Nicotinic Acid

Nicotinic Acid is a Vitamin B belonging to the triglyceride synthesis Inhibitor.

Nicotinic Acid is used in the treatment of Dyslipidemias and as Dietary Supplement. It is also used to treat Pellagra.

Nicotinic Acid is readily absorbed from the GI tract and is widely distributed in body tissues and appears in breast milk and gets excreted Via urine in small amounts as an unchanged drug. Plasma elimination half-life: 20-45 min.

Nicotinic Acid shows common side effects like Headache, dizziness, Diarrhea, sore throat, runny nose, sneezing, joint pain, etc.

Nicotinic Acid is available in the form of Oral Tablets, Capsules, and powder.

Nicotinic Acid is available in India, Germany, Japan, France, USA

Nicotinic Acid is bioconverted to nicotinamide which is further converted to nicotinamide adenine dinucleotide (NAD+) and the hydride equivalent (NADH), which are coenzymes necessary for tissue metabolism, lipid metabolism, and glycogenolysis. The mechanism by which niacin (in lipid-lowering doses) affects plasma lipoproteins is not fully understood. It may involve several actions, including partial inhibition of the release of free fatty acids from adipose tissue and increased lipoprotein lipase activity, which may increase the rate of chylomicron triglyceride removal from plasma. Ultimately, niacin reduces total cholesterol, apolipoprotein (apo) B, triglycerides, VLDL, LDL, and lipoprotein (a) and increases HDL and other important components and subfractions.

Nicotinic Acid is available in the form of Oral Powder, Capsules, And tablets.

Tablets or Capsules should be administered with or without food twice a day.

Nicotinic Acid is used in the treatment of Dyslipidemias and as Dietary Supplements. It is also used to treat Pellagra

Nicotinic Acid is a derivative of vitamin B3 and is incorporated into coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which are involved in multiple cellular metabolic pathways. Nicotinic Acid also reduces total serum cholesterol, LDL, VLDL, apolipoprotein B and triglycerides, and increases HDL cholesterol.

Nicotinic Acid is approved for use in the following clinical indications

Dietary supplement: Use as a dietary supplement.

Dyslipidemias: Treatment of dyslipidemias (Fredrickson types IIa and IIb or primary hypercholesterolemia) as mono- or adjunctive therapy; to lower the risk of recurrent MI in patients with a history of MI and hyperlipidemia; to slow progression or promote regression of coronary artery disease; adjunctive therapy for severe hypertriglyceridemia in adults at risk of pancreatitis

Although not approved there have been certain off label use documented for Nicotinic Acid which includes:

• Pellagra

Nicotinic Acid is available in various strengths as 250 mg, 500 mg, 750 mg, 1000 mg

Nicotinic Acid is available in the form of Oral Powder, Capsules and Tablets.

• Dosage Adjustment for Pediatric Patients:

Dyslipidemias: Very limited data available : Note: Niacin (nicotinic Acid) is rarely used in pediatric patients for treatment of dyslipidemias and is not considered a primary agent nor a routine secondary, adjunctive agent for dyslipidemia management in pediatric patients.

Children ≥10 years and Adolescents : Oral:

Regular release: Initial: 100 to 250 mg/day in 3 divided doses with meals; maximum initial daily dose: 10 mg/kg/day; increase weekly by 100 mg/day or increase every 2 to 3 weeks by 250 mg/day as tolerated; evaluate efficacy and adverse effects with laboratory tests at 20 mg/kg/day or 1,000 mg/day (whichever is less); continue to increase if needed and as tolerated; re-evaluate at each 500 mg increment; daily doses up to 2,250 mg/day have been used.

Sustained release: Reported range: 500 to 1,500 mg/day; initiate at a low dose administered once daily (based on experience in adults); reported initial daily dose has not exceeded 10 mg/kg/day; titrate every 3 to 4 weeks (in adults, doses are titrated every 4 weeks).

Pellagra; treatment: Children and Adolescents: Oral: Regular release: 50 to 300 mg/day in divided doses 3 times daily; usual treatment duration is 3 to 4 weeks

Hypercholesterolemia: Reducing the amount of saturated and trans fats in the diet to lower cholesterol and heart disease risk. To reduce levels of “bad” cholesterol, limit the intake of the following foods, which contain high levels of saturated and trans fats: fatty meat, such as lamb and pork.

Nicotinic Acid is contraindicated in patients with

• Hypersensitivity to niacin, niacinamide, or any component of the formulation; active hepatic disease or significant or unexplained persistent elevations in hepatic transaminases; active peptic ulcer; arterial hemorrhage

Disease-related concerns:

• Gastrointestinal disease: Use is not recommended in patients with gastroparesis, other severe GI motility disorders, a history of major GI tract surgery, or patients at risk for bowel obstruction. Use tablets with caution in patients with dysphagia or swallowing disorders; use the oral suspension form of Nicotinic Acid due to large tablet size and risk for esophageal obstruction. Discontinue if symptoms of bowel obstruction occur (eg, severe abdominal pain, severe constipation).

• Hypertriglyceridemia: Bile acid sequestrants can increase serum triglyceride concentrations; severely elevated triglycerides can cause acute pancreatitis. The manufacturer contraindicates use if triglycerides exceed 500 mg/dL and in patients with a history of hypertriglyceridemia-induced pancreatitis. The American College of Cardiology/American Heart Association recommends avoiding use in patients with baseline fasting triglyceride levels ≥300 mg/dL ). Use with caution in patients using insulin, thiazolidinediones, or sulfonylureas (may cause increased triglyceride concentrations). Discontinue if symptoms of acute pancreatitis occur (eg, severe abdominal pain with or without nausea and vomiting).

• Patients susceptible to fat-soluble vitamin deficiencies: Use with caution in patients susceptible to fat-soluble vitamin deficiencies. Absorption of fat soluble vitamins A, D, E, and K may be decreased; patients should take vitamins ≥4 hours before Nicotinic Acid

• Phenylketonuria: Some products may contain phenylalanine; use with caution.

Nicotinic Acid may cause liver problems, and using it with substantial quantities of ethanol may increase that risk.

Nicotinic Acid is present in breast milk.

Concentrations of Nicotinic Acid in breast milk increase with supplementation. When used as a dietary supplement, the recommended dietary allowance of Nicotinic Acid is increased in breastfeeding patients compared to non-breastfeeding patients. Doses of Nicotinic Acid for the treatment of dyslipidemias are greater than those used as a dietary supplement. Due to the potential for serious adverse reactions in the breastfed infant (including hepatoxicity), the manufacturer recommends that breastfeeding be discontinued when Nicotinic Acid is used for treatment of dyslipidemias

Pregnancy Category C

When used as a dietary supplement, the recommended dietary allowance of niacin is increased during pregnancy compared to non-pregnant patients.

It is not known if Nicotinic Acid at lipid-lowering doses is harmful to the developing fetus. If a patient becomes pregnant while receiving niacin for primary hypercholesterolemia, Nicotinic Acid should be discontinued. If a patient becomes pregnant while receiving Nicotinic Acid for hypertriglyceridemia, the benefits and risks of continuing Nicotinic Acid should be assessed on an individual basis.

Should be taken with meal; low-fat meal if treating dyslipidemia. Avoid alcohol, hot or spicy foods/liquids around the time of niacin dose.

• Common Adverse effects

Flushing, sensation of heat, faintness, pounding in the head, tingling, itching, headache, dizziness, tachycardia, palpitations, dyspnea, sweating, chills, edema.

• Less Common Adverse effects

Dryness of skin, pruritus, hyperpigmentation, rash, cramps, cough, diarrhea, nausea and vomiting, anorexia, activation of peptic ulcer, eye disorders including cystoid macular edema and toxic amblyopia

• Rare Adverse effects

Abnormal LFTs, jaundice; hypophosphataemia, reduced platelet counts, prolonged prothrombin time, arrhythmias, hypersensitivity reactions including angioedema; insomnia, myalgia and hypotension.

• Increased risk of myopathy and rhabdomyolysis w/ concomitant HMG-CoA reductase inhibitors.
• Reduced bioavailability w/ colestyramine or colestipol. Decreased metabolic clearance w/ aspirin.
• May potentiate effects of ganglionic blocking agents and vasoactive drugs resulting in postural hypotension.

The common side effects of Nicotinic Acid include the following

Common

● Pounding in the head, tingling, itching, headache, dizziness, tachycardia, palpitations, dyspnoea, sweating, chills, oedema; dryness of skin, pruritus, hyperpigmentation, rash, cramps.

Symptoms: Severe local GI effects (e.g., constipation).

Management: Location and degree of obstruction, presence or absence of normal gut motility would determine treatment.

Pharmacodynamic

Nicotinic Acid is a derivative of vitamin B3 and is incorporated into coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which are involved in multiple cellular metabolic pathways. Nicotinic Acid also reduces total serum cholesterol, LDL, VLDL, apolipoprotein B and triglycerides, and increases HDL cholesterol.

Pharmacokinetics

• Absorption: Readily absorbed from the GI tract.
• Distribution: Widely distributed in body tissues and appears in breast milk.
• Metabolism: Converted to N-methylnicotinamide, 2-pyridone and 4-pyridone derivatives.
• Excretion: Via urine in small amounts as unchanged drug. Plasma elimination half-life: 20-45 min.

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1364710/
2. https://reference.medscape.com/drug/colestid-Nicotinic Acid -342452
3. https://go.drugbank.com/drugs/DB00375
4. https://www.sciencedirect.com/topics/medicine-and-dentistry/Nicotinic Acid
5. https://europepmc.org/article/med/6988203