Topical Calcineurin Inhibitors

Topical calcineurin inhibitors (tacrolimus and pimecrolimus) are non-steroidal anti-inflammatory agents used for atopic eczema and for sensitive sites where steroid atrophy is a concern. They suppress T-cell activation without causing skin atrophy or telangiectasia, so they suit long-term and facial use.

Mechanism. Binding to FKBP-12 forms a complex that inhibits calcineurin, blocks nuclear factor of activated T cells and prevents transcription of interleukin-2 and other cytokines. They also reduce mast cell mediator release.

Pharmacokinetics. Tacrolimus ointment is absorbed little through intact skin (blood levels usually under 1 ng/mL) and more through inflamed, eroded or erythrodermic skin. Pimecrolimus cream is absorbed even less. Penetration is poorer than for steroids in thick or lichenified skin.

• Tacrolimus ointment 0.03 percent and 0.1 percent: moderate to severe atopic eczema; the 0.1 percent strength has higher potency, comparable to a potent steroid in adults.
• Pimecrolimus cream 1 percent: mild to moderate atopic eczema; weaker.

Adult and child regimens.

• Tacrolimus 0.03 percent ointment (from 2 years of age) or 0.1 percent (from 16 years): apply twice daily to affected areas until clearance, then reduce to once daily; for maintenance in frequent relapse, apply twice weekly (for example Monday and Thursday) to previously affected sites, reviewed every 12 months.
• Pimecrolimus 1 percent: twice daily at the first sign of eczema, from 3 months to 2 years in some regions and in older children and adults.
• Off-label: facial and flexural eczema, periorbital dermatitis, seborrhoeic dermatitis, intertriginous psoriasis, facial psoriasis, lichen planus (oral and genital), vitiligo (tacrolimus 0.1 percent twice daily on face and neck, for at least 6 months, with phototherapy for best effect), genital lichen sclerosus (second line).

Selection. Use when steroids have failed or caused atrophy, for the face, eyelids, flexures and genitalia, and for maintenance. Combine with emollients. Apply to dry skin and do not cover with occlusive dressings.

Contraindications. Hypersensitivity; skin infection that is untreated; Netherton syndrome and erythroderma (systemic absorption); congenital or acquired immunodeficiency; pregnancy and breastfeeding unless clearly needed (limited data).

Serious and common effects. Burning and itching during the first days (reduce by applying to cool, dry skin and starting with the lower strength); flushing with alcohol; skin infections including eczema herpeticum, molluscum and warts; folliculitis. A boxed warning in some regions describes a theoretical risk of skin cancer and lymphoma from long-term use. Studies have not confirmed a causal risk, but sun exposure and phototherapy are minimised and use in people under 2 years is avoided.

Interactions. Systemic CYP3A4 inhibitors (erythromycin, azole antifungals, calcium channel blockers) can raise levels when large areas are treated.

Monitoring. Review at 2 to 4 weeks; annual review in maintenance; examine for skin cancer in at-risk patients; sun protection advice.

Special groups. Children: avoid under 2 years. Older adults: no adjustment. Region: strong sun exposure in East Africa calls for firm sun protection advice and avoidance of unnecessary prolonged use; cost and availability limit use.