Nicotinic acid

Usage

• Nicotinic acid, also known as niacin or vitamin B3, is prescribed for treating dyslipidemia (high cholesterol and triglycerides), specifically elevated total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), and triglycerides (TG). It also increases high-density lipoprotein cholesterol (HDL-C). It is also used to reduce the risk of recurrent nonfatal myocardial infarction in patients with a history of MI and hyperlipidemia. Niacin is indicated as adjunctive therapy for treatment of adult patients with severe hypertriglyceridemia who present a risk of pancreatitis. Additionally, it is used to treat pellagra, a condition caused by niacin deficiency.
• Pharmacological Classification: Lipid-lowering agent, Vitamin.

Alternate Names

• Niacin
• Vitamin B3
• Nicotinamide (a related compound, also a form of vitamin B3)
• Brand names: Niacor, Niaspan

How It Works

• Pharmacodynamics: Nicotinic acid reduces the hepatic synthesis of very-low-density lipoproteins (VLDL) and LDL, ultimately leading to lower levels of LDL-C and TG. It also increases HDL-C levels. The precise mechanism is not fully elucidated but involves inhibition of diacylglycerol acyltransferase 2 (DGAT2), an enzyme essential for triglyceride synthesis.
• Pharmacokinetics:
  • Absorption: Well-absorbed orally.
  • Metabolism: Converted to nicotinamide and other metabolites in the liver.
  • Elimination: Primarily renal excretion.

Dosage

Standard Dosage

Adults:

• Dyslipidemia: Initial dose: 250 mg orally at bedtime. Gradually increase every 4-7 days to 1.5-2 g/day in divided doses. Maximum dose: 6 g/day. Extended-release: Initial dose: 500 mg at bedtime. Increase every 4 weeks to 1-2 g/day.
• Pellagra: 300-500 mg/day orally in divided doses.
• Hartnup disease: 50-200 mg/day orally.

Children:

• Pellagra: 100-300 mg/day orally in divided doses.
• Other indications: Dosage should be determined by a physician.

Special Cases:

• Elderly Patients: Start with lower doses and titrate carefully.
• Patients with Renal Impairment: Dose adjustment may be necessary.
• Patients with Hepatic Dysfunction: Contraindicated in active liver disease. Monitor liver function tests.
• Patients with Comorbid Conditions: Use with caution in diabetes, gout, peptic ulcer disease, and hypotension.

Clinical Use Cases

Dosing in these settings should be guided by the underlying condition and patient-specific factors and is not generally indicated for these specific clinical use cases:

• Intubation: Not applicable.
• Surgical Procedures: Not applicable.
• Mechanical Ventilation: Not applicable.
• Intensive Care Unit (ICU) Use: Not applicable.
• Emergency Situations: Not applicable.

Dosage Adjustments

• Adjust dose based on individual response and tolerance.
• Reduce dose in patients with renal or hepatic impairment.

Side Effects

Common Side Effects

• Flushing (warmth, redness, itching, tingling)
• Headache
• Dizziness
• Itching
• Nausea
• Vomiting
• Abdominal pain
• Diarrhea

Rare but Serious Side Effects

• Liver damage
• Myopathy
• Rhabdomyolysis
• Peptic ulcer activation
• Severe hypotension
• Cardiac arrhythmias

Long-Term Effects

• Glucose intolerance or hyperglycemia
• Hyperuricemia
• Hepatotoxicity (with prolonged high doses)

Adverse Drug Reactions (ADR)

• Anaphylaxis (rare)
• Angioedema (rare)

Contraindications

• Active liver disease
• Active peptic ulcer disease
• Arterial bleeding
• Hypersensitivity to niacin

Drug Interactions

• Alcohol: Increased risk of liver damage and flushing.
• Allopurinol: May require higher doses of allopurinol to control gout.
• Anticoagulants/Antiplatelet drugs: Increased risk of bleeding.
• Antihypertensives: Additive hypotensive effect.
• Statins: Increased risk of myopathy and rhabdomyolysis.
• Hepatotoxic drugs: Increased risk of liver damage.
• Other medications metabolized by CYP450 enzymes: Potential for drug interactions.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: C (Avoid high doses used for dyslipidemia). Adequate intake for pregnancy is 18 mg NE/day.
• May pass into breast milk. Adequate intake for lactation is 17 mg NE/day.

Drug Profile Summary

• Mechanism of Action: Reduces hepatic VLDL and LDL synthesis, increases HDL-C.
• Side Effects: Flushing, headache, dizziness, itching, gastrointestinal upset, liver toxicity (high doses).
• Contraindications: Active liver disease, peptic ulcer, arterial bleeding.
• Drug Interactions: Alcohol, anticoagulants, antihypertensives, statins, hepatotoxic drugs.
• Pregnancy & Breastfeeding: Caution advised. Avoid high doses.
• Dosage: Varies depending on indication and patient factors. See Dosage section.
• Monitoring Parameters: Lipid panel, liver function tests, blood glucose, uric acid.

Popular Combinations

• Statins: Although it may increase side effects, niacin is sometimes combined with statins for enhanced lipid-lowering effects. Bile acid sequestrants or other lipid-lowering therapies may be considered.

Precautions

• Pre-existing liver disease, peptic ulcer disease, gout, diabetes, hypotension, and alcohol use.
• Monitor liver function, blood glucose, and uric acid levels during therapy.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Nicotinic acid?

A: The dosage depends on the indication and individual patient factors. For dyslipidemia in adults, it typically starts at 250 mg orally at bedtime and is gradually increased. For pellagra, 300-500 mg/day in divided doses is common. Pediatric and other dosages should be determined by a physician.

Q2: What is the most common side effect of nicotinic acid?

A: Flushing, characterized by warmth, redness, itching, and tingling, is the most common side effect.

Q3: How can flushing be managed?

A: Taking nicotinic acid with meals or taking aspirin 30 minutes prior can help reduce flushing. Slow titration of dose is also helpful.

Q4: Is nicotinic acid safe during pregnancy?

A: High doses used for dyslipidemia should be avoided during pregnancy. Low doses for nutritional supplementation are generally considered safe, but a physician should be consulted.

Q5: Can nicotinic acid interact with other medications?

A: Yes, nicotinic acid can interact with several medications, including alcohol, anticoagulants, antihypertensives, and statins. A full medication review should be conducted before starting niacin therapy.

Q6: What should be monitored in patients taking nicotinic acid?

A: Liver function tests, blood glucose, and uric acid should be monitored regularly, particularly with higher doses. Lipid panel monitoring is also needed to assess treatment efficacy.

Q7: Are there any contraindications to using nicotinic acid?

A: Yes, contraindications include active liver disease, active peptic ulcer disease, arterial bleeding, and hypersensitivity to niacin.

Q8: What is the difference between nicotinic acid and nicotinamide?

A: Both are forms of vitamin B3, but nicotinic acid is primarily used for its lipid-lowering effects, while nicotinamide is usually used for treating niacin deficiency and does not generally have the same lipid effects. Nicotinamide also typically causes less flushing.

Q9: Can nicotinic acid be used with statins?

A: It can be used with statins, but this combination increases the risk of muscle-related side effects such as myopathy and rhabdomyolysis. This combination should be used cautiously with careful monitoring.