Niacin

Trade Names:Niacin- Tablets 50 mg- Tablets 100 mg- Tablets 250 mg- Tablets 500 mg

Trade Names:Niacin- Capsules, controlled-release 125 mg- Capsules, controlled-release 250 mg- Capsules, controlled-release 400 mg- Capsules, controlled-release 500 mg

Trade Names:Niacin- Tablets, controlled-release 1,000 mg

Trade Names:Niacor- Tablets 500 mg

Trade Names:Niaspan- Tablets, extended-release 500 mg- Tablets, extended-release 750 mg- Tablets, extended-release 1,000 mg

Trade Names:Slo-Niacin- Tablets, controlled-release 250 mg- Tablets, controlled-release 500 mg- Tablets, controlled-release 750 mg

Pharmacology

At pharmacologic doses, reduces total cholesterol, LDL cholesterol, apolipoprotein B (ApoB), and triglycerides, while increasing HDL cholesterol. Also causes peripheral vasodilation, especially cutaneous vessels.

Pharmacokinetics

Absorption

Niacin is rapidly and extensively absorbed from GI tract (60% to 76% of dose). T _max is 30 to 60 min, and C _max is 15 to 30 mcg/mL.

Metabolism

Rapid and extensive first-pass metabolism of niacin in liver.

Elimination

Niacin is eliminated in urine (approximately 60% to 88% as unchanged and metabolic). Plasma t _½ is 20 to 45 min.

Special Populations

Steady-state plasma concentrations and metabolites are generally higher in women.

Extended-release tablets are contraindicated in patients with active liver disease.

No data available; however, use with caution.

Indications and Usage

Dietary supplement for prevention and treatment of niacin deficiency; adjunct to diet for the reduction of elevated total, LDL, ApoB, and triglyceride levels, and to decrease HDL in patients with primary hypercholesterolemia and mixed dyslipidemia when the response to diet and other nonpharmacologic measures alone has been inadequate; to reduce the risk of recurrent nonfatal MI in patients with history of MI and hypercholesterolemia ( Niaspan only); Niaspan in combination with bile acid–binding resin to slow progression or promote regression of atherosclerotic disease in patients with history of coronary artery disease; Niaspan in combination with lovastatin for the treatment of primary cholesterolemia and mixed dyslipidemia in patients taking lovastatin who require further triglyceride lowering or HDL raising and who may benefit from having niacin added to their regimen or in patients receiving niacin who require further LDL lowering who may benefit from having lovastatin added to their regimen; Niaspan in combination with a bile acid–binding resin as an adjunct to diet for adult patients with primary hypercholesterolemia (type ΙΙa); adjunctive therapy for treatment of adult patients with very high serum triglyceride levels (types IV and V hyperlipidemia) who present a risk of pancreatitis.

Contraindications

Significant or unexplained liver disease; active peptic ulcer; arterial hemorrhaging; hypersensitivity to niacin or any component of the product.

Dosage and Administration

PO RDA: 16 mg/day for adult men. 14 mg/day for adult women. 18 mg/day during pregnancy. 17 mg/day during lactation.

PO RDA: 2 mg/day for infants up to 6 months of age. 4 mg/day for infants 7 to 12 months of age. 6 mg/day for children 1 to 3 yr of age. 8 mg/day for children 4 to 8 yr of age. 12 mg/day for children 9 to 13 yr of age. 16 mg/day for adolescents 14 to 18 yr of age.

PO 500 mg at bedtime for 1 to 4 wk, then 1,000 mg at bedtime during wk 5 to 8. If response is inadequate and patient tolerates dose, the dose may be increased by no more than 500 mg in a 4-wk period (max, 2,000 mg/day). If lipid response is insufficient, or if a higher dose is not well tolerated, some patients may benefit from combination therapy with a bile acid–binding resin or an HMG-CoA reductase inhibitor.

PO Initiate therapy at 250 mg after evening meal. The frequency of dose and total daily dose can be increased every 4 to 7 days until a dose of 1.5 to 2 g/day (in divided doses) is reached. If hyperlipidemia is not adequately controlled after 2 mo, increase dosage at 2- to 4-wk intervals to 1 g 3 times daily (max, 6 g/day).

General Advice

• Administer with food or milk to reduce flushing. Do not provide hot liquids with or immediately after administration.
• Administer extended-release tablets ( Niaspan ) at bedtime, after a low-fat snack.
• If ordered, administer nonenteric–coated aspirin or an NSAID (eg, ibuprofen) 30 min before the niacin dose to help ameliorate distressing or persistent flushing.
• Advise patient to swallow modified-release (eg, timed-release, controlled-release, sustained-release, extended-release) tablet whole and not to crush, chew, open, or break the tablet. Scored tablets may be split on the score line but the half-tablet should be swallowed whole.

Storage/Stability

Store at 59° to 86°F. Store Niaspan between 68° and 77°F.

Drug Interactions

May increase flushing or pruritus and should be avoided near time of niacin administration.

Effects of ganglionic-blocking agents and vasoactive drugs may be potentiated, resulting in postural hypotension.

Metabolic Cl of nicotinic acid may be decreased.

Because niacin may bind to bile acid sequestrants, separate the administration times by as much as possible, allowing at least 4 to 6 h between ingestion of bile acid–binding resins and niacin administration.

Increased risk of myopathy and rhabdomyolysis.

Laboratory Test Interactions

May produce fluorescent substances, which may cause false elevation in some fluorometric measurements of urinary catecholamines. May produce false-positive reaction with cupric sulfate solution used for urinary glucose determination.

Adverse Reactions

Cardiovascular

Atrial fibrillation or other cardiac arrhythmias; hypotension; orthostasis; palpitations; syncope; tachycardia.

CNS

Headache (11%); dizziness; insomnia; migraine; nervousness; paresthesia; syncope.

Dermatologic

Pruritus (6%); rash (5%); acanthosis nigricans; dry skin; flushing; hyperpigmentation; maculopapular rash; sweating; urticaria.

EENT

Cystoid macular edema; rhinitis; toxic amblyopia.

GI

Diarrhea (11%); nausea (10%); vomiting (8%); dyspepsia (6%); abdominal pain (5%); activation of peptic ulcer; eructation; flatulence; peptic ulceration.

Hematologic-Lymphatic

Prolongation in PT, reductions in platelet count.

Hepatic

Abnormal LFTs; jaundice; liver damage.

Hypersensitivity

Anaphylaxis; angioedema; laryngismus, larynx edema, tongue edema; vesiculobullous rash.

Lab Tests

Elevations in amylase, fasting glucose, LDH, total bilirubin, and uric acid; reductions in phosphorus.

Metabolic

Decreased glucose tolerance; gout; hyperuricemia.

Musculoskeletal

Leg cramps; myalgia; myasthenia.

Respiratory

Dyspnea.

Miscellaneous

Pain (5%); asthenia; chills; edema; face edema, peripheral edema.

Precautions

Pregnancy

Category A ( Category C if used in doses above RDA).

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established for doses exceeding nutritional requirements. Extended-release preparations not recommended for children.

Hepatic Function

Use with caution in patients who consume substantial quantities of alcohol or who have a history of liver disease.

Special Risk Patients

Use drug with caution when administering to patients with gallbladder disease, hepatobiliary disease, arterial bleeding, glaucoma, history of jaundice, diabetes mellitus, anticoagulant therapy, renal function impairment, gout, or peptic ulcer.

Use with caution in patients with unstable angina or who are in the acute phase of an MI.

Flushing

Commonly appears with oral therapy. Aspirin 30 min before niacin or an NSAID (eg, ibuprofen) may decrease flushing.

Heart disease

People who have recurrent chest pain (angina) or who recently suffered a heart attack should take niacin only under the supervision of a health care provider.

Hepatic toxicity

Severe hepatic toxicity has been reported in patients substituting sustained-release niacin for immediate-release niacin at equivalent doses.

Product substitution

Do not substitute equivalent doses for sustained-release niacin preparations or immediate-release niacin. Severe hepatic toxicity, including fulminant hepatic necrosis, has occurred in patients who have substituted sustained-release niacin for immediate-release niacin at equivalent doses.

Rhabdomyolysis

May occur when used in combination with HMG-CoA reductase inhibitors.

Overdosage

Symptoms

No information available.

Patient Information

• Explain LDL-cholesterol and triglyceride treatment goals.
• Advise patient that dose of medication may change, based on results of cholesterol and triglyceride blood tests, in an effort to reach LDL-cholesterol and triglyceride treatment goals.
• Advise patient using extended-release tablets ( Niaspan ) to take prescribed dose once daily at bedtime after a low-fat snack.
• Advise patient using modified-release (eg, timed-release, controlled-release, sustained-release, extended-release) tablets to swallow tablets whole and not to crush, chew, or break the tablet. Advise patient that scored tablets may be split on the score line but to swallow the half-tablet whole.
• Caution patient that taking this medication on an empty stomach increases the risk of flushing, itching, and stomach distress.
• Caution patient that drinking alcohol or hot drinks around the time of medication administration will increase the risk of flushing.
• Caution patient that if medication is not taken for an extended length of time (eg, more than 7 days) to contact health care provider before restarting the medication. Advise patient that retitration of the dose of medication may be required.
• Emphasize to patient importance of other modalities on cholesterol control: dietary changes (eg, reduced saturated fat intake, increase soluble fiber intake), weight control, regular exercise, and smoking cessation.
• Advise patient that drug helps control, but not does cure, cholesterol or triglyceride abnormality and to continue taking drug as prescribed when LDL-cholesterol and triglyceride treatment goals have been met.
• Instruct patient to continue taking other cholesterol-lowering medications as prescribed by health care provider.
• Advise patient that flushing, itching, tingling, headache, and a sensation of warmth, especially of the face and upper body, which may last for several hours after dosing, are common adverse reactions of therapy when starting, increasing the dose, or changing the brand of niacin. Advise patient that these symptoms, if they occur, usually go away after several weeks of consistent use. Advise patient to notify health care provider if these effects occur and become intolerable or do not improve. Advise patient that taking nonenteric–coated aspirin or an NSAID (eg, ibuprofen) 30 min before niacin dose may ameliorate this problem and to discuss this potential therapy with health care provider before starting.
• Caution patients that if flushing awakens them during the night, to rise slowly to reduce the risk of dizziness or fainting.
• Advise patient who is also taking a bile acid sequestrant (eg, cholestyramine) to take the niacin at least 2 h before or 4 h or more after the sequestrant.
• Instruct patient to immediately notify health care provider if they experience any unexplained muscle pain, tenderness, and/or weakness, unquenchable thirst, frequent urination, frequent episodes of dizziness, persistent flu-like symptoms (eg, generally not well feeling, loss of appetite, nausea, vomiting), or dark urine, or if they note any other unusual unexplained feelings (eg, sudden onset of joint pain).
• Instruct diabetic patient to monitor blood glucose more frequently when drug is started or dose is changed and to inform health care provider of significant changes in readings.
• Advise women of childbearing potential to use effective contraception during treatment with niacin.

Copyright © 2009 Wolters Kluwer Health.