Niacor

Description

Niacin, also known as nicotinic acid, is a water-soluble B-complex vitamin and antihyperlipidemic agent, classified chemically as 3-pyridinecarboxylic acid. The compound has a molecular weight of 123.11 and a structural formula of C₆H₅NO₂. Niacin appears as a white, crystalline powder that is sparingly soluble in water. Each NIACOR® 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 consistent with 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. Consideration for liver biopsy should be given 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.

Before 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 advised, and adjustments to diet or hypoglycemic therapy may be required.

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.

Side Effects

Patients receiving nicotinic acid may experience a range of adverse reactions, which can be categorized by seriousness and frequency.

Serious adverse reactions include cases of severe hepatic toxicity, such as 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 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 recommended, and liver biopsy may be considered if elevations continue post-discontinuation.

Additionally, rare cases of rhabdomyolysis have been reported in patients receiving lipid-altering doses (≥1 g/day) of nicotinic acid in conjunction with 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 include cardiovascular effects such as atrial fibrillation, other cardiac arrhythmias, orthostasis, and hypotension. Gastrointestinal disturbances may manifest as 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 may include decreased glucose tolerance, hyperuricemia, and gout. Eye-related adverse reactions consist of toxic amblyopia and cystoid macular edema. The nervous system may be affected, with headache reported among patients.

Warnings indicate that nicotinic acid may potentiate the effects of ganglionic blocking agents and vasoactive drugs, leading to postural hypotension. Concomitant use of aspirin may decrease the metabolic clearance of nicotinic acid, although the clinical significance remains unclear. Patients are advised to avoid alcohol and hot drinks during drug ingestion, as these may exacerbate flushing and pruritus. Diabetic patients may experience a dose-related increase in glucose intolerance, necessitating close observation and potential adjustments in diet or hypoglycemic therapy. Caution is advised when administering nicotinic acid to patients with unstable angina or during the acute phase of myocardial infarction, particularly if they are also receiving vasoactive medications such as nitrates, calcium channel blockers, or adrenergic blocking agents. Elevated uric acid levels have been noted with nicotinic acid therapy, warranting caution in patients predisposed to gout.

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 exercise caution when prescribing these combinations and consider monitoring blood pressure to mitigate the risk of hypotensive episodes.

The concomitant use of aspirin may decrease the metabolic clearance of nicotinic acid; however, the clinical significance of this interaction remains unclear. It is advisable to monitor patients for any potential adverse effects when these medications are used together.

Additionally, the consumption of alcohol or hot drinks 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 and enhance tolerability.

Packaging & NDC

The table below lists all NDC Code configurations of Niacor (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

Elderly patients may require special consideration when administering nicotinic acid, as geriatric use has not been specifically studied. Caution should be exercised due to the potential for reduced kidney function in this population, which can influence the pharmacokinetics of the drug.

Increased sensitivity to side effects is often observed in elderly patients, necessitating careful monitoring and possible dosage adjustments to mitigate adverse reactions. It is essential to perform liver function tests on all patients undergoing therapy; however, particular attention should be given to elderly patients, who may have a heightened risk of hepatic dysfunction.

Additionally, diabetic elderly patients may experience a dose-related increase in glucose intolerance and should be closely monitored for this effect. Caution is also advised for elderly patients with a history of jaundice, hepatobiliary disease, or peptic ulcer, as they may be at an elevated risk for adverse effects associated with nicotinic acid therapy.

Pregnancy

Nicotinic acid has not been studied in animal reproduction studies, and its effects on fetal outcomes in humans remain unclear. There is insufficient data to determine whether nicotinic acid, at doses typically used for lipid disorders, can cause fetal harm or affect reproductive capacity in pregnant women.

For women receiving nicotinic acid for the treatment of primary hypercholesterolemia (Types IIa or IIb), it is recommended that the drug be discontinued upon confirmation of pregnancy. In cases where women are being treated for hypertriglyceridemia (Types IV or V) and conceive, a careful assessment of the benefits and risks of continuing nicotinic acid therapy should be conducted on an individual basis. Healthcare professionals should consider these factors when managing treatment in pregnant patients or those of childbearing potential.

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

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 was administered to mice for a lifetime as a 1% solution in drinking water, and the results indicated that it was not carcinogenic. 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. Additionally, nicotinic acid was found to be negative for mutagenicity in the Ames test. There have been no studies conducted to assess impairment of fertility. No information is available regarding teratogenic or non-teratogenic effects.

Postmarketing Experience

Postmarketing experience has identified several adverse events reported voluntarily or through surveillance programs.

Severe hepatic toxicity, including cases of fulminant hepatic necrosis, has been observed in patients who substituted sustained-release nicotinic acid products for immediate-release nicotinic acid at equivalent doses. Additionally, rare instances of rhabdomyolysis have been reported in conjunction with the concomitant use 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, along with orthostasis and hypotension, have also been documented. Gastrointestinal disturbances, including dyspepsia, vomiting, diarrhea, peptic ulceration, jaundice, and abnormal liver function tests, have been noted.

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

Ocular effects such as toxic amblyopia and cystoid macular edema have been recorded, along with headache as a common complaint among patients.

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 important 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 essential 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, the clinical significance of which remains unclear; therefore, these patients should be observed closely. Adjustments to diet and/or hypoglycemic therapy may be necessary for diabetic or potentially diabetic individuals.

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. 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 flushing of the skin is a common side effect, which can be minimized by pretreatment with aspirin or non-steroidal anti-inflammatory drugs. It is also important to communicate that tolerance to flushing typically develops rapidly over several weeks. Patients should avoid consuming alcohol or hot beverages at the time of drug ingestion, as these may exacerbate flushing and pruritus.

For women receiving nicotinic acid for primary hypercholesterolemia, the medication should be discontinued if pregnancy occurs. In cases where a woman being treated for hypertriglyceridemia conceives, a careful assessment of the benefits and risks of continuing therapy should be conducted on an individual basis. Additionally, a decision should be made regarding whether to discontinue nursing or the medication, considering the importance of the drug to the mother, as it is not known if nicotinic acid is excreted in human milk.

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 thereafter (approximately every six months). Special attention is warranted for patients exhibiting elevated serum transaminase levels; in such cases, repeat measurements should be conducted promptly and more frequently. If transaminase levels rise to three times the upper limit of normal and remain elevated, discontinuation of the drug is advised, and liver biopsy may be considered if elevations persist post-discontinuation.

Clinicians should exercise caution when prescribing nicotinic acid to patients with unstable angina or during the acute phase of myocardial infarction, especially if these patients are also on vasoactive medications such as nitrates, calcium channel blockers, or adrenergic blocking agents. Diabetic patients may experience a dose-related increase in glucose intolerance, necessitating close observation and potential adjustments in diet or hypoglycemic therapy. Additionally, the concomitant use of alcohol or hot beverages should be avoided during drug administration to mitigate the risk of exacerbated flushing and pruritus.

FDA Insert (PDF)

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

View full prescribing information (PDF)