DermNet provides Google Translate, a free machine translation service. Note that this may not provide an exact translation in all languages


Cutaneous adverse reactions to calcineurin inhibitors

Author: Dr Jacqueline Deen, Dermatology Principal House Officer, Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia. DermNet NZ Editor in Chief: Adjunct A/Prof. Amanda Oakley, Dermatologist, Hamilton, New Zealand. Copy edited by Gus Mitchell. November 2019.


What are calcineurin inhibitors?

Calcineurin inhibitors are drugs that work by inhibiting the calcium-dependent protein phosphatase calcineurin, an enzyme that results in activation of T lymphocytes through the upregulation of interleukin-2 and related cytokines, and leads to immunosuppression [1].

What are topical calcineurin inhibitors used for?

The calcineurin inhibitors tacrolimus and pimecrolimus are indicated for the treatment of atopic dermatitis.

They are commonly used off-label in dermatology for:

Topical calcineurin inhibitors are free of many adverse effects of topical corticosteroids, such as striae, cutaneous atrophy, glaucoma, rebound flares and systemic absorption, or the potential for hypothalamic pituitary–adrenal axis (HPA) suppression.

Indications for topical calcineurin inhibitors

What are oral calcineurin inhibitors used for?

Oral calcineurin inhibitors are commonly used for immunosuppression after solid organ transplantation. Occasionally, ciclosporin and tacrolimus may also be used to treat immune-mediated diseases including psoriasis and atopic dermatitis; however, their use is mainly restricted to patients who have failed to respond to conventional therapy [3].

What are the cutaneous side effects of topical calcineurin inhibitors?

The most commonly reported side effect of topical calcineurin inhibitors is local skin irritation (burning, pruritus, and erythema) at the application site. However, this is usually transient and decreases over time (usually within one month).

Other adverse effects may include:

There is no evidence to support the theoretical concern that topical calcineurin inhibitors may increase the risk of malignancy, such as basal cell carcinoma, cutaneous squamous cell carcinoma, melanoma and cutaneous lymphoma. Information reporting this risk is based on data from animal studies, case reports in a small number of patients, and knowledge of how these drugs work [2,4,5].

Potential adverse effects of topical calcineurin inhibitors

What are the cutaneous side effects of oral calcineurin inhibitors?

The adverse effects of tacrolimus and ciclosporin are generally similar. These include:

Adverse effects of oral calcineurin inhibitors




  1. Malvezzi P, Rostaing L. The safety of calcineurin inhibitors for kidney-transplant patients. Expert Opin Drug Saf. 2015;14(10):1531–46. doi:10.1517/14740338.2015.1083974. PubMed
  2. Sehgal VN, Srivastava G, Dogra S. Tacrolimus in dermatology-pharmacokinetics, mechanism of action, drug interactions, dosages, and side effects: part I. Skinmed. 2008;7(1):27–30. doi:10.1111/j.1540-9740.2007.06485.x. PubMed
  3. Azzi JR, Sayegh MH, Mallat SG. Calcineurin inhibitors: 40 years later, can't live without ... J Immunol. 2013;191(12):5785–91. doi:10.4049/jimmunol.1390055. Journal
  4. Fleischer AB Jr, Boguniewicz M. An approach to pruritus in atopic dermatitis: a critical systematic review of the tacrolimus ointment literature. J Drugs Dermatol. 2010;9(5):488–98.PubMed
  5. Undre NA, Moloney FJ, Ahmadi S, Stevenson P, Murphy GM. Skin and systemic pharmacokinetics of tacrolimus following topical application of tacrolimus ointment in adults with moderate to severe atopic dermatitis. Br J Dermatol. 2009;160(3):665–9. doi:10.1111/j.1365-2133.2008.08974.x. PubMed

On DermNet

Other websites

Books about skin diseases


Related information

Sign up to the newsletter