Niacin

Description

Niacin Extended-release Tablets, USP, are formulated with niacin, a therapeutic antihyperlipidemic agent. Niacin, also known as nicotinic acid or 3-pyridinecarboxylic acid, appears as a white, crystalline powder that is highly soluble in water. The structural formula of niacin is provided in the accompanying documentation.

These unscored, red, film-coated tablets are designed for oral administration and are available in two strengths: 500 mg and 1000 mg of niacin. In addition to niacin, the tablets contain several inactive ingredients, including black iron oxide, colloidal silicon dioxide, hydroxypropyl cellulose, lecithin, polyethylene glycol, polyvinyl alcohol, red iron oxide, sodium stearyl fumarate, talc, titanium dioxide, and yellow iron oxide. The formulation adheres to the USP Dissolution Test 5 standards.

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 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. 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 1000 mg to 2000 mg once daily. It is important to note that doses exceeding 2000 mg daily are not advised. Careful monitoring of the patient's response and tolerance to the medication is essential during the titration 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 function.

Active peptic ulcer disease is a contraindication, as the product may aggravate the condition.

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 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 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.

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

Caution is warranted when prescribing niacin extended-release tablets to patients with unstable angina or during the acute phase of a myocardial infarction (MI). The potential for exacerbating these conditions necessitates careful evaluation of the risk-benefit ratio.

Furthermore, niacin extended-release tablets can lead to increased 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 monitoring is recommended to manage potential hyperglycemia 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.

Severe 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. 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).

Additionally, niacin extended-release tablets may elevate serum glucose levels, warranting close monitoring of glucose levels in diabetic or potentially diabetic patients, especially during the initial months of treatment or following dose adjustments.

Other important considerations include the presence of active liver disease, which may manifest as unexplained persistent elevations in hepatic transaminase levels, active peptic ulcer disease, arterial bleeding, and known hypersensitivity to the 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 tablets 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

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 involving niacin extended-release tablets, 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. Additionally, other clinical experiences have not identified significant differences in responses to the treatment between geriatric patients and younger individuals.

However, it is important to note that greater sensitivity to the effects of the medication cannot be ruled out in some older individuals. Therefore, healthcare providers should exercise caution when prescribing niacin extended-release tablets to elderly patients, considering the potential for increased sensitivity. Monitoring for adverse effects and therapeutic response is recommended to ensure the safety and efficacy of treatment in this population.

Pregnancy

Pregnant patients receiving niacin extended-release tablets for the treatment of hyperlipidemia should discontinue the medication upon recognition of pregnancy. For those being treated for hypertriglyceridemia, healthcare providers should assess the individual risks and benefits of continuing niacin extended-release tablets during pregnancy. It is essential for patients 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 the use of niacin extended-release tablets in pregnant women are insufficient to evaluate the 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.

Treatment of hypercholesterolemia is generally not necessary during pregnancy, as 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 2-4% and 15-20%, 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 extended-release tablets.

Renal Impairment

Patients with renal impairment may experience an increased risk of myopathy and rhabdomyolysis when taking niacin extended-release tablets. This risk is particularly heightened in elderly patients, those with diabetes, and individuals with uncontrolled hypothyroidism. Careful monitoring is advised for patients with reduced kidney function, especially when niacin is used in conjunction with statins. Dosing adjustments may be necessary based on the patient's renal status to mitigate these risks.

Hepatic Impairment

Patients with hepatic impairment may experience severe hepatic toxicity when substituting sustained-release niacin for immediate-release niacin at equivalent doses. Due to the potential for liver enzyme abnormalities, it is essential to monitor liver enzymes, specifically hepatic transaminases, before and during treatment. Persistent elevations in these enzymes may indicate compromised liver function and necessitate further evaluation and potential adjustment of therapy.

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 experts 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.

Currently, there are no studies available that assess the effects of niacin on impairment of fertility. Furthermore, no investigations have been conducted regarding the carcinogenicity, mutagenicity, or impairment of fertility associated with niacin extended-release tablets.

Postmarketing Experience

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

Patients who experience flushing at night are advised to rise slowly, particularly if they feel dizzy, faint, or are taking blood pressure medications. It is important to educate patients about the symptoms of flushing and to differentiate these from the symptoms of a myocardial infarction.

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.

Niacin extended-release tablets should be taken at bedtime, following a low-fat snack, as administration on an empty stomach is not recommended. Patients must be instructed not to break, crush, or chew the tablets; they should be swallowed whole to ensure proper absorption.

In the event of an interruption in dosing, patients should contact their physician prior to restarting therapy, as re-titration is recommended. Patients should also be vigilant and notify their physician promptly of any unexplained muscle pain, tenderness, or weakness. It is essential for patients to discuss all medications they are taking, 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 taking niacin extended-release tablets. Additionally, they should avoid alcohol, hot beverages, and spicy foods around the time of administration to further reduce the likelihood of flushing.

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 accordance with the National Drug Code (NDC) specifications. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), in compliance with USP Controlled Room Temperature guidelines. Proper storage conditions are essential to maintain the integrity and efficacy of the product.

Additional Clinical Information

Patients receiving niacin extended-release tablets should undergo regular laboratory tests to monitor liver function, specifically serum transaminase levels (AST and ALT). These tests should be conducted before initiating treatment, every 6 to 12 weeks during the first year, and periodically thereafter, approximately every six months. Clinicians should also be aware that niacin can increase fasting blood glucose levels, necessitating frequent monitoring to prevent adverse effects.

Additionally, niacin therapy has been associated with small but statistically significant dose-related reductions in platelet count (mean decrease of 11% at 2000 mg), increases in prothrombin time (mean increase of approximately 4%), and elevated uric acid levels, which may pose a risk for patients predisposed to gout. There are also small but statistically significant reductions in phosphorus levels (mean decrease of 13% at 2000 mg) observed with niacin use.

FDA Insert (PDF)

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

View full prescribing information (PDF)