Nicotinic Acid, Vitamin B3
Action And Clinical Pharmacology: Niacin and niacinamide are water-soluble B complex vitamins. In vivo, niacin is converted to niacinamide, a constituent of nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which are coenzymes involved in glycogenolysis, tissue respiration and lipid metabolism. Niacin deficiency results in pellagra, a chronic wasting disease characterized by dermatitis, dementia and diarrhea.
Niacin produces peripheral vasodilation, a process believed to be mediated by prostacyclin, which affects the cutaneous vessels of the upper body. Tolerance to this effect usually develops after about 2 weeks of treatment.
Niacin has been reported to stimulate histamine release resulting in increased gastric motility and acid production which may activate peptic ulcer. Reports have also indicated that large doses of niacin may decrease uric acid excretion and impair glucose tolerance. These effects may result in precipitation of an episode of gout in susceptible patients and may necessitate adjustment of diet and antihyperglycemic therapy in diabetic patients.
Niacin decreases the rate of hepatic synthesis of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) while raising high-density lipoprotein in serum, both in normal individuals and patients with type II, III, IV or V hyperlipoproteinemia. This has led to a lowering of serum cholesterol by 10 to 15% and triglycerides by 20 to 30%. Niacinamide is not effective in lowering serum cholesterol.
Pharmacokinetics: Niacin and niacinamide are readily absorbed from the gastrointestinal tract. Following oral administration, niacin-induced vasodilation occurs within 20 minutes and persists for about 20 to 60 minutes. These effects are manifested by symptoms of flushing, itching and tingling sensations, and are accompanied by an increase in skin temperature.
Niacin is metabolized in the liver to niacinamide when taken in physiologic doses. When therapeutic doses are taken, only a portion is converted to niacinamide. The remainder is eventually excreted unchanged in the urine. Niacinamide is widely distributed in the body and is further metabolized in the liver before being excreted in the urine.
Dietary tryptophan is converted to niacin at a rate of 1 mg niacin for every 60 mg tryptophan.
Indications And Clinical Uses: Niacin and niacinamide are used in the prophylaxis and treatment of pellagra. Niacin is used as adjunctive therapy in addition to diet and other measures to lower elevated serum cholesterol and triglycerides in patients with type II, III, IV or V hyperlipoproteinemia. Niacinamide is not effective for the reduction of serum cholesterol levels.
Contra-Indications: Hypersensitivity to niacin or niacinamide. At larger doses used to treat pellagra and lower cholesterol, niacin is contraindicated in individuals with hepatic dysfunction, active peptic ulcer, diabetes mellitus, severe hypotension, hyperuricemia with a history of gouty arthritis.
Precautions: Patients with gallbladder disease or history of jaundice, liver disease or peptic ulcer should be monitored closely while taking niacin. Liver function tests should be conducted frequently in the initial stages of therapy and periodically thereafter.
Niacin and niacinamide may cause hyperglycemia. Periodic blood glucose monitoring is advised, especially in the early phase of therapy.
Elevated uric acid levels have occurred; therefore, niacin must be used with caution in patients predisposed to gout (see Contraindications).
Niacin may cause false elevation in fluorometric determinations of urinary catecholamines and false-positive results may be obtained for urinary glucose when Benedict’s reagent is used. Niacin has also been reported to give false-positive results for blood bilirubin tests.
Drug Interactions: Due to an additive vasodilating effect, postural hypotension may occur when niacin is added to the therapeutic regimen of patients taking adrenergic blocking agents.
Niacin appears to increase the risk of myopathy when used in antihyperlipidemic doses concurrently with fluvastatin, lovastatin, pravastatin or simvastatin. Patients should be advised to report any pain, tenderness or muscle weakness to their physician.
Because niacin can cause hyperglycemia, dosage adjustment of insulin or oral antihyperglycemic therapy may be required in diabetic patients.
Pregnancy: Safety has not been established. Although fetal abnormalities have not been reported with niacin, its use in lowering elevated serum cholesterol requires high dosages, and animal reproduction or teratology studies have not been done.
Lactation: Niacin is distributed into breast milk. Problems have not been reported with intake of normal daily requirements, but there is no information pertaining to higher doses used in the treatment of hyperlipidemia.
Children: Studies on use in children are insufficient.
Adverse Reactions: The more common adverse effects of niacin therapy are dose related and generally seen with high doses used to treat hyperlipidemia. Severe generalized flushing (due to peripheral cutaneous vasodilation) that may be accompanied by burning, stinging or tingling sensations, gastrointestinal symptoms (nausea, vomiting, bloating, flatulence, heartburn, diarrhea), pruritus and hypotension. The severity of these effects can be decreased by starting therapy at lower doses and gradually tapering upward. Flushing usually subsides over several weeks, despite continuation of niacin therapy.
Long term use of large doses of niacin has also been associated with rash, hyperpigmentation, dry skin, xerostomia, hyperuricemia which may precipitate gout, activation of peptic ulcer, blurred vision, hyperglycemia and abnormal liver function test results.
Niacinamide lacks vasodilating effects but is not effective in the lowering of serum cholesterol levels. Parenteral solutions of B complex vitamins containing niacinamide may cause flushing, itching or burning of the skin in patients susceptible to the effects of niacinamide. Niacinamide has also caused hyperhidrosis, nausea and abdominal cramps.
Dosage And Administration: To prevent deficiency, adequate dietary intake is preferred over supplementation whenever possible. For information on dietary sources of niacin see Vitamin Food Sources in the Clin-Info section. For a listing of recommended daily intake of niacin for different patient groups, see Recommended Nutrient Intake in the Clin-Info section. Dosage of niacin and niacinamide must be carefully adjusted according to the patient’s response and tolerance. In the treatment and prophylaxis of pellagra, niacin and niacinamide can be administered in equivalent doses.
Treatment of Pellagra: Adults: 300 to 500 mg daily in divided doses.
Children: 100 to 300 mg daily in divided doses.
Antihyperlipidemic (niacin only): Efforts should initially be made to lower serum cholesterol through dietary and weight control measures. Many clinicians recommend 1.5 to 6 g daily, given in 2 to 4 divided doses. Some patients may require up to 9 g daily to achieve the desired reductions in serum cholesterol and triglyceride concentrations. Some clinicians recommend beginning with 100 mg orally 3 times daily with meals, increasing the daily dose by 300 mg at 4 to 7-day intervals as necessary.
Usual antihyperlipidemic maintenance dose: 1 to 2 g 3 times daily (maximum 6 g/day). To minimize flushing, administration of 325 mg ASA 1 hour prior to niacin has been recommended.
Serum cholesterol and triglyceride concentrations should be determined prior to initiation of therapy and regularly (every 3 to 6 months) during treatment.
NIACIN NIACINAMIDE General Monograph, Nicotinic Acid, Vitamin B3Nicotinamide Vitamin