mycophenolic-acid and Dyspepsia

Gastrointestinal (GI) symptoms in renal transplant recipients may be caused due to mycophenolic acid (MPA) toxicity. Using small bowel capsule endoscopy (SBCE) we examined the impact of conversion from Mycophenolate Mofetil (MMF) to enteric-coated formulation of Mycophenolate Sodium (EC-MPS) given to treat GI mucosal lesions.. Adult kidney-only recipients at least 30 days after transplant, presenting with GI symptoms while receiving MMF completed a Gastrointestinal Symptom Rating Scale (GSRS) questionnaire, underwent SBCE, and had MMF substituted by EC-MPS. After 30 days, GSRS and SBCE were repeated and findings were compared to baseline values. Patients who were still on EC-MPS 6-24 months post-conversion were contacted for completing a follow-up GSRS questionnaire and SBCE.. Eighteen out of 23 subjects completed the first part of the study. Subjects' median ages and post-transplant time were 47.5 years old and 4.5 months, respectively. Tacrolimus, MMF and prednisone was the main regimen (94%), with a median MMF dose of 750 mg BID. The average baseline GSRS was 2.99 ± 0.81; it significantly decreased to 2.19 ± 0.8 at 30 days post-conversion. At baseline, 50 had gastric and 89% had small bowel lesions. At 30 days, 29 and 62% of the SBCE were still showing gastric and small bowel lesions, respectively. Of 5 patients in the study extension, 4 had abnormal SBCE findings but have been reporting improvement in their symptoms.. Stomach and small bowel mucosal lesions are common in kidney recipients with GI symptoms when treated with MMF. Conversion to EC-MPS for 30 days significantly alleviated the GI symptoms; however, no evident correlation with SBCE findings was found.

Topics: Abdominal Pain; Adult; Aged; Capsule Endoscopy; Diarrhea; Drug Substitution; Dyspepsia; Follow-Up Studies; Heartburn; Humans; Immunosuppressive Agents; Intestine, Small; Kidney Transplantation; Middle Aged; Mycophenolic Acid; Prospective Studies; Stomach; Surveys and Questionnaires; Tablets, Enteric-Coated

Two open-label studies demonstrated that conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) significantly reduces gastrointestinal (GI) symptom burden and improves GI-specific health-related quality of life. Using a randomized design, this study evaluated changes in GI symptoms and health-related quality of life in patients converted from MMF to EC-MPS versus patients who continued with MMF-based treatment.. In this 4-week, multicenter, randomized, prospective, double-blind, parallel-group trial, renal transplant recipients with GI symptoms receiving MMF plus a calcineurin inhibitor ± corticosteroids were randomized to an equimolar dose of EC-MPS+MMF placebo or continue on their MMF-based regimen+EC-MPS placebo. The primary efficacy outcome was a change from baseline in total Gastrointestinal Symptom Rating Scale score of a minimally important difference of more than or equal to 0.3.. Three hundred ninety-six patients (EC-MPS group: n=199; MMF group: n=197) were included. A greater proportion of EC-MPS patients (62%) reached the primary efficacy outcome compared with MMF patients (55%); however, the difference was not statistically significant (P=0.15). EC-MPS patients had a significantly greater decrease in the Gastrointestinal Symptom Rating Scale indigestion syndrome dimension versus MMF patients. Within the subgroups of patients with diabetes, patients transplanted 6 to 12 months of study enrollment, and patients on steroids, a statistically significant greater proportion of EC-MPS versus MMF patients reached the primary efficacy outcome.. Conversion from MMF to EC-MPS may be associated with improvements in presence and severity of GI symptoms, particularly in patients with indigestion, diabetes, on steroids, and in patients converted between 6 and 12 months posttransplantation.

Topics: Adrenal Cortex Hormones; Adult; Calcineurin Inhibitors; Diabetes Mellitus; Double-Blind Method; Dyspepsia; Enzyme Inhibitors; Female; Gastrointestinal Diseases; Humans; Immunosuppressive Agents; Kidney Transplantation; Longitudinal Studies; Male; Middle Aged; Mycophenolic Acid; Tablets, Enteric-Coated

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