Tacrolimus and PSC

[Guest guest]

Again, I thought this might be of general interest, but it's a pity

about the adverse effects!

Liver Int. 2007 May;27(4):451-3.

Tacrolimus for the treatment of primary sclerosing cholangitis.

Talwalkar JA, Gossard AA, Keach JC, nsen RA, Petz JL, Lindor KD.

Division of Gastroenterology & Hepatology, Mayo Clinic College of

Medicine, Rochester, MN, USA.

Background: Results from a pilot investigation with tacrolimus for

primary sclerosing cholangitis (PSC) demonstrated biochemical

improvement without excessive drug toxicity. To date, no confirmatory

study has been performed. Aims: We sought to determine the safety and

efficacy of tacrolimus in PSC. Methods: An open-label, phase II study

of tacrolimus 0.05 mg/kg twice daily for 1 year was performed. Target

whole-blood concentrations ranged between 3 and 7 ng/ml. Results: A

total of 16 patients were enrolled. The median age was 50 years

(range, 28-68), with 31% being women. The median serum alkaline

phosphatase was 903 U/l, AST 88 U/l, total bilirubin 0.9 mg/dl, and

albumin 3.8 g/dl. Based primarily on drug-related adverse events,

only eight (50%) patients completed 1 year of therapy. After 1 year

of therapy, however, significant improvements in median serum

alkaline phosphatase (903 vs. 483, P=0.0001) and AST levels (88 vs.

78, P=0.002) were observed in these patients. The median tacrolimus

level in patients completing 1 year of therapy was 4.0 ng/ml. Drug-

related adverse events, however, were responsible for 31% of

participants withdrawing from the study. Conclusions: Despite

significant improvements in serum alkaline phosphatase, oral

tacrolimus is poorly tolerated in patients with PSC. PMID: 17403184.

Best regards,

Dave

(father of (21); PSC 07/03; UC 08/03)