tacrolimus and Purpura

Tacrolimus (FK506, Prograf) is marketed for the prophylaxis of organ rejection following allogenic liver or kidney transplantation. A previously conducted, randomized, 24-subject, crossover bioavailability study of 1 and 5 mg capsules (one period each) failed to demonstrate bioequivalence. A single-dose, four-period, four-sequence, randomized, crossover, replicate study (N = 32) was therefore used to evaluate the bioequivalence of the marketed 1 and 5 mg capsules in healthy volunteers. Tacrolimus blood concentrations were measured serially over 72 hours using a commercially available ELISA assay. Noncompartmental pharmacokinetic parameters were determined. Ninety percent CIs of log-transformed parameter ratios were 90.5-101.9, 87.1-101.7, and 89.7-103.8 for Cmax, AUC0-t, and AUC0-infinity, respectively. Since all values were within 80% to 125%, the capsules are bioequivalent. Based on %CVs, intersubject variability was approximately two to three times greater than intrasubject variability. The safety of single 5 mg oral tacrolimus doses administered to healthy volunteers at 7-day intervals was also ascertained.

Topics: Abdominal Pain; Adult; Area Under Curve; Arthralgia; Capsules; Cross-Over Studies; Diarrhea; Dose-Response Relationship, Drug; Female; Headache; Humans; Immunosuppressive Agents; Knee Joint; Male; Purpura; Tacrolimus; Therapeutic Equivalency

Immunothrombocytopenic purpura is a possible complication after liver transplant. The therapy for immunothrombocytopenic purpura after liver transplant is similar to that of primary immunothrombocytopenic purpura. This therapy consists of corticosteroids, intravenous immunoglobulin, and immunosuppressive agents such as cyclosporine and rituximab. There are a few cases of immunothrombocytopenic purpura in patients who recovered after cessation of tacrolimus administration. Here, we show an intractable case of immunothrombocytopenic purpura in a living related liver transplant recipient treated with some of these. We observed complete remission after switch ofthe immunosuppressive agent from tacrolimus to cyclosporine. The patient was an infant girl aged 18 months who underwent livingr elated liver transplant for biliary atresia when she was 6 months old. Liver graft was a left lateral segment from her father. Purpura and severe thrombocytopenia developed after 11 months.There was no effect of the first-line therapies, as described in the Japan guidelines for immunothrombocytopenic purpura.Thrombocytopenia was extreme, as shown by a blood count of 0 platelets/μL. Administration of rituximab was started. However, her platelet count had not increased 8 weeks after rituximab initiation. As a trial therapy, we switched tacrolimus to cyclosporine. She showed complete remission 1 month after this drug conversion. Thus, a switch from tacrolimus to other immunosuppressive agents as a therapy for immunothrombocytopenic purpura after living related liver transplant should be considered.

Topics: Cyclosporine; Female; Humans; Immunosuppressive Agents; Infant; Liver Transplantation; Purpura; Rituximab; Tacrolimus; Thrombocytopenia; Treatment Outcome

Topics: Administration, Topical; Child; Dermatologic Agents; Humans; Lichenoid Eruptions; Male; Pigmentation Disorders; Purpura; Tacrolimus; Treatment Outcome