Preliminary report on the use of oral tacrolimus (FK506) in the treatment of complicated proximal small bowel and fistulizing Crohn's disease

Am J Gastroenterol. 1997 May;92(5):876-9.

Abstract

Background: Tacrolimus (FK506) has a mechanism of action similar to cyclosporine. Unlike standard oral cyclosporine, tacrolimus is well absorbed orally, even from diseased small bowel mucosa.

Objective: To report the use of oral tacrolimus in three patients with complicated proximal small bowel or fistulizing Crohn's disease as a "bridge" to methotrexate or 6-mercaptopurine.

Case reports: Oral tacrolimus was started at doses of 0.15-0.29 mg/kg/day and adjusted to a whole blood tacrolimus concentration range of 10-20 ng/ml. Case 1: Gastroenterostomy for gastroduodenal Crohn's disease complicated by recurrent gastrointestinal hemorrhage from persistent duodenal ulceration. Case 2: Diffuse jejunoileal Crohn's disease, seven prior stricturoplasties, and a postoperative small intestinal fistula causing an abdominal abscess. Case 3: Perianal and pouch-vaginal fistulae after colectomy and ileal pouch-anal anastomosis in a patient with Crohn's disease. All three patients had good oral absorption of tacrolimus, rapid clinical improvement of their Crohn's disease, and began long-term remission maintenance treatment with either methotrexate (n = 2) or 6-mercaptopurine (n = 1). Dose dependent side effects resulting from tacrolimus therapy occurred in all three patients (nephrotoxicity, hyperkalemia, diarrhea, nausea, flushing, headache, tremor, paresthesias, and insomnia).

Conclusions: Oral tacrolimus (0.15-0.29 mg/kg/day) is well absorbed in patients with Crohn's disease with proximal small bowel involvement or fistulae and appears to be of clinical benefit as a rapidly acting "bridge" to long-term therapy with methotrexate or 6-mercaptopurine.

Publication types

  • Case Reports

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Crohn Disease / complications*
  • Crohn Disease / drug therapy*
  • Crohn Disease / physiopathology
  • Female
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Intestinal Absorption
  • Intestinal Fistula / drug therapy*
  • Intestinal Fistula / etiology
  • Intestinal Fistula / physiopathology
  • Intestine, Small / drug effects*
  • Intestine, Small / pathology
  • Intestine, Small / physiopathology
  • Male
  • Tacrolimus / administration & dosage
  • Tacrolimus / adverse effects
  • Tacrolimus / therapeutic use*

Substances

  • Immunosuppressive Agents
  • Tacrolimus