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nicotinic acid (niacin, vitamin B3, Niaspan)

Indications: - familial HDL deficiency - treatment of pellagra (niacin deficiency) - dietary supplement - hyperlipidemia* - hypercholesterolemia, hypertriglyceridemia - coronary artery disease* - secondary prevention in patients with cardiovascular disease* - adjunct therapy for peripheral vascular disease * may not be useful as adjunct therapy in patients with hyperlipidemia * lowers risk of non-fatal myocardial infarction or non-fatal stroke in patients not taking statins [17] * does not lower risk of fatal myocardial infarctions, fatal stroke or all-cause mortality in patients taking statins [17] Contraindications: 1) peptic ulcer 2) gout 3) active liver disease 4) paroxysmal atrial fibrillation 5) severe hypotension 6) flushing to alter urine drug tests [8] 7) diabetes (relative contraindication) 8) no benefit as adjunct to statin therapy for patients with low HDL cholesterol & high serum triglycerides [14] or low HDL cholesterol high LDL cholesterol* [16] 9) does not reduce myocardial infarction, stroke, or all-cause mortality when used for primary or secondary prevention of cardiovascular disease [18] * sustained-release niacin [14,16] combined with laropriant [16] Dosage: Schedule A: 1st week: 100 mg PO TID 2nd week: 200 mg PO TID 3rd week: 300 mg PO TID 4th week: 400 mg PO TID 5th week: 500 mg PO TID 6th week: 600 mg PO TID 7th week: 700 mg PO TID 8th week: 800 mg PO TID 9th week: 900 mg PO TID 10th week: 1000 mg PO TID Schedule B: 1st week: 200 mg PO TID 2nd week: 400 mg PO TID 3rd week: 600 mg PO TID 4th week: 800 mg PO TID 5th week: 1000 mg PO TID 6th week: 1200 mg PO TID 7th week: 1400 mg PO TID 8th week: 1600 mg PO TID Average effective dose: 2.0-2.5 g/day Max dose: 8 g/day Capsules: 100 mg, 500 mg Tablets: 50 mg, 100 mg, 250 mg, 500 mg Niaspan: - sustained release (over 8-12 hours) (QHS) [6] - less hepatotoxic than other sustained-release forms [7] - may have benefits similar to immediate-release niacin [10] Pharmacokinetics: 1) vasodilation occurs with 20 minutes & persists for 20-60 minutes 2) depending upon the dose, niacin is converted to nicotinamide -> nicotinamide is metabolized in the liver 3) elimination in urine 4) elimination 1/2life is 45 minutes Monitor: 1) serum glucose baseline, within 6-8 weeks, then annually a) more frequent monitoring if clinically indicated b) stop or reduce niacin dose if fasting serum glucose is > 126 mg/dL 2) liver function tests baseline, then every 6-12 weeks for 1 year, then periodically (every 6 months) - stop or reduce niacin dose if serum ALT is > 2.5X upper limit of reference interval [5] 3) serum uric acid baseline, 6-8 weeks later, then annually 4) serum creatine kinase periodically if myalgias or muscle weakness 5) serum K+ periodically if myalgias or muscle weakness 6) serum phosphate periodically in patients at high risk of hypophosphatemia [13] Adverse effects: 1) not common (1-10%) - headache, cutaneous flushing, itching & tingling*, hepatotoxicity% (especially with sustained release form), jaundice, bloating, flatulence, increased sebaceous gland activity 2) uncommon (< 1%) - rash, wheezing, tachycardia, syncope, dizziness#, vasovagal episodes, chronic liver damage, blurred vision, cystoid macular edema 3) other a) hyperglycemia: increased insulin requirements b) acanthosis nigricans c) increased uric acid, gout [5] d) nausea/vomiting e) activation of peptic ulcer disease f) may increase serum homocysteine levels - 17% increase at 1000 mg/day - 55% increase at 3000 mg/day g) hypophosphatemia (dose-dependent) [13] h) myositis [5] i) diarrhea [5] j) serum levels of terminal metabolites of excess niacin, N1-methyl-2-pyridone-5-carboxamide & N1-methyl-4-pyridone-3-carboxamide may be associated with increased 3-year risk of major cardiovascular events (RR=1.1-3.2) [18] * less frequent with sustained-release forms may be minimized by giving 325 mg of aspirin or 200 mg of ibuprofen 30 minutes before niacin # if dizziness occurs, avoid sudden changes in posture % niaspan may be less heptatoxic than other sustained-release forms [6] Drug interactions: 1) HMG CoA reductase inhibitors in combination may increase the risk of myopathy & rhabdomyolysis 2) niacin MAY BE USED with gemfibrozil [5] Test interactions: 1) false elevation of fluorometric determination of urinary catecholamines 2) false positive urinary glucose (Benedict's reagent) Mechanism of action: 1) at pharmacologic doses, lowers total cholesterol, triglycerides, LDL & increases HDL 2) inhibits lipolysis in adipose tissue 3) decreases esterfication of triglycerides in the liver 4) increases lipoprotein lipase activity 6) maximal effect (2-6g/day) a) total cholesterol: decrease of 25% b) LDL cholesterol: decrease of 30% c) HDL cholesterol: increase of 40% d) triglycerides: decrease of 50% e) lipoprotein (Lp): decrease of 30% 7) binds to nicotinic acid receptor Pathology: - deficiency of nicotinic acid (niacin) is pellagra

Interactions

drug adverse effects of anti-hyperlipidemic agents

Related

effect of niacin on serum lipids & glucose isonicotinic acid; pyridine-4-carboxylic acid; 4-carboxypyridine; 4-picolinic acid nicotinic acid receptor 1; G-protein coupled receptor 109A; G-protein coupled receptor HM74A (GPR109A, HCAR2, HM74A) pellagra (niacin deficiency, vitamin B3 deficiency)

Specific

methylnicotinate (Nikomet, Trigenolline, Caffearine)

General

anti-hyperlipidemic agent B vitamin carboxylate pyridine

Properties

MISC-INFO: elimination route KIDNEY LIVER 1/2life 45 MINUTES pregnancy-category C safety in lactation ?

Database Correlations

PUBCHEM correlations Kegg map/map00760

References

  1. Kaiser Permanente prescriber guidelines, 1999
  2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  3. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  4. Prescriber's Letter 7(2):8, Feb. 2000
  5. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 17. American College of Physicians, Philadelphia 1998, 2006, 2015
  6. Prescriber's Letter 11(5):27 2004 Detail-Document#: 200504 (subscription needed) http://www.prescribersletter.com
  7. Prescriber's Letter 11(5):27 2004 What You Should Know About Niacin Detail-Document#: 211207 (subscription needed) http://www.prescribersletter.com
  8. Prescriber's Letter 14(6): 2007 Niacin Abuse in the Attempt to Alter Urine Drug Tests Detail-Document#: 230606 (subscription needed) http://www.prescribersletter.com
  9. Prescriber's Letter 14(8): 2007 New Niaspan Formulation Detail-Document#: 230808 (subscription needed) http://www.prescribersletter.com
  10. Vogt A et al, Prolonged-release nicotinic acid for the management of dyslipidemia: an update including results from the NAUTILUS study. Vasc Health Risk Manag. 2007;3(4):467-79. PMID: 17969377
  11. Prescriber's Letter 16(12): 2009 COMMENTARY: Ezetimibe vs. Niacin for Atherosclerosis: The ARBITER 6-HALTS Study PATIENT HANDOUT: What You Should Know About Niacin Detail-Document#: 251212 (subscription needed) http://www.prescribersletter.com
  12. Prescriber's Letter 17(1): 2010 Second-Line Therapy of Dyslipidemia RESOURCE: Niacin Titration Schedule PATIENT HANDOUT: What You Should Know About Niacin COMMENTARY: Ezetimibe vs. Niacin for Atherosclerosis: The ARBITER 6-HALTS Study CHART: Non-Statin Lipid-Lowering Agents Detail-Document#: 260101 (subscription needed) http://www.prescribersletter.com
  13. Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Liver Function Test Scheduling Detail-Document#: 260704 (subscription needed) http://www.prescribersletter.com
  14. NIH News: Thursday, May 26, 2011 NIH stops clinical trial on combination cholesterol treatment Lack of efficacy in reducing cardiovascular events prompts decision http://www.nih.gov/news/health/may2011/nhlbi-26.htm - Prescriber's Letter 18(7): 2011 Niacin Plus Statin to Reduce Cardiovascular Risk: AIM-HIGH Study Detail-Document#: 270701 (subscription needed) http://www.prescribersletter.com - The AIM-HIGH Investigators. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med 2011 Nov 15 PMID: 22085343 http://www.nejm.org/doi/full/10.1056/NEJMoa1107579
  15. Deprecated Reference
  16. The HPS2-THRIVE Collaborative Group. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med 2014 Jul 17; 371:203. PMID: 25014686 http://www.nejm.org/doi/full/10.1056/NEJMoa1300955 - Anderson TJ et al. Safety profile of extended-release niacin in the AIM-HIGH trial. N Engl J Med 2014 Jul 17; 371:288. PMID: 25014706 http://www.nejm.org/doi/full/10.1056/NEJMc1311039
  17. Keene D et al. Effect on cardiovascular risk of high density lipoprotein targeted drug treatments niacin, fibrates, and CETP inhibitors: Meta-analysis of randomised controlled trials including 117,411 patients. BMJ 2014 Jul 18; 349:g4379 PMID: 25038074
  18. Yancey JR, Rey JB. Use of Niacin for Primary or Secondary Prevention of Cardiovascular or Cerebrovascular Events. Am Fam Physician. 2018 Apr 1;97(7):436-437. PMID: 29671561 Medscape https://www.medscape.com/viewarticle/895259_2
  19. Ferral M, Wang Z, Anderson JT et al A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk. Nature Medicine 2024 volume 30, pages 424-234 PMID: 38374343 https://www.nature.com/articles/s41591-023-02793-8

Component-of

alpha tocopheryl acetate/ascorbate/beta carotene/cobalamin/ergocalciferol/folic acid/nicotinic acid/pantothenate/pyridoxine/retinol/riboflavin/thiamine ascorbate/biotin/calcium carbonate/cobalamin/dextran/folic acid/iron dextran/nicotinic acid/pantothenate/pyridoxine/riboflavin/thiamine ascorbate/biotin/cholecalciferol/cobalamin/folic acid/nicotinic acid/pantothenate/pyridoxine/riboflavin/thiamine ascorbate/biotin/cobalamin/copper sulfate/ferrous fumarate/folic acid/magnesium sulfate/manganese sulfate/nicotinic acid/pantothenate/polysaccharide iron complex/pyridoxine/riboflavin/thiamine/zinc sulfate ascorbate/biotin/cobalamin/folic acid/nicotinic acid/pantothenate/pyridoxine/riboflavin/thiamine ascorbate/calcium carbonate/cholecalciferol/choline bitartrate/cobalamin/docosahexaenoate/eicosapentaenoate/ferrous fumarate/folic acid/nicotinic acid/potassium iodide/pyridoxine/riboflavin/thiamine/vitamin e/zinc oxide ascorbate/cholecalciferol/cobalamin/folic acid/magnesium oxide/nicotinic acid/polysaccharide iron complex/potassium iodide/pyridoxine/riboflavin/thiamine/vitamin a/vitamin e/zinc oxide ascorbate/cholecalciferol/cobalamin/nicotinic acid/pyridoxine/riboflavin/sodium fluoride/thiamine/vitamin a/vitamin e ascorbate/cobalamin/folic acid/nicotinic acid/pyridoxine/riboflavin/sodium fluoride/thiamine/vitamin a/vitamin d/vitamin e ascorbate/cobalamin/nicotinic acid/pyridoxine/riboflavin/thiamine/vitamin a/vitamin d/vitamin e ascorbate/ferrous fumarate/folic acid/nicotinic acid/polysaccharide iron complex ascorbate/ferrous sulfate/nicotinic acid/pyridoxine/riboflavin/thiamine/vitamin a/vitamin d/vitamin e Herbal Rescue HMG CoA reductase inhibitor/nicotinic acid inositol/nicotinic acid laropiprant/nicotinic acid {Niaspan, laropiprant} (Cordaptive) lovastatin/nicotinic acid (Advicor, Nicostatin) nicotinic acid/simvastatin (Simcor)