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 chemical formula for niacin is C₆H₅NO₂, with a molecular weight of 123.11 g/mol. 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 modifications and other nonpharmacologic measures have proven inadequate.

Additionally, nicotinic acid is indicated 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. These patients typically present with serum triglyceride levels exceeding 2,000 mg/dL, along with elevations in very low-density lipoprotein (VLDL) cholesterol and fasting chylomicrons (Type V hyperlipidemia).

Therapy with nicotinic acid may also be considered for patients with triglyceride levels between 1,000 and 2,000 mg/dL who have a history of pancreatitis or recurrent abdominal pain suggestive 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 occasionally 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, liver function tests are essential for all patients undergoing therapy with nicotinic acid. Serum transaminase levels, including ALT (SGPT), should be monitored prior to initiating treatment, every six to twelve weeks during the first year, and periodically thereafter, approximately every six months. Special attention is warranted for patients who exhibit 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 necessary. Liver biopsy should be considered if elevations persist beyond the cessation of therapy.

Nicotinic acid should be administered with caution in individuals who consume significant amounts 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. Additionally, rare instances of rhabdomyolysis have been associated with the concurrent use of lipid-altering doses (≥1 g/day) of nicotinic acid and HMG-CoA reductase inhibitors. Physicians considering combined therapy should carefully evaluate the potential benefits and risks, monitoring patients for any signs of muscle pain, tenderness, or weakness, particularly during the initial months of therapy and during any dosage adjustments. Periodic serum creatine phosphokinase (CPK) and potassium levels should be assessed in these patients, although such monitoring does not guarantee the prevention of severe myopathy.

Prior to initiating nicotinic acid therapy, efforts should be made to manage hyperlipidemia through appropriate dietary modifications, 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 monitored during treatment. Regular assessments of liver function tests and blood glucose levels are recommended 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 uncertain; therefore, close observation is warranted, and adjustments to diet or hypoglycemic therapy may be necessary.

Caution is also advised when administering nicotinic acid to patients with unstable angina or during the acute phase of myocardial infarction, especially if they are receiving vasoactive medications such as nitrates, calcium channel blockers, or adrenergic blocking agents. Elevated uric acid levels have been observed with nicotinic acid therapy, necessitating careful use in patients predisposed to gout.

In summary, comprehensive monitoring and careful patient selection are critical to mitigate the risks associated with nicotinic acid therapy.

Side Effects

Adverse reactions associated with nicotinic acid therapy have been observed across various systems, with some reactions categorized by seriousness and frequency.

Serious Adverse Reactions:

Liver dysfunction is a significant concern, with cases of severe hepatic toxicity, including fulminant hepatic necrosis, reported in patients who substituted sustained-release nicotinic acid products for immediate-release formulations at equivalent doses. Liver function tests are essential for all patients undergoing therapy with nicotinic acid. Monitoring of serum transaminase levels, including ALT (SGPT), should occur before 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 advised, and liver biopsy may be considered if elevations continue post-discontinuation. Caution is advised in patients with a history of liver disease or those consuming substantial alcohol, as active liver diseases or unexplained transaminase elevations are contraindications for nicotinic acid use.

Skeletal muscle-related adverse reactions include rare cases of rhabdomyolysis, particularly when nicotinic acid is administered alongside lipid-altering doses (≥1 g/day) of HMG-CoA reductase inhibitors. Physicians should carefully evaluate the risks and benefits of combined therapy and monitor patients for signs of muscle pain, tenderness, or weakness, especially during the initial months of treatment or dosage adjustments. Periodic serum creatine phosphokinase (CPK) and potassium determinations may be warranted, although such monitoring does not guarantee prevention of severe myopathy.

Common Adverse Reactions:

Cardiovascular effects may include atrial fibrillation, other cardiac arrhythmias, orthostasis, and hypotension. Gastrointestinal reactions are also prevalent, with reports of dyspepsia, vomiting, diarrhea, peptic ulceration, jaundice, and abnormal liver function tests. Dermatological reactions can range from mild to severe cutaneous flushing, pruritus, hyperpigmentation, acanthosis nigricans, and dry skin. Metabolic effects include decreased glucose tolerance, hyperuricemia, and gout. Eye-related adverse reactions may involve toxic amblyopia and cystoid macular edema. Additionally, headache has been noted among nervous system and psychiatric reactions.

Additional Considerations:

Nicotinic acid may enhance the effects of ganglionic blocking agents and vasoactive drugs, leading to postural hypotension. The concomitant use of aspirin may decrease the metabolic clearance of nicotinic acid, although the clinical significance of this interaction remains unclear. Patients are advised to avoid alcohol and hot drinks during drug ingestion, as these may exacerbate flushing and pruritus.

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 drinks in conjunction with nicotinic acid may exacerbate side effects such as flushing and pruritus. Therefore, it is recommended that patients avoid these substances at the time of drug ingestion to minimize adverse effects.

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 is advised when considering the use of this medication in these populations.

Geriatric Use

Elderly patients may exhibit increased sensitivity to the side effects of nicotinic acid. Due to the potential for reduced kidney function in this population, dosage adjustments may be necessary to ensure safety and efficacy. Caution is advised when prescribing nicotinic acid to geriatric patients, particularly those with a history of liver disease or other comorbidities.

Regular monitoring of liver function tests is recommended for elderly patients undergoing therapy with nicotinic acid to detect any adverse effects early. Additionally, geriatric patients may experience a dose-related rise in glucose intolerance; therefore, close observation of glucose levels is advised during treatment.

Special attention should also be given to elderly patients who consume substantial quantities of alcohol, as this may significantly increase the risk of liver toxicity associated with nicotinic acid.

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 nursing 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

There is no specific information regarding renal impairment, dosage adjustments, special monitoring, or safety considerations for patients with reduced kidney function provided in the insert text. Healthcare professionals should exercise caution and consider individual patient factors when prescribing to patients with renal impairment, as the absence of detailed guidance necessitates careful clinical judgment.

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.

Potential symptoms of overdose may vary depending on the specific substance involved; however, general signs may include altered mental status, cardiovascular instability, and respiratory distress.

Management procedures should focus on the immediate assessment of the patient's condition, including vital signs and level of consciousness. Continuous monitoring is essential, and symptomatic treatment should be provided as necessary.

In cases of severe overdose, additional interventions may be required, such as the administration of activated charcoal if the patient presents within a suitable timeframe and is not at risk of aspiration.

Healthcare professionals are advised to consult local poison control centers or toxicology experts for guidance on specific antidotes or advanced treatment protocols tailored to the substance involved in the overdose.

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

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. Rare cases of rhabdomyolysis have been noted in conjunction with the concomitant administration of lipid-altering doses (≥1 g/day) of nicotinic acid and HMG-CoA reductase inhibitors.

Cardiovascular events such as atrial fibrillation and other cardiac arrhythmias, as well as orthostasis and hypotension, have been documented. Gastrointestinal disturbances including dyspepsia, vomiting, diarrhea, peptic ulceration, jaundice, and abnormal liver function tests have also been reported.

Cutaneous reactions such as mild to severe flushing, pruritus, hyperpigmentation, acanthosis nigricans, and dry skin have been observed. Additionally, metabolic effects including decreased glucose tolerance, hyperuricemia, and gout have been noted.

Ocular effects such as toxic amblyopia and cystoid macular edema have been reported. Headache has also been documented as an adverse event.

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 starting 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, necessitating close observation and potential adjustments to their diet or hypoglycemic therapy.

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; therefore, it should be used with caution in patients who are predisposed to gout.

Patients should be informed that flushing of the skin is a common side effect, which can often be minimized by pretreatment with aspirin or non-steroidal anti-inflammatory drugs. It is important to communicate that tolerance to flushing typically develops rapidly over several weeks.

Patients should also be instructed to avoid taking nicotinic acid on an empty stomach to help reduce gastrointestinal distress. For women receiving nicotinic acid for primary hypercholesterolemia, it is crucial to discontinue the medication if they become pregnant. In cases where a woman being treated for hypertriglyceridemia conceives, the benefits and risks of continuing therapy should be evaluated on an individual basis.

Lastly, as it is not known whether nicotinic acid is excreted in human milk, healthcare providers should discuss with patients the decision to either discontinue nursing or the medication, considering the importance of the drug to the mother’s health.

Storage and Handling

The product is supplied in a tight container as defined by the United States Pharmacopeia (USP), equipped with a child-resistant closure. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), with permissible excursions between 15° to 30°C (59° to 86°F) in accordance with USP Controlled Room Temperature guidelines.

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 and subsequently every six to twelve weeks during the first year, with periodic assessments approximately every six months thereafter. Special attention is warranted for patients exhibiting 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 advised, 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 mitigate flushing and pruritus. Diabetic patients may experience increased glucose intolerance, warranting close observation and potential adjustments in diet or hypoglycemic therapy. For women of childbearing age, discontinuation of nicotinic acid is recommended if pregnancy occurs during treatment for primary hypercholesterolemia, while the decision to continue therapy for hypertriglyceridemia should be made on a case-by-case basis.

FDA Insert (PDF)

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

View full prescribing information (PDF)