Kojic Acid 3% | Niacinamide 3% | Tretinoin 0.02%

Route: Topical. Apply a thin layer to the affected skin area(s) once daily (typically at night as directed, due to tretinoin photosensitivity). Avoid eyes, nostrils, lips, and mucous membranes. Use sunscreen with SPF ≥30 daily during treatment. Apply to dry skin (wait 20–30 minutes after washing) to reduce irritation from tretinoin. Begin use gradually as directed by the prescriber.

All dosing is prescriber-determined:

• Typically applied once nightly to hyperpigmented areas. Prescribers may direct alternate-night application initially to minimize retinoid irritation.
• Clinical response for hyperpigmentation generally requires 8–12 weeks of consistent use.
• Sunscreen use is mandatory during the treatment period (tretinoin increases UV sensitivity and kojic acid sensitizes skin).

• Kojic Acid 3%: Chelates the copper ions at the active site of tyrosinase, competitively inhibiting the enzyme that catalyzes tyrosine → DOPA → dopaquinone in the melanin biosynthesis pathway. Also acts as a free radical scavenger, reducing oxidative upregulation of melanogenesis.
• Niacinamide 3%: Inhibits the transfer of melanin-containing melanosomes from melanocytes to surrounding keratinocytes via a post-synthesis mechanism (not tyrosinase inhibition), thereby reducing epidermal pigmentation. Additionally increases ceramide and free fatty acid synthesis, improving skin barrier function and reducing inflammation (TEWL reduction), which indirectly supports tolerability of concurrent retinoid use.
• Tretinoin 0.02%: Binds RAR-alpha, RAR-beta, and RAR-gamma nuclear receptors, altering gene expression to increase keratinocyte mitosis and accelerate cornified cell detachment and turnover, dispersing melanin granules and removing hyperpigmented corneocytes more rapidly. Blocks inflammatory mediators, stimulates procollagen I and III synthesis, and inhibits matrix metalloproteinases (MMPs). At 0.02%, a conservative concentration is used to provide efficacy with reduced irritation, appropriate for patients with sensitive skin or phototype III–VI skin at higher ochronosis risk from other depigmenting agents.

Prescribed for management of melasma, post-inflammatory hyperpigmentation (PIH), solar lentigines, and general photoaging in patients where a gentler but multi-mechanistic depigmenting regimen is desired. The low tretinoin concentration (0.02%) reduces the incidence of retinoid dermatitis while still providing epidermal turnover benefits. Niacinamide at 3% provides anti-inflammatory and barrier-supportive effects that improve tolerability of the formulation.

Monitoring: Improvement in MASI (Melasma Area and Severity Index) or clinical pigmentation scoring at 8–12 weeks; assess for contact sensitization (kojic acid), retinoid dermatitis (erythema, peeling, dryness from tretinoin); enforce strict sun avoidance and SPF ≥30 sunscreen use. Avoid during pregnancy (retinoids are teratogenic).

Contraindications:

• Pregnancy or women planning to conceive (tretinoin is teratogenic — Category X for systemic retinoids; topical risk is low but avoid as a precaution).
• Known hypersensitivity to any component.
• Concurrent use of topical products containing high concentrations of alpha-hydroxy acids or chemical exfoliants without prescriber guidance (cumulative irritation risk).

Warnings & Precautions:

• Tretinoin dramatically increases photosensitivity — daily SPF ≥30 broad-spectrum sunscreen is mandatory.
• Kojic acid can cause contact sensitization and allergic contact dermatitis; discontinue if significant erythema or vesiculation occurs.
• Avoid in eczematous, sunburned, or broken skin.
• Avoid eye contact.

Drug Interactions:

• Tretinoin: avoid concurrent topical products with benzoyl peroxide, sulfur, salicylic acid, or resorcinol (potential inactivation of tretinoin and/or cumulative irritation).
• Photosensitizing drugs (tetracyclines, fluoroquinolones, thiazides): increased UV sensitivity compounded by tretinoin.

Common Side Effects: Retinoid dermatitis (dryness, peeling, erythema, mild stinging) — typically transient during first 4–6 weeks; kojic acid-related contact sensitization; photosensitivity.

Store at room temperature (15°C–25°C), away from light and heat. Protect from freezing. Tretinoin is light-sensitive; store in original opaque container. Kojic acid may discolor (yellow to brown) upon oxidation — product discoloration may indicate degradation. Use within the beyond-use date specified by Genesis Compounding.

Can I use this in the daytime?

This formulation is typically prescribed for nighttime application due to tretinoin's photosensitivity-increasing effect. Always apply SPF ≥30 broad-spectrum sunscreen in the morning during treatment.

Why is only 0.02% tretinoin used?

The lower tretinoin concentration is intentionally selected to provide epidermal turnover and depigmenting benefits while minimizing retinoid dermatitis (dryness, peeling, irritation), making the regimen more tolerable — particularly in darker Fitzpatrick skin types that may be prone to PIH from inflammation.

How is kojic acid different from hydroquinone?

Kojic acid inhibits tyrosinase by chelating copper at its active site; hydroquinone inhibits tyrosinase through substrate competition and also has cytotoxic effects on melanocytes at higher concentrations. Kojic acid is often used in patients where hydroquinone is not appropriate or has caused ochronosis with long-term use.

Is this FDA-approved?

No. This is a patient-specific, prescriber-directed 503A compounded preparation from Genesis Compounding, not FDA-approved as a compounded drug.

How long before I see improvement?

Clinical improvement in hyperpigmentation generally becomes visible after 8–12 weeks of consistent use with daily sunscreen. Your prescriber will monitor response and adjust therapy as needed.