tacrolimus and Vomiting

The tolerance and pharmacokinetics (PK) of tacrolimus (T) by the addition of mycophenolate mofetil (MMF) in stable kidney transplant patients (6/group) on long-term tacrolimus-based therapy were investigated. Patients received combination T and MMF therapy at three MMF doses: 1, 1.5, and 2 g/day administered twice daily. A 12-hour blood PK profile for T was obtained prior to MMF dosing; concomitant 12-hour profiles for T, mycophenolic acid (MPA), and mycophenolic acid glucuronide (MPAG) were obtained after 2 weeks of administration. Tolerance was monitored through 3 months. The intra- and intergroup PK of T were variable. The mean AUC0-12 of T for each group was increased after 2 weeks of concomitant MMF administration, but the increase was not statistically significant. Both drugs were well tolerated. Gastrointestinal events were of interest as such have been attributed to both T and MMF. Events reported were diarrhea, nausea, dyspepsia, and vomiting. Other common adverse events were headache, hypomagnesemia, and tremors. Most were mild, although a few were considered to be moderate. There was no apparent relationship between the incidence of any adverse event and MMF treatment group. In the present study, the coadministration of T and MMF did not significantly alter T pharmacokinetics.

Topics: Adult; Area Under Curve; Diarrhea; Dose-Response Relationship, Drug; Drug Interactions; Dyspepsia; Female; Glucuronates; Glucuronides; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Metabolic Clearance Rate; Middle Aged; Mycophenolic Acid; Nausea; Prodrugs; Tacrolimus; Vomiting

Pain induced by calcineurin inhibitors is a rare complication of unknown pathogenesis. We have reported herein a 7-year-old child who presented with abdominal pain, vomiting, and weight loss showing no significant findings after an extensive laboratory and imaging workup. After conversion from tacrolimus to sirolimus, there was complete resolution of the gastrointestinal symptoms and pain; the patient displays excellent renal function. Calcineurin inhibitor-induced pain syndrome is diagnosis of exclusion but must be considered because the withdrawal of this immunosuppressive agent is associated with improvement in symptoms and quality of life.

Topics: Abdominal Pain; Calcineurin Inhibitors; Child; Drug Substitution; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Sirolimus; Tacrolimus; Treatment Outcome; Vomiting; Weight Loss

Serial changes in the circulating and cerebrospinal fluid (CSF) cytokine levels were assessed in a patient with Sjogren's syndrome (SS)-associated meningoencephalomyelitis. A 16-yr-old girl diagnosed as having primary SS at 8 yr of age presented headache and vomiting. CSF studies revealed lymphocyte-dominant pleocytosis and high IgM index, but no evidence of infection. Disturbed consciousness and diffuse slow waves on electroencephalogram led to the diagnosis of SS-meningoencephalitis. The clinical condition subsided after a cycle of dexamethasone therapy, however, 2 months later urinary retention and paresthesia of the lower body developed. Craniospinal magnetic resonance imaging (MRI) showed extensive intraparenchymal lesions with high T2-weighted signal intensity adjacent to the posterior left horn of lateral ventricle of the brain and the longitudinal lesion from C5 to T10 of the spinal cord. High-dose methyl-prednisolone and subsequent tacrolimus therapy has effectively controlled the activity of SS-meningoencephalomyelitis. Monitoring of systemic and CSF cytokine levels during the course of illness revealed that CSF interleukin-6, but not interferon-gamma or tumor necrosis factor-alpha levels were the sensitive indicator of disease activity. The unique cytokine profile, differing from those of infectious meningitis may be useful for predicting the central nervous system involvement in autoimmune disease.

Topics: Adolescent; Anti-Inflammatory Agents; Biomarkers; Brain; Cytokines; Dose-Response Relationship, Drug; Female; Headache; Humans; Immunosuppressive Agents; Interleukin-6; Magnetic Resonance Imaging; Meningoencephalitis; Methylprednisolone; Monitoring, Physiologic; Myelitis; Predictive Value of Tests; Sjogren's Syndrome; Spinal Cord; Tacrolimus; Treatment Outcome; Vomiting

Successful use of cyclosporine in organ transplant can be associated with unwanted side-effects that can affect graft function. We report three kidney transplant recipients in whom severe migraine headache occurred as a side-effect of cyclosporine therapy. This endangered graft survival in all three and eventually led to loss of graft in two.

Topics: Adult; Cyclosporine; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Migraine Disorders; Renal Insufficiency; Reoperation; Tacrolimus; Vomiting

The immunosuppressive agent FK permitted increased kidney transplant survival in dogs over a wide dose range, but with weight loss and manifold evidence of toxicity. The best use of FK at low doses was in combination with CyA and Pred.

Topics: Animals; Body Weight; Cyclosporins; Dogs; Drug Evaluation, Preclinical; Drug Synergism; Drug Therapy, Combination; Graft Rejection; Immunosuppressive Agents; Kidney Transplantation; Prednisolone; Pyridines; Tacrolimus; Vomiting

Topics: Animals; Dogs; Drug Evaluation, Preclinical; Immunosuppressive Agents; Kidney Transplantation; Postoperative Complications; Pyridines; Tacrolimus; Vasculitis; Vomiting