Update on the Use of Tacrolimus in Pediatrics

Kristi Higgins, PharmD


Pediatr Pharm. 2018;24(12) 

In This Article

Novel Uses for Tacrolimus

Studies have shown tacrolimus to be useful in the treatment of refractory ulcerative colitis (UC). The first case series showing the efficacy of tacrolimus for adult patients with irritable bowel disease (IBD) was in 1998. There have since been several retrospective studies showing the efficacy of tacrolimus in pediatric patients for this indication. One early study included 46 pediatric patients with corticosteroid-refractory colitis who were initiated at a tacrolimus dose of 0.1 mg/kg twice a day and titrated to trough levels of 10–15 ng/mL for induction, and 5–10 ng/mL once in remission. This study showed that 93% of patients treated with tacrolimus avoided immediate colectomy.[11]

A subsequent retrospective review evaluated 18 patients with ulcerative colitis treated with oral tacrolimus. Of the patients included in the study, nine patients were steroid-resistant and nine were steroid-dependent. Patients were started on tacrolimus 0.2 mg/kg divided BID with goal levels of 10–15 ng/mL for the first 2 weeks, followed by goals of 7–12 ng/mL for maintenance.

Seventeen patients (94%) responded to tacrolimus therapy, with an average time to response of 8.5 days. The patients with steroid-dependent UC were more likely to achieve prolonged remission, with only two of the nine (22%) requiring colectomy. All nine of the patients with steroid resistant UC ultimately proceeded to undergo colectomy.[12] It should be noted that the long-term prognosis for these patients is not promising despite initial benefit with tacrolimus. Retrospective studies in adults have shown that the relapse-free survival rate decreases with time.

Another innovative use of tacrolimus is as an ointment formulation for the treatment of atopic dermatitis (AD). Tacrolimus is passively absorbed into the skin and reduces skin inflammation and pruritus in AD, blocking T cell activation by binding to the cytosolic immunophilin receptor to form a complex that inhibits the activity of the enzyme calcineurin.[13] Protopic (tacrolimus) ointment was made available in December 2000 as both a 0.03% and 0.1% concentration.

McCollum and colleagues reviewed the safety and efficacy of tacrolimus ointment in pediatric patients with mild to severe atopic dermatitis. Although the 0.03% formulation is the only one currently indicated for use in children between the ages of 2–15 years, short-term placebo controlled trials have evaluated both strengths in pediatric patients. When compared to placebo, tacrolimus ointment offered rapid relief from the symptoms of atopic dermatitis, with the most improvement seen in the first week of treatment. Tacrolimus ointment has also been shown to be more efficacious and have a similar safety profile compared to pimecrolimus cream, as well as some topical corticosteroids, for short-term management of atopic dermatitis.[14]