Niacin

Description

Niacin Extended-release Tablets, USP, are formulated as film-coated, unscored tablets intended for oral administration. Each tablet contains niacin (nicotinic acid or 3-pyridinecarboxylic acid), an antihyperlipidemic agent effective at therapeutic doses. The tablets are available in two strengths: 500 mg and 1000 mg of niacin.

Niacin is presented as a white, crystalline powder that is highly soluble in water. The tablets are red in color and 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 during the early stages of therapy. Subsequent dose adjustments may be made, with increments not exceeding 500 mg every four weeks.

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. Healthcare professionals should monitor patients closely during the titration phase to ensure safety and efficacy.

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 and lead to complications.

Patients experiencing arterial bleeding, as the use of this product may increase the risk of further bleeding.

Those with known hypersensitivity to any components of the product, 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 function is recommended for these populations.

Liver enzyme abnormalities may occur during treatment with niacin extended-release tablets. Persistent elevations in hepatic transaminases have been documented, necessitating routine monitoring of liver enzymes both prior to and throughout the duration of therapy. This monitoring is essential to ensure early detection of potential hepatic complications.

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

Furthermore, niacin extended-release tablets can lead to increased serum glucose levels. It is imperative to closely monitor glucose levels in diabetic patients or those at risk of developing diabetes, particularly during the initial months of treatment or following any dose adjustments. Regular glucose monitoring will aid in managing 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. Additionally, persistent elevations in hepatic transaminase levels can occur, necessitating monitoring of liver enzymes before and during treatment.

It is important to use this medication with caution in patients with unstable angina or during the acute phase of a myocardial infarction (MI). Niacin extended-release tablets may also 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. Other 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 product components.

Drug Interactions

Caution is advised when co-administering niacin with statins, as this combination may elevate the risk of myopathy and rhabdomyolysis. It is recommended that healthcare providers closely monitor patients for signs of muscle-related adverse effects when these agents are used together.

Bile acid sequestrants possess a high binding capacity for niacin. Therefore, it is essential that these medications be administered at least 4 to 6 hours prior to the administration of niacin extended-release tablets to ensure optimal therapeutic efficacy and minimize potential interactions.

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

Pediatric patients aged 16 years and younger have not been studied in pharmacokinetic trials. Therefore, there is limited information regarding the pharmacokinetics of this medication in this population. Healthcare professionals should consider this lack of data when prescribing to pediatric patients and monitor for efficacy and safety accordingly.

Geriatric Use

Elderly patients, defined as those aged 65 years and older, have not been the subject of pharmacokinetic studies for this medication. As a result, there is limited information regarding the drug's pharmacokinetics in this population. Healthcare providers should exercise caution when prescribing this medication to geriatric patients, considering the potential for altered drug metabolism and excretion associated with aging.

Due to the absence of specific data, it is advisable to closely monitor elderly patients for any adverse effects and to consider potential dose adjustments based on individual clinical circumstances and overall health status.

Pregnancy

Pregnant patients should be advised to inform their healthcare provider of a known or suspected pregnancy to discuss the potential need for discontinuation of niacin extended-release tablets. The decision to continue or discontinue therapy should be made based on a careful assessment of the benefits and risks, considering the specific circumstances of the patient. Healthcare providers should refer to the relevant sections of the prescribing information for additional guidance on the use of niacin in pregnant patients.

Lactation

Lactating mothers should inform their healthcare provider of a known or suspected pregnancy to discuss whether niacin extended-release tablets should be discontinued. There is no specific data available regarding the excretion of niacin in breast milk or its effects on breastfed infants. Therefore, healthcare providers should consider the potential risks and benefits when prescribing niacin extended-release tablets to lactating mothers.

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. Additionally, patients with reduced kidney function who are concurrently treated with a statin should be closely monitored due to the potential for exacerbated adverse effects. It is advisable for healthcare professionals to consider these factors when prescribing niacin extended-release tablets to patients with renal impairment.

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 before and during treatment. Persistent elevations in hepatic transaminases may occur, necessitating careful evaluation of liver function throughout the course of therapy. Adjustments to dosing or treatment regimens should be considered based on the patient's liver function status and the results of liver enzyme monitoring.

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 procedures should focus on stabilizing the patient, which may involve monitoring vital signs, providing oxygen support, and administering intravenous fluids as necessary. It is crucial to assess the patient's clinical status continuously and to provide symptomatic treatment as required.

In cases of severe overdose, consultation with a poison control center or toxicology specialist is recommended to guide further management and intervention strategies.

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 impairment of fertility associated with niacin. Furthermore, no investigations have been performed regarding the carcinogenicity, mutagenicity, or impairment of fertility specifically for niacin extended-release tablets.

Postmarketing Experience

Postmarketing experience has identified reports of various adverse reactions associated with the use of the product. These include hepatotoxicity, myopathy, and rhabdomyolysis, as well as elevated liver enzymes. Gastrointestinal events such as gastrointestinal bleeding, nausea, vomiting, abdominal pain, diarrhea, constipation, and dyspepsia have also been reported.

Allergic reactions, including anaphylaxis and angioedema, were noted, along with other dermatological reactions such as flushing, pruritus, rash, dry skin, erythema, skin ulceration, and photosensitivity. Cardiovascular effects reported include atrial fibrillation and palpitations, while neurological symptoms encompass dizziness, headache, fatigue, sleep disturbances, depression, anxiety, memory loss, confusion, and suicidal ideation.

Metabolic changes such as hyperglycemia and gout have been documented. Sensory changes, including vision changes, hearing changes, and tinnitus, were also reported. These adverse reactions were observed in the postmarketing setting and may not have been identified during clinical trials.

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. These tablets should be taken at bedtime, following a low-fat snack, as administration on an empty stomach is not recommended. Patients should be instructed to swallow the tablets whole and not to break, crush, or chew them.

In the event of an interruption in dosing, patients should contact their physician prior to restarting therapy, as re-titration is recommended. Patients must promptly notify their physician of any unexplained muscle pain, tenderness, or weakness, and they should discuss all medications, including both prescription and over-the-counter products, 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 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, the treatment may lead to small but statistically significant reductions in platelet count and phosphorus levels, as well as increases in prothrombin time and uric acid levels, which warrants caution in patients with a predisposition to gout.

For patient counseling, it is important to closely monitor diabetic or potentially diabetic patients during the initial months of niacin therapy or following dose adjustments, as dietary modifications or changes in hypoglycemic therapy may be required. Furthermore, caution is advised when niacin is used in conjunction with anticoagulants, with careful monitoring of platelet counts and prothrombin time recommended in these cases.

FDA Insert (PDF)

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

View full prescribing information (PDF)