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

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.