg per day PO or a target dose of extended-release niacin 2000 mg per day PO. There was a significant reduction from baseline in the mean carotid intima-media thickness (CIMT) at 8 and 14 months (-0.0102 +/- 0.0030 mm, p = 0.001; -0.0142 +/- 0.0041 mm, p = 0.01, respectively) in the niacin group; no significant changes were observed in the ezetimibe group. Although there was a greater reduction in LDL-C in the ezetimibe group (-17.6 +/- 20.1 mg/dL) compared to the niacin group (-10 +/- 24.5 mg/dL), there was an increase in the CIMT in the ezetimibe group that was inversely related to the change in LDL-C. The incidence of major adverse cardiovascular events (i.e., myocardial infarction, myocardial revascularization, hospital admission for ACS, or death due to coronary heart disease) was also significantly increased in the ezetimibe group compared to the niacin group (5% vs. 1%, p = 0.04). In another study, 71 patients receiving a statin with low HDL (less than 40 mg/dL) and vascular disease were randomized to modified-release niacin titrated to 2000 mg/day or placebo. After 12 months, the addition of niacin resulted in a mean decrease in carotid artery wall area of 1.1 +/- 2.6 mm2 compared with an increase of 1.2 +/- 3.0 mm2 in the placebo group. Additionally, mean HDL increased 23% and LDL-C was reduced 19% at 12 months in the niacin group; no significant differences were reported in the placebo group, although there was no statin dose alteration during the study. The NIA Plaque study, presented at the American Heart Association (AHA) 2009 Scientific Sessions, randomized 145 patients to 1500 mg/day of extended-release niacin or placebo for 18 months; additionally, patients received a statin titrated to reach target NCEP ATP III LDL-C. Although LDL-C was significantly reduced in both groups and the niacin group experienced significant increases in HDL, there was no significant difference between the 2 groups in the change in the internal carotid artery wall volume, suggesting that the addition of niacin to a statin did not reduce the progression of atherosclerosis compared to statin monotherapy. However, patients in NIA Plaque were older, had a lower incidence of diabetes mellitus and glucose intolerance, and had a higher average baseline HDL (55 mg/dL) than those in the previously mentioned studies.

    To reduce the risk of recurrent nonfatal myocardial infarction (myocardial infarction prophylaxis) in patients with a history of myocardial infarction and hyperlipidemia.
    Oral dosage (Niaspan)
    Adults and Adolescents older than 16 years

    500 mg PO at bedtime weeks 1 thru 4, then 1000 mg PO at bedtime weeks 5 thru 8. After week 8, titrate to patient response and tolerance. If response to 1000 mg/day is inadequate, increase dose to 1500 mg/day PO at bedtime. If response to 1500 mg/day is inadequate, increase dose to 2000 mg/day PO. The usual maintenance dosage is 1000 to 2000 mg PO once daily at bedtime. The daily dose should not be increased more than 500 mg in any 4-week period. Maximum dosage is 2000 mg/day. Women may respond at lower doses than men.

    For adjunctive therapy in the treatment of peripheral vascular disease (PVD)† and circulatory disorders.
    NOTE: Nicotinic acid is active as a vasodilatory agent but nicotinamide (niacinamide) does not have vasodilatory properties. Do not use nicotinamide to treat PVD.
    Oral dosage (regular-release niacin as nicotinic acid only)
    Adults

    100 to 150 mg PO 3 to 5 times daily.

    For adjunctive therapy in the treatment of tinnitus†.
    Oral dosage (regular-release niacin as nicotinic acid only)
    Adults

    50 to 100 mg PO when symptoms occur. Nicotinic acid has been used historically for this purpose, but well-controlled clinical studies are not available. Anecdotal reports suggest that niacin may also worsen tinnitus. Increased microcirculation of the inner ear is the assumed mechanism of action. Nicotinamide (niacinamide) does not produce vasodilation and should not be used for tinnitus.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Maximum dosages listed are for the treatment of hyperlipidemia.

    Adults

    6 g/day PO for immediate-release products; 2 g/day PO for Niaspan.

    Geriatric

    6 g/day PO for immediate-release products; 2 g/day PO for Niaspan.

    Adolescents

    Up to 3 g/day PO for immediate release products; doses more than 1.5 g/day PO may not be tolerated. Safe and effective use of Niaspan has not been established.

    Children

    Up to 3 g/day PO for immediate release products; doses more than 1.5 g/day PO may not be tolerated. Safe and effective use of Niaspan has not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Therapeutic doses of niacin (i.e., prescription formulations) are contraindicated for use in active liver disease. No dosage adjustment is needed when administering niacin to meet recommended dietary intake.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available. No dosage adjustment is needed when administering niacin to meet recommended dietary intake. Use caution when administering higher dosages.
     
    Intermittent hemodialysis
    Specific guidelines not available; see dosage in renal impairment.

    ADMINISTRATION

     
    NOTE: Some sustained-release nicotinic acid (niacin) formulations have a lower incidence of flushing but a higher incidence of hepatotoxicity when compared to immediate-release dosage forms.

    Oral Administration

    NOTE: Nicotinic acid is active as a hypolipidemic agent but nicotinamide (niacinamide) is not (see Mechanism of Action). Do not use nicotinamide dosage forms to treat hyperlipidemias.
    NOTE: Sustained- and regular-release dosage forms are not bioequivalent and are not interchangeable. Different extended-release tablet strengths are not bioequivalent. For example, two 500 mg tablets of Niaspan are not bioequivalent to one 1000 mg Niaspan tablet based on single-dose studies.
    All dosage forms: Administer following meals to minimize gastrointestinal irritation and improve bioavailability.

    Oral Solid Formulations

    Extended-release dosage forms: Administer extended-release products intact; do not chew or crush. Do not cut in half unless scored. Administer Niaspan at bedtime after a low-fat snack.

    Oral Liquid Formulations

    Niacin oral solutions: dosage should be measured using a calibrated measuring device.

    Injectable Administration

    Use parenteral route only if use of the oral route is not possible.
    Niacin (vitamin B3) is also available as a component of several parenteral B-vitamin or multivitamin combinations, see the specific product for appropriate dosage and administration information.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Direct IV injection:
    Dilute commercially available injection solution to a concentration of 2 mg/ml.
    Administer IV at a rate not to exceed 2 mg/min.
     
    Intermittent or continuous infusion:
    Dilute appropriate dose in 500 ml of NS or other compatible IV large-volume solution.
    Administer at a rate not to exceed 2 mg/minute.

    Intramuscular Administration

    Use only if product is labeled for IM use.
    No dilution necessary.
    Inject deeply into a large muscle.

    Subcutaneous Administration

    Use only if the product is labeled for SC use. 
    Inject subcutaneously taking care not to inject intradermally.

    STORAGE

    Generic:
    - Avoid excessive heat (above 104 degrees F)
    - Store at room temperature (between 59 to 86 degrees F)
    Niacor:
    - Store at room temperature (between 59 to 86 degrees F)
    Niaspan:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Nicomide-T:
    - Protect from freezing
    - Store at room temperature (between 59 to 86 degrees F)
    Slo-Niacin :
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Patients who have a known hypersensitivity to niacin or any product component should not be given the drug.
     
    While steady state plasma concentrations of niacin are generally higher in women than in men, the absorption, metabolism, and excretion of niacin appears to be similar in both genders. Women have been reported to have greater response to the lipid-lowering effects of nicotinic acid (niacin) when compared to men.
     
    No overall differences in safety and efficacy were observed between geriatric and younger individuals receiving niacin. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity for some older individuals cannot be ruled out.

    Alcoholism, gallbladder disease, hepatic disease

    Niacin is contraindicated in patients who have significant or unexplained hepatic disease. Patients who consume large quantities of ethanol (alcoholism), who have risk factors for hepatic disease, or who have a past-history of gallbladder disease, jaundice, or hepatic dysfunction may receive niacin with close clinical observation. Elevations in liver function tests (LFTs) appear to be dose-related. Some sustained-release nicotinic acid (niacin) formulations have a higher incidence of hepatotoxicity when compared to immediate-release dosage forms. Extended-release nicotinic acid preparations (e.g., Niaspan, Slo-Niacin) should not be substituted for equivalent dosages of immediate-release (crystalline) niacin (e.g., Niacor and others). Follow the manufacturer-recommended initial dosage titration schedules for extended-release products, regardless of previous therapy with other niacin formulations. Monitor LFTs in all patients during therapy at roughly 6-month intervals or when clinically indicated. If transaminase levels (i.e., ALT or AST) rise to 3 times the upper limit of normal, or clinical symptoms of hepatic dysfunction are present, niacin should be discontinued.

    Peptic ulcer disease

    Nicotinic acid (niacin) can stimulate histamine release, which, in turn, can stimulate gastric acid output. Niacin is contraindicated in patients with active peptic ulcer disease (PUD) because it can exacerbate PUD symptoms. Use niacin with caution in patients with a past history of peptic ulcer disease or in those on maintenance therapy to prevent PUD recurrence.

    Acute myocardial infarction, angina, driving or operating machinery, hypotension, orthostatic hypotension

    Due to its vasodilatory action, nicotinic acid (niacin) should be used with caution in those patients with uncorrected hypotension (or predisposition to orthostatic hypotension), acute myocardial infarction, or unstable angina, particularly when vasodilator medications such as nitrates, calcium channel blockers, or adrenergic blocking agents are coadministered (see Drug Interactions). Because the vasodilatory response to niacin may be more dramatic at the initiation of treatment, activities requiring mental alertness (e.g., driving or operating machinery) should not be undertaken until the response to niacin is known.

    Gout

    Niacin, especially in high doses, can cause hyperuricemia. Niacin should be prescribed cautiously to patients with gout (or predisposed to gout). These individuals should be advised not to purchase OTC forms of niacin without the guidance of a physician.

    Hypophosphatemia

    Niacin, especially in high doses, can cause hypophosphatemia. Although the reductions in phosphorus levels are usually transient, clinicians should monitor serum phosphorus periodically in those at risk for this electrolyte imbalance.

    Rhabdomyolysis

    Rare cases of rhabdomyolysis have been reported in patients taking lipid-altering dosages of nicotinic acid (niacin) and statin-type agents concurrently (see Drug Interactions). Patients undergoing combined therapy should be carefully monitored for muscle pain, tenderness, or weakness, particularly in the early months of treatment or during periods of upward dose titration of either drug. While periodic CPK and potassium determinations may be considered, there is no evidence that these tests will prevent the occurrence of severe myopathy. If rhabdomyolysis occurs, the offending therapies should be discontinued.

    Diabetes mellitus

    Niacin, especially in high doses, may cause hyperglycemia. Niacin should be prescribed cautiously to patients with diabetes mellitus. These individuals should be advised not to purchase OTC forms of niacin without the guidance of a physician. Niacin has also been reported to cause false-positive results in urine glucose tests that contain cupric sulfate solution (e.g., Benedict's reagent, Clinitest).

    Children, infants, neonates

    Niacin therapy has been used safely in children for the treatment of nutritional niacin deficiency. However, the safety and effectiveness of nicotinic acid for the treatment of dyslipidemias have not been established in neonates, infants and children <= 16 years of age. Nicotinic acid has been used for the treatment of dyslipidemia in pediatric patients under select circumstances. Children may have an increased risk of niacin-induced side effects versus adult populations. At least one pediatric study has concluded that niacin treatment should be reserved for treatment of severe hypercholesterolemia under the close-supervision of a lipid specialist. In general, the National Cholesterol Education Program (NCEP) does not recommend drug therapy for the treatment of children with dyslipidemias until the age of 10 years or older.

    Pregnancy

    Since niacin is an essential nutrient, one would expect it to be safe when administered during pregnancy at doses meeting the recommended daily allowance (RDA). However, when used in doses greater than the RDA for dyslipidemia or for the treatment of pellagra, the potential for embryofetal toxicity is not known. Available data on niacin use for the treatment of dyslipidemia in pregnant women are insufficient to evaluate the associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal reproduction studies to evaluate niacin therapy during pregnancy have not been conducted. It is recommended to discontinue niacin therapy for the treatment of hyperlipidemia once pregnancy is detected. For pregnant patients taking niacin for hypertriglyceridemia, the individual risks and benefits of continuing niacin therapy should be assessed. The potential benefits of high-dose niacin therapy should be weighed against the potential risks since toxicological studies have not been performed.

    Breast-feeding

    Niacin is present in human milk and the amount of niacin increases with maternal supplementation. There is no information regarding the effects of niacin on the breastfed infant or the effects on milk production when used for dyslipidemia. Breast-feeding is not recommended during niacin therapy when used to treat dyslipidemia, due to the potential for serious adverse reactions in the breastfed infant, including hepatotoxicity. Niacin, in the form of niacinamide, is excreted in breast milk in proportion to maternal intake. Niacin supplementation is only needed in those lactating women who do not have adequate dietary intake. The Recommended Daily Allowance (RDA) of the National Academy of Science for niacin during lactation is 20 mg. There are no safety data regarding the use of nicotinic acid in doses above the RDA during breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Renal disease, renal failure, renal impairment

    Use niacin with caution in patients with renal disease (renal failure or severe renal impairment) since niacin metabolites are excreted through the kidneys. It appears that no special precautions are needed when administering niacin to meet the recommended nutritional daily allowance (RDA). Use caution when administering higher dosages.

    Anticoagulant therapy, bleeding, coagulopathy, surgery, thrombocytopenia

    Nicotinic acid (niacin) occasionally causes slight decreases in platelet counts or increased prothrombin times and should be used with caution in patients with thrombocytopenia, coagulopathy, or who are receiving anticoagulant therapy. Patients who will be undergoing surgery should have blood counts monitored. Nicotinic acid (niacin) is contraindicated in patients with arterial bleeding.

    Geriatric

    The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents (e.g., geriatric adults) of long-term care facilities (LTCFs). According to OBRA, glucose and liver function tests should be evaluated regularly because niacin interferes with glucose control, can aggravate diabetes, and can exacerbate active gallbladder disease and gout. Flushing is a common side effect of niacin.

    ADVERSE REACTIONS

    Severe

    rhabdomyolysis / Delayed / 0.2-0.2
    laryngospasm / Rapid / Incidence not known
    atrial fibrillation / Early / Incidence not known
    laryngeal edema / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    peptic ulcer / Delayed / Incidence not known
    hepatic necrosis / Delayed / Incidence not known
    hepatic failure / Delayed / Incidence not known
    renal tubular obstruction / Delayed / Incidence not known
    macular edema / Delayed / Incidence not known

    Moderate

    angina / Early / Incidence not known
    peripheral vasodilation / Rapid / Incidence not known
    bullous rash / Early / Incidence not known
    orthostatic hypotension / Delayed / Incidence not known
    palpitations / Early / Incidence not known
    hypotension / Rapid / Incidence not known
    edema / Delayed / Incidence not known
    dyspnea / Early / Incidence not known
    peripheral edema / Delayed / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    jaundice / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    hyperglycemia / Delayed / Incidence not known
    diabetes mellitus / Delayed / Incidence not known
    gout / Delayed / Incidence not known
    hyperuricemia / Delayed / Incidence not known
    hypophosphatemia / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    myopathy / Delayed / Incidence not known
    myasthenia / Delayed / Incidence not known
    blurred vision / Early / Incidence not known

    Mild

    flushing / Rapid / 55.0-69.0
    diarrhea / Early / 7.0-14.0
    nausea / Early / 4.0-11.0
    vomiting / Early / 0-9.0
    pruritus / Rapid / 0-8.0
    cough / Delayed / 0-8.0
    rash / Early / 0-5.0
    syncope / Early / Incidence not known
    headache / Early / Incidence not known
    vesicular rash / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    chills / Rapid / Incidence not known
    diaphoresis / Early / Incidence not known
    dizziness / Early / Incidence not known
    maculopapular rash / Early / Incidence not known
    dyspepsia / Early / Incidence not known
    abdominal pain / Early / Incidence not known
    flatulence / Early / Incidence not known
    eructation / Early / Incidence not known
    fatigue / Early / Incidence not known
    muscle cramps / Delayed / Incidence not known
    myalgia / Early / Incidence not known
    asthenia / Delayed / Incidence not known
    insomnia / Early / Incidence not known
    weakness / Early / Incidence not known
    paresthesias / Delayed / Incidence not known
    xerosis / Delayed / Incidence not known
    skin hyperpigmentation / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acarbose: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Acetohexamide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Albiglutide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Alogliptin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Alogliptin; Metformin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Alogliptin; Pioglitazone: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Alpha-blockers: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Alpha-glucosidase Inhibitors: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Amlodipine; Atorvastatin: (Major) There is no clear indication for routine use of niacin in combination with atorvastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with atorvastatin. Carefully weigh the potential benefits and risk of combined therapy. If coadministered, use the lowest atorvastatin dose necessary and closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that periodic monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Discontinue atorvastatin immediately if myopathy is diagnosed or suspected.
    Angiotensin II receptor antagonists: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Angiotensin-converting enzyme inhibitors: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Aspirin, ASA; Pravastatin: (Major) There is no clear indication for routine use of niacin in combination with pravastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with pravastatin. If coadministered, consider lower starting and maintenance does of pravastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue pravastatin immediately if myopathy is diagnosed or suspected.
    Atorvastatin: (Major) There is no clear indication for routine use of niacin in combination with atorvastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with atorvastatin. Carefully weigh the potential benefits and risk of combined therapy. If coadministered, use the lowest atorvastatin dose necessary and closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that periodic monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Discontinue atorvastatin immediately if myopathy is diagnosed or suspected.
    Atorvastatin; Ezetimibe: (Major) There is no clear indication for routine use of niacin in combination with atorvastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with atorvastatin. Carefully weigh the potential benefits and risk of combined therapy. If coadministered, use the lowest atorvastatin dose necessary and closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that periodic monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Discontinue atorvastatin immediately if myopathy is diagnosed or suspected.
    Beta-blockers: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Bile acid sequestrants: (Moderate) In vitro studies have shown that bile acid sequestrants bind niacin. Roughly 98% of niacin was bound to colestipol, and 10 to 30% of niacin was bound to cholestyramine. These results suggest that at least 4 to 6 hours should elapse between the ingestion of bile-acid-binding resins and the administration of niacin.
    Calcium-channel blockers: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents, especially calcium-channel blockers. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Canagliflozin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Canagliflozin; Metformin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Carbamazepine: (Moderate) Niacin may inhibit the CYP3A4 metabolism of carbamazepine, resulting in elevated carbamazepine plasma concentrations. Serum carbamazepine concentrations should be monitored if niacin is added during carbamazepine therapy. It may be necessary to reduce the dose of carbamazepine.
    Central-acting adrenergic agents: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. Clonidine has been shown to inhibit niacin-induced flushing. The interaction is harmless unless niacin augments the hypotensive actions of clonidine.
    Cerivastatin: (Contraindicated) The risk of myopathy increases when HMG-Co-A reductase inhibitors are administered concurrently with antilipemic doses of niacin.
    Chlorpropamide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Dapagliflozin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Dapagliflozin; Metformin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Dapagliflozin; Saxagliptin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Dulaglutide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Empagliflozin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Empagliflozin; Linagliptin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Empagliflozin; Linagliptin; Metformin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Empagliflozin; Metformin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Eplerenone: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Epoprostenol: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents, especially epoprostenol. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Ertugliflozin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Ertugliflozin; Metformin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Ertugliflozin; Sitagliptin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Ethanol: (Moderate) Alcohol-containing beverages or hot beverages/foods can exacerbate cutaneous vasodilation caused by niacin and should be avoided around the time of niacin ingestion. In general, this interaction would not be harmful, but might decrease patient tolerance of niacin. alcohol and niacin, particularly sustained-release niacin, are both potentially hepatotoxic. Although no data are available regarding enhanced hepatotoxicity, excessive alcohol use should be discouraged. (Moderate) Ethanol-containing beverages or hot beverages/foods can exacerbate cutaneous vasodilation caused by niacin and should be avoided around the time of niacin ingestion. In general, this interaction would not be harmful, but might decrease patient tolerance of niacin. Ethanol and niacin, particularly sustained-release niacin, are both potentially hepatotoxic. Although no data are available regarding enhanced hepatotoxicity, excessive ethanol use should be discouraged.
    Exenatide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Ezetimibe; Simvastatin: (Major) There is no clear indication for routine use of niacin in combination with simvastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with simvastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue simvastatin immediately if myopathy is diagnosed or suspected. Coadministration is not recommended in Chinese patients, as the risk of myopathy is greater in this population. It is unknown if this risk applies to other Asian patients.
    Fluvastatin: (Major) There is no clear indication for routine use of niacin in combination with fluvastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with fluvastatin. If coadministered, consider lower starting and maintenance does of fluvastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue fluvastatin immediately if myopathy is diagnosed or suspected.
    Glimepiride: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Glimepiride; Rosiglitazone: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Glipizide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Glipizide; Metformin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Glyburide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Glyburide; Metformin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Iloprost: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Incretin Mimetics: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Insulin Degludec; Liraglutide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Insulin Glargine; Lixisenatide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Insulins: (Moderate) Monitor patients receiving insulin closely for changes in diabetic control when niacin, niacinamide is instituted or discontinued. Dosage adjustments may be necessary. Niacin interferes with glucose metabolism and can result in hyperglycemia. When used at daily doses of 750 to 2000 mg, niacin significantly lowers LDL cholesterol and triglycerides while increasing HDL cholesterol. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy.
    Linagliptin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Linagliptin; Metformin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Liraglutide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Lixisenatide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Loop diuretics: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Lovastatin: (Major) There is no clear indication for routine use of niacin in combination with lovastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with lovastatin. If coadministered, consider lower starting and maintenance does of lovastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue lovastatin immediately if myopathy is diagnosed or suspected.
    Lovastatin; Niacin: (Major) There is no clear indication for routine use of niacin in combination with lovastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with lovastatin. If coadministered, consider lower starting and maintenance does of lovastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue lovastatin immediately if myopathy is diagnosed or suspected.
    Mecamylamine: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Metformin: (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Metformin; Repaglinide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Metformin; Rosiglitazone: (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Metformin; Saxagliptin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Metformin; Sitagliptin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Miglitol: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Nateglinide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Niacin; Simvastatin: (Major) There is no clear indication for routine use of niacin in combination with simvastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with simvastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue simvastatin immediately if myopathy is diagnosed or suspected. Coadministration is not recommended in Chinese patients, as the risk of myopathy is greater in this population. It is unknown if this risk applies to other Asian patients.
    Pioglitazone; Glimepiride: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Pioglitazone; Metformin: (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Pitavastatin: (Major) There is no clear indication for routine use of niacin in combination with pitavastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with pitavastatin. If coadministered, consider lower starting and maintenance does of pitavastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue pitavastatin immediately if myopathy is diagnosed or suspected.
    Potassium-sparing diuretics: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Pramlintide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Pravastatin: (Major) There is no clear indication for routine use of niacin in combination with pravastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with pravastatin. If coadministered, consider lower starting and maintenance does of pravastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue pravastatin immediately if myopathy is diagnosed or suspected.
    Red Yeast Rice: (Major) Since compounds in red yeast rice are chemically similar to and possess actions similar to lovastatin, patients should avoid this dietary supplement if they currently take drugs known to increase the risk of myopathy when coadministered with HMG-CoA reductase inhibitors. Niacin (as nicotinic acid, vitamin B3 in antilipemic doses) directly increases the risk of myopathy.
    Repaglinide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Reserpine: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Rosuvastatin: (Major) There is no clear indication for routine use of niacin in combination with rosuvastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with rosuvastatin. If coadministered, consider lower starting and maintenance does of rosuvastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue rosuvastatin immediately if myopathy is diagnosed or suspected.
    Rosuvastatin; Ezetimibe: (Major) There is no clear indication for routine use of niacin in combination with rosuvastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with rosuvastatin. If coadministered, consider lower starting and maintenance does of rosuvastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue rosuvastatin immediately if myopathy is diagnosed or suspected.
    Saxagliptin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Semaglutide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Simvastatin: (Major) There is no clear indication for routine use of niacin in combination with simvastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with simvastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue simvastatin immediately if myopathy is diagnosed or suspected. Coadministration is not recommended in Chinese patients, as the risk of myopathy is greater in this population. It is unknown if this risk applies to other Asian patients.
    Simvastatin; Sitagliptin: (Major) There is no clear indication for routine use of niacin in combination with simvastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with simvastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue simvastatin immediately if myopathy is diagnosed or suspected. Coadministration is not recommended in Chinese patients, as the risk of myopathy is greater in this population. It is unknown if this risk applies to other Asian patients. (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Sitagliptin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Sulfonylureas: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Telbivudine: (Moderate) The risk of myopathy may be increased if niacin is coadministered with telbivudine. Physicians considering concomitant treatment should weigh carefully the potential benefits and risks; and should monitor patients for any signs or symptoms of unexplained muscle pain, tenderness, or weakness, particularly during periods of upward dosage titration.
    Thiazide diuretics: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Thiazolidinediones: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Tolazamide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Tolbutamide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Treprostinil: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Vasodilators: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents, especially peripheral vasodilators. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. The interaction is harmless unless niacin augments the hypotensive actions of clonidine.
    Warfarin: (Moderate) Niacin (nicotinic acid) is occasionally associated with small but statistically significant increases (mean 4%) in prothrombin time. While rare, there is a possibility that an interaction would occur in some patients stabilized on warfarin. It appears prudent to monitor the INR periodically.

    PREGNANCY AND LACTATION

    Pregnancy

    Since niacin is an essential nutrient, one would expect it to be safe when administered during pregnancy at doses meeting the recommended daily allowance (RDA). However, when used in doses greater than the RDA for dyslipidemia or for the treatment of pellagra, the potential for embryofetal toxicity is not known. Available data on niacin use for the treatment of dyslipidemia in pregnant women are insufficient to evaluate the associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal reproduction studies to evaluate niacin therapy during pregnancy have not been conducted. It is recommended to discontinue niacin therapy for the treatment of hyperlipidemia once pregnancy is detected. For pregnant patients taking niacin for hypertriglyceridemia, the individual risks and benefits of continuing niacin therapy should be assessed. The potential benefits of high-dose niacin therapy should be weighed against the potential risks since toxicological studies have not been performed.

    Niacin is present in human milk and the amount of niacin increases with maternal supplementation. There is no information regarding the effects of niacin on the breastfed infant or the effects on milk production when used for dyslipidemia. Breast-feeding is not recommended during niacin therapy when used to treat dyslipidemia, due to the potential for serious adverse reactions in the breastfed infant, including hepatotoxicity. Niacin, in the form of niacinamide, is excreted in breast milk in proportion to maternal intake. Niacin supplementation is only needed in those lactating women who do not have adequate dietary intake. The Recommended Daily Allowance (RDA) of the National Academy of Science for niacin during lactation is 20 mg. There are no safety data regarding the use of nicotinic acid in doses above the RDA during breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Mechanism of Action: Dietary requirements for niacin can be met by the ingestion of either nicotinic acid or nicotinamide; as vitamins, both have identical biochemical functions. As pharmacologic agents, however, they differ markedly. Nicotinic acid is not directly converted into nicotinamide by the body; nicotinamide is only formed as a result of coenzyme metabolism. Nicotinic acid is incorporated into a coenzyme known as nicotinamide adenine dinucleotide (NAD) in erythrocytes and other tissues. A second coenzyme, nicotinamide adenine dinucleotide phosphate (NADP), is synthesized from NAD. These two coenzymes function in at least 200 different redox reactions in cellular metabolic pathways. Nicotinamide is released from NAD by hydrolysis in the liver and intestines and is transported to other tissues; these tissues use nicotinamide to produce more NAD as needed. Together with riboflavin and other micronutrients, the NAD and NADP coenzymes work to convert fats and proteins to glucose and assist in the oxidation of glucose.In addition to its role as a vitamin, niacin (nicotinic acid) has other dose-related pharmacologic properties. Nicotinic acid, when used for therapeutic purposes, acts on the peripheral circulation, producing dilation of cutaneous blood vessels and increasing blood flow, mainly in the face, neck, and chest. This action produces the characteristic "niacin-flush". Nicotinic acid-induced vasodilation may be related to release of histamine and/or prostacyclin. Histamine secretion can increase gastric motility and acid secretion. Flushing may result in concurrent pruritus, headaches, or pain. The flushing effects of nicotinic acid appear to be related to the 3-carboxyl radical on its pyridine ring. Nicotinamide (niacinamide), in contrast to nicotinic acid, does not contain a carboxyl radical in the 3 position on the pyridine ring and does not appear to produce flushing.Nicotinic acid may be used as an antilipemic agent, but nicotinamide does not exhibit hypolipidemic activity. Niacin reduces total serum cholesterol, LDL, VLDL, and triglycerides, and increases HDL cholesterol. The mechanism of nicotinic acid's antilipemic effect is unknown but is unrelated to its biochemical role as a vitamin. One of nicotinic acid's primary actions is decreased hepatic synthesis of VLDL. Several mechanisms have been proposed, including inhibition of free fatty acid release from adipose tissue, increased lipoprotein lipase activity, decreased triglyceride synthesis, decreased VLDL-triglyceride transport, and an inhibition of lipolysis. This last mechanism may be due to niacin's inhibitory action on lipolytic hormones. Nicotinic acid possibly reduces LDL secondary to decreased VLDL production or enhanced hepatic clearance of LDL precursors. Nicotinic acid elevates total HDL by an unknown mechanism, but is associated with an increase in serum levels of Apo A-I and lipoprotein A-I, and a decrease in serum levels of Apo-B. Nicotinic acid is effective at elevating HDL even in patients whose only lipid abnormality is a low-HDL value. Niacin does not appear to affect the fecal excretion of fats, sterols, or bile acids. Clinical trial data suggest that women have a greater hypolipidemic response to niacin therapy than men at equivalent doses.

    PHARMACOKINETICS

    Nicotinic acid may be administered by the oral or parenteral routes. Nicotinamide is administered orally. Niacin is widely distributed throughout the body and it concentrates in the liver, spleen, and adipose tissue. Niacin undergoes rapid and extensive first-pass metabolism that is dose-rate specific and, at the doses used to treat dyslipidemia, saturable. Niacin is conjugated with glycine to form nicotinuric acid (NUA), which is then excreted in the urine. Some reversible metabolism from NUA back to niacin may occur in small amounts. The other pathway results in the formation of NAD. Nicotinamide is most likely released after the formation of NAD. Nicotinamide does not have hypolipidemic activity, and is further metabolized in the liver to produce N-methylnicotinamide (MNA) and nicotinamide-N-oxide (NNO). MNA is metabolized to two other N-methylated compounds known as 2PY and 4PY, which are excreted in the urine. The formation of 2PY predominates over 4PY in humans. Roughly 12% of nicotinic acid is excreted unchanged in the urine with normal dosages. Greater proportions of niacin are renally excreted unchanged as dosages exceed 1000 mg/day and metabolic pathways become saturated.

    Oral Route

    Both nicotinic acid and nicotinamide are well-absorbed by the oral route. Following oral administration of an immediate-release niacin product, absorption is rapid, and peak plasma levels are achieved in about 45 minutes. Extended-release formulations reach peak concentrations in 4—5 hours. Administration with food maximizes bioavailability and minimizes GI intolerance. Peripheral vasodilation is seen within 20 minutes after administration of an immediate-release product and may last for up to 1 hour. The rate of onset of vasodilation is slower with sustained-release forms and may attenuate the severity of flushing.