Niacin

Description

Niacin, also known as nicotinic acid, is a water-soluble B-complex vitamin and antihyperlipidemic agent, classified chemically as 3-pyridinecarboxylic acid. It is presented as a white, crystalline powder that is sparingly soluble in water. The structural formula of niacin is C₆H₅NO₂, with a molecular weight of 123.11. Each Niacin Tablet, intended for oral administration, contains 500 mg of nicotinic acid. The formulation also includes inactive ingredients such as croscarmellose sodium, hydrogenated vegetable oil, magnesium stearate, and microcrystalline cellulose.

Uses and Indications

This drug is indicated as an adjunct to diet for the reduction of elevated total and low-density lipoprotein (LDL) cholesterol levels in patients with primary hypercholesterolemia (Types IIa and IIb) when dietary measures alone have proven inadequate. It is also indicated for use in conjunction with a bile-acid binding resin.

Additionally, this drug serves as adjunctive therapy for adult patients with very high serum triglyceride levels (Types IV and V hyperlipidemia) who are at risk of pancreatitis and have not achieved adequate control through dietary efforts. Specifically, it is indicated for patients with serum triglyceride levels exceeding 2,000 mg/dL, as well as those with elevations of very low-density lipoprotein (VLDL) cholesterol and fasting chylomicrons (Type V hyperlipidemia).

Therapy with this drug may also be considered for patients with triglyceride elevations between 1,000 and 2,000 mg/dL who have a history of pancreatitis or recurrent abdominal pain typical of pancreatitis.

It is important to note that therapy with lipid-altering agents should be part of a comprehensive approach to managing multiple risk factors in individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia.

Dosage and Administration

The usual adult dosage of nicotinic acid is 1 to 2 grams administered two or three times daily. Dosing should be individualized based on the patient's response to therapy. Treatment should commence with one-half tablet (250 mg) taken as a single daily dose following the evening meal.

The frequency of dosing and the total daily dose may be increased every four to seven days until the desired levels of LDL cholesterol and/or triglycerides are achieved, or until the first-level therapeutic dose of 1.5 to 2 grams per day is reached. If hyperlipidemia remains inadequately controlled after two months at this initial dosage, the dosage may be further increased at intervals of two to four weeks, up to a maximum of 3 grams per day (1 gram three times per day).

In patients exhibiting marked lipid abnormalities, higher doses may be necessary; however, the total daily dosage should generally not exceed 6 grams. It is important to note that sustained-release (modified-release, timed-release) nicotinic acid preparations should not be substituted for equivalent doses of immediate-release (crystalline) nicotinic acid.

Contraindications

Nicotinic acid is contraindicated in patients with a known hypersensitivity to any component of this medication. Use is also contraindicated in individuals with significant or unexplained hepatic dysfunction, as well as those with active peptic ulcer disease due to the potential for exacerbation of these conditions. Additionally, the presence of arterial bleeding contraindicates the use of nicotinic acid, given the risk of further complications.

Warnings and Precautions

Cases of severe hepatic toxicity, including fulminant hepatic necrosis, have been reported in patients who substituted sustained-release (modified-release, timed-release) nicotinic acid products for immediate-release (crystalline) nicotinic acid at equivalent doses. Therefore, nicotinic acid should be used with caution in individuals who consume substantial quantities of alcohol or have a history of liver disease. The presence of active liver diseases or unexplained transaminase elevations constitutes a contraindication for the use of nicotinic acid.

Rare instances of rhabdomyolysis have been associated with the concomitant administration of lipid-altering doses (≥1 g/day) of nicotinic acid and HMG-CoA reductase inhibitors. Physicians considering combined therapy with these agents must carefully evaluate the potential benefits and risks. Patients should be closely monitored for any signs and symptoms of muscle pain, tenderness, or weakness, particularly during the initial months of therapy and during any upward dosage titration of either medication.

Before initiating therapy with nicotinic acid, it is advisable to attempt to control hyperlipidemia through appropriate dietary measures, exercise, and weight reduction in obese patients, as well as addressing any underlying medical conditions. Patients with a history of jaundice, hepatobiliary disease, or peptic ulcer should be closely observed during treatment. Regular monitoring of liver function tests and blood glucose levels is essential to ensure that the drug does not adversely affect these organ systems. Diabetic patients may experience a dose-related increase in glucose intolerance, the clinical significance of which remains unclear. Therefore, diabetic or potentially diabetic patients should be monitored closely, and adjustments to diet and/or hypoglycemic therapy may be necessary.

Caution is also warranted when administering nicotinic acid to patients with unstable angina or during the acute phase of myocardial infarction, especially if these patients are receiving vasoactive medications such as nitrates, calcium channel blockers, or adrenergic blocking agents. Additionally, elevated uric acid levels have been observed with nicotinic acid therapy; thus, it should be used with caution in patients predisposed to gout.

Liver function tests are recommended for all patients undergoing therapy with nicotinic acid. Serum transaminase levels, including ALT (SGPT), should be monitored prior to treatment initiation, every six to twelve weeks during the first year, and periodically thereafter (e.g., approximately every six months). Special attention should be given to patients who develop elevated serum transaminase levels; in such cases, measurements should be repeated promptly and conducted more frequently. If transaminase levels indicate progression, particularly if they rise to three times the upper limit of normal and remain persistent, discontinuation of the drug is warranted. Liver biopsy should be considered if elevations persist beyond the cessation of therapy.

For patients receiving combined therapy with HMG-CoA reductase inhibitors and nicotinic acid, periodic serum creatine phosphokinase (CPK) and potassium determinations should be considered to monitor for potential adverse effects.

Side Effects

Adverse reactions associated with nicotinic acid therapy have been observed in clinical trials and postmarketing experiences, and they can be categorized by seriousness and frequency.

Serious adverse reactions include cardiovascular events such as atrial fibrillation and other cardiac arrhythmias, as well as orthostasis and hypotension. Additionally, there have been reports of severe hepatic toxicity, including fulminant hepatic necrosis, particularly in patients who have substituted sustained-release nicotinic acid products for immediate-release formulations at equivalent doses. Liver function tests are essential for all patients undergoing therapy, with serum transaminase levels monitored before treatment and periodically thereafter. Special attention is warranted for patients with elevated transaminase levels, and if these levels rise to three times the upper limit of normal and persist, discontinuation of the drug is recommended.

Rare cases of rhabdomyolysis have been reported in patients receiving lipid-altering doses of nicotinic acid in conjunction with HMG-CoA reductase inhibitors. Physicians should carefully consider the risks and benefits of this combination therapy and monitor patients for muscle pain, tenderness, or weakness, especially during the initial months of treatment or dosage adjustments.

Common adverse reactions include gastrointestinal disturbances such as dyspepsia, vomiting, diarrhea, and peptic ulceration. Patients may also experience skin reactions, including mild to severe cutaneous flushing, pruritus, hyperpigmentation, acanthosis nigricans, and dry skin. Metabolic effects such as decreased glucose tolerance, hyperuricemia, and gout have also been noted, with diabetic patients potentially experiencing a dose-related increase in glucose intolerance.

Ocular adverse reactions include toxic amblyopia and cystoid macular edema. Neurologically, headache has been reported among participants.

Patients with a history of jaundice, hepatobiliary disease, or peptic ulcer should be closely monitored during therapy. Caution is advised for those with unstable angina or in the acute phase of myocardial infarction, particularly if they are receiving vasoactive medications. Elevated uric acid levels may occur, necessitating caution in patients predisposed to gout. Additionally, concomitant consumption of alcohol or hot beverages may exacerbate flushing and pruritus and should be avoided during drug administration.

Drug Interactions

Nicotinic acid has been observed to potentiate the effects of ganglionic blocking agents and vasoactive drugs, which may lead to postural hypotension. Clinicians should monitor patients for signs of hypotension when these agents are used concurrently.

The co-administration of aspirin may result in a decreased metabolic clearance of nicotinic acid; however, the clinical significance of this interaction remains unclear. It is advisable to consider this potential interaction when prescribing these medications together.

Additionally, the consumption of alcohol or hot beverages in conjunction with nicotinic acid may exacerbate side effects such as flushing and pruritus. Patients are advised to avoid these substances at the time of drug ingestion to minimize discomfort.

Packaging & NDC

The table below lists all NDC Code configurations of Niacin, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

Safety and effectiveness in pediatric patients, including children and adolescents, have not been established. Therefore, caution should be exercised when considering the use of this medication in these populations.

Geriatric Use

Geriatric patients may present with reduced kidney function, which can influence the pharmacokinetics of nicotinic acid. This alteration necessitates careful monitoring, as elderly patients may also demonstrate increased sensitivity to side effects. While there are no specific dosage adjustments recommended for this population, caution is advised due to the potential for heightened adverse reactions.

Particular attention should be given to elderly patients with a history of liver disease or those who consume substantial amounts of alcohol, as they may be at an elevated risk for hepatic toxicity. Furthermore, the safety and effectiveness of nicotinic acid in geriatric patients have not been specifically established, underscoring the importance of careful consideration prior to prescribing this medication to elderly individuals.

Pregnancy

Animal reproduction studies have not been conducted with nicotinic acid, and it is not known whether nicotinic acid at doses typically used for lipid disorders can cause fetal harm when administered to pregnant women or affect reproductive capacity. For women receiving nicotinic acid for primary hypercholesterolemia (Types IIa or IIb), the drug should be discontinued if pregnancy occurs. In cases where a woman being treated with nicotinic acid for hypertriglyceridemia (Types IV or V) conceives, the benefits and risks of continued drug therapy should be assessed on an individual basis. Healthcare professionals are advised to consider these factors when managing treatment in pregnant patients.

Lactation

It is not known whether this drug is excreted in human milk. Due to the potential for serious adverse reactions in breastfed infants from lipid-altering doses of nicotinic acid, lactating mothers should consider the importance of the drug to their health when making a decision to either discontinue nursing or discontinue the drug.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available prescribing information. There are no dosage adjustments, special monitoring requirements, or safety considerations outlined for individuals with reduced kidney function. Healthcare professionals should exercise caution and consider the lack of data when prescribing to this patient population.

Hepatic Impairment

Patients with hepatic impairment may experience severe hepatic toxicity, including fulminant hepatic necrosis, particularly when substituting sustained-release (modified-release, timed-release) nicotinic acid products for immediate-release (crystalline) nicotinic acid at equivalent doses.

Liver function tests are essential for all patients undergoing therapy with nicotinic acid. Serum transaminase levels, including alanine aminotransferase (ALT, SGPT), should be monitored prior to the initiation of treatment, every six to twelve weeks during the first year, and periodically thereafter, approximately every six months.

In patients who exhibit elevated serum transaminase levels, it is crucial to repeat measurements promptly and increase the frequency of monitoring. If transaminase levels indicate progression, particularly if they rise to three times the upper limit of normal and remain persistent, discontinuation of the drug is warranted. In cases where elevations persist beyond the cessation of nicotinic acid, a liver biopsy should be considered.

Caution is advised when administering nicotinic acid to patients with a history of significant alcohol consumption and/or prior liver disease. Additionally, the presence of active liver diseases or unexplained transaminase elevations constitutes a contraindication for the use of nicotinic acid.

Overdosage

In the event of an overdose, it is imperative that healthcare professionals implement supportive measures to manage the situation effectively.

Recommended Actions

Upon suspicion of an overdose, immediate assessment of the patient's clinical status is essential. This includes monitoring vital signs and providing symptomatic treatment as necessary.

Potential Symptoms

While specific symptoms of overdose may vary depending on the substance involved, healthcare providers should remain vigilant for any signs of toxicity that may arise.

Management Procedures

Management of an overdose should focus on supportive care, which may include intravenous fluids, oxygen supplementation, and other interventions tailored to the patient's needs. Continuous monitoring and reassessment are crucial to ensure patient safety and to address any complications that may develop.

In all cases of overdose, consultation with a poison control center or toxicology expert is recommended to guide further management and treatment options.

Nonclinical Toxicology

Nicotinic acid administered to mice for a lifetime as a 1% solution in drinking water did not demonstrate carcinogenic potential. The dosage received by the mice was approximately 6 to 8 times the human equivalent of 3,000 milligrams per day, calculated on a milligram per square meter basis.

In addition, nicotinic acid was found to be negative for mutagenicity in the Ames test, indicating no evidence of genetic mutation.

No studies have been conducted to evaluate the potential impairment of fertility associated with nicotinic acid.

Postmarketing Experience

Postmarketing experience has identified rare cases of rhabdomyolysis associated with the concomitant administration of lipid-altering doses (≥1 g/day) of nicotinic acid and HMG-CoA reductase inhibitors. Additionally, severe hepatic toxicity, including fulminant hepatic necrosis, has been reported in patients who substituted sustained-release (modified-release, timed-release) nicotinic acid products for immediate-release (crystalline) nicotinic acid at equivalent doses.

Liver function tests are recommended for all patients undergoing therapy with nicotinic acid. Serum transaminase levels, including ALT (SGPT), should be monitored prior to treatment initiation, every six to twelve weeks during the first year, and periodically thereafter, approximately every six months. Special attention is warranted for patients exhibiting elevated serum transaminase levels; in such cases, measurements should be repeated promptly and conducted more frequently. If transaminase levels indicate progression, particularly if they rise to three times the upper limit of normal and remain persistent, discontinuation of the drug is advised. Liver biopsy may be considered if elevations persist beyond the cessation of therapy.

Nicotinic acid should be administered with caution in patients who consume significant amounts of alcohol or have a history of liver disease. Active liver diseases or unexplained transaminase elevations are contraindications for the use of nicotinic acid. Physicians considering combined therapy with HMG-CoA reductase inhibitors and nicotinic acid should carefully evaluate the potential benefits and risks, monitoring patients for any signs or symptoms of muscle pain, tenderness, or weakness, especially during the initial months of therapy and during any dosage titration. Periodic serum creatine phosphokinase (CPK) and potassium determinations may be warranted in these situations; however, such monitoring does not guarantee the prevention of severe myopathy.

Patient Counseling

Patients should be advised to manage hyperlipidemia through appropriate dietary changes, regular exercise, and weight reduction, particularly in those who are obese, prior to initiating therapy with nicotinic acid. It is essential for healthcare providers to closely monitor patients with a history of jaundice, hepatobiliary disease, or peptic ulcer during nicotinic acid therapy.

Frequent monitoring of liver function tests and blood glucose levels is recommended to ensure that the medication does not adversely affect these organ systems. Diabetic patients should be informed that they may experience a dose-related increase in glucose intolerance; therefore, close observation is necessary, and adjustments to their diet or hypoglycemic therapy may be required.

Caution is advised when prescribing nicotinic acid to patients with unstable angina or during the acute phase of myocardial infarction, especially if they are also receiving vasoactive medications such as nitrates, calcium channel blockers, or adrenergic blocking agents. Additionally, elevated uric acid levels have been associated with nicotinic acid therapy, so it should be used with caution in patients who are predisposed to gout.

Patients should be informed that the consumption of alcohol or hot beverages may exacerbate side effects such as flushing and pruritus, and these should be avoided at the time of drug ingestion. For women receiving nicotinic acid for primary hypercholesterolemia, it is crucial to discontinue the medication if pregnancy occurs. In cases where a woman being treated for hypertriglyceridemia conceives, the benefits and risks of continuing therapy should be evaluated on an individual basis.

It is currently unknown whether nicotinic acid is excreted in human milk; therefore, a decision should be made regarding the discontinuation of nursing or the medication, considering the importance of the drug to the mother. Lastly, the safety and effectiveness of nicotinic acid in children and adolescents have not been established, and caution should be exercised in this population.

Storage and Handling

Dispensed in a tight container as defined by the United States Pharmacopeia (USP), the product is equipped with a child-resistant closure to ensure safety.

Storage conditions require the product to be maintained at a temperature range of 20° to 25°C (68° to 77°F). Temporary excursions are permissible between 15° to 30°C (59° to 86°F), in accordance with USP guidelines for controlled room temperature.

Additional Clinical Information

Liver function tests are essential for all patients undergoing therapy with nicotinic acid. Clinicians should monitor serum transaminase levels, including ALT (SGPT), prior to treatment initiation, every six to twelve weeks during the first year, and periodically thereafter, approximately every six months. Special attention is warranted for patients with elevated serum transaminase levels, necessitating prompt repeat measurements and more frequent monitoring. If transaminase levels rise to three times the upper limit of normal and persist, discontinuation of the drug is recommended, and liver biopsy may be considered if elevations continue post-discontinuation.

Patient counseling should emphasize caution in individuals with unstable angina or during the acute phase of myocardial infarction, especially when combined with vasoactive medications. Patients should avoid concomitant alcohol and hot beverages to reduce the risk of flushing and pruritus. Diabetic patients may experience increased glucose intolerance, warranting close observation and potential adjustments in diet or hypoglycemic therapy. Women who become pregnant while on nicotinic acid for primary hypercholesterolemia should discontinue the drug, while those treated for hypertriglyceridemia should have their treatment assessed individually. Additionally, the excretion of nicotinic acid in human milk is unknown, prompting a careful decision regarding nursing versus drug continuation based on the drug's importance to the mother.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Niacin as submitted by Emerald Therapeutics, LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)