Usage
Nicotinamide, a form of vitamin B3 (niacin), is prescribed for preventing and treating niacin deficiency (pellagra). Pellagra is characterized by dermatitis, diarrhea, and dementia. It is also used to treat and prevent hyperphosphatemia in patients with chronic kidney disease. Furthermore, Nicotinamide has shown promise in reducing the risk of non-melanoma skin cancers, specifically actinic keratosis and squamous cell carcinoma, in high-risk individuals. The evidence of its efficacy in other conditions like atrial fibrillation and heart failure, or as an adjunct treatment for lung adenocarcinoma, is still under investigation and not yet established standard practice.
Pharmacological Classification: Vitamin, water-soluble. Nicotinamide is also classified as an anti-hyperphosphatemic agent when used in that capacity.
Mechanism of Action: Nicotinamide is a precursor to nicotinamide adenine dinucleotide (NAD+), a crucial coenzyme involved in numerous metabolic reactions. By increasing NAD+ levels, Nicotinamide can support cellular energy production and protect cells from damage, potentially contributing to its therapeutic effects.
Alternate Names
Niacinamide, Nicotinic acid amide
Brand Names: Niagen®, Tru Niagen®
How It Works
Pharmacodynamics: Nicotinamide is converted into NAD+ in the body, which is a critical coenzyme for numerous redox reactions. It is involved in energy metabolism, DNA repair, and cell signaling. Its therapeutic effect in skin cancer is likely due to DNA repair and anti-inflammatory effects.
Pharmacokinetics:
- Absorption: Nicotinamide is well-absorbed orally.
- Metabolism: Converted to NAD+ and other metabolites.
- Elimination: Primarily renal excretion.
Mode of Action: Nicotinamide acts as a precursor to NAD+, influencing various cellular processes, including cellular energy production, DNA repair, and inflammation.
Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Binds to benzodiazepine receptors (at high doses). Inhibits poly(ADP-ribose) polymerase (PARP), may be involved in its anti-inflammatory action.
Elimination Pathways: Primarily excreted unchanged in urine.
Dosage
Standard Dosage
Adults:
- Niacin Deficiency: 300-500 mg/day orally, divided into doses. May also be given intravenously (IV) or intramuscularly (IM).
- Hyperphosphatemia: 500 mg to 2 g/day orally, divided into doses. Titration may be needed based on serum phosphate levels.
- Skin Cancer Prevention: 500 mg twice daily orally.
Children: Dosages vary depending upon the specific indication and are generally weight-based. Consult specialized pediatric resources.
Special Cases:
- Elderly Patients: Start with lower doses and monitor for side effects.
- Patients with Renal Impairment: Dose adjustment may be necessary. Monitor kidney function.
- Patients with Hepatic Dysfunction: Use with caution. Monitor liver function.
- Patients with Comorbid Conditions: Careful monitoring is required in patients with diabetes, as nicotinamide can affect blood sugar control.
Clinical Use Cases Nicotinamide’s use in these settings is largely experimental and not yet an established part of standard clinical protocols for these scenarios:
- Intubation: No established dosage.
- Surgical Procedures: No established dosage.
- Mechanical Ventilation: No established dosage.
- Intensive Care Unit (ICU) Use: No established dosage.
- Emergency Situations: No established dosage.
Dosage Adjustments: Adjustments may be necessary for renal/hepatic impairment, considering estimated glomerular filtration rate (eGFR) and liver function tests.
Side Effects
Common Side Effects:
Gastrointestinal upset (nausea, vomiting), headache, fatigue. Flushing (more common with nicotinic acid than nicotinamide).
Rare but Serious Side Effects:
Hepatotoxicity (liver damage), particularly at high doses.
Long-Term Effects: Potential for hepatotoxicity with prolonged high-dose use.
Adverse Drug Reactions (ADR): Severe allergic reactions (rare), hepatotoxicity.
Contraindications
- Absolute: Severe liver disease, active peptic ulcer, arterial bleeding, hypersensitivity to nicotinamide.
- Relative: Gallbladder disease, gout, diabetes mellitus (requires blood glucose monitoring), renal impairment (dose adjustment needed), pre-existing cardiovascular disease.
Drug Interactions
- Antihypertensive Medications: May enhance the effects of antihypertensives.
- Alcohol: Can exacerbate flushing.
- Other Niacin Forms: Avoid concurrent use of different niacin forms.
Pregnancy and Breastfeeding
Nicotinamide is considered possibly safe during pregnancy and breastfeeding when taken in recommended amounts. However, high doses should be avoided unless explicitly recommended by a physician.
Drug Profile Summary
- Mechanism of Action: NAD+ precursor, involved in numerous metabolic processes.
- Side Effects: GI upset, headache, fatigue, flushing (less common than nicotinic acid), hepatotoxicity (rare).
- Contraindications: Severe liver disease, active peptic ulcer, arterial bleeding, hypersensitivity.
- Drug Interactions: Antihypertensives, alcohol.
- Pregnancy & Breastfeeding: Possibly safe in recommended doses.
- Dosage: Varies depending on indication; see above.
- Monitoring Parameters: Liver function tests (LFTs), renal function, blood glucose (in diabetics).
Popular Combinations Nicotinamide is often included in multivitamin supplements, particularly B-complex vitamins.
Precautions
- General Precautions: Baseline liver function tests (LFTs) before starting high-dose therapy.
- Specific Populations: Monitor diabetics for changes in blood sugar control.
- Lifestyle Considerations: Limit alcohol intake to minimize flushing.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Nicotinamide?
A: The dosage varies depending on the indication. See the detailed dosage section above.
Q2: What are the common side effects of Nicotinamide?
A: Common side effects include gastrointestinal upset (nausea, vomiting), headache, and fatigue. Flushing is less common with nicotinamide than with nicotinic acid.
Q3: What are the serious side effects of Nicotinamide?
A: The most serious side effect is hepatotoxicity, which is more likely with high doses. Liver function tests should be monitored, especially with prolonged use.
Q4: Is Nicotinamide safe during pregnancy?
A: Nicotinamide is considered possibly safe during pregnancy when taken in recommended amounts. Consult a physician for appropriate dosing during pregnancy.
Q5: Can Nicotinamide interact with other medications?
A: Yes, Nicotinamide can interact with antihypertensive medications, potentially enhancing their effects. It can also interact with alcohol, increasing the risk of flushing.
Q6: What is the role of Nicotinamide in skin cancer prevention?
A: Nicotinamide, through its role in DNA repair and by potentially reducing UV-induced immunosuppression, can reduce the risk of actinic keratosis and non-melanoma skin cancers in high-risk individuals.
Q7: What should be monitored in patients taking Nicotinamide?
A: Liver function tests, especially in patients taking high doses. Blood glucose should be monitored in patients with diabetes. Renal function should be monitored in patients with renal impairment.
Q8: What is the difference between Nicotinamide and Nicotinic acid?
A: Both are forms of vitamin B3. However, nicotinic acid is more likely to cause flushing, while nicotinamide is generally better tolerated.
Q9: How is Nicotinamide administered?
A: Nicotinamide is typically administered orally as tablets or capsules. It can also be given intravenously or intramuscularly, particularly for treating severe niacin deficiency.
Q10: What is the role of Nicotinamide in treating hyperphosphatemia?
A: Nicotinamide can reduce phosphate absorption in the gut, which can help lower serum phosphate levels in patients with chronic kidney disease.
