Hydroquinone

Hydroquinone (1,4-dihydroxybenzene) is a topical depigmenting agent. In the US it is available on prescription in Tri-Luma cream (fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05%). Since the CARES Act OTC monograph reform of 2020, hydroquinone can no longer be marketed in nonprescription skin-lightening products without FDA approval. Lake Hills Pharmacy compounds topical hydroquinone preparations as a 503A pharmacy on patient-specific prescriptions.

Tri-Luma cream is FDA labeled for short-term treatment of moderate to severe melasma of the face, used with sun avoidance and sunscreen. Prescribers use compounded topical hydroquinone, alone or with other agents, for melasma, post-inflammatory hyperpigmentation, solar lentigines and other hyperpigmentation.

Hydroquinone inhibits tyrosinase, the enzyme that converts tyrosine to DOPA and then to melanin, reducing melanin synthesis. It also generates reactive oxygen species and quinones within melanocytes that damage melanosomes and melanocyte membranes. Its effect is reversible, and pigment can return with sun exposure or after stopping.

Hydroquinone is absorbed through the skin to a meaningful degree; studies of topical application have reported systemic absorption of a substantial fraction of the applied dose. Absorbed drug is conjugated to glucuronide and sulfate metabolites and excreted in urine. In formulation, hydroquinone oxidizes to p-benzoquinone, which turns the preparation brown; antioxidants and light protection slow this.

• Hypersensitivity to hydroquinone or any component of the preparation, including sulfites where present.

• Exogenous ochronosis: gradual blue-black darkening of treated skin with prolonged use, reported more often in darker skin types and with higher strengths. Discontinue if it appears; it may be persistent.
• Irritation and allergic contact dermatitis: test a small area first when the prescriber directs; stop if vesicles, marked erythema or itching develop.
• Sun exposure: UV exposure reverses depigmentation. Daily broad-spectrum sunscreen and sun avoidance are part of therapy.
• Sulfites: many hydroquinone products contain sodium metabisulfite, which can cause allergic and asthmatic reactions in sensitive people.
• Hypopigmentation and confetti-like depigmentation can occur, particularly with higher strengths or application beyond the target area. Avoid the eyes and mucous membranes.

• No clinically important systemic interactions are established for topical use.
• Use with benzoyl peroxide or hydrogen peroxide can cause transient dark staining of the skin.
• Additive irritation with other topical irritants, including retinoids, alpha-hydroxy acids and resorcinol.

Common: erythema, burning, stinging, dryness and pruritus. Less common: allergic contact dermatitis, hypopigmentation, nail discoloration. Rare with long-term use: exogenous ochronosis and colloid milium.

Adequate human pregnancy data are lacking. Because systemic absorption is meaningful, many prescribers defer hydroquinone during pregnancy. It is not known whether hydroquinone passes into breast milk; use during breastfeeding is a prescriber decision.

Assess response and tolerability at regular intervals set by the prescriber, watching for irritation, contact dermatitis, hypopigmentation and early signs of ochronosis, and reassess the need for continued use.

• Tri-Luma (fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05%) Cream Prescribing Information, Galderma Laboratories.
• Coronavirus Aid, Relief, and Economic Security (CARES) Act of 2020, OTC monograph reform provisions.
• Lexicomp Drug Information, Wolters Kluwer.