Niacin

Description

Niacin extended-release tablets USP contain niacin, USP, an antihyperlipidemic agent effective at therapeutic doses. Niacin, also known as nicotinic acid or 3-pyridinecarboxylic acid, appears as white crystals or a crystalline powder. It is sparingly soluble in water, soluble in boiling alcohol, and freely soluble in boiling water and in solutions of alkali hydroxides and carbonates, while being very slightly soluble in ether.

These tablets are white to off-white, film-coated, and intended for oral administration. They are available in three strengths: 500 mg, 750 mg, and 1,000 mg of niacin, USP. The formulation includes inactive ingredients such as colloidal silicon dioxide, hydrogenated castor oil, hypromellose, lactose monohydrate, magnesium stearate, polyethylene glycol, and titanium dioxide. The USP dissolution test for this product is currently pending.

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 4 weeks, based on patient tolerance and clinical response.

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 per day are not advised. Careful monitoring of the patient’s response to therapy is essential to ensure optimal dosing and to mitigate potential adverse effects.

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 a contraindication, as the product may aggravate the condition and lead to complications.

The presence of arterial bleeding contraindicates the use of this product, as it may increase the risk of further bleeding.

Additionally, individuals with known hypersensitivity to any components of the product should avoid its use to prevent 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.

Monitoring liver enzyme levels is essential, as persistent elevations in hepatic transaminases may occur during treatment. It is advised to conduct liver function tests before initiating therapy and periodically throughout treatment to ensure patient safety.

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 and monitoring.

Furthermore, niacin extended-release tablets can 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 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 tablets may elevate 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 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, as this combination may elevate the 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 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 should be exercised when considering the use of niacin in this population, as there is insufficient data to support its use 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. However, it is important to note that while the clinical experience has not identified significant differences in responses between geriatric patients and younger individuals, the possibility of greater sensitivity in some older patients cannot be excluded.

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 optimal management in this population. No specific dosage adjustments are indicated based solely on age; however, clinical judgment should guide treatment decisions in geriatric patients.

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 the use of niacin extended-release tablets 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

The potential for niacin extended-release tablets to be excreted in breast milk and its effects on breastfed infants are not well established. The available data on the use of niacin extended-release tablets in lactating mothers are insufficient to evaluate the risk of adverse effects in nursing infants.

Due to the unknown risks associated with niacin extended-release tablets, it is recommended that lactating mothers discontinue the use of these tablets when pregnancy is recognized. Healthcare providers should assess the individual risks and benefits of continuing niacin extended-release tablets in lactating mothers who are being treated for hyperlipidemia or hypertriglyceridemia.

Patients are advised to inform their healthcare provider of any known or suspected pregnancy while using 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. It is essential to monitor liver enzymes, as persistent elevations in hepatic transaminases can occur. Therefore, liver function should be assessed prior to initiating treatment and monitored throughout the course of therapy to ensure patient safety and to detect any potential liver-related complications promptly.

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 dose of 3,000 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 fertility impairment associated with niacin extended-release tablets.

Postmarketing Experience

Postmarketing experience has identified several adverse reactions associated with the use of the product. 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 inform patients about the symptoms of flushing and to distinguish them from those 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. 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, faint, or 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 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), in accordance 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 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. Additionally, niacin treatment may lead to an increase in fasting blood glucose levels, necessitating frequent monitoring, especially in diabetic patients who may experience dose-related glucose intolerance.

Patients may also experience a statistically significant reduction in platelet count, with a mean decrease of 11% at a dosage of 2,000 mg. Furthermore, niacin has been associated with small but significant increases in prothrombin time (approximately +4%) and elevated uric acid levels, which warrants caution in individuals predisposed to gout. There are also dose-related reductions in phosphorus levels, averaging a decrease of 13% at the same dosage.

FDA Insert (PDF)

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

View full prescribing information (PDF)