Niacin

Description

Niacin extended-release tablets, USP contain niacin, 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 sparingly soluble in water. The structural formula of niacin is provided in the product specifications.

These unscored, pink, film-coated tablets are designed for oral administration and are available in three strengths: 500 mg, 750 mg, and 1,000 mg of niacin USP. In addition to niacin, the tablets include inactive ingredients such as hypromellose, hydrogenated vegetable oil Type I, glyceryl behenate, colloidal silicon dioxide, magnesium stearate, partially hydrolyzed polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, iron oxide red, and iron oxide yellow.

Niacin extended-release tablets, USP meet the requirements of USP Dissolution Test 3.

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 may slow the progression or promote regression of atherosclerotic disease in patients with a history of coronary artery disease (CAD) and hyperlipidemia. It is also indicated as an adjunct to diet for the reduction of elevated TC and LDL-C in adult patients with primary hyperlipidemia. Furthermore, this drug is indicated 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, USP, should be administered at bedtime alongside a low-fat snack to enhance tolerability. The initial dose must be set at 500 mg once daily to minimize the risk of side effects during the early stages of therapy. Subsequent dose adjustments may be made, but should not exceed an increase of 500 mg within any 4-week period.

The recommended maintenance dose ranges from 1,000 mg to 2,000 mg once daily. It is important to note that doses exceeding 2,000 mg daily are not advised. Careful monitoring of the patient's response and tolerance to the medication is essential throughout the treatment process.

Contraindications

Use of this product is contraindicated in the following conditions:

Patients with active liver disease, including those with unexplained persistent elevations in hepatic transaminase levels, should not use this product due to the potential for exacerbating liver dysfunction.

Active peptic ulcer disease is another contraindication, as the product may aggravate the condition and lead to complications.

The presence of arterial bleeding contraindicates the use of this product, given the risk of worsening the bleeding.

Additionally, individuals with known hypersensitivity to any components of the product should avoid its use to prevent severe allergic 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 tablets. The risk of developing myopathy and rhabdomyolysis is particularly heightened in elderly patients, as well as in those with diabetes, renal failure, or uncontrolled hypothyroidism. Additionally, patients concurrently treated with statins are at an increased risk. Regular assessment of muscle symptoms and creatine kinase levels is recommended for these populations.

Liver enzyme abnormalities may occur, with persistent elevations in hepatic transaminases being a concern. It is essential to monitor liver enzymes both before initiating treatment and periodically during therapy to detect any potential hepatic issues 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.

Furthermore, 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 blood glucose assessments are recommended to manage this risk effectively.

Side Effects

Patients may experience a range of adverse reactions while using the medication. The most common adverse reactions reported include flushing, diarrhea, nausea, vomiting, increased cough, and pruritus.

Serious adverse reactions have also been observed. Notably, severe hepatic toxicity has occurred in patients who substituted sustained-release niacin for immediate-release niacin at equivalent doses. Myopathy has been reported in patients taking niacin extended-release tablets, with an increased risk for myopathy and rhabdomyolysis particularly among elderly patients, those with diabetes, renal failure, or uncontrolled hypothyroidism, and patients concurrently treated with a statin.

Additionally, persistent elevations in hepatic transaminase levels can occur, necessitating monitoring of liver enzymes before and during treatment. Caution is advised when administering this medication to patients with unstable angina or during the acute phase of a myocardial infarction (MI). Furthermore, niacin extended-release has been shown to increase serum glucose levels; therefore, glucose levels should be closely monitored in diabetic or potentially diabetic patients, especially during the initial months of treatment or following dose adjustments.

Contraindications for the use of this medication 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.

Drug Interactions

Caution is advised when co-administering niacin 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 reduced efficacy of niacin.

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 necessary 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. No overall differences in safety and effectiveness were observed 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, greater sensitivity in some older patients cannot be ruled out.

Healthcare providers should exercise caution when prescribing niacin extended-release to elderly patients. Monitoring for potential adverse effects and assessing the need for dosage adjustments may be warranted, given the possibility of increased sensitivity in this population.

Pregnancy

Discontinuation of niacin extended-release tablets is recommended upon recognition of pregnancy in patients using the medication for hyperlipidemia treatment. For those receiving niacin extended-release tablets for hypertriglyceridemia, healthcare providers should assess the individual risks and benefits of continuing therapy during pregnancy. Patients are advised to inform their healthcare provider of any known or suspected pregnancy.

The potential for embryofetal toxicity associated with the doses of niacin in niacin extended-release tablets remains unknown. Current data on niacin use in pregnant women are insufficient to determine a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Furthermore, animal reproduction studies have not been conducted with niacin or niacin extended-release tablets.

It is important to note that the treatment of hypercholesterolemia is generally not necessary during pregnancy. Given that atherosclerosis is a chronic process, the discontinuation of lipid-lowering drugs during pregnancy is unlikely to significantly impact the long-term outcomes of primary hypercholesterolemia for most patients. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown; however, in the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is approximately 2 to 4% and 15 to 20%, respectively.

Lactation

Niacin is present in human milk, and the concentration of niacin increases with maternal supplementation. However, there is no information available regarding the effects of the doses of niacin in niacin extended-release tablets on breastfed infants or on milk production.

Due to the potential for serious adverse reactions in breastfeeding infants, including hepatotoxicity, it is advised that lactating mothers refrain from breastfeeding during treatment with niacin.

Renal Impairment

Patients with renal impairment should use niacin extended-release with caution, as no studies have been performed in this population. The risk of myopathy and rhabdomyolysis is increased in patients with reduced kidney function, particularly among elderly patients, those with diabetes, renal failure, or uncontrolled hypothyroidism, and patients concurrently treated with a statin. Monitoring for adverse effects is recommended in these patients to ensure safety and efficacy.

Hepatic Impairment

Patients with hepatic impairment should use niacin extended-release with caution, particularly those with a past history of liver disease or those who consume substantial quantities of alcohol. The use of niacin extended-release is contraindicated in individuals with active liver disease, unexplained transaminase elevations, or significant or unexplained hepatic dysfunction.

Severe hepatic toxicity has been reported in patients who substituted sustained-release niacin for immediate-release niacin at equivalent doses. Therefore, it is essential to monitor liver enzymes before and during treatment, as persistent elevations in hepatic transaminase levels can occur. Regular monitoring will help ensure patient safety and facilitate timely intervention if liver function deteriorates.

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 to identify any deterioration in the patient's status.

In cases where the specific substance is known, targeted interventions may be necessary, including the administration of antidotes if applicable. Fluid resuscitation and other supportive therapies should be considered based on the clinical presentation.

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

Nonclinical Toxicology

Niacin administered to mice for a lifetime as a 1% solution in drinking water demonstrated no carcinogenic potential. The dosage received by the mice was approximately 6 to 8 times the human equivalent of 3,000 mg/day, calculated on a mg/m² basis.

In terms of mutagenicity, niacin was found to be negative in the Ames test, indicating no evidence of mutagenic effects.

Currently, there are no available studies assessing the impairment of fertility associated with niacin. Additionally, no investigations have been conducted regarding the carcinogenicity, mutagenicity, or fertility impairment of niacin extended-release formulations.

Postmarketing Experience

Postmarketing experience has identified several adverse reactions associated with the use of niacin extended-release tablets. Reports have included muscle pain, tenderness, or weakness. Additionally, flushing, characterized by warmth, redness, itching, and/or tingling of the skin, has been noted as a common side effect. This flushing may diminish after several weeks of consistent use and is more likely to occur at the initiation of therapy or during dose increases. The severity of flushing can vary among individuals.

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 tablets.

Patients should take niacin extended-release tablets at bedtime, following a low-fat snack, as administration on an empty stomach is not recommended. It is crucial that these tablets are swallowed whole and not broken, crushed, or chewed. In the event of an interruption in dosing, patients should contact their physician prior to restarting therapy, as re-titration is recommended.

Patients must be vigilant and notify their physician promptly if they experience any unexplained muscle pain, tenderness, or weakness. They should also discuss all medications, including both prescription and over-the-counter drugs, with their physician. Flushing, characterized by warmth, redness, itching, and/or tingling of the skin, is a common side effect of niacin therapy. 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 primarily during sleep. If they awaken due to flushing, they should rise slowly, particularly 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 may take aspirin (up to the recommended dose of 325 mg) approximately 30 minutes before dosing. Additionally, they should avoid alcohol, hot beverages, and spicy foods around the time of taking niacin extended-release tablets. Patients should notify their physician if they are taking vitamins or other nutritional supplements that contain niacin or nicotinamide. They 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 a tight container 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° and 30°C (59° and 86°F) in accordance with USP Controlled Room Temperature guidelines.

Additional Clinical Information

Liver-related tests are essential for all patients undergoing therapy with niacin extended-release. Clinicians should monitor serum transaminase levels, including AST and ALT, prior to treatment, every 6 to 12 weeks during the first year, and periodically thereafter, approximately every 6 months. Additionally, niacin treatment may lead to increased fasting blood glucose levels, necessitating frequent monitoring to ensure no adverse effects occur. There are also small but statistically significant dose-related reductions in platelet count and increases in prothrombin time associated with niacin extended-release. Elevated uric acid levels may occur, warranting caution in patients predisposed to gout, and there are also small reductions in phosphorus levels.

Patients with a history of jaundice, hepatobiliary disease, or peptic ulcer should be closely monitored during treatment. Diabetic patients or those at risk for diabetes require careful observation, especially during initial treatment or dose adjustments, as dietary or hypoglycemic therapy modifications may be necessary. Caution is advised when niacin extended-release is used alongside anticoagulants, with close monitoring of platelet counts and prothrombin time recommended.

FDA Insert (PDF)

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

View full prescribing information (PDF)