Niacin
Niacin
Generic Name
Niacin
Mechanism
- Receptor‑mediated: Niacin binds to the G‑protein‑coupled receptor GPR109A (also known as HM74A) on adipocytes and macrophages, inhibiting lipolysis.
- Lipoprotein modulation:
- ↓ Free fatty acids (FFA) → ↓ hepatic VLDL synthesis → ↓ LDL and triglycerides.
- ↑ Hepatic ApoA‑I synthesis → ↑ HDL cholesterol.
- Anti‑inflammatory: By reducing macrophage foam cell formation, niacin mitigates atherogenesis.
Pharmacokinetics
| Parameter | Value | Notes |
| Absorption | Oral – 50–70 % bioavailability; peak plasma level 4–6 h post‑dose. | Food enhances absorption but may delay egress. |
| Distribution | Widely distributed; lipophilic. | Penetrates adipose tissue. |
| Metabolism | Hepatic (mainly via N‑acetylation). | No major drug interactions but alcohol may potentiate hepatotoxicity. |
| Elimination | Renal (≈30 %) and fecal. | Half‑life 3–4 h (immediate‑release); extended‑release deposits last ~18 h. |
| Special Populations | Renal or hepatic impairment – dose adjustment; avoid in decompensated liver disease. |
Indications
- Hyperlipidemia
- ↑ HDL > 100 mg/dL
- ↓ LDL and triglycerides, especially in atherogenic dyslipidemia.
- Statin‑intolerance in patients requiring lipid modification.
- Pellagra: deficiency of niacin → dermatitis, diarrhea, dementia.
- Treating hyperuricemia (in some low‑dose regimens).
Contraindications
| Contraindication | Rationale |
| Decompensated hepatic disease | Risk of severe hepatotoxicity. |
| Hepatic dysfunction | See above. |
| Peptic ulcer disease | Niacin can aggravate ulcer episodes. |
| Gout/Hyperuricemia | Niacin exacerbates serum uric acid. |
| Hypersensitivity to nicotinic acid | Avoid. |
| Severe hypertriglyceridemia (>600 mg/dL) | May precipitate pancreatitis when coupled with niacin. |
Warnings:
• Monitor liver function; dose adjustment in mild hepatic disease.
• Avoid concomitant alcohol.
• Use caution in patients with uncontrolled diabetes; niacin can impair glucose tolerance.
Dosing
| Formulation | Typical Dose | Titration |
| Immediate‑Release (IR) | 100–300 mg 1–3×/day (max 1.5–2 g/day) | Start 100 mg at night → ↑ 100 mg q12 h every 72 h. |
| Extended‑Release (ER) | 500–1000 mg once daily | Start 500 mg nightly → ↑ 500 mg every 5–7 days. |
• Administration: Take with meals to reduce flushing.
• Flushing prevention: concurrent aspirin 325 mg taken 30 min before; topical diphenhydramine cream 10 % or oral antihistamines.
• Avoid: smoking (exacerbates flush) and alcohol (liver toxicity).
• Special guidance: For statin‑intolerance, start with IR at low dose, then shift to ER.
Adverse Effects
- Common
- Flushing, itching, erythema → mitigated by antihistamines.
- Gastro‑intestinal upset (nausea, vomiting).
- Headache, dizziness.
- Hyperuricemia → gout flare risk.
- Hyperglycemia/insulin resistance.
- Serious
- Hepatotoxicity: transaminase ↑≥3× ULN, jaundice.
- Myopathy (rare, especially when combined with statins).
- Severe hypersensitivity reactions: rash, angioedema.
Monitoring
| Parameter | Frequency | Goals |
| Liver function tests (ALT/AST) | Baseline, 4 weeks, then monthly for 6 mo | 30 %. |
| Fasting glucose/HbA1c | Baseline, every 3 mo | No >10 % rise in HbA1c. |
| Serum uric acid | Baseline (if gout history), then yearly | Avoid rise >2 mg/dL. |
| Renal function | Baseline, every 6 mo | GFR >45 mL/min/1.73 m² for ER. |
Clinical Pearls
- Flushing is dose‑related; starting at the lowest dose significantly reduces morbidity and enhances adherence.
- Aspirin + Niacin: Aspirin (325 mg) or ibuprofen ± antihistamine pre‑dose is highly effective in flushing management.
- Gastric acid reduction: Taking niacin with a strong acid‑suppressing agent (e.g., PPIs) diminishes GI irritation.
- Non‑statin combinations: Niacin preserves HDL when used with icosapent ethyl or ezetimibe but may synergize adverse hepatic effects.
- Gout consideration: In patients with gout, a lower maintenance dose (<1 g) or alternative lipid agents may be preferable.
Key Takeaway: Niacin uniquely augments HDL and lowers LDL/triglycerides but demands vigilant monitoring of hepatic function and glucose tolerance, especially in high‑dose or chronic therapy.