Mycophenolate Sodium In Patients Research Articles

Efficacy and safety of enteric-coated mycophenolate sodium in patients withde novoand maintenance renal transplantation

To evaluate the efficacy and safety of enteric-coated mycophenolate sodium (EC-MPS) in renal transplant patients treated de novo and for maintenance. The efficacy and safety data of EC-MPS in renal transplant patients treated de novo and for maintenance in our hospital from July 2009 to March 2013 were reviewed. Thirty-one patients treated with EC-MPS de novo were included: there were 16 male and 15 female patients. The acute allograft rejection rate was 12.9% (4/31) and pneumonia occurred in 25.8% patients (8/31); the allograft survival rate was 96.7% (30/31) with a patient survival rate of 96.7% (30/31). Gastrointestinal side effects occurred in four patients (12.9%). Only one patient discontinued EC-MPS and treatment was converted to bredinin because of gastrointestinal intolerance. Thirty-nine patients receiving mycophenolate mofetil (MMF) de novo treatment served as a control group. Five (13.2%) of 38 patients developed serious acute rejection and 10 patients (26.3%) had pulmonary infection. Eight (21.1%) patients suffered abdominal distention, diarrhoea and other gastrointestinal adverse reactions; the symptoms improved significantly after treatment change to mizoribine. Compared with the MMF de novo group, the allograft function, blood cell counts and urine protein were similar in the EC-MPS de novo treatment group. The incidence of gastrointestinal side effects was obviously lower in the EC-MPS group than in the MMF group, and there was no difference in serious acute rejection and pulmonary infection between the groups. The study also included 23 renal transplantation maintenance patients who suffered from chronic diarrhoea and treatment was changed to EC-MPS treatment. This change to EC-MPS was at 77months after transplantation. The gastrointestinal symptoms improved significantly in 21 patients after conversion. Compared with the results at 1week, no obvious deterioration in serum creatinine, cystatin or estimated glomerular filtration rate was found at 1, 3 and 12months after the change. In addition, there was no marked decline in blood cell counts and no significant increase in urine protein. The outcome of EC-MPS treatment in clinical practice of de novo kidney transplant patients was good, with high patient and graft survivals. In maintenance patients it induced an improvement in gastrointestinal side effects and a stable allograft function.

Evaluation of Efficacy and Safety of Mycophenolate Sodium in Patients With De Novo and Maintenance Renal Transplantation: Results of a Multicenter, Prospective, Observational Study

Objective This study evaluates the effect of enteric-coated mycophenolate sodium (EC-MPS) on patient and graft survivals, the incidence of rejection episodes, and graft function among de novo and maintenance renal transplant recipients. Patients and Methods This open label, multicenter, prospective, post-marketing observational study of 470 renal transplantation patients at 23 centers in Turkey includes 331 de novo patients whose mean age was 29.6 ± 13.2 years and 139 maintenance patients of 34.0 ± 13.0 years. The latter subjects had EC-MPS substituted for mycophenolate mofetil or added to the immunosuppressive therapy. Patients were followed for 12 months to evaluate graft function and treatment failure. Results The most common primary disease requiring transplantation was glomerulonephritis (24.3%). De novo and maintenance groups were similar in terms of overall rejection rates and acute rejection incidence whereas chronic rejection was evident only among the latter cohort ( P < 0.001). Time to an acute rejection episode was significantly longer among maintenance rather than de novo patients (220.8 versus 18.7 months; P = 0.015). Overall, 12 and 36 month survival rates were 91.6 ± 1.3% and 86.9% ± 0.3% among subjects experiencing acute rejection versus 99.7 ± 0.2% and 50.3% for those displaying chronic rejection. Among maintenance group no deterioration of renal function was observed after conversion from mycophenolate mofetil to EC-MPS. The incidences of leukopenia, new-onset anemia, or liver dysfunction were similar between de novo and maintenance patients. Gastrointestinal discomfort was more prevalent among the maintenance group, reaching a significant level at the fourth visit ( P < 0.05). EC-MPS dose reduction was required in only 16.7% of patients at visit, it was more frequent among the de novo group (17.9 versus 13.8%). Conclusion EC-MPS was an effective adjunctive therapy for de novo as well as maintenance renal transplant recipients in the Turkish population due to a relatively low incidence of dose reductions necessitated by adverse events as well as with an increased likelihood of long-term graft survival.

Therapeutic drug monitoring of mycophenolate mofetil and enteric-coated mycophenolate sodium in patients with systemic lupus erythematosus

Objective: Mycophenolic acid (MPA), the active form of mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), is used to treat systemic lupus erythematosus (SLE). MMF and EC-MPS pharmacokinetics were examined to devise guidance for therapeutic drug monitoring (TDM) for SLE patients with normal renal function.Research design and methods: This observational study included 21 patients receiving MMF (1000 mg twice daily) and 14 taking EC-MPS (720 mg twice daily). MPA AUC between 0 and 12 h (AUC0–12h), Cmax, Tmax, and 12-h trough concentrations (C12h) were determined.Results: Means of dose-normalized MMF– or EC-MPS–MPA Cmax were 64.6 ± 25 and 61.4 ± 27.1 h mg/l, respectively. MPA Tmax for EC-MPS was longer and more variable than for MMF. MMF-MPA AUC0–12h and C12h were correlated (r = 0.78, p = 0.0001), but EC-MPS–MPA Cmax and single concentrations were weakly correlated. A limited-sampling strategy (LSS) combining Cmax and C12h gave satisfactory predictive performance to estimate MPA AUC0–12h after EC-MPS administration.Conclusions: For TDM in SLE patients with GFR > 60 ml/min/1.73 m2, C12h after MMF ingestion could predict MPA AUC0–12h, while an LSS around Tmax should be used for patients on EC-MPS.

Efficacy of enteric-coated mycophenolate sodium in patients with resistant-type lupus nephritis: a prospective study

The role of mycophenolate mofetil (MMF) is still controversial in the treatment of cyclophosphamide-resistant proliferative lupus nephritis (PLN). Enteric-coated mycophenolate sodium (EC-MPS) has less gastrointestinal adverse effects than MMF and is, therefore, increasingly utilised in organ transplantation. The aim of this study was to compare the efficacy and safety of EC-MPS versus an extended-course of intravenous cyclophosphamide (ED-IVCY) in resistant-type PLN. Thirty-one, biopsy-proven PLN, patients who failed to respond to an induction of IVCY were enrolled in a prospective, open-labelled, historically controlled study. Patients received 6 month of EC-MPS (720 mg b.i.d.) treatment. The patients in the ED-IVCY group, collected from a database, received a repeated 6-month course of monthly IVCY 0.5-1 g/m(2) of body surface area. Both groups received 0.5-1 mg/kg/day of prednisolone. Primary outcomes were partial or complete responses. A repeated kidney biopsy was performed to evaluate the histological response. No serious adverse events or patient deaths were observed during the study. Both groups had comparable baseline characteristics. At 6 months, the EC-MPS group had a comparable response rate with the ED-IVCY group. There were significantly less adverse events in the EC-MPS group. Repeated biopsies showed significant improvement in the EC-MPS group. EC-MPS provides salutary efficacy and safety in the treatment of resistant-type PLN and can be a suitably alternative treatment to ED-IVCY.

Pharmacokinetics of enteric-coated mycophenolate sodium: comparative study in patients with autoimmune disease and renal allograft

Background: Recently, mycophenolic acid drugs have gained interest in the treatment of autoimmune diseases. However, only limited pharmacokinetic data are available on enteric-coated mycophenolate sodium in non-transplant indications. Objective: This study compared the pharmacokinetics of mycophenolic acid from enteric-coated mycophenolate sodium in patients with autoimmune disease and renal transplant recipients. Methods: Twelve autoimmune disease patients (mainly with antineutrophil cytoplasmic antibody-associated vasculitis) and 11 stable renal transplant patients, all of whom had been on enteric-coated mycophenolate sodium for ≥ 10 weeks, received an oral dose of enteric-coated mycophenolate sodium of 720 mg under fasting conditions. Blood samples for the determination of mycophenolic acid in the plasma were collected over 24 h. Results. Overall, no significant difference was found between both groups for their 0 – 12 h and 0 – 24 h areas under the concentration–time curve, Cmax, Tmax, C0 h, C12 h and C24 h, although the mean Cmax was numerically higher by 39% in the autoimmune disease patients (autoimmune disease 27.3 ± 17.4 mg/l and renal transplant 19.6 ± 15.7 mg/l). Patients on concomitant ciclosporin tended to have a lower mycophenolic acid exposure than patients on a non-ciclosporin regimen. The intersubject variabilities in the mycophenolic acid pharmacokinetics were high in both patient populations (around 40% for the area under the curve values). Both groups exhibited a weak and non-significant correlation between their mycophenolic acid trough (C12 h) levels and mycophenolic acid 0 – 12 h area under the curve (autoimmune disease r = 0.482 and renal transplant r = 0.138), whereas in the autoimmune disease group the mean C1.5 h and C2 h concentrations provided a satisfactory association with the 0 – 12 h area under the curve (for both r > 0.7 and p < 0.001). Conclusion: These data suggest that mycophenolic acid exposure (in terms of the area under the curve) from enteric-coated mycophenolate sodium is comparable in autoimmune disease and renal transplant patients. The mycophenolic acid trough levels did not reflect the systemic exposure to mycophenolic acid adequately; a limited sampling strategy for estimating mycophenolic acid exposure in autoimmune disease patients should include times around C1.5 h and/or C2 h reflecting Tmax if further studies confirm its usefulness.

Efficacy of enteric‐coated mycophenolate sodium in patients with active lupus nephritis

The ideal treatment of lupus nephritis has yet to be defined. Both cyclophosphamide and mycophenolate mofetil have been used with encouraging results, but adverse events are frequently seen. There are no data on the use of enteric-coated mycophenolate sodium. We retrospectively reviewed 12 patients with active forms of lupus nephritis (1 class III, 7 class IV and 4 class V) treated with enteric-coated mycophenolate sodium combined with corticosteroids. The mean age of the patients was 32.3 +/- 11.2 years and the average length of follow up was 25.9 +/- 8.9 months. The mean serum creatinine clearance was 93 +/- 30.1 mL/min per 1.73 m(2) and the mean proteinuria level was 4.5 +/- 3.6 g/day. All had features that warranted aggressive treatment. Mycophenolate sodium was given for 12.9 +/- 9.7 months with an averaged starting dose of 1350 +/- 163 mg/day. Six patients attained complete remission and six attained partial remission with treatment. The mean interval to attain first remission (complete or partial) was 8.3 +/- 5.7 weeks. At last follow up, all patients were in complete or partial remission. Apart from herpes zoster that developed in one patient, no other significant side-effects were encountered. Enteric-coated mycophenolate sodium was effective and well-tolerated in the treatment of active lupus nephritis.

Better Mycophenolic Acid 12-Hour Trough Level After Enteric-Coated Mycophenolate Sodium in Patients With Gastrointestinal Intolerance to Mycophenolate Mofetil

Introduction Enteric-coated mycophenolate sodium (EC-MPS) is the enteric-coated salt form of mycophenolic acid (MPA), the active component of the prodrug mycophenolate mofetil. EC-MPS was developed to reduce the upper-gastrointestinal (GI) effects of mycophenolate mofetil. There are no studies available comparing trough plasma levels in patients with GI intolerance to MMF when they are converted to EC-MPS. Aim To compare the GI tolerance and the MPA levels in patients previously treated with MMF in whom this drug was replaced by EC-MPS. Materials and methods A prospective study was conducted in 133 renal transplant patients after conversion from MMF to EC-MPS (median time posttransplant 42 months, range 1 to 240 months). The causes for EC-MPS switching were GI intolerance to MMF (51.9%; group A), low trough plasma levels with MMF (29.3%; group B), and others (18.8%; group C). These patients were converted to equipotent doses of EC-MPS. Results The trough plasma MPA levels increased from 1.5 ± 1.1 μg/mL at baseline to 2.5 ± 2.0 μg/mL at 1 month postconversion despite the equipotent EC-MPS doses not being increased. These higher plasma levels were maintained throughout the study. In group A, this increase was from 1.8 ± 1.0 to 2.7 ± 2.1 μg/mL ( P = .01) and in group B from 0.8 ± 0.4 to 2.4 ± 1.4 μg/mL ( P < .001). The doses and levels of calcineurin inhibitor decreased from baseline. Creatinine clearance improved from 56.5 ± 24.7 mg/dL at baseline to 61.9 ± 28.6 at 6 months postconversion ( P = .02). There was a statistically significant increase in hemoglobin levels. In group A, the GI tolerance improved in 78% of the patients. Conclusions At equipotent doses, patients converted to EC-MPS have higher and more adequate levels of MPA. At 6 months postconversion, we observed an improvement of the renal function, probably due to a reduction of calcineurin inhibitor drugs. However, the possibility that a better immunosuppressive efficacy as demonstrated by more suitable trough plasma levels may have been a contributing factor cannot be discarded.

Conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in patients with gastrointestinal side effects: case studies

The potential benefit of the current mycophenolic acid, mycophenolate mofetil, has not yet been fully achieved in clinical transplantation because of its gastrointestinal side effects. Dose splitting, dose reduction, and drug discontinuation are strategies that are used to manage gastrointestinal symptoms. However, recently reported registry data suggest these alterations result in inadequate graft protection, leading to increased late acute rejection rates and decreased longterm graft survival. To investigate the potential use of the new enteric-coated formulation of mycophenolic acid therapy, mycophenolate sodium, and its suggested improved side effects profile. Five patients who previously had or were currently experiencing gastrointestinal side effects while taking mycophenolate mofetil were selected at random. These patients were initially switched to an equimolar dose of enteric-coated mycophenolate sodium. An increase in mycophenolate sodium doses was attempted according to symptoms. Changes in kidney function and gastrointestinal symptom scores were recorded before and after conversion. No episodes of acute rejection were observed in any patients during or after conversion. All patients experienced an overall improvement in gastrointestinal symptom scores following conversion, and an increase in mycophenolate sodium dose was achieved in 1 patient.

Conversion from Mycophenolate Mofetil to Enteric-Coated Mycophenolate Sodium in Patients with Gastrointestinal Side Effects: Case Studies

The potential benefit of the current mycophenolic acid, mycophenolate mofetil, has not yet been fully achieved in clinical transplantation because of its gastrointestinal side effects. Dose splitting, dose reduction, and drug discontinuation are strategies that are used to manage gastrointestinal symptoms. However, recently reported registry data suggest these alterations result in inadequate graft protection, leading to increased late acute rejection rates and decreased longterm graft survival. To investigate the potential use of the new enteric-coated formulation of mycophenolic acid therapy, mycophenolate sodium, and its suggested improved side effects profile. Five patients who previously had or were currently experiencing gastrointestinal side effects while taking mycophenolate mofetil were selected at random. These patients were initially switched to an equimolar dose of enteric-coated mycophenolate sodium. An increase in mycophenolate sodium doses was attempted according to symptoms. Changes in kidney function and gastrointestinal symptom scores were recorded before and after conversion. No episodes of acute rejection were observed in any patients during or after conversion. All patients experienced an overall improvement in gastrointestinal symptom scores following conversion, and an increase in mycophenolate sodium dose was achieved in 1 patient.