Topical

Topical

  • Tacrolimus (Protopic)
  • Pimecrolimus (Elidel)
  • Pregnancy category C

  • Protopic 0.03 & 0.1% ointment
  • Elidel 1% cream

  • Binds FK506 binding proteins (similar to cyclophilin function) which binds calcineurin inhibiting its ability to dephosphorylate Nuclear factor of activated T-cells 1 (NFAT-1) decreasing Interleukin-2, T cell activation & proliferation
  • Transient ↑ in substance P release via activation of transient receptor potential vanilloid 1 (TRPV1) leading to burning sensation, with eventual desensitization of transient receptor potential vanilloid 1 (TRPV1); explaining efficacy in pruritus

Food and drug administration (FDA) 

  • 2nd line for moderate-severe atopic dermatitis) > 2 years of age
    • Protopic 0.1% >16 years of age
    • Protopic 0.03% >2 years of age
  • (In Canada approved as maintenance treatment if frequent recurrences)

Off-label

  • Allergic contact dermatitis, seborrheic dermatitis, oral lichen planus, Psoriasis, vitiligo, cutaneous lupus, lichen sclerosis, granuloma faciale, rosacea

Absolute

  • Hypersensitivity to tacrolimus or ingredients

Relative

  • < 2 years of age
  • Active skin infection (at treated site)

Skin

  • Local irritation (most common & transient)
  • Transient burning (1-2 weeks)
  • Flushing after alcohol ingestion
  • Rosacea-like dermatitis
  • Acne
  • Reactivation of Herpes simplex virus
  • Eczema herpeticum
  • Possible molluscum 
  • Malignancy risk (black box warning)

  • Significant systemic absorption in patients with Netherton syndrome

    (Tacrolimus only)

Note

  • In patients with atopic dermatitis treated with topical calcineurin inhibitors, decreased Staphylococcus aureus colonization of skin was observed 

Black box warning 

  • Controversial
  • In 2006, black boxed warning concerning theoretical risk of malignancy
  • However most recent literature failed to show association, so international experts recently concluded that the warning is not justified & recommended its removal