Niacin

Description

Niacin extended-release tablets contain niacin, USP, an antihyperlipidemic agent effective at therapeutic doses. Niacin, also known as nicotinic acid or 3-pyridinecarboxylic acid, is presented as a white, crystalline powder that is highly soluble in water. The tablets are unscored, film-coated, and intended for oral administration, available in two strengths: 500 mg and 1000 mg of niacin.

The 500 mg tablets are light orange to orange, round in shape, and are debossed with ‘AN 321’ on one side, while the other side is plain. The 1000 mg tablets are light orange to orange, capsule-shaped, and are debossed with ‘AN 323’ on one side, with the opposite side remaining plain. In addition to niacin, the extended-release tablets contain several inactive ingredients, including FD&C yellow #6/sunset yellow FCF aluminum lake, hydroxyethyl cellulose, hypromellose, iron oxide red, iron oxide yellow, polyethylene glycol 400, stearic acid, and titanium dioxide.

Uses and Indications

This drug is indicated for the reduction of elevated total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), and triglycerides (TG), as well as for the increase of high-density lipoprotein cholesterol (HDL-C) in patients with primary hyperlipidemia and mixed dyslipidemia.

Additionally, it is indicated to reduce the risk of recurrent nonfatal myocardial infarction in patients with a history of myocardial infarction and hyperlipidemia. When used in combination with a bile acid binding resin, this drug slows the progression or promotes regression of atherosclerotic disease in patients with a history of coronary artery disease (CAD) and hyperlipidemia.

This drug is also indicated as an adjunct to diet for the reduction of elevated TC and LDL-C in adult patients with primary hyperlipidemia, and for the reduction of TG in adult patients with severe hypertriglyceridemia.

No teratogenic or nonteratogenic effects have been reported.

Dosage and Administration

Niacin extended-release tablets are to be administered orally at bedtime, accompanied by a low-fat snack to enhance tolerability. The initial dose should be set at 500 mg once daily to minimize the risk of side effects. Increments in dosage should not exceed 500 mg within any four-week period.

The recommended maintenance dose ranges from 1000 mg to 2000 mg once daily. It is important to note that doses exceeding 2000 mg per day are not advised.

Contraindications

Use of this product is contraindicated in the following situations:

Patients with active liver disease, including those with unexplained persistent elevations in hepatic transaminase levels, due to the potential for exacerbation of liver function.

Individuals with active peptic ulcer disease, as the product may aggravate the condition.

Patients experiencing arterial bleeding, where the use of this product could pose significant risks.

Those with known hypersensitivity to any components of the product, to prevent adverse reactions.

Warnings and Precautions

Severe hepatic toxicity has been reported in patients who substitute sustained-release niacin for immediate-release niacin at equivalent doses. Healthcare professionals should exercise caution when making such substitutions and closely monitor patients for signs of liver dysfunction.

Myopathy has been observed in patients taking niacin extended-release formulations. The risk of developing myopathy and rhabdomyolysis is particularly heightened in elderly patients, those with diabetes, renal failure, or uncontrolled hypothyroidism, as well as in patients concurrently treated with statins. It is imperative to assess the patient's overall health status and medication regimen to mitigate these risks.

Monitoring liver enzyme levels is essential, as persistent elevations in hepatic transaminases may occur during treatment. Healthcare providers should conduct baseline liver enzyme tests and continue to monitor these levels throughout the course of therapy to detect any abnormalities early.

Caution is advised when administering niacin extended-release to patients with unstable angina or during the acute phase of a myocardial infarction (MI). The potential for exacerbating these conditions necessitates careful evaluation and monitoring.

Additionally, niacin extended-release has been shown to increase serum glucose levels. Therefore, glucose levels should be closely monitored in diabetic patients or those at risk of developing diabetes, particularly during the initial months of treatment or following any dose adjustments. Regular monitoring will help ensure that any significant changes in glucose levels are promptly addressed.

Side Effects

Most common adverse reactions observed in patients include flushing, diarrhea, nausea, vomiting, increased cough, and pruritus. These reactions are generally mild and transient.

Severe adverse reactions have been reported, particularly in patients substituting sustained-release niacin for immediate-release niacin at equivalent doses, leading to severe hepatic toxicity. Myopathy has also been noted in patients taking niacin extended-release, with an increased risk for myopathy and rhabdomyolysis among elderly patients, those with diabetes, renal failure, or uncontrolled hypothyroidism, and patients concurrently treated with a statin. Persistent elevations in hepatic transaminases can occur, necessitating monitoring of liver enzymes before and during treatment.

Caution is advised when administering niacin extended-release to patients with unstable angina or during the acute phase of a myocardial infarction (MI). Additionally, niacin can elevate serum glucose levels; therefore, glucose levels should be closely monitored in diabetic or potentially diabetic patients, particularly during the initial months of treatment or following dose adjustments.

Contraindications for niacin include active liver disease, which may manifest as unexplained persistent elevations in hepatic transaminase levels, active peptic ulcer disease, arterial bleeding, and known hypersensitivity to any components of the product.

In clinical studies involving 979 patients, 21% were aged 65 and over. No significant differences in safety and effectiveness were observed between older and younger patients; however, greater sensitivity in some older individuals cannot be ruled out. The safety and effectiveness of niacin therapy in pediatric patients aged 16 years or younger have not been established.

Niacin is excreted into human milk, but the specific infant dose or the percentage of the maternal dose is unknown. Due to the potential for serious adverse reactions in nursing infants from lipid-altering doses of nicotinic acid, a decision should be made regarding the continuation of nursing or the drug, considering the importance of the medication to the mother. No studies have been conducted with niacin extended-release in nursing mothers.

Pregnancy Category C indicates that animal reproduction studies have not been performed with niacin or niacin extended-release. It remains unclear whether niacin at doses typically used for lipid disorders can cause fetal harm when administered to pregnant women or affect reproductive capacity. If a woman receiving niacin for primary hyperlipidemia becomes pregnant, the drug should be discontinued. For women treated with niacin for hypertriglyceridemia who conceive, the benefits and risks of continued therapy should be evaluated on an individual basis.

Drug Interactions

Caution is advised when prescribing niacin in conjunction with statins due to the potential increased risk of myopathy and rhabdomyolysis. Clinicians should monitor patients closely for signs of muscle-related adverse effects and consider dosage adjustments as necessary.

Bile acid sequestrants possess a high binding capacity for niacin. Therefore, it is recommended that these agents be administered at least 4 to 6 hours prior to the administration of niacin extended-release formulations to minimize the risk of interaction and ensure optimal therapeutic efficacy.

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

The safety and effectiveness of niacin therapy in pediatric patients aged 16 years and younger have not been established. Therefore, caution is advised when considering the use of niacin in this population. Further studies are needed to determine appropriate dosing and potential outcomes in children and adolescents.

Geriatric Use

In clinical studies of niacin extended-release, 21% of the 979 patients evaluated were aged 65 years and older. The data indicate that there are no overall differences in safety and effectiveness between elderly patients and their younger counterparts. However, it is important to note that while the clinical experience has not identified significant differences in responses between geriatric patients and younger individuals, the possibility of greater sensitivity in some older patients cannot be excluded.

Healthcare providers should exercise caution when prescribing niacin extended-release to elderly patients, considering the potential for increased sensitivity. Monitoring for adverse effects and therapeutic efficacy is recommended to ensure optimal treatment outcomes in this population.

Pregnancy

Pregnancy Category C. Animal reproduction studies have not been conducted with niacin or niacin extended-release. The effects of niacin at doses typically used for lipid disorders on fetal outcomes are not well established, and it is unknown whether niacin can cause fetal harm or affect reproductive capacity when administered to pregnant women.

If a woman receiving niacin for primary hyperlipidemia becomes pregnant, the drug should be discontinued. In cases where a woman being treated with niacin for hypertriglyceridemia conceives, the benefits and risks of continued therapy should be assessed on an individual basis. Healthcare professionals are advised to consider these factors when prescribing niacin to women of childbearing potential.

Lactation

Niacin is excreted into human milk; however, the actual dose received by breastfed infants or the percentage of the maternal dose is not known. Due to the potential for serious adverse reactions in nursing infants from lipid-altering doses of nicotinic acid, lactating mothers should consider whether to discontinue nursing or to discontinue the drug, weighing the importance of the medication to the mother. No studies have been conducted to evaluate the effects of niacin extended-release in nursing mothers.

Renal Impairment

Patients with renal impairment may experience an increased risk of myopathy and rhabdomyolysis when taking niacin extended-release. This risk is particularly heightened in elderly patients, those with diabetes, and individuals with uncontrolled hypothyroidism. Additionally, patients with renal failure should be closely monitored due to the potential for altered drug clearance and the associated risks. It is advisable to consider these factors when determining the appropriate dosing and monitoring strategies for patients with reduced kidney function.

Hepatic Impairment

Patients with hepatic impairment may experience severe hepatic toxicity when substituting sustained-release niacin for immediate-release niacin at equivalent doses. It is essential to monitor liver enzymes, as persistent elevations in hepatic transaminases can occur. Therefore, liver function should be assessed before initiating treatment and periodically during therapy to ensure patient safety and to manage any potential adverse effects related to liver function.

Overdosage

In the event of an overdose, it is imperative that healthcare professionals implement supportive measures to manage the patient's condition 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 of an overdose should focus on stabilizing the patient and addressing any life-threatening symptoms. This may involve monitoring vital signs, providing oxygen support, and administering intravenous fluids as necessary.

Healthcare providers are advised to consult local poison control centers or toxicology specialists for guidance on specific antidotes or additional treatment protocols that may be appropriate based on the substance involved in the overdose.

Prompt recognition and intervention are crucial in minimizing the potential complications associated with an overdose.

Nonclinical Toxicology

Niacin 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 3000 mg/day, calculated on a mg/m² basis. Additionally, niacin was found to be negative for mutagenicity in the Ames test.

There have been no studies conducted to evaluate the effects of niacin on impairment of fertility. Furthermore, no investigations have been performed regarding the carcinogenicity, mutagenicity, or impairment of fertility associated with niacin extended-release formulations.

Postmarketing Experience

Postmarketing experience has identified cases of hepatotoxicity, which include elevated liver enzymes and instances of liver failure. Additionally, cases of myopathy and rhabdomyolysis have been reported, particularly among patients using niacin in combination with statins. Reports of gastrointestinal bleeding have also emerged in patients taking niacin extended-release formulations.

Furthermore, severe skin reactions have been noted, including cases of Stevens-Johnson syndrome and toxic epidermal necrolysis. Instances of hypersensitivity reactions, such as angioedema and anaphylaxis, have been documented in the postmarketing setting.

Patient Counseling

Patients should be advised to adhere to the National Cholesterol Education Program (NCEP) recommended diet, engage in a regular exercise program, and undergo periodic testing of a fasting lipid panel to effectively manage their cholesterol levels.

It is important for patients to inform any healthcare professionals prescribing new medications that they are currently taking niacin extended-release. This ensures that all healthcare providers are aware of the patient's medication regimen.

Patients should take niacin extended-release tablets at bedtime, following a low-fat snack. Administration on an empty stomach is not recommended, as it may increase the risk of side effects. Additionally, these tablets should not be broken, crushed, or chewed; they must be swallowed whole to ensure proper absorption.

In the event of an interruption in dosing, patients should contact their physician before restarting therapy, as re-titration of the dosage may be necessary. Patients should also be instructed to promptly notify their physician of any unexplained muscle pain, tenderness, or weakness, and to discuss all medications they are taking, including both prescription and over-the-counter drugs.

Flushing, characterized by warmth, redness, itching, and/or tingling of the skin, is a common side effect of niacin therapy. Patients should be informed that this side effect may subside after several weeks of consistent use and is more likely to occur with the initiation of therapy or during dose increases. By taking the medication at bedtime, patients may experience flushing during sleep. If they awaken due to flushing, they should rise slowly, especially if they feel dizzy or faint, or if they are taking blood pressure medications. Patients should be educated on the symptoms of flushing and how they differ from those of a myocardial infarction.

To minimize flushing, patients should avoid the ingestion of alcohol, hot beverages, and spicy foods around the time of taking niacin extended-release. Furthermore, patients should notify their physician if they are taking vitamins or other nutritional supplements that contain niacin or nicotinamide.

Patients should also inform their physician if they experience any symptoms of dizziness or if they are diabetic and notice changes in their blood glucose levels.

Storage and Handling

The product is supplied in accordance with the following specifications: it is available in various package configurations, with specific NDC numbers provided upon request.

For optimal storage conditions, the product should be maintained at a temperature range of 20° to 25°C (68° to 77°F), in compliance with USP Controlled Room Temperature guidelines. It is essential to ensure that the product is stored in a suitable container to protect its integrity. Special handling requirements should be observed to maintain the quality and efficacy of the product throughout its shelf life.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

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

View full prescribing information (PDF)