tacrolimus and Abdominal-Pain

There is a need for safe and effective alternative treatments for patients with moderate to severe psoriasis.. Pimecrolimus is a calcineurin inhibitor that is being investigated in oral form for the treatment of psoriasis.. A double-blind, randomized, parallel-group, dose-finding study was performed. Healthy adult outpatients with moderate to severe chronic plaque-type psoriasis (n = 143) were randomized to receive oral placebo or pimecrolimus 10 mg, 20 mg or 30 mg twice daily (b.d.) for 12 weeks.. The Psoriasis Area and Severity Index (PASI) was used to assess clinical severity of psoriasis. Results were analysed at weeks 7 (primary endpoint) and 13. Safety was assessed by monitoring all adverse events, laboratory investigations (blood chemistry, urinalysis, haematology) and physical examinations.. The change from baseline in PASI at week 7 showed a dose-dependent effect. The differences between each of the two higher doses of pimecrolimus and placebo were statistically significant (P < 0.001; ANOVA). The mean percentage decreases from baseline in PASI in the placebo group and pimecrolimus 10 mg, 20 mg and 30 mg b.d. groups at week 7 were 3.1%, 22.2%, 51.3% and 54.0%, respectively. Most adverse events were of mild or moderate severity. The only adverse event to show a dose-response relationship was a transient feeling of warmth. No clinically relevant effects on laboratory parameters were observed, and no increase in skin infection with pimecrolimus was seen.. Oral pimecrolimus produces a dose-dependent reduction in psoriasis severity, with doses of 20 mg and 30 mg b.d. being the most effective and well tolerated.

Topics: Abdominal Pain; Adult; Aged; Blood Glucose; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Psoriasis; Severity of Illness Index; Skin; Sleep Initiation and Maintenance Disorders; Statistics as Topic; Tacrolimus; Treatment Outcome

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

Topics: Abdominal Pain; Aged; Fatigue; Female; Humans; Lupus Erythematosus, Systemic; Pancytopenia; Panniculitis, Lupus Erythematosus; Panniculitis, Peritoneal; Prednisolone; Tacrolimus; Tomography, X-Ray Computed

The porphyrias are a group of disorders of the heme biosynthesis pathway that may present with acute life-threatening attacks, commonly exacerbated by a wide variety of medications. Many newer immunosuppressive medications, which are in use following kidney transplantation, have not been fully explored in acute porphyrias.. A 53-year-old woman received a kidney from a deceased donor, after being on hemodialysis for 4 years. Hereditary coproporphyria was diagnosed at age 19 years. We administered tacrolimus, mycophenolate mofetil and steroid immunosuppression. In the immediate post-transplant periods she displayed abdominal pain and transient uroporphyrin elevation in parallel with slightly elevated (15 ng/mL) tacrolimus concentrations. As the target tacrolimus level was achieved, these findings disappeared.. Tacrolimus, mycophenolate- mofetil, and steroid therapy for hereditery coproporphyri was safe, in the long term.

Topics: Abdominal Pain; Coproporphyria, Hereditary; Drug Monitoring; Female; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Middle Aged; Mycophenolic Acid; Risk Factors; Tacrolimus; Treatment Outcome

Topics: Abdominal Pain; Adult; Anti-Bacterial Agents; Cephalosporins; Everolimus; Humans; Immunosuppressive Agents; Kidney; Kidney Transplantation; Lymphocele; Male; Mycophenolic Acid; Prednisolone; Radiography; Scapula; Sirolimus; Tacrolimus; Ultrasonography

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

Tacrolimus, a relatively new therapeutic option for patients with corticosteroid-refractory Crohn's disease or ulcerative colitis, is a substrate for the apically directed efflux transporter P-glycoprotein (P-gp). Duodenal biopsy specimens obtained from a patient with corticosteroid-refractory Crohn's disease and with significantly higher-than-average tacrolimus dose requirements were analyzed for P-gp by Western blot. The P-gp content in this patient was more than double that in specimens obtained from 9 of 10 healthy subjects. Elevated intestinal P-gp could have resulted in decreased tacrolimus absorption, thereby leading to decreased blood concentration and decreased efficacy in this patient. The cause and prevalence of this phenomenon are unknown.

Topics: Abdominal Pain; Adult; ATP Binding Cassette Transporter, Subfamily B, Member 1; Biomarkers; Biopsy, Needle; Blotting, Western; Crohn Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Gastrointestinal Hemorrhage; Humans; Immunohistochemistry; Immunosuppressive Agents; Intestinal Mucosa; Prognosis; Sensitivity and Specificity; Severity of Illness Index; Tacrolimus

Topics: Abdominal Pain; Drug Interactions; Family; Female; Gastrointestinal Diseases; Humans; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Male; Mycophenolic Acid; Tacrolimus

Calcineurin inhibition with tacrolimus has been used after renal transplantation (RTPL) as rescue therapy for insufficient immunological control or if cyclosporin A (CSA) toxicity occurred. Neurologic side-effects occur but are rare in children, usually presenting as tremor; however, serious complications, e.g. the posterior leukoencephalopathy syndrome are also documented. Twenty children (10 girls) were switched to tacrolimus: 11 (55%) for immunological reasons (n = 9: steroid-resistant rejection; n = 2: recurrent rejections) and nine for CSA side-effects. Tacrolimus was started at a median of 8 wk (range 10 d to 8.7 yr) after RTPL and was continued for a median of 2.5 yr (range 5 wk to 4.6 yr). Renal function significantly improved over a period of 12 months following conversion to tacrolimus (glomerular filtration rate 56 +/- 19 vs. 66 +/- 16 mL/min/1.73 m2; p < 0.03; n = 13). Fifteen of 20 (75%) patients tolerated tacrolimus well. The most frequent side-effects were neuropsychological and behavioral symptoms in three children, ranging from anorexia nervosa-like symptoms with weight loss, amenorrhea, depression and school problems to severe insomnia and to aggressive and anxious behavior in one child. Only the latter child was exposed to toxic tacrolimus blood levels. All side-effects were fully reversible after discontinuation of tacrolimus. In conclusion, tacrolimus had a beneficial effect on renal function and was well tolerated in the majority of pediatric patients. However, neuropsychologic and behavioral side-effects are important and maybe underrecognized in children.

Topics: Abdominal Pain; Adolescent; Aggression; Amenorrhea; Child; Child Behavior Disorders; Cyclosporine; Depression; Diabetes Mellitus; Drug Resistance; Female; Gingival Hyperplasia; Graft Rejection; Humans; Hypertrichosis; Immunosuppressive Agents; Kidney Diseases; Kidney Transplantation; Male; Sleep Initiation and Maintenance Disorders; Tacrolimus; Weight Loss

Recent advances, first and foremost the development of new immunosuppressive agents, have markedly improved the outcome of intestinal transplantation, which is a treatment option for patients with serious intestinal diseases who have become dependent on total parenteral nutrition. The first small bowel transplantation in Sweden was performed at Huddinge Hospital in 1997, in the adult patient with intestinal pseudo-obstruction. The article reports the course of this patient and an update of international progress in intestinal transplantation.

Topics: Abdominal Pain; Adult; Fatal Outcome; Female; Graft Rejection; History, 20th Century; Humans; Immunosuppressive Agents; Intestinal Mucosa; Intestinal Obstruction; Intestine, Small; Middle Aged; Postoperative Complications; Tacrolimus