Amela

Approved Indication:

• Melasma (Moderate to Severe Facial Melasma):
  This triple combination is approved for the short-term treatment of moderate to severe melasma of the face, particularly in adults. It is used when other treatments like monotherapy with hydroquinone or retinoids have proven insufficient.

Clinically Accepted Off-label Uses:

• Post-inflammatory Hyperpigmentation (PIH):
  Used to lighten dark patches resulting from acne, eczema, or skin injury in darker skin tones.
• Solar Lentigines (Age Spots):
  Occasionally prescribed to fade age spots caused by sun exposure.
• Hyperpigmentation due to Hormonal Therapy:
  Used in skin discoloration related to contraceptive use or hormone replacement therapy.
• Adjunctive Use in Acne-related Hyperpigmentation:
  Applied in specific acne-prone skin with persistent dark marks post acne lesion healing.

Adults (≥18 years):

• Apply a thin layer once daily at night to the affected facial areas.
• Therapy is typically limited to 8 weeks.
• Avoid applying to unaffected skin.
• Use broad-spectrum sunscreen (SPF ≥30) during the day.

Pediatric Use:

• Not recommended for individuals under 18 years due to safety concerns and lack of data.

Elderly:

• Use with caution; no specific dose adjustment needed but monitor for skin thinning or irritation.

Renal/Hepatic Impairment:

• No dosage adjustment established, but topical application minimizes systemic exposure.

Route of Administration:

• Topical (external use only).
• Avoid application to eyes, mucous membranes, broken skin, or areas affected by eczema.

This triple-combination therapy works synergistically to treat melasma:

• Hydroquinone (4%): Inhibits the enzymatic oxidation of tyrosine to melanin by blocking tyrosinase, thereby reducing melanin formation and causing skin lightening.
• Tretinoin (0.05%): A vitamin A derivative that promotes epidermal turnover, disperses melanin granules, and enhances penetration of hydroquinone into the skin.
• Fluocinolone Acetonide (0.01%): A mild corticosteroid that reduces inflammation and irritation commonly associated with tretinoin and hydroquinone, improving tolerability and reducing erythema.

Together, the combination targets melanin overproduction, pigment deposition, and inflammation to enhance treatment effectiveness.

As a topical preparation, systemic absorption is minimal but possible, particularly with prolonged use, large surface areas, or occlusion.

• Hydroquinone:
• Absorption: Low percutaneous absorption; increased in broken or inflamed skin.
• Metabolism: Liver metabolism to conjugated metabolites.
• Elimination: Renal excretion.
• Tretinoin:
• Absorption: Up to 2% systemic absorption.
• Metabolism: Hepatic metabolism via CYP26.
• Elimination: Primarily biliary and renal.
• Fluocinolone Acetonide:
• Absorption: Up to 2% systemic bioavailability with topical use.
• Metabolism: Hepatic metabolism.
• Elimination: Excreted in urine.

Onset of Visible Effect: Typically within 2–4 weeks of consistent use.
Half-life (systemic, if absorbed): Not clinically significant for topical use.

• Pregnancy:
  Tretinoin is teratogenic in animal studies. Although topical absorption is low, the combination is generally not recommended during pregnancy.
  FDA Pregnancy Category: C (Tretinoin); C (Fluocinolone); Not assigned (Hydroquinone).
  Use only if clearly needed and the benefits outweigh the risks.
• Lactation:
  Excretion of any of the three components into breast milk is unknown. Caution is advised, and avoid application to the breast or chest area during breastfeeding to prevent infant exposure.

• Primary Class: Skin Depigmenting Agent / Anti-Melasma Agent
• Subclasses:
• Hydroquinone – Melanin synthesis inhibitor
• Tretinoin – Topical retinoid
• Fluocinolone – Low-potency corticosteroid

• Known hypersensitivity to hydroquinone, tretinoin, fluocinolone, or any component of the formulation.
• Presence of eczema, rosacea, perioral dermatitis, or broken/infected skin at application site.
• Pregnancy (especially first trimester) – use only when absolutely necessary.
• Use in children under 12 years – contraindicated.
• Photodermatitis or history of severe sun sensitivity.

• Photosensitivity: Avoid sun exposure; use sunscreen and protective clothing.
• Skin Atrophy: Long-term corticosteroid use can thin skin and increase infection risk.
• Hypopigmentation or Paradoxical Hyperpigmentation: May occur, especially with misuse.
• Irritation or Allergic Reactions: Redness, peeling, or contact dermatitis may develop.
• Systemic Absorption Risks: Especially if used on large areas or under occlusion.
• Avoid use around eyes, mucosal areas, or damaged skin.
• Discontinue if severe irritation or allergic reaction occurs.

Common Side Effects (Local):

• Mild burning, stinging, or dryness
• Peeling or redness
• Pruritus (itching)
• Skin tightness

Less Common / Serious:

• Telangiectasia (spider veins)
• Skin thinning or striae
• Post-inflammatory hypopigmentation
• Exogenous ochronosis (from prolonged hydroquinone use)
• Acneiform eruptions

Rare but Serious:

• Allergic contact dermatitis
• Steroid-induced rosacea
• Systemic corticosteroid effects (with prolonged or high-dose use)

Timing: Most reactions occur within 1–2 weeks of initiation; intensity may peak at 2–4 weeks.

• Photosensitizing agents (e.g., tetracyclines, thiazides): May enhance UV sensitivity.
• Other topical products with alcohol, astringents, or exfoliants: Increase risk of irritation.
• Keratolytics or acne agents (benzoyl peroxide, salicylic acid): Risk of irritation when used together.
• Systemic retinoids (e.g., isotretinoin): Avoid concurrent use due to additive retinoid toxicity.
• CYP450 Involvement: Minimal with topical use, but systemic tretinoin metabolism involves CYP26 isoforms.

• FDA Guidance: Reaffirmed short-term use only (up to 8 weeks) and emphasized mandatory sun protection.
• Dermatology Guidelines (AAD, EADV):
• Continue to recommend triple therapy as the gold standard for melasma, but with clear caution for long-term use, especially concerning hydroquinone and corticosteroid risks.
• Emphasis on intermittent use or cycling the treatment to reduce side effects.
• Regulatory Caution (Europe): Hydroquinone is banned in some EU countries for cosmetic use due to ochronosis and safety concerns.

• Temperature: Store below 25°C (77°F).
• Humidity: Protect from moisture; keep tightly closed.
• Light: Store in a light-resistant container.
• Handling:
• Do not freeze.
• Shake gently before use if in lotion form.
• Use clean fingers or applicator to avoid contamination.