Niacin Extended-Release Tablets - Doses, Uses, Side Effects, and Much More

What Are Niacin Extended-Release Tablets?

Niacin extended-release tablets lower triglyceride levels and increase high-density lipoprotein (HDL) levels, or good cholesterol, in the body. Patients are advised to limit alcohol consumption while on therapy with Niacin. Patients must notify the healthcare professional if they skip several doses of the medication, as resuming therapy may require dosing adjustments.

Are Niacin Extended-Release Tablets Approved by the FDA?

Niacin extended-release tablets were approved by the U.S. Food and Drug Administration (FDA) in July 1997 for the treatment of high cholesterol and for the secondary prevention of various cardiovascular diseases (CVD).

How Does Niacin Work?

The body uses Niacin for a range of functions, some of which are listed below:

• Niacin can reduce lipids and apolipoprotein B (apo B)-containing lipoproteins by altering either the liver's production of triglycerides, which breaks down apo B, or the adipose tissue's lipolysis.

• It inhibits the activity of an enzyme called hepatocyte diacylglycerol acyltransferase-2. This action limits the amount of triglycerides available for very low-density lipoproteins (VLDL) by blocking the final step of triglyceride synthesis in hepatocytes. Low-density lipoproteins, the catabolic byproduct of VLDL, are also reduced, and apolipoprotein B is intracellularly degraded due to this action.

• Additionally, the high-density lipoprotein (HDL) catabolism receptor is inhibited by Niacin, increasing HDL levels and half-life.

Available Doses:

• Niacin extended-release tablets are only available with a prescription from a doctor.

• The physician will adjust the dosing based on the medication's response and improve disease control.

• Niacin is available in 250 mg (milligrams), 500 mg, 750 mg, and 1000 mg extended-release tablets.

• The starting dose is 500 mg orally once daily at bedtime, which is titrated to a maximum of 2000 mg daily.

Warnings:

• Liver Damage: Liver toxicity and damage have been reported in patients who have taken Niacin extended-release tablets. Hence, caution is required while using the medication, especially in patients with liver diseases or for those who consume alcohol (moderate to heavy drinkers). If signs of liver damage (yellowing of skin, dark-colored urine, light-colored stools, and severe abdominal pain) arise, the medication should be discontinued immediately.

• Rhabdomyolysis: It is a condition characterized by the breakdown of muscle tissue and the release of muscle fibers into the bloodstream. Niacin has rarely been shown to cause this condition, especially when used concurrently with other cholesterol-lowering agents in the statin class (Simvastatin, Lovastatin, etc.). Hence, concomitant administration of these classes of drugs is not advised.

For Patients

When and Why to Take Niacin Extended-Release Tablets?

• Niacin is indicated for the treatment of high cholesterol levels.

• It is also called vitamin B3 and is involved in boosting circulation, converting nutrients into energy, increasing the amount of good cholesterol in the body, and lowering triglyceride levels.

How Effective are Niacin Extended-Release Tablets?

• Niacin extended-release tablets have been shown to lower triglycerides by 25% and increase HDL cholesterol by 30%. It has also been shown to decrease the risk of heart disease.

• In patients who have already experienced a heart attack and have high cholesterol, Niacin extended-release tablets are also used to reduce their chance of having another heart attack.

• When used with a bile acid-binding resin (another cholesterol medication), the extended-release tablets of Niacin have been shown to slow down or minimize the buildup of plaque (fatty deposits) in the arteries in patients with high cholesterol and coronary artery disease.

• Combining Niacin extended-release pills with another cholesterol-lowering drug (Simvastatin) does not prevent heart attacks or strokes in people with heart disease and well-controlled cholesterol any more than Simvastatin alone.

Things to Inform the Doctor Before Taking Niacin Extended-Release Tablets:

It is necessary to inform the doctor if any of the following conditions are present:

• Diabetes: Niacin extended-release tablets have been shown to affect blood sugar levels. Hence, inform the doctor if the patient is diabetic, and report any changes in blood sugar levels to the physician immediately.

• Gout: It is a condition in which the joints are inflamed. Niacin can raise blood uric acid levels, which is a contributing factor in the development of gout. Hence, the medication should be used with caution in patients with a previous gout diagnosis.

• Kidney Problem: Niacin extended-release tablets can lower phosphorus levels in patients with chronic kidney disease. Hence, monitoring is required in individuals with kidney disorders on this therapy.

• Pregnancy: It is unknown how Niacin extended-release tablets affect the unborn baby. Talk to the doctor if the patient is pregnant or intends to conceive while using the medication.

• Breastfeeding: Niacin has been shown to pass into breast milk. Hence, breastfeeding is not recommended while on therapy with Niacin extended-release tablets. If breastfeeding is necessary, the doctor may prescribe other cholesterol-lowering medications.

• Drugs: Inform the doctor about all medications the patient is taking, including prescription, nonprescription, supplements, and vitamins. Niacin extended-release tablets and other drugs may affect each other's efficacy, leading to an interaction between these drugs.

Administration of the following medications should be reported to the physician before the therapy:

• • Other medicines to lower cholesterol or triglycerides.

  • Aspirin.

  • Blood pressure-lowering medications.

  • Blood-thinning drugs.

  • Consumption of alcohol.

How to Take Niacin Extended-Release Tablets?

• The doctor may recommend blood tests and follow-up consultations to assess the progress of the therapy. Follow the doctor's or pharmacist's directions carefully.

• Niacin extended-release tablets should be taken exactly as prescribed by the doctor.

• Consume the entire Niacin extended-release pill. The medications must not be chewed, broken, or crushed before being swallowed.

• Niacin extended-release tablets should be taken once daily at bedtime following a low-fat snack. Extended-release Niacin pills should not be consumed on an empty stomach.

• Niacin extended-release tablets are not the same as other supplements of the vitamin. Without first consulting, the doctor never switches between niacin and folic acid, which can lead to serious complications like liver damage.

• Do not alter the dosage unless the doctor instructs or to stop taking Niacin extended-release pills.

• Patients taking Niacin extended-release tablets might notice an inactive matrix tablet going through their stools. Patients should be made aware that the active drug has already been absorbed by the time they see the inert matrix tablet.

• Re-initiation of the therapy after discontinuation must be done only after proper instructions from the doctor.

• Other cholesterol-lowering medications such as Colestipol and Cholestyramine should not be co-administered with Niacin extended-release tablets due to the potential interaction risk. There should be at least four to six hours between these medications with Niacin.

What Are the Side Effects of Niacin Extended-Release Tablets?

The major adverse effects of Niacin extended-release tablets include:

• Flushing.

• Nausea.

• Increased cough.

• Diarrhea.

• Vomiting.

• Rash.

Flushing is the most common side effect of extended-release Niacin tablets. It happens when tiny blood vessels near the skin surface (especially on the face, neck, chest, or back) open wider. Flushing only sometimes happens.

If it does, it usually occurs within 2 to 4 hours after taking Niacin extended-release tablets. Flushing may last for a few hours. It is more likely to occur when the patient first starts taking Niacin extended-release tablets or when the dose increases. Flushing may get better after several weeks.

Symptoms of flushing may constitute any or all of the following:

• Redness.

• Warmth.

• Itching.

• Tingling of the skin.

The patient should get up slowly when flushes are experienced during the nighttime, especially in the following cases:

• Take medication to lower blood pressure.

• Avoid drinking hot beverages like coffee, using alcohol, or consuming spicy meals right before taking Niacin extended-release pills to reduce the risk of flushing.

• To alleviate an upset stomach, take Niacin extended-release tablets along with a low-fat snack.

• If symptoms of liver damage like yellowing of the skin, dark-colored urine, light-colored stools, and severe abdominal pain are experienced, stop taking the drug and seek immediate medical attention.

• Cardiac attacks can happen to those who have excessive cholesterol and heart disease. An extended-release Niacin tablet flushing reaction may not be the same as heart attack symptoms. The signs of a heart attack brought on by heart disease, rather than a flushing reaction, include shortness of breath, sweating, nausea, lightheadedness, and pain in the arms, back, neck, jaw, stomach, and other upper body areas.

• The discomfort, pressure, squeezing, fullness, or pain the patient experiences during a heart attack may linger for a few minutes or recur. Heart attacks can start slowly without much pain or discomfort, but can also be rapid and intense.

• The side effects should be reported to a healthcare professional for medical intervention.

What Should Be Done if a Dose Is Missed?

If a dose is missed, use the medication as soon as it is remembered. However, if it is almost time for the next dose, skip the previous one and continue as scheduled. Avoid double-dosing to make up for a missed dose. If the doses are not taken for longer, re-initiation of therapy should only be done under the guidance of a healthcare professional. For any queries, contact the pharmacist or the doctor.

What Should Be Done to Treat a Niacin Extended-Release Tablet Overdose?

In case of an overdose, immediately contact a healthcare professional or the nearest poison control center.

How to Store Niacin Extended-Release Tablets?

• Keep the medication formulations out of reach of pets and children.

• Do not use this medication after the expiration date listed on the tube and carton. The last day of that month is the expiration date.

• Store no longer than 25 degrees Celsius.

• Avoid freezing the medication.

• Keep the closed tube out of direct sunlight.

• Never dispose of medications in wastewater or household garbage. Find out from the pharmacist how to dispose of expired medications. These actions will help protect the environment.

Avoid Self-Medication:

Avoid taking this drug without the proper directions from a pharmacist or doctor. Avoid recommending the medication to others, and do not take it on someone else's advice. Different people react to medications differently, and some may even react worse. Hence, follow the healthcare professional's directions for drug use.

For Doctors

Indication:

Niacin extended-release tablets are indicated for the following conditions.

• Severe triglyceridemia.

• Hyperlipidemia.

• Myocardial infarction in patients with a history of hyperlipidemia and myocardial infarction.

• Coronary arteriosclerosis.

Dosing:

1. Primary Hypercholesterolemia:

• Starting with 500 mg intervals every four weeks based on tolerability and efficacy to a maximum dose of 2000 mg/day.

• Maintenance Therapy: 1000 to 2000 mg orally once daily.

2. Severe Hypertriglyceridemia:

• Starting with 500 mg orally once daily at bedtime, which may be titrated in 500 mg intervals every four weeks based on tolerability and efficacy to a maximum dose of 2000 mg/day.

• Maintenance Therapy Dosing: 1000 to 2000 mg orally once daily.

Dosing Considerations:

Niacin extended-release tablets are contraindicated in patients with hepatic impairment, active liver disease, unexplained hepatic dysfunction, and unexplained transaminase levels.

What Are the Pharmacological Aspects of Niacin?

Mechanism of Action:

Niacin's ability to alter lipid profiles remains incompletely understood. In addition to increased lipoprotein lipase activity, which may speed up the clearance of chylomicron triglycerides from plasma, it may also partially limit the free fatty acid release from adipose tissues. Niacin does not affect the fecal excretion of lipids, sterols, or bile acids, but it does tend to slow down the rate of hepatic production of VLDL and LDL.

Pharmacodynamics:

Niacin is used to treat vitamin deficiencies, hyperlipidemia, dyslipidemia, and hypertriglyceridemia, and to lower the risk of myocardial infarction. Niacin increases high-density lipoprotein levels while decreasing very low-density lipoprotein and low-density lipoprotein levels. Myopathy and rhabdomyolysis are more likely to occur in those taking Niacin with Lovastatin or Simvastatin who have diabetes, renal failure, untreated hypothyroidism, or are elderly.

Pharmacokinetics:

1. Absorption: When taken orally, around 60 to 76 percent of Niacin is quickly and thoroughly absorbed from the gut. Niacin should be used with a low-fat meal or snack to increase absorption and decrease the risk of gastrointestinal (GI) distress.

2. Distribution: Niacin and its metabolites are concentrated in the liver, kidney, and adipose tissue, according to investigations in mice employing radiolabeled Niacin.

3. Metabolism: Niacin undergoes extensive and rapid first-pass metabolism, which is species- and dose-rate-specific. Hence, the drug's pharmacokinetic profile is complex. One metabolic pathway in humans involves a direct conjugation step with glycine to produce nicotinuric acid (NUA). After that, NUA is eliminated in the urine. However, a slight reversible metabolism may convert NUA back to Niacin.

In an alternate process, nicotinamide adenine dinucleotide (NAD) is produced. It is uncertain if nicotinamide is created before or after NAD is synthesized. N-methylnicotinamide (MNA) and nicotinamide-N-oxide are at least two products of the subsequent metabolism of nicotinamide (NNO). N-methyl-2-pyridone-5-carboxamide (2PY) and N-methyl-4-pyridone-5-carboxamide are the products of further metabolizing MNA (4PY).

These metabolic pathways are saturable at the levels required to treat hyperlipidemia, accounting for the nonlinear relationship between Niacin dose and plasma concentrations observed with many Niacin extended-release tablets. Although the other metabolites' activity is unknown, nicotinamide does not exhibit hypolipidemic activity.

4. Excretion: Niacin is primarily excreted in the urine. Approximately 60 to 75 percent of the Niacin dose given as Niacin extended-release tablets was recovered in the urine after single and multiple doses as Niacin and metabolites; up to 12 percent was recovered as unaltered Niacin after multiple dosing. The dose administered affected the ratio of metabolites recovered in the urine.

Toxicity

Clinical Toxicity:

Mild to Moderate Toxicity:

• Niacin overdose symptoms include epigastric discomfort or abdominal pain, nausea, vomiting, a warm sensation, chills, and sporadic rash (diffuse, red, flat, and coalescent), mostly affecting the scalp, face, and legs. Subacute sustained-release Niacin overdoses have been linked to lactic acidosis.

• Supportive and symptomatic care is provided. Observe the vital signs. Vomiting and nausea could start. Replace IV fluids and electrolytes as needed; monitor fluids and electrolytes.

Severe Toxicity:

• A severe Niacin overdose has been associated with severe hypotension (11,000 mg). Supportive and symptomatic care is provided. Watch for vital signs, such as rising blood pressure. Individuals with tachycardia or other dysrhythmias undergo continuous cardiac monitoring and receive a baseline ECG to assess for potential QT interval changes. Dopamine, Norepinephrine, and IV 0.9 percent NaCl (sodium chloride) at 10 to 20 mL/kg are used to treat hypotension.

• Intravenous administration can result in anaphylactic responses in the event of allergic reactions.

• Antihistamines can treat mild to moderate allergic responses with or without inhaled beta-adrenergic agonists, Corticosteroids, or Epinephrine. Severe anaphylaxis can also be treated with oxygen replacement, vigorous airway control, epinephrine administration, ECG monitoring, and intravenous fluids.

Clinical Studies:

Niacin has been shown to be an effective diet therapy drug for treating hyperlipoproteinemia, either alone or in combination with other lipid-altering medications.

Study: 162 nonsmoking males who had undergone coronary bypass surgery participated in the Cholesterol-Lowering Atherosclerosis Study (CLAS), a randomized, placebo-controlled, angiographic trial assessing combination colestipol and Niacin therapy. The global coronary artery change score was the primary cardiac objective for each subject. When native arteries and grafts were considered, 61 percent of patients in the placebo cohort (n = 82) showed disease progression by global change score after two years, compared to only 38.8 percent of drug-treated subjects (n = 80). Disease regression also happened more frequently in the drug-treated group (16.2 percent versus 2.4 percent; p =0.002).

Warnings and Precautions:

• Cardiovascular: Caution must be taken in patients with unstable angina or the acute phase of myocardial infarction, especially with concurrent use of vasoactive drugs like calcium channel blockers, nitrates, adrenergic blocking agents, etc.

• Endocrine and Metabolic: Monitoring is advised due to potential increases in fasting blood sugar. Individuals prone to gout should use this medication cautiously because uric acid levels may increase. Monitoring is advised if phosphorus levels decrease.

• Gastrointestinal: Monitoring is advised in patients with a history of peptic ulcer. Monitoring is recommended.

• Hematologic: Prothrombin time may rise; monitoring is advised, especially if anticoagulants are also being taken concurrently. Platelet count reduction is possible, particularly when anticoagulants are used concurrently.

• Hepatic: Monitoring is advised in cases of jaundice or hepatobiliary illness. Liver function parameters may be abnormal; monitoring is advised.

• Musculoskeletal: In patients with diabetes, renal insufficiency, or untreated hypothyroidism, rhabdomyolysis has been described when statins are used concurrently; monitoring is advised.

• Renal: Use with caution in patients with renal impairment.

What Are the Contraindications of Niacin?

The following conditions are contraindicated for Niacin extended-release tablets:

• Known history of hypersensitivity to the inactive or active ingredients of Niacin.

• History of active liver disease or unexplained persistent elevations in hepatic transaminases.

• If the patient has an active peptic ulcer.

• Arterial bleeding.

What Are the Drug Interactions of Niacin?

• Niacin should not be co-administered with HMG CoA (hydroxymethylglutaryl-coenzyme A) inhibitors due to the increased risk of rhabdomyolysis.

• As part of antihypertensive therapy, Niacin may enhance the effects of ganglionic blocking and vasoactive medicines, causing postural hypotension.

• Taking Aspirin together with Niacin extended-release tablets may reduce its metabolic clearance. However, the clinical significance of this interaction is unclear.

• The ability of bile acid sequestrants like Colestipol and Cholestyramine to bind Niacin was investigated in vitro. Niacin was mostly linked to Colestipol (about 98 percent) and Cholestyramine (10 to 30 percent). These findings imply that there should be at least 4 and no more than 6 hours between taking bile acid-binding resins and administering Niacin extended-release tablets.

• Consuming alcohol or hot beverages concurrently with Niacin may worsen flushing and itchiness and should be avoided.

• Vitamins and other dietary supplements with high concentrations of Niacin or closely related chemicals, such as nicotinamide, can subsequently increase the risk of side effects.

Other Specifications:

1. Niacin in Pregnant Women: There is insufficient data regarding the safety of the drug for pregnant women.

2. Niacin in Lactating Women: Although Niacin is excreted into human milk, it is unknown how much is given to infants or how much of the maternal dose is given to infants. A judgment should be made on whether to stop nursing or take the medication due to the possibility of major adverse effects in breastfeeding infants from lipid-altering doses of nicotinic acid, taking into account the necessity of the medication for the mother. Niacin extended-release tablets have not yet been studied in nursing mothers.

3. Niacin in Pediatrics: The efficacy of Niacin extended-release tablets has yet to be established in children under 16.

4. Niacin in Geriatrics: 21 percent of the 979 individuals who participated in clinical trials of Niacin extended-release tablets showed no differences in safety and effectiveness observed between these and younger patients.

5. Niacin in Patients With Renal Impairment: There needs to be adequate data on the effect of Niacin on patients with renal impairment. Caution is required while administering Niacin to patients with chronic kidney injury.6. Niacin in Patients With Hepatic Impairment: Precaution is required for patients who consume excessive amounts of alcohol or have a history of liver illness. Niacin is not recommended in cases of active liver disorders or unexplained transaminase increases.