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 highly soluble in water. The tablets are unscored, orange, and film-coated, designed for oral administration, and are available in two strengths: 500 mg and 1000 mg of niacin. In addition to niacin, the formulation includes inactive ingredients such as hypromellose, povidone, stearic acid, and polyethylene glycol, along with coloring agents including FD&C yellow #6/sunset yellow FCF Aluminum Lake, synthetic red and yellow iron oxides, and titanium dioxide. It is important to note that the FDA-approved dissolution test specifications for these tablets differ from those established by the USP.

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 should be administered at bedtime, accompanied by a low-fat snack to enhance tolerability. The initial dose for therapy should be set at 500 mg once daily at bedtime, which is essential for minimizing the incidence and severity of side effects that may arise during the early stages of treatment.

The dosage may be increased by no more than 500 mg at intervals of no less than 4 weeks, allowing for careful monitoring of patient response and side effects. 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 recommended.

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 hemorrhagic events.

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, those with diabetes, renal failure, or uncontrolled hypothyroidism, as well as in patients concurrently treated with statins. Regular assessment of muscle symptoms and function is recommended for these high-risk groups.

Monitoring of liver enzymes is essential, as persistent elevations in hepatic transaminases can occur during treatment. It is advised that liver enzymes be evaluated prior to initiating therapy and periodically throughout the treatment course to detect any abnormalities early.

Caution is warranted 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 these conditions necessitates careful consideration of the risk-benefit profile in such patients.

Additionally, niacin extended-release tablets may elevate 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 therapy or following any dose adjustments. Regular monitoring will help manage any 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. These reactions are generally mild and may resolve with continued use.

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. Additionally, niacin extended-release tablets may 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.

It is important to note the contraindications associated with this medication. Patients with active liver disease, which may manifest as unexplained persistent elevations in hepatic transaminase levels, active peptic ulcer disease, arterial bleeding, or known hypersensitivity to the product components should not use this medication.

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 significant 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 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

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.

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. Furthermore, additional clinical experience has not revealed any significant differences in responses to the treatment between geriatric patients and younger individuals.

However, it is important to note that greater sensitivity to the medication may be present 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

There is no relevant information regarding the use of this medication in lactating mothers or its effects on breastfed infants. Healthcare professionals should consider the absence of data when advising lactating mothers on the use of this medication.

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 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. Therefore, it is crucial to exercise caution in this population.

Monitoring of liver function is essential, as persistent elevations in hepatic transaminases can occur. Liver enzymes should be assessed before initiating treatment and periodically during therapy to ensure patient safety and to detect any potential liver-related adverse effects promptly.

Additionally, it is advised to use this medication with caution in patients who have unstable angina or are in the acute phase of a myocardial infarction (MI), as these conditions may further complicate the management of patients with compromised 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 the immediate stabilization of the patient. This includes monitoring vital signs, ensuring airway patency, and providing supplemental oxygen if necessary. In cases where specific antidotes are available, they should be administered as indicated.

Continuous assessment and supportive care are essential throughout the management process to mitigate any adverse effects and to ensure the patient's safety. It is crucial for healthcare providers to remain vigilant and responsive to the evolving clinical picture during an overdose scenario.

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 carcinogenesis, mutagenesis, or impairment of fertility specifically for niacin extended-release tablets.

Postmarketing Experience

Postmarketing experience has identified several adverse reactions associated with the use of the product. These include hepatotoxicity, myopathy, and rhabdomyolysis. Additionally, elevated liver enzymes, gastrointestinal bleeding, and pancreatitis have been reported. Allergic reactions, such as rash, pruritus, and angioedema, have also been documented. Severe flushing reactions and other cardiovascular events have been noted as well.

Reports of these adverse reactions have been received from various sources, including spontaneous reports and clinical studies.

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. They should also promptly notify their physician of any unexplained muscle pain, tenderness, or weakness, and 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, flushing will most likely occur during sleep. If patients are awakened by flushing at night, they should get up slowly, especially if they feel dizzy or faint, or if they are taking blood pressure medications. It is essential to educate patients 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 various package configurations, with specific NDC numbers available upon request. It should be stored at a temperature range of 20º to 25º C (68º to 77º F). Temporary excursions are permissible between 15º to 30º C (59º to 86º F), in accordance with USP Controlled Room Temperature guidelines. Proper container requirements must be adhered to, and special handling needs should be followed to ensure product integrity.

Additional Clinical Information

Liver-related tests are essential for all patients undergoing therapy with niacin extended-release tablets. 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 also lead to increased fasting blood glucose levels, necessitating frequent monitoring to ensure no adverse effects occur. Additionally, the medication has been associated with small but statistically significant dose-related reductions in platelet count (mean of -11% at 2000 mg), increases in prothrombin time (mean of approximately +4%), elevated uric acid levels, and reductions in phosphorus levels (mean of -13% at 2000 mg). Caution is advised in patients predisposed to gout.

Patients with diabetes or those at risk for diabetes should be closely monitored during the initial months of treatment or following dose adjustments, as dietary or hypoglycemic therapy modifications may be required. Furthermore, when niacin extended-release tablets are used in conjunction with 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 Macleods Pharmaceuticals Limited. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)