Generic Name

Hydroquinone

Mechanism

Hydroquinone selectively inhibits the enzyme *tyrosinase*, the rate‑limiting step in melanin synthesis.
• ↓ Conversion of tyrosine → dopaquinone → melanin
• Leads to reduced eumelanin and pheomelanin production in keratinocytes and melanocytes
• Acts on both epidermis and basal layer, producing a bleaching effect after repeated application

Pharmacokinetics

• Absorption: Minimal systemic absorption when used topically (≤ 0.2% of applied dose).
• Distribution: Concentrates in epidermal cells; negligible penetration into deeper dermal layers.
• Metabolism: Primarily reduced to *hydroquinone‑quinone* and conjugated to glucuronic acid/glutathione.
• Excretion: Urinary excretion of metabolites; very low plasma levels.
• Half‑life: Local skin elimination ~48–72 h; systemic half‑life < 5 h (if orally ingested).

Indications

• Melasma (commonly in fair‑to‑middle‑skin‑tone patients)
• Solar lentigines / liver spots
• Post‑inflammatory hyperpigmentation (e.g., acne, dermatitis)
• Café‑au‑lait spots (adjunct to laser or cryotherapy)
• Other hyperpigmentary dermatoses when combined with *tretinoin* or *azelaic acid*

Contraindications

• Pregnancy & lactation: Category C; avoid due to theoretical risks of fetal teratogenicity and excretion into breast milk.
• Photosensitivity disorders or concomitant photosensitizing drugs (e.g., doxycycline).
• Active dermatitis, eczema, or other skin barrier defects – may increase systemic absorption.
• Allergy to hydroquinone or phenolic compounds – avoids contact dermatitis.
• Long‑term (> 6 months) use: risk of *exogenous ochronosis* (blue–black discoloration) and potential carcinogenicity (controversial).
• Use with systemic NSAIDs or anticoagulants may exacerbate irritation.

Dosing

• OTC (2–4% emulsion/cream):
• Apply thin layer to affected areas twice daily (morning & evening).
• Use after cleansing; avoid sun‑exposure (see below).
• Prescription (20% gel/ointment/cream):
• Typically once daily (nighttime) for 3–6 months.
• Alternating with *tretinoin* (daily) or *azelaic acid* reduces irritation.
• Reapplication in sun‑exposed areas is discouraged;
• Combine with a broad‑spectrum SPF ≥ 30 sunscreen during daylight.

Preparation tip: Avoid mixing with strong emollients or oils that can enhance penetration and lead to ochronosis.

Adverse Effects

Common (local):
• Skin irritation, erythema, pruritus
• Contact dermatitis (allergic)
• Mild burning or stinging

Serious / Rare:
• Exogenous ochronosis (bluish‑black hyperpigmentation, usually after ≥ 2 years of use)
• Systemic toxicity (in cases of high systemic absorption) – nausea, headache, fatigue
• Potential carcinogenicity – longstanding risk remains under debate; limiting use to < 6 months mitigates concern

Monitoring

• Clinical skin assessment: redness, scaling, pigmentation changes at baseline and every 4–6 weeks.
• Patient diary of sun‑exposure & ointment use.
• Biopsy or dermoscopy if ochronosis suspected.
• Pregnancy status and breastfeeding – avoid use.
• Serum creatinine if concomitant nephrotoxic drugs (rare).

Clinical Pearls

• “Peak bleaching” occurs after 3–4 weeks; patients should be counseled on realistic timelines.
• Combination therapy: using *tretinoin* daily or *azelaic acid* during the day potentiates efficacy and reduces irritation.
• Patient education: emphasize strict sunscreen use; even a single sunny outing can reverse benefits or worsen pigmentation.
• Patch‑testing is advisable for patients with a history of allergic contact dermatitis (especially with phenolic products).
• Alternate‑day application can reduce risk of ochronosis while maintaining therapeutic effect.
• Post‑treatment “wash‑out” period (1–2 weeks) before initiating laser or chemical peeling improves outcomes and reduces flare.

Bottom line: Topical hydroquinone remains the gold‑standard depigmenting agent when used appropriately, with attention to dosage, duration, and protective measures against photosensitive side‑effects.