Niacin

Description

Niacin extended-release tablets contain niacin, USP, which serves as an antihyperlipidemic agent 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 structural formula of niacin is provided in the accompanying documentation.

These tablets are unscored, film-coated, and exhibit a light orange to orange coloration, intended for oral administration. They are available in two strengths: 500 mg and 1,000 mg of niacin per tablet. In addition to niacin, the formulation includes several inactive ingredients: 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 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 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, as well as in those with diabetes, renal failure, or uncontrolled hypothyroidism. Additionally, patients who are concurrently treated with statins are at an increased risk. It is imperative for healthcare providers 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 can occur during treatment. Baseline liver enzyme tests should be conducted prior to initiating therapy, with ongoing monitoring throughout the treatment course to detect any abnormalities promptly.

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 of the patient's clinical status.

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 assessment of glycemic control is recommended to prevent complications associated with hyperglycemia.

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, with an increased risk for myopathy and rhabdomyolysis particularly among elderly patients, those with diabetes, renal failure, or uncontrolled hypothyroidism, as well as patients concurrently treated with a statin.

Monitoring of liver enzymes is essential, as persistent elevations in hepatic transaminase levels can occur. Liver enzymes should be assessed 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 has the potential 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.

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, as this combination may elevate the risk of myopathy and rhabdomyolysis. Clinicians should consider monitoring for signs and symptoms of muscle-related adverse effects in patients receiving both therapies.

Bile acid sequestrants possess a significant 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 potential interactions 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

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 absorption, distribution, metabolism, and excretion in this population.

Healthcare providers should exercise caution when prescribing this medication to geriatric patients, considering the potential for altered pharmacokinetics and increased sensitivity to the drug's effects. Close monitoring for efficacy and adverse reactions is recommended in this demographic, and dosage adjustments may be necessary based on clinical judgment and individual patient response.

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. The decision to continue or discontinue therapy should be made in consideration of the benefits and risks associated with niacin use during pregnancy. Healthcare providers should evaluate the individual circumstances of each patient, including the potential impact on fetal outcomes, when making treatment decisions.

Lactation

Lactating mothers should inform their healthcare provider of a known or suspected pregnancy to discuss whether niacin extended-release 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 to lactating 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. 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. 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 situation effectively.

Potential symptoms of overdose may vary depending on the specific substance involved; however, general signs may include alterations in consciousness, respiratory distress, or cardiovascular instability.

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. It is crucial to consult local poison control centers or relevant clinical guidelines for further recommendations tailored to the specific overdose scenario.

Overall, prompt recognition and appropriate supportive care are vital in mitigating the effects of an overdose and ensuring patient safety.

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 3,000 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 for niacin extended-release formulations.

Postmarketing Experience

Postmarketing experience has identified several adverse reactions associated with the use of the product. 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 of niacin therapy. This flushing may subside after several weeks of consistent use of niacin extended-release formulations. The severity of flushing can vary and is more likely to occur upon initiation of therapy or during dose increases.

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.

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 promptly notify their physician of any unexplained muscle pain, tenderness, or weakness. They should also 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. 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, particularly if they feel dizzy, faint, or are on 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. 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 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

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. Niacin treatment may lead to increased fasting blood glucose levels, necessitating frequent monitoring, especially in diabetic patients who may experience dose-related glucose intolerance. Additionally, niacin extended-release has been associated with statistically significant reductions in platelet count, increases in prothrombin time, elevated uric acid levels, and reductions in phosphorus levels.

Patients with a history of jaundice, hepatobiliary disease, or peptic ulcer should be closely monitored during niacin therapy. Caution is advised for patients with unstable angina or in the acute phase of a myocardial infarction, particularly if they are receiving vasoactive medications. Diabetic patients should be observed closely, especially during initial treatment or dose adjustments, as dietary or hypoglycemic therapy modifications may be required. Furthermore, when niacin extended-release is used alongside anticoagulants, careful monitoring of platelet counts and prothrombin time is recommended.

FDA Insert (PDF)

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

View full prescribing information (PDF)