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