nicotinic acid (niacin, vitamin B3, Niaspan)
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Pathology
- deficiency of nicotinic acid (niacin) is pellagra
Indications
- familial HDL deficiency
- treatment of pellagra (niacin deficiency)
- dietary supplement
- hyperlipidemia*
- 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
- peptic ulcer
- gout
- active liver disease
- paroxysmal atrial fibrillation
- severe hypotension
- flushing to alter urine drug tests[8]
- diabetes (relative contraindication)
- 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]
- 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
- vasodilation occurs with 20 minutes & persists for 20-60 minutes
- depending upon the dose, niacin is converted to nicotinamide
- nicotinamide is metabolized in the liver
- elimination in urine
- elimination 1/2life is 45 minutes
elimination via kidney
elimination via liver
1/2life = 45 minutes
Monitor
- serum glucose baseline, within 6-8 weeks, then annually
- more frequent monitoring if clinically indicated
- stop or reduce niacin dose if fasting serum glucose is > 126 mg/dL
- 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]
- serum uric acid baseline, 6-8 weeks later, then annually
- serum creatine kinase periodically if myalgias or muscle weakness
- serum K+ periodically if myalgias or muscle weakness
- serum phosphate periodically in patients at high risk of hypophosphatemia[13]
Adverse effects
- not common (1-10%)
- headache, cutaneous flushing, itching & tingling*, hepatotoxicity% (especially with sustained release form), jaundice, bloating, flatulence, increased sebaceous gland activity
- uncommon (< 1%)
- rash, wheezing, tachycardia, syncope, dizziness#, vasovagal episodes, chronic liver damage, blurred vision, cystoid macular edema
- other
- hyperglycemia: increased insulin requirements
- acanthosis nigricans
- increased uric acid, gout[5]
- nausea/vomiting
- activation of peptic ulcer disease
- may increase serum homocysteine levels
- hypophosphatemia (dose-dependent)[13]
- myositis[5]
- diarrhea[5]
- 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
- HMG CoA reductase inhibitors in combination may increase the risk of myopathy & rhabdomyolysis
- niacin MAY BE USED with gemfibrozil[5]
Test interactions
- false elevation of fluorometric determination of urinary catecholamines
- false positive urinary glucose (Benedict's reagent)
Mechanism of action
- at pharmacologic doses, lowers total cholesterol, triglycerides, LDL & increases HDL
- inhibits lipolysis in adipose tissue
- decreases esterfication of triglycerides in the liver
- increases lipoprotein lipase activity
- maximal effect (2-6g/day)
- total cholesterol: decrease of 25%
- LDL cholesterol: decrease of 30%
- HDL cholesterol: increase of 40%
- triglycerides: decrease of 50%
- lipoprotein<a> (Lp<a>): decrease of 30%
- binds to nicotinic acid receptor
More general terms
More specific terms
Additional terms
- 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)
Component of
- alpha tocopheryl acetate/ascorbate/beta carotene/cobalamin/ergocalciferol/folic acid/nicotinic acid/pantothenate/pyridoxine/retinol/riboflavin/thiamine
- inositol/nicotinic acid
- ascorbate/ferrous fumarate/folic acid/nicotinic acid/polysaccharide iron complex
- ascorbate/cobalamin/folic acid/nicotinic acid/pyridoxine/riboflavin/sodium fluoride/thiamine/vitamin a/vitamin d/vitamin e
- ascorbate/cholecalciferol/cobalamin/nicotinic acid/pyridoxine/riboflavin/sodium fluoride/thiamine/vitamin a/vitamin e
- ascorbate/cholecalciferol/cobalamin/folic acid/magnesium oxide/nicotinic acid/polysaccharide iron complex/potassium iodide/pyridoxine/riboflavin/thiamine/vitamin a/vitamin e/zinc oxide
- 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/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/cholecalciferol/cobalamin/folic acid/nicotinic acid/pantothenate/pyridoxine/riboflavin/thiamine
- ascorbate/biotin/calcium carbonate/cobalamin/dextran/folic acid/iron dextran/nicotinic acid/pantothenate/pyridoxine/riboflavin/thiamine
- ascorbate/cobalamin/nicotinic acid/pyridoxine/riboflavin/thiamine/vitamin a/vitamin d/vitamin e
- ascorbate/ferrous sulfate/nicotinic acid/pyridoxine/riboflavin/thiamine/vitamin a/vitamin d/vitamin e
- ascorbate/biotin/cobalamin/folic acid/nicotinic acid/pantothenate/pyridoxine/riboflavin/thiamine
- HMG CoA reductase inhibitor/nicotinic acid
- Herbal Rescue
- lovastatin/nicotinic acid (Advicor, Nicostatin)
- inositol hexaniacinate ('No flush' niacin)
- nicotinic acid/simvastatin (Simcor)
- laropiprant/nicotinic acid {Niaspan, laropiprant} (Cordaptive)
References
- ↑ Kaiser Permanente prescriber guidelines, 1999
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Prescriber's Letter 7(2):8, Feb. 2000
- ↑ 5.0 5.1 5.2 5.3 5.4 5.5 Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 17. American College of Physicians, Philadelphia 1998, 2006, 2015
- ↑ 6.0 6.1 6.2 Prescriber's Letter 11(5):27 2004 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=200504&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 7.0 7.1 Prescriber's Letter 11(5):27 2004 What You Should Know About Niacin Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=211207&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 8.0 8.1 Prescriber's Letter 14(6): 2007 Niacin Abuse in the Attempt to Alter Urine Drug Tests Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=230606&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Prescriber's Letter 14(8): 2007 New Niaspan Formulation Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=230808&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 10.0 10.1 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: https://www.ncbi.nlm.nih.gov/pubmed/17969377
- ↑ 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#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=251212&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 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#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=260101&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 13.0 13.1 13.2 Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Liver Function Test Scheduling Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=260704&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 14.0 14.1 14.2 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#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=270701&pb=PRL (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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22085343 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1107579 - ↑ Deprecated Reference
- ↑ 16.0 16.1 16.2 16.3 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. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25014686 <Internet> 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. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25014706 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMc1311039 - ↑ 17.0 17.1 17.2 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: https://www.ncbi.nlm.nih.gov/pubmed/25038074
- ↑ 18.0 18.1 18.2 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: https://www.ncbi.nlm.nih.gov/pubmed/29671561 Medscape https://www.medscape.com/viewarticle/895259_2
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/38374343 https://www.nature.com/articles/s41591-023-02793-8
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