Long-term safety of tacrolimus ointment in atopic dermatitis

Expert Opin Drug Saf. 2009 Jul;8(4):501-6. doi: 10.1517/14740330902969441.


Background: Tacrolimus ointment has shown efficacy as monotherapy in both short- and long-term studies in atopic dermatitis. Absorption of tacrolimus after topical application is dependent on the barrier function of the skin. Absorption through the intact epidermis is very low and eczematic skin a little higher. In comparison to systemic tacrolimus used for prevention and treatment of rejection after organ transplantation, the bioavailability of topical tacrolimus in patients with atopic dermatitis is between 3 and 4%. Long-term safety studies of up to 4 years have not shown adverse events associated with systemic use of immunosuppressive agents, that is, increased risk of infections, lymphomas or skin cancers. Despite these findings, many physicians remain concerned about possible long-term malignancies associated with long-term treatment with a topical calcineurin inhibitor.

Objective: To identify in the published literature possible long-term safety issues associated with topical tacrolimus treatment.

Methods: PubMed was used to identify studies of atopic dermatitis therapy in which tacrolimus ointment was used for at least 6 months. We evaluated the safety data available from these studies. In addition, some safety data were evaluated from clinical follow-up of our own patients who have used tacrolimus ointment intermittently for up to 14 years.

Conclusions: During a follow-up period of 4 years in clinical studies, no increased risk of infections or cancer was associated with long-term use of tacrolimus ointment. Only short-term adverse events were detected. They included increased burning and stinging of the skin, and a temporary increase in skin infections. No signs of immunosuppression were observed after 1 - 4 years of intermittent treatment with tacrolimus ointment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Administration, Topical
  • Dermatitis, Atopic / drug therapy*
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • Ointments / administration & dosage
  • Ointments / adverse effects*
  • Skin Diseases / chemically induced*
  • Skin Neoplasms / chemically induced
  • Tacrolimus / administration & dosage
  • Tacrolimus / adverse effects*
  • Tacrolimus / therapeutic use


  • Immunosuppressive Agents
  • Ointments
  • Tacrolimus