Gacozema

Approved Indications:

• Chronic plaque psoriasis: Used topically for the treatment of stable, thick, scaly psoriatic plaques, particularly on the trunk and limbs.
• Localized hyperkeratotic dermatoses: In select cases, such as palmoplantar keratoderma (off-label), where hyperproliferation of keratinocytes is present.

Clinically Accepted Off-label Use:

• Seborrheic dermatitis and ichthyosis vulgaris: In mild to moderate cases, salicylic acid in combination may help reduce scaling and thickened skin (used cautiously).

Route of Administration: Topical, for external use only.

Recommended Application (Adults):

• Apply a thin layer of the combination preparation directly to psoriatic plaques once daily, typically in the evening.
• Allow the preparation to remain on the skin for 30 minutes to 1 hour, then wash off thoroughly with lukewarm water and mild soap (short-contact therapy).
• Duration: Usually 6 to 12 weeks depending on response and tolerability.

Special Instructions:

• Apply carefully only to affected areas; avoid contact with normal skin, mucous membranes, eyes, and broken skin.
• Use gloves during application to avoid staining and irritation.
• Do not occlude unless specifically advised by a physician.

Pediatrics:

• Not routinely recommended for children under 12 years of age due to irritation risk and limited data.

Elderly:

• Use with caution due to increased skin sensitivity; no specific dose adjustment required.

Hepatic/Renal Impairment:

• Not systemically absorbed to a clinically significant extent; no dose adjustment required, but use cautiously if skin barrier is impaired.

• Dithranol (Anthralin): Exerts antiproliferative effects by inhibiting mitochondrial activity and DNA synthesis in keratinocytes, thereby normalizing epidermal cell turnover. It also has anti-inflammatory properties by reducing neutrophil chemotaxis and superoxide production.
• Boric Acid: Acts as a mild antiseptic and astringent. It stabilizes dithranol by preventing oxidation and limits surrounding skin irritation. It also exerts a weak antifungal and antibacterial effect.
• Salicylic Acid: A keratolytic agent that dissolves intercellular cement, softens the stratum corneum, and enhances penetration of dithranol. It facilitates desquamation and reduces scale in hyperkeratotic lesions.

Together, this combination provides synergistic effects in reducing inflammation, normalizing keratinocyte proliferation, and removing psoriatic scales.

This combination is minimally absorbed systemically when used appropriately.

• Absorption:
• Dithranol: Minimal percutaneous absorption when used as directed; excessive application or damaged skin may increase absorption.
• Salicylic Acid: Approximately 6–9% may be absorbed; absorption increases with damaged skin or occlusion.
• Boric Acid: Very limited absorption through intact skin; significant absorption possible if applied to broken skin.
• Distribution/Metabolism:
• Dithranol is metabolized locally in the skin.
• Salicylic acid is hydrolyzed to salicylate and metabolized hepatically.
• Boric acid is not metabolized and is excreted unchanged.
• Elimination:
• Salicylates and absorbed components (if any) are excreted renally.
• Dithranol is inactivated upon oxidation and does not accumulate systemically.

• Pregnancy:
• Dithranol: Not assigned a specific FDA pregnancy category; animal reproductive studies are not available. Use only if clearly needed.
• Salicylic acid: Category C (use with caution, especially on large areas).
• Boric acid: Not recommended during pregnancy due to potential for systemic absorption and toxicity in high doses.
• Overall: Use with caution in pregnancy; avoid prolonged or extensive application.
• Lactation:
• No data on excretion into breast milk.
• Avoid application to the breast area to prevent ingestion by the infant.

• Primary Class: Anti-psoriatic combination
• Subclasses:
• Dithranol: Antipsoriatic, anti-proliferative agent
• Salicylic Acid: Keratolytic
• Boric Acid: Mild antiseptic and stabilizing agent

• Known hypersensitivity to dithranol, salicylic acid, boric acid, or any excipients
• Acute, inflamed, or pustular psoriasis
• Application to face, genitalia, or mucous membranes
• Broken, abraded, or infected skin
• Children under 12 years (relative contraindication)
• Pregnant or breastfeeding women (use with caution)

• Irritation and burning may occur; discontinue if severe
• Skin staining (yellow-brown) is common and may persist temporarily
• Avoid contact with eyes, mouth, and sensitive areas
• Photosensitivity may occur; avoid excessive sun exposure
• Use only as directed; improper use may cause severe skin irritation or systemic toxicity (especially boric acid in large doses)

Common:

• Local skin irritation, redness, burning sensation
• Temporary discoloration of skin or hair (due to dithranol)
• Mild peeling or dryness (due to salicylic acid)

Less Common:

• Erythema or eczema-like reactions
• Perilesional hyperpigmentation

Rare/Serious:

• Severe irritation or ulceration from overuse
• Systemic salicylate toxicity (if used excessively or on broken skin)
• Systemic boric acid toxicity (nausea, vomiting, renal issues with overuse)

Timing of Onset: Typically occurs within 1–2 weeks of initiation

• Other topical irritants (e.g., retinoids, corticosteroids):
• Risk of increased irritation or reduced effectiveness
• Systemic salicylates (e.g., aspirin):
• Cumulative salicylate toxicity if used over large areas
• Keratolytic agents:
• May enhance salicylic acid absorption and irritancy
• No CYP450 involvement noted, as systemic absorption is minimal under recommended use

• Clinical practice updates now favor short-contact therapy (30–60 minutes) with dithranol over traditional overnight regimens to minimize irritation
• Combination with stabilizers like boric acid is recommended to reduce perilesional damage
• Salicylic acid continues to be favored as a penetration enhancer for topical antipsoriatics in evidence-based psoriasis guidelines (AAD, NICE)

• Temperature: Store below 25°C (77°F)
• Protection: Keep away from direct light and moisture
• Packaging: Use tightly closed container to avoid oxidation
• Handling:
• Wear gloves to avoid staining hands
• Avoid contact with clothing, fabrics, and plastic surfaces
• Do not refrigerate or freeze