Niacinamide

Pellagra (Deficiency)

For the treatment of active pellagra, healthcare providers typically prescribe 50 mg to 100 mg orally three to four times daily. The total daily dose usually ranges from 300 mg to 500 mg depending on the severity of symptoms.

Skin Cancer Prevention (Off-label)

Based on the landmark ONTRAC study, the standard dose for high-risk individuals is 500 mg twice daily. This regimen should be maintained long-term, as the protective effects diminish once the medication is discontinued.

Acne Vulgaris (Topical)

Topical formulations containing 4% to 5% niacinamide are typically applied to affected areas twice daily after cleansing.

Pediatric dosing for pellagra is highly individualized based on age and weight. Typical ranges are 50 mg to 300 mg daily in divided doses. Niacinamide should only be administered to children under the direct supervision of a pediatrician.

Renal Impairment

No specific dosage adjustments are generally required for mild to moderate renal impairment; however, caution is advised in patients with end-stage renal disease due to the accumulation of metabolites.

Hepatic Impairment

Use with caution in patients with active liver disease. While niacinamide is less hepatotoxic than nicotinic acid, high doses can still stress hepatic function.

Elderly Patients

No specific age-related adjustments are standard, but providers should consider the overall health and renal function of the patient.

• Oral: May be taken with or without food. If stomach upset occurs, taking the dose with a meal may improve tolerance.
• Topical: Apply a thin layer to clean, dry skin. Avoid contact with eyes and mucous membranes.
• Storage: Store at room temperature (20°C to 25°C) away from moisture and direct sunlight.

If you miss a dose, take it as soon as you remember. If it is almost time for your next scheduled dose, skip the missed dose and resume your regular schedule. Do not double the dose to catch up.

Signs of acute overdose may include severe nausea, vomiting, dizziness, and potential liver enzyme elevations. In case of suspected overdose, contact a poison control center or seek emergency medical attention immediately.

> Important: Follow your healthcare provider's dosing instructions. Do not adjust your dose without medical guidance.

Niacinamide is generally very well-tolerated. When taken at standard doses, side effects are minimal. Some patients may experience:

• Mild Gastrointestinal Upset: This may include nausea, bloating, or flatulence (gas). These symptoms usually resolve as the body adjusts to the supplement.
• Topical Irritation: For cream or gel forms, mild stinging or redness may occur upon application.

• Headache: Some patients report mild tension-type headaches shortly after oral dosing.
• Dizziness: A transient feeling of lightheadedness.
• Pruritus (Itching): Itching of the skin without a visible rash.

• Increased Blood Glucose: High doses may slightly interfere with glycemic control in predisposed individuals.
• Hyperuricemia: Rare instances of elevated uric acid levels, which could potentially trigger gout in susceptible patients.

> Warning: Stop taking Niacinamide and call your doctor immediately if you experience any of these:

• Hepatotoxicity (Liver Injury): Symptoms include yellowing of the eyes or skin (jaundice), dark urine, severe upper abdominal pain, and persistent nausea. This is more common with doses exceeding 3 grams per day.
• Severe Allergic Reaction (Anaphylaxis): Symptoms include swelling of the face, lips, or tongue; difficulty breathing; or a widespread, blistering skin rash.
• Visual Changes: Blurred vision or changes in color perception (rarely associated with high-dose B3 analogs).

Prolonged use of high-dose niacinamide (over 1.5 grams daily) may lead to persistent elevations in liver enzymes. Regular monitoring by a healthcare provider is necessary for those on long-term, high-dose therapy.

No FDA black box warnings currently exist for Niacinamide. It is considered safe for the general population when used within established Recommended Dietary Allowance (RDA) or prescribed therapeutic ranges.

Report any unusual symptoms to your healthcare provider.

Niacinamide should be used with caution in individuals with a history of liver disease, gallbladder disease, or gout. While it is safer than nicotinic acid regarding cardiovascular effects and flushing, it is still a pharmacologically active substance that can influence metabolic pathways.

No FDA black box warnings for Niacinamide.

• Hepatotoxicity Risk: Although rare at doses below 1,500 mg daily, niacinamide has been associated with liver enzyme elevations. Patients with pre-existing liver conditions should be monitored closely.
• Diabetes Mellitus: High doses of niacinamide may cause a slight decrease in insulin sensitivity. Patients with diabetes should monitor their blood glucose levels more frequently when starting or increasing the dose.
• Peptic Ulcer Disease: Use with caution if you have a history of stomach ulcers, as B3 vitamins may stimulate gastric acid secretion.
• Allergic Reactions: Hypersensitivity to niacinamide or any components of the formulation (such as dyes or fillers) can occur.

For patients taking therapeutic doses (e.g., 1,000 mg/day or more) for extended periods, healthcare providers may recommend:

• Liver Function Tests (LFTs): Baseline and periodic checks of ALT, AST, and bilirubin.
• Blood Glucose: Periodic monitoring for patients with pre-diabetes or diabetes.
• Uric Acid Levels: For patients with a history of gout.

Niacinamide is not known to impair the ability to drive or operate heavy machinery. However, if you experience dizziness, avoid these activities until the symptom resolves.

Chronic alcohol consumption can deplete B-vitamin stores, including niacinamide. Conversely, excessive alcohol use while taking high doses of niacinamide may increase the risk of liver strain. It is best to limit alcohol intake during therapy.

There is no known withdrawal syndrome associated with niacinamide. However, if used for skin cancer prevention, the protective benefits stop almost immediately upon discontinuation. Always discuss stopping the medication with your doctor first.

> Important: Discuss all your medical conditions with your healthcare provider before starting Niacinamide.

There are no absolute drug-drug contraindications where Niacinamide must never be used; however, certain combinations require extreme caution.

• Carbamazepine (Tegretol): Niacinamide may decrease the clearance of carbamazepine, leading to increased blood levels and potential toxicity (e.g., ataxia, double vision). Blood level monitoring is recommended.
• Primidone (Mysoline): Similar to carbamazepine, niacinamide may increase primidone levels, potentially increasing sedation.

• Statins (HMG-CoA Reductase Inhibitors): While the risk is much lower than with nicotinic acid, combining high-dose niacinamide with statins may theoretically increase the risk of myopathy (muscle breakdown).
• Anti-platelet/Anticoagulant Drugs: Niacinamide may have very mild inhibitory effects on platelet aggregation. Use caution with drugs like warfarin, aspirin, or clopidogrel.

• High-Fat Meals: May slightly delay the absorption of oral niacinamide but does not significantly reduce the total amount absorbed.
• Alcohol: Increases the risk of hepatotoxicity when combined with high-dose niacinamide therapy.

• Other B-Vitamins: Taking niacinamide as part of a B-complex is generally safe, but ensure the total dose across all supplements does not exceed the tolerable upper intake level (UL).
• Hepatotoxic Herbs: Avoid combining high-dose niacinamide with herbs known to stress the liver, such as kava or comfrey.

• Urinary Catecholamines: Niacinamide may cause false-positive results in certain fluorometric tests for urinary catecholamines.
• Blood Glucose Tests: May slightly elevate readings in diabetic patients.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking.

• Hypersensitivity: Known allergy to niacinamide, nicotinic acid, or any inactive ingredient in the product. Reactions can range from mild rashes to anaphylaxis.
• Active Liver Disease: Because niacinamide is metabolized in the liver, use in patients with active hepatitis or unexplained elevations in liver enzymes is contraindicated.

• Active Peptic Ulcer: High doses may exacerbate gastric acid secretion, potentially worsening an active ulcer.
• Gout: Patients with a history of gout should use niacinamide cautiously, as it may interfere with the excretion of uric acid.
• Hemorrhage: Due to potential (though minor) effects on platelet function, use caution in patients with active bleeding disorders.

Patients who have experienced severe reactions to Nicotinic Acid (Niacin) should be closely monitored when taking Niacinamide, although many patients who cannot tolerate the 'flush' of niacin can safely take niacinamide.

> Important: Your healthcare provider will evaluate your complete medical history before prescribing Niacinamide.

FDA Pregnancy Category: C (at pharmacological doses). At Recommended Dietary Allowance (RDA) levels, niacinamide is considered safe and essential during pregnancy. However, high therapeutic doses (e.g., for skin cancer prevention) have not been extensively studied in pregnant women. It should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus.

Niacinamide is naturally present in human breast milk. Supplemental use at RDA levels is considered safe. The effects of high-dose maternal supplementation on the nursing infant are not well-documented; therefore, caution and medical consultation are advised for doses exceeding the RDA.

Niacinamide is approved for use in children for the treatment of pellagra. It is generally safe when used at appropriate age-based doses. It is not recommended for pediatric use in skin cancer prevention or acne unless specifically directed by a specialist, as long-term safety data in children for these indications are limited.

Clinical studies have not identified significant differences in response between elderly and younger patients. However, because elderly patients are more likely to have decreased renal function or be taking multiple medications (polypharmacy), healthcare providers should monitor for potential drug interactions and renal clearance issues.

Niacinamide metabolites are excreted renally. In patients with significant kidney disease, these metabolites may accumulate. While not typically toxic, dosage reduction or increased monitoring may be necessary in Stage 4 or 5 Chronic Kidney Disease (CKD).

Niacinamide should be avoided in patients with severe hepatic impairment (Child-Pugh Class C). In mild to moderate impairment, frequent monitoring of liver enzymes is required if therapeutic doses are prescribed.

> Important: Special populations require individualized medical assessment.

Niacinamide acts as a precursor to the essential cofactors NAD+ and NADP+. These molecules are vital for the transfer of electrons in redox reactions. Specifically, it supports the function of Sirtuins (enzymes involved in longevity and stress response) and PARP (enzymes involved in DNA repair). By maintaining cellular NAD+ pools, niacinamide prevents the 'energy crisis' in cells exposed to UV radiation, thereby facilitating DNA repair and reducing the expression of inflammatory mediators.

The onset of action for pellagra symptoms is rapid (24-48 hours). For inflammatory skin conditions, the pharmacodynamic effect on sebum and cytokines typically requires 4 to 8 weeks of consistent dosing. Unlike niacin, niacinamide does not significantly alter lipid profiles (cholesterol or triglycerides) at standard doses.

| Parameter | Value |

|---|---|

| Bioavailability | ~100% (Oral) |

| Protein Binding | <25% |

| Half-life | 1 - 2 hours |

| Tmax | 0.5 - 1 hour |

| Metabolism | Hepatic (N-methylation to MNA) |

| Excretion | Renal (>90% as metabolites) |

• Molecular Formula: C6H6N2O
• Molecular Weight: 122.12 g/mol
• Solubility: Highly soluble in water and ethanol.
• Structure: An amide of nicotinic acid (pyridine-3-carboxamide).

Niacinamide is classified as a Vitamin B Complex Member and a Vitamin B3 Analog. In the EPC system, it is categorized as an Adenosine Receptor Agonist [EPC] due to its modulatory effects on adenosine signaling pathways.