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TreatmentSteroid-sparingBNF 13.5

Topical calcineurin inhibitors

TCI · tacrolimus · pimecrolimus · macrolactam immunomodulators

Topical calcineurin inhibitors (TCIs) — tacrolimus 0.03% / 0.1% ointment and pimecrolimus 1% cream — are non-steroidal anti-inflammatory agents licensed for atopic eczema. They are widely used off-label for vitiligo, psoriasis, lichen planus, contact dermatitis, lichen sclerosus, perioral dermatitis, post-Mohs eczematous reactions, ICI-related eczematous dermatitis and recalcitrant cutaneous lupus / dermatomyositis. UK BAD / NICE guidance and the long-standing FDA "black-box" lymphoma / skin-cancer warning have prompted detailed safety analysis — current consensus is reassuring with appropriate use.

CurrentLast reviewed 16 May 2026

Mechanism

  • Bind FKBP-12 → inhibit calcineurin phosphatase → blocks NFAT dephosphorylation and translocation → suppresses IL-2 / cytokine transcription in T cells.
  • Does not affect collagen / fibroblast → no skin atrophy (cf TCS).
  • Penetration limited by molecular size; minimal systemic absorption.
  • Stings on application — common transient side effect; tolerated within 1-2 weeks.

Agents

AgentStrengthLicensed
Tacrolimus ointment (Protopic)0.03% (child >2 y); 0.1% (adult)Moderate-severe atopic eczema; second-line.
Pimecrolimus cream (Elidel)1%Mild-moderate atopic eczema; child >2 y / adult.

Indications

  • Licensed: atopic eczema (especially face, flexures, eyelids, perioral, genital).
  • Off-label / NICE-supported / widely-used:
    • Vitiligo (especially face, neck — first-line; reduces depigmentation rebound).
    • Lichen planus (oral, cutaneous, genital).
    • Lichen sclerosus (especially child / genital).
    • Discoid lupus / SCLE.
    • Perioral dermatitis.
    • Seborrhoeic dermatitis (face).
    • Allergic / irritant contact dermatitis (steroid-sparing maintenance).
    • Post-burn / post-Mohs eczematous wound reactions.
    • Cutaneous GVHD.
    • Inverse psoriasis.
    • ICI-related eczematous dermatitis.

Safety considerations

  • Black-box warning (FDA 2006; UK MHRA aligned):
    • Theoretical risk of cutaneous lymphoma and non-melanoma skin cancer based on animal data.
    • Long-term post-marketing surveillance (PETITE registry, JOELLE) and large RCT meta-analyses do not show increased lymphoma / NMSC risk with topical use in atopic eczema.
    • Most expert UK bodies regard TCIs as safe second-line therapy.
  • Local effects:
    • Burning / stinging on application (50%; transient).
    • Erythema, pruritus.
    • Alcohol intolerance (rare flush).
    • Folliculitis, herpes flare.
  • Photosensitivity: avoid intense UV / sunbed during use; emollient daily SPF 30+ photoprotection.
  • Live vaccines: hold TCI 2 weeks before / after live vaccine (theoretical immune suppression at site).
  • Pregnancy: category C; use only if benefit outweighs risk.

Practical use

  • Apply thin layer to affected skin BD; maintenance 2-3× weekly after control achieved.
  • Avoid application to acutely infected skin (HSV, impetigo).
  • Counsel about transient stinging — most patients accommodate.
  • Use as steroid-sparing for face / eyelid / genital eczema after initial TCS control.
  • In vitiligo: apply BD; combine with sun-avoidance and gentle photoprotection.
  • In LS / genital LP: useful steroid-sparing maintenance in selected specialist practice where steroid toxicity or intolerance is a concern.
  • Document the FDA black-box warning and discuss the more reassuring cohort evidence — patients may ask about lymphoma / skin-cancer risk; provide evidence-based reassurance.
  • Cost-conscious prescribing — generic tacrolimus / pimecrolimus formulations widely available in NHS.

References

  1. Reitamo S et al. Tacrolimus ointment for atopic dermatitis: long-term safety. J Am Acad Dermatol. 2008;58:S29-S37.
  2. Paul C et al. Pimecrolimus cream 1% in the treatment of atopic dermatitis: a 1-year safety study. Pediatrics. 2006;117:e811-e821.
  3. Asgari MM et al. Association between topical calcineurin inhibitor use and keratinocyte carcinoma risk among adults with atopic dermatitis. JAMA Dermatol. 2020;156:1064-1071.
  4. NICE TA82. Tacrolimus and pimecrolimus for atopic eczema. London: NICE; 2004 (re-affirmed).
  5. British Association of Dermatologists. Topical calcineurin inhibitors: patient information leaflet. London: BAD; 2025.

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