Nicotinic Acid

From Anvita Health Wiki

Contents 1 Indications 2 Contraindications 3 Dosage 4 Pharmacokinetics 5 Monitor 6 Adverse-effects 7 Drug-interactions 8 Test-interactions 9 Mechanism-of-action 10 More General Terms 11 Additional Terms 12 Internet Database 13 References

Indications

• adjunct therapy in patients with hyperlipidemia
• adjunct therapy for peripheral vascular disease
• treatment of pellagra
• dietary supplement

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]
  

• pregnancy category = c
• safety in lactation = ?

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
• nausea/vomiting
• activation of peptic ulcer disease
• may increase serum homocysteine levels

• 17% increase at 1000 mg/day
• 55% increase at 3000 mg/day

• hypophosphatemia (dose-dependent) [13]

• * 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

• pyridine
• carboxylate
• B vitamin
• anti-hyperlipidemic agent

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, HM74A)

Internet Database

Kegg: [1]
PubChem: 938
PubChem: 71558
PubChem: 937
PubChem: 3015837
PubChem: 1983223
PubChem: 197944
PubChem: 119797
PubChem: 119797
PubChem: 82583
PubChem: 71571
PubChem: 23472
PubChem: 16098
PubChem: 5914

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, American College of Physicians, Philadelphia 1998, 2006
6. Prescriber's Letter 11(5):27 2004 Detail-Document#: [2] (subscription needed) [3]
7. Prescriber's Letter 11(5):27 2004 What You Should Know About Niacin Detail-Document#: [4] (subscription needed) [5]
8. Prescriber's Letter 14(6): 2007 Niacin Abuse in the Attempt to Alter Urine Drug Tests Detail-Document#: [6] (subscription needed) [7]
9. Prescriber's Letter 14(8): 2007 New Niaspan Formulation Detail-Document#: [8] (subscription needed) [9]
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: [10]
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#: [11] (subscription needed) [12]
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#: [13] (subscription needed) [14]
13. Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Liver Function Test Scheduling Detail-Document#: [15] (subscription needed) [16]
14. NIH News: Thursday, May 26, 2011 NIH stops clinical trial on combination cholesterol treatment Lack of efficacy in reducing cardiovascular events prompts decision [17]
    - Prescriber's Letter 18(7): 2011 Niacin Plus Statin to Reduce Cardiovascular Risk: AIM-HIGH Study Detail-Document#: [18] (subscription needed) [19]
    - 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: [20] <Internet> [21]

nicotinic acid (niacin, vitamin B3, Niaspan)