Gastrointestinal side effects in liver transplant recipients taking enteric‐coated mycophenolate sodium vs. mycophenolate mofetil

In the setting of liver transplantation, mycophenolate mofetil (MMF) may be used as an adjuvant therapy for immunosuppression to prevent graft rejection; however, its use may be limited due to severe gastrointestinal (GI) side effects. In contrast, enteric‐coated mycophenolate sodium (EC‐MPS) may be associated with less severe side effects and hence better tolerability. We compared the side effects of EC‐MPS to MMF in liver transplant patients in a de novo study (Study I—randomized, prospective, double‐blinded) and a conversion study (Study II). In both studies, the severity of GI symptoms was assessed at various time points using the Gastrointestinal Symptoms Rating Scale (GSRS) survey, a validated survey of GI symptoms (abdominal pain, reflux, indigestion, diarrhea, and constipation). In Study I, the symptoms of 30 recipients receiving EC‐MPS (n = 15) were compared to 15 recipients receiving MMF. A multivariate analysis of variance (MANOVA) of the total GSRS scores and symptom syndrome subscores revealed no significant difference (p > 0.05) between the two medications over time. A conversion study (Study II) with 29 participants, however, showed that over time, all GI symptoms improved significantly (p < 0.001) when the patients were treated with EC‐MPS instead of MMF.     

Reduction of gastrointestinal complications in renal graft recipients after conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium

Gastrointestinal (GI) complications such as diarrhea or indigestion frequently occur in renal graft recipients treated with mycophenolate mofetil (MMF), requiring dose reductions to reduce side effects, thereby increasing the risk of rejection episodes and graft loss. In a prospective clinical trial, the immunosuppressive therapy of renal graft recipients was converted from MMF to enteric-coated mycophenolate sodium (EC-MPS) to identify a strategy to reduce GI symptoms without dose reduction. At baseline and 6-8 weeks later patients filled in 4 questionnaires related to GI symptoms and general and health-related quality of life. In 15 German study centers, 196 renal graft recipients (mean age 49.5 ± 13.5 years; male/female, 120/76) were included; 51.0% of patients suffered from GI complications at baseline. The Gastrointestinal Symptom Rating Scale score decreased significantly (P < .001) in patients with GI complications from 2.61 ± 0.86 at baseline to 2.14 ± 0.86 at visit 2. Health-related and general quality of life improved significantly. Fifty percent of patients with GI symptoms and 34% of the total per protocol population reported an improvement of their physical condition after converting the medication. In conclusion, conversion from MMF to EC-MPS reduces GI complications in renal graft recipients, reduces the patients' physical discomfort, and maintains their quality of life.(ClinicalTrials.gov number NCT00149968.)     

Conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in renal transplant recipients with gastrointestinal tract disorders

OBJECTIVE: The objective of this prospective study was to evaluate the effect of conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) in renal transplant recipients with gastrointestinal tract (GI) reverse effects using patient-reported outcomes instrument. METHODS: A multicenter, open-label, prospective study was undertaken in renal transplant recipients treated with MMF. In patients experiencing GI tract symptoms, treatment was changed to equimolar EC-MPS (myfortic). At baseline and visit 2 (4-6 weeks after baseline), patients completed the Gastrointestinal Symptom Rating Scale (GSRS) and Gastrointestinal Quality of Life Index (GIQLI), and physicians completed the Overall Treatment Effect (OTE) scale at visit 2. A difference of 0.5 or greater in the OTE score is indicative of clinical relevance. RESULTS: Of 154 patients screened, 118 fulfilled the inclusion or exclusion criteria. Eighty-five men and 33 women with a mean age of 41.6 years participated in this study. Median time since transplantation was 12 months. Mean (SD) dose of MMF reported at baseline was 1209.4 (422.89) mg/d. More than 50% of patients reported MMF-associated nausea, dyspepsia, and abdominal pain. After conversion to an equimolar dose of EC-MPS, patients showed improvement in GI symptoms. This benefit was predominantly observed in patients with moderate to severe symptoms at baseline. On the GSRS, patients reported a significant (P < .05) reduction in symptom burden across all parameters (reflux, 36%; diarrhea, 38%; indigestion, 36%; constipation, 28%; and abdominal pain, 40%). On the GIQLI also, significant (P < .05) improvement was reported (symptoms, 18%; emotional status, 22%; physical functioning, 21%, and use of medical treatment, 18%). On the OTE scale, 84.7% of patients reported improvement in GI symptoms. CONCLUSION: In patients with moderate to severe GI symptoms, changing treatment from MMF to EC-MPS significantly reduces GI-related symptom burden and improves GI-specific quality of life.     

Improvement of gastrointestinal symptoms after conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in liver transplant patients

As many as 50% of liver transplant patients suffer gastrointestinal (GI) disturbances post-transplant. Conversion from mycophenolate mofetil (MMF) to mycophenolate sodium (EC-MPS) alleviates GI symptom burden in renal transplant recipients. We employed a validated patient and physician-reported assessment to evaluate the impact of conversion to EC-MPS in liver transplant patients. This is a prospective, longitudinal, single-center, open-label pilot study. Thirty-one MMF-treated liver transplant patients with GI symptoms were converted to equimolar EC-MPS. Gastrointestinal Symptom Rating Scale (GSRS), GI Quality of Life, SF-12v2 and physician-reported assessments were used to evaluate GI symptom burden and severity. A significant improvement in overall GSRS score was noted from baseline (2.57; 95% CI 2.12-3.10) to one month (1.90; 1.68-2.12; p = 0.0007) and three months (1.82; 1.60-2.04; p = 0.0002) post-conversion with significant reductions in all subgroups except Reflux. The overall Gastrointestinal Quality of Life Index (GIQLI) score also showed significant increase in health-related quality of life between one month (90.89; 84.04-97.75) and three months (100.04; 94.57-105.51; p = 0.0009), with all subgroups except social functioning (p = 0.0861) and medical treatment (p = 0.3156) demonstrating significant improvements. This pilot study demonstrates improvement in GI symptom burden when converting from equimolar doses of MMF to EC-MPS. This benefit persisted for three months without evidence of rejection.     

Long‐term dosing patterns of enteric‐coated mycophenolate sodium or mycophenolate mofetil with tacrolimus after renal transplantation

MORE was a four‐yr, prospective, observational study at 40 transplant centers in the US. Data were analyzed to evaluate changes in mycophenolic acid (MPA) dosing over time in 904 de novo kidney transplant recipients receiving enteric‐coated mycophenolate sodium (EC‐MPS, n = 616) or mycophenolate mofetil (MMF, n = 288) with tacrolimus. Induction therapy and steroid treatment were similar in the two subpopulations. The proportion of patients receiving the maximal recommended MPA dose was 80.5%, 43.9%, 39.2%, 34.6%, and 30.1% at baseline and years 1, 2, 3, and 4, respectively. More patients received the maximal recommended MPA dose with EC‐MPS vs. MMF at month 1 (79.2% vs. 71.7%, p = 0.016), month 3 (68.5% vs. 56.9%, p = 0.001), and month 6 (52.9% vs. 44.0%, p = 0.028). Multivariate analysis showed the risk of biopsy‐proven acute rejection, graft loss or death to be similar for EC‐MPS vs. MMF. Estimated glomerular filtration rate (GFR) was similar with EC‐MPS vs. MMF at all time points. There were no significant differences in any category of adverse event between the EC‐MPS and MMF cohorts during follow‐up, including gastrointestinal events. In conclusion, MPA dose was maintained more effectively in the first six months after kidney transplantation using EC‐MPS vs. MMF, without an increase in adverse events.     

Adverse drug reaction driven immunosuppressive drug manipulations: a single-center comparison of enteric-coated mycophenolate sodium vs. mycophenolate mofetil

Abstract: Enteric‐coated mycophenolate sodium (MPS) has been developed to help circumvent the upper gastrointestinal side‐effects of mycophenolic acid by facilitating drug release in the small intestine. Many questions regarding the side‐effect profile of MPS remain. Therefore, the purpose of this study is to review a single‐center’s experience with mycophenolate mofetil (MMF) and MPS. Methods: This retrospective, sequential cohort analysis of de novo renal and pancreas transplants (n = 198) compared MMF 500 mg b.i.d. to MPS 360 mg b.i.d. in conjunction with antibody induction, tacrolimus, and steroids. Results: There were fewer adverse event driven drug manipulations in the MPS group at 90 d (4% MPS vs. 17% MMF) and 180 d (10% MPS vs. 24% MMF, p = 0.006, log‐rank) after transplantation. There was a trend toward fewer GI‐related hospital admissions in the MPS arm (7% MPS vs. 13% MMF, p = 0.18). Allograft outcomes including patient survival, graft survival, acute rejection, serum creatinine, and infection were similar. Conclusion: This single‐center, sequential cohort study demonstrates that MPS is associated with fewer adverse event driven drug manipulations while maintaining similar safety and allograft outcomes.     

Comparison of enteric-coated mycophenolate sodium with mycophenolate mofetil in living renal allograft transplantation

OBJECTIVE: Enteric-coated mycophenolate sodium (MPS) has been developed to decrease the GI side effects of mycophenolate mofetil (MMF). We did a retrospective analysis of 112 patients to compare the safety and efficacy of enteric coated MPS vs MMF in living renal transplantation. METHODS: Patients were divided into two groups. Group A who received MPS [Novartis, Basel, Switzerland] [1.08-1.44 g/d] included 53 patients of mean age 33.5 +/- 11.9 yrs, and M:F gender ratio 37:15 with a mean donor age of 43.2 +/- 9.9 years. Group B who received MMF [1.5-2.0 g/d] included 59 subjects of mean age 33.2 +/- 9.9 yrs and M:F gender ratio 57:6, with a mean donor age of 41.4 +/- 10.9 years. All patients received cyclosporine and prednisolone in addition to mycophenolate. Mean follow-up in the two groups was 11.6 +/- 7.0 and 12.6 +/- 8.5 months, respectively. RESULTS: There were 11 (20.7%) rejection episodes in Group A and 12 (20.3%) rejection episodes in Group B (P = NS). Incidence of CMV disease was 9.61% and 10.1%, and of other infections, 88.7% and 74.7% in Groups A and Group B, respectively [P = NS]. The incidence of GI (18.9% & 20.3%) and hematologic toxicities (9.4% & 5.1%) were similar in the groups. Patient and graft survivals in Group A were 91.9% & 86.6%, and in Group B was 91.3% & 91.3%, respectively [P = NS]. CONCLUSION: Mycophenolate sodium is an alternative immunosuppressant to mycophenolate mofetil in kidney transplant recipients with a similar efficacy and safety profile.     

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 microg/mL at baseline to 2.5 +/- 2.0 microg/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 microg/mL (P = .01) and in group B from 0.8 +/- 0.4 to 2.4 +/- 1.4 microg/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.     

The impact of conversion from mycophenolate mofetil to mycophenolate sodium among renal transplant recipients on a sirolimus-based regimen

OBJECTIVE: To examine the benefits of conversion from mycophenolate mofetil (MMF) to mycophenolic acid sodium (MPS) among renal transplant patients on sirolimus-based immunosuppression. METHODS: Alternate renal transplant recipients who were converted from MMF to MPS immediately (group A, n = 21) or 90 days thereafter (group B, n = 19) completed the Gastrointestinal Symptom Rating Scale and the Gastrointestinal Quality of Life Index (GIQLI) questionnaires at days 90 and 180. Similarly, at the completion of the study 20 members of groups A plus B (converted to MPS) and 19 patients who initially declined to participate (continuous MMF) completed the questionnaires. RESULTS: At 90 days after conversion, members of group A showed fewer responses to "feeling unwell" and to flatulence, which regressed in group B at 180 days, although more persons in the latter cohort complained of bloating. The average scores of cohort A on the GIQLI at day 180 were significantly better than those at day 90. Compared with a control cohort of continuous MMF treatment, members of cohorts A plus B showed lower incidences of diarrhea, dysphagia, and eructations but greater incidences of constipation and not feeling fit. CONCLUSION: Conversion from MMF to MPS offers subjective benefits for patients on maintenance therapy with mycophenolic acid in combination with sirolimus.     

A comparison of mycophenolate mofetil with mycophenolate sodium in renal transplant recipients on tacrolimus-based treatment

We compared the tolerability and efficacy of mycophenolate mofetil (MMF) versus mycophenolate sodium (MPS) among renal transplant recipients on tacrolimus-based immunosuppression. The 105 patients who underwent kidney transplantation between January 2002 and March 2008 and were treated with steroid, tacrolimus, and a mycophenolic acid compound were enrolled in the study. From patient files we collected on demographics data, donors, immunosuppressive drug doses, biochemical and hematologic parameters, gastrointestinal and hematologic side effects, and kidney function. Fifty-six patients were prescribed MMF and 49 of them were taking MPS. Demographic parameters and pretransplantation dialysis duration were similar between the 2 groups. After the third month, the MPS dose was higher than that of MMF. There were no clinically important differences between the 2 groups, regarding other immunosuppressive drug doses. Gastrointestinal side effects were similar: 42.4% in the MMF versus 44.8% in the MPS group (P = .846). Six patients in the MMF group and 1 patient in the MPS group underwent a switch of the mycophenolic acid therapy due to severe gastrointestinal side effects (P = .183). Biopsy-proven acute rejection was reported in 6 patients on MMF and 7 patients on MPS therapy (P = .768). The log-rank test evaluating a 50% reduction in glomerular filtration rate (GFR) showed no significant difference between the 2 groups (P = .719). No deaths were recorded during the study period; there was only 1 graft loss, which occurred in the MMF group. We did not observe a significant difference in tolerability and efficacy between the 2 widely used mycophenolic acid derivatives. Economic considerations can be an important factor when choosing the drug.     

Improvement in 3-month patient-reported gastrointestinal symptoms after conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in renal transplant patients

BACKGROUND: The benefit of conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) in terms of gastrointestinal symptom burden has been evaluated previously using patient-reported outcomes. However, data are lacking concerning the sustained effect of conversion over time, and the potential impact of concomitant calcineurin inhibitor. METHODS: In this 3-month, prospective, multicenter, longitudinal, open-label trial, MMF-treated renal transplant patients with gastrointestinal symptoms receiving cyclosporine or tacrolimus were converted to equimolar doses of EC-MPS. Change in gastrointestinal symptom burden was evaluated using a validated Gastrointestinal Symptom Rating Scale (GSRS). RESULTS: A significant improvement in GSRS score was observed from baseline (2.61, 95% CI 2.54-2.68) to month 1 (1.87, 95% CI 1.81-1.93) after conversion to EC-MPS and was sustained to month 3 (1.81, 95% CI 1.74-188; both P<0.0001 versus baseline). The mean change in overall GSRS score from baseline to month 1 was -0.74 overall (cyclosporine: -0.73 and tacrolimus: -0.74; all P<0.0001 versus baseline), with a slight further improvement (-0.79) at month 3 (cyclosporine: -0.82 and tacrolimus: -0.78; all P<0.0001 versus baseline). A significant improvement in GSRS subscale scores was also observed in the total population regardless of calcineurin inhibitor at month 1, sustained to month 3 (all P<0.0001 versus baseline). The improvement in GSRS score postconversion was similar in African-American and non-African-American patients, and in diabetic and nondiabetic patients. CONCLUSIONS: This exploratory study in 728 patients demonstrates that following conversion from MMF to EC-MPS, regardless of concomitant calcineurin inhibitor, GSRS is improved and sustained over 3 months.     

Mycophenolic acid dose reductions result in poor long-term renal allograft survival: comparison between mycophenolate sodium and mycophenolate mofetil

Mycophenolate acid (MPA) therapy is associated with a decrease in acute rejection rates and excellent renal allograft survival. Unfortunately, mycophenolate mofetil (MMF) is associated with significant adverse effects (AE), which, in many cases, preclude full-dose therapy. Previously, lower MMF drug exposure was significantly associated with a greater risk of rejection. Patients who had a ≥50% dose reduction of MMF experienced a lower graft survival compared to those who tolerated full-dose MMF. Mycophenolate sodium (MPS) was designed to lessen MPA-associated AE. In this retrospective study, we studied the tolerability and long-term outcomes in renal transplant recipients (RTR) treated with MPS versus MMF. Four hundred forty-nine RTRs who received MPS or MMF for more than 3 months were classified into three groups: group 1: MMF-treated; group 2: MPS-treated; and group 3; patients who converted from MMF to MPS due to AE. Donor and recipient demographics as well as induction and maintenance immunosuppressive therapies were similar in all groups. Patient survival was not different in all groups. However, long-term graft survival was lower in patients whose dose of either MPS or MMF was reduced by ≥50%. Moreover, a ≥50% MPA dose reduction was associated with a higher rate of rejection compared to full dose (38% vs 21%, respectively, P < .01). Compared to patients treated initially with MMF, fewer MPS-treated recipients required dose reductions (65% vs 42%, respectively, P < .001). Furthermore, 38% of patients in group 3 tolerated full-dose MPS despite previous intolerance to MMF. Finally, the long-term graft survival was best in MPS-treated RTR and worst in those who converted from MMF to MPS due to AE. We conclude that MPS is better tolerated than MMF, which may explain the superior graft outcome in RTR who were treated with MPS from the onset.     

Randomized crossover study to assess the inter‐ and intrasubject variability of morning mycophenolic acid concentrations from enteric‐coated mycophenolate sodium and mycophenolate mofetil in stable renal transplant recipients

Tedesco‐Silva H, Felipe CR, Park SI, Pinheiro‐Machado PG, Garcia R, Slade A, Schmouder R, Medina‐Pestana JO. Randomized crossover study to assess the inter‐ and intrasubject variability of morning mycophenolic acid concentrations from enteric‐coated mycophenolate sodium and mycophenolate mofetil in stable renal transplant recipients.
Clin Transplant 2010: 24: E116–E123.
© 2009 John Wiley & Sons A/S. Abstract: The delayed release of mycophenolic acid (MPA) from enteric‐coated mycophenolate sodium (EC‐MPS, myfortic^®) may have an impact on the variability of MPA trough (C_{0 h}) levels. A randomized, two‐period crossover study was performed in 24 maintenance renal transplants to evaluate the inter‐ and intrasubject variability of MPA predose levels from EC‐MPS and mycophenolate mofetil (MMF, CellCept^®), both in combination with cyclosporine. Patients received EC‐MPS (720 mg b.i.d.) and MMF (1000 mg b.i.d.) for a period of 21 d each. MPA plasma levels were measured over the final seven consecutive days at ?1, 0, 1, 2, and 3 h after the morning MPA dose. Intersubject coefficients of variation (%CV) for MPA troughs were 47.5% (95% CI, 34.1–80.3) and 54.4% (40.0–86.8) for EC‐MPS and MMF, respectively; intrasubject %CVs were 62.7% (55.1–72.9) and 42.8% (37.9–49.2). High MPA C_{0 h} levels >10 μg/mL were rarely observed with both EC‐MPS (1.8%) and MMF (0.6%). Mean MPA area under the curve (AUC)_{0–3 h} was comparable between treatments, while MPA C_{0 h} was on average 46% higher with EC‐MPS. In conclusion, predose MPA trough level monitoring appears of limited value during EC‐MPS and MMF therapy given the large intrasubject variability in MPA C_{0 h} levels with both treatments.     

Patient-reported gastrointestinal symptom burden and health-related quality of life following conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium

BACKGROUND: The benefit of converting renal transplant recipients with gastrointestinal (GI) complaints from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) has not been evaluated using patient-reported outcomes. METHODS: A multicenter, open-label, prospective study was undertaken in MMF-treated renal transplant patients. Patients experiencing GI complaints were converted to equimolar EC-MPS (Cohort A). Patients without GI complaints remained on MMF (Cohort B). At baseline and Visit 2 (4-6 weeks postbaseline), patients completed the Gastrointestinal Symptom Rating Scale (GSRS), Gastrointestinal Quality of Life Index (GIQLI) and Psychological General Well-being Index (PGWBI). At Visit 2, patients and physicians completed the Overall Treatment Effect (OTE) scale for GI symptoms. Additionally, patients completed the OTE for health-related quality of life (HRQoL). Minimal important difference (MID) was calculated for GSRS and GIQLI based on patients' and physicians' OTE evaluation. RESULTS: Of 328 patients enrolled (i.e. the intent-to-treat and safety populations), 278 formed the per-protocol population (Cohort A, n=177; Cohort B, n=101). At baseline, Cohort A had significantly worse scores on all GSRS, GIQLI and PGWBI subscales compared to Cohort B (all P<0.0001). All GSRS, GIQLI and PGWBI subscale scores improved significantly in Cohort A between baseline and Visit 2 (all P<0.0001). Mean improvements in all GSRS subscales and most GIQLI subscores exceeded the calculated MID. GSRS, GIQLI and PGWBI subscales remained stable in Cohort B. CONCLUSION: This first exploratory study indicates that converting patients with mild, moderate or severe GI complaints from MMF to EC-MPS significantly reduces GI-related symptom burden and improves patient functioning and well-being.     

Quality of life in renal transplant recipients following conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium

INTRODUCTION: Tolerance to immunosuppresant treatment has considerable impact on adherence to therapy and on the outcome of renal transplantation. Recent data indicate better gastrointestinal tolerance to enteric-coated mycophenolate sodium (EC-MPS) than to the classic mycophenolate mofetil (MMF) formulation. AIM: This study assessed the effect of conversion therapy from MMF to EC-MPS on gastrointestinal tolerance and quality of life in renal transplant recipients. METHODS: This open observational study analyzed the outcomes of conversion from MMF to EC-MPS among renal transplant patients with gastrointestinal complaints. At baseline (B) and at 8 weeks postconversion patients were assessed by the Gastrointestinal Quality of Life Index (GIQLI) questionnaire as well as by clinical evaluation (acute rejection, infection) and analytical determinations. RESULTS: We analyzed 18 recipients of cadaveric renal transplants of mean age of 54 +/- 9 years including 61% men and one retransplant. Our patients had stable renal function with mean creatinine of 1.9 +/- 0.7 mg/dL. Baseline treatment included cyclosporine-MMF-prednisone (33%) or FK-MMF-prednisone (66%). Bioequivalent conversion was carried out at 50 +/- 29 months posttransplantation. Conversion to EC-MPS resulted in an improvement in overall quality of life (total score: baseline 106.61 vs 8 weeks 116.89; P < .01). Improvements were observed in the following GIQLI subscales: gastrointestinal symptoms (3.12 vs 3.48, P < .001), physical function (2.54 vs 2.76, P = .003), medical treatment (2.17 vs 2.50, P = .031), and emotion (3.08 vs 3.39, P = .001). No changes were observed in the social function subscale. The hemogram and renal function remained stable; there were no episodes of rejection or infection. CONCLUSION: Conversion from MMF to an EC-MPS formulation was associated with improvements in gastrointestinal complaints and quality of life among renal transplant recipients.     

Enteric-coated mycophenolate sodium in de novo and maintenance kidney-pancreas transplant recipients

Ricart MJ, Oppenheimer F, Andrés A, Morales JM, Alonso Á, Fernández C, on behalf of the Epi‐trasplante Study, MIDATA Kidney–Pancreas Sub‐study Group. Enteric‐coated mycophenolate sodium in de novo and maintenance kidney–pancreas transplant recipients.
Clin Transplant 2011 DOI: 10.1111/j.1399‐0012.2011.01526.x.
© 2011 John Wiley & Sons A/S. Abstract: Background: Our objective was to describe efficacy and safety of enteric‐coated mycophenolate sodium (EC‐MPS) in de novo and maintenance recipients of kidney–pancreas transplant in the clinical practice. Methods: Observational, multicentre, prospective, 12‐month study. Results: We included 24 de novo and 24 maintenance patients. EC‐MPS mean (±SD) doses at initiation in de novo patients were 1440 ± 0 vs. 1268 ± 263 mg/d at month 12 (M12). Patient and renal graft survival at one yr were 100%, and pancreatic graft survival was 83.3% (two losses owing to technical failure and two owing to rejection). In the maintenance cohort, EC‐MPS was introduced at a median (P25–P75) of 30 (6–71) months after transplant. Baseline doses were 585 ± 310 vs. 704 ± 243 mg/d at M12. In this group, a significant increase in creatinine clearance was observed (65 ± 22 at baseline vs. 74 ± 20 mL/min at M12, p = 0.011). Patient, renal, and pancreatic graft survival were 100%, 95.8%, and 100%, respectively (one kidney graft loss owing to rejection). During follow‐up, one patient from each group discontinued EC‐MPS. Conclusions: The efficacy of EC‐MPS in the clinical practice of kidney–pancreas transplantation is good, with high patient and grafts survival at 12 months, and good safety profile. The maintenance group displayed an improvement in renal function.     

Long-term efficacy and safety of mycophenolate mofetil in liver transplant recipients with calcineurin inhibitor-induced renal dysfunction

Long-term survival after orthotopic liver transplantation (OLT) is mainly influenced by adverse events caused by immunosuppression. Several studies have shown the efficacy of mycophenolate mofetil (MMF) in improving calcineurin inhibitor (CI)-induced nephrotoxicity with concomitant reduction or withdrawal of CI. In this prospective study we assessed the long-term effect and safety of MMF. Thirty-two OLT recipients with significant renal impairment due to either cyclosporine A (n=25) or tacrolimus (n=7) were enrolled in this study. CIs were reduced stepwise by at least 70%. Mean serum creatinine had decreased from 2.63±0.39 to 1.74±0.34 mg/dl after 1 month, and this improvement was maintained within a follow-up period of 4.8±0.6 (range 3.1–6.0) years, without major immunological or non-immunological side effects. Of all participants, 88% showed a significant reduction, and 41% even a normalization, in their serum creatinine level. In addition, MMF conversion, within 6 months of OLT, appears to be crucial in order to improve or even normalize renal function. This study demonstrates the long-term efficacy and safety of MMF in OLT recipients with CI-induced nephropathy.This work was supported by Verein zur Förderung der Forschung in Gastroenterologie und Hepatologie an der Universität Innsbruck     

Enteric-Coated Mycophenolate Sodium: One-Way Conversion From Mycophenolate Mofetil and De Novo Use in Stable Liver Transplant Recipients

Enteric-coated mycophenolate sodium (EC-MPS) is a formulation of mycophenolic acid (MPA) that releases the active molecule in the intestine reducing drug-related gastrointestinal (GI) side effects. The aim of present work was to summarize the use of EC-MPS for one-way conversion from mycophenolate mofetil (MMF) due to GI side effects and for de novo administration in a stable liver transplant population. In 10 patients on MMF and low-dose calcineurin inhibitors (CNI), significant GI side effects suggested drug conversion to ameliorate subjective symptoms. In 5 patients, EC-MPS was initiated de novo together with reduction of CNI for prevention of long-term renal failure. Conversion was carried out at equivalent MMF/EC-MPS dosages. Reevaluation at 2 months after conversion showed that no episode of rejection or infection occurred, and white blood cell count, CNI levels and doses, and creatinine clearance did not vary significantly. In 70% of converted patients there was a reduction of GI symptoms, especially diarrhea. Eighty percent suspended proton pump inhibitors. The de novo-treated patients showed no significant GI side effects. In conclusion, conversion from MMF to EC-MPS demonstrated significant GI symptom relief and de novo drug administration was well tolerated.     

Effectiveness and safety of mycophenolate mofetil as monotherapy in liver transplantation

INTRODUCTION: Calcineurin inhibitors (CIs) cause substantial long-term morbidity and mortality among orthotopic liver transplantation (OLT) patients. Our aim was to evaluate the effectiveness and safety of mycophenolate mofetil (MMF) among OLT patients with CI-related side effects. PATIENTS: Thirty three adult patients, including 29 men and 4 women of mean age 57 years, underwent OLT between 1986 and 2000 under treatment with CIs (28 cyclosporine and five tacrolimus). Mean follow-up after OLT was 59 months. Adverse effects were renal dysfunction in 26, hypertension in 23, and neurotoxicity in two. MMF was added gradually while simultaneously reducing the dosage of CI. RESULTS: After a mean 15-months follow-up of MMF treatment, CIs had been withdrawn in 28 patients (85%). The mean time from the initiation of MMF and CI withdrawal was 5 months. During the first year of follow-up chronic renal dysfunction improved in 16 of 26 patients (61.6%) accompanied by a decreased serum creatinine and urea and an increase in creatinine clearance. Among 13/23 (56.5%) hypertensive patients, there was a significant decrease in blood pressure or the number of antihypertensive drugs (P<.05). One patient with neurotoxicity improved. Twenty-two patients (66%) displayed adverse events: five rejections (15%) including four acute episodes, controlled by CI re-introduction, and one chronic reaction. The most frequent adverse effects were herpes simplex infection in 10 patients (30%), asthenia in nine (27%), diarrhea in five (15%) and thrombocytopenia in four (12%). Nevertheless, only six patients (19%) required MMF dose reduction, namely, three patients with GI intolerance, two with repeated VHS infections, and one with anemia. CONCLUSIONS: MMF monotherapy improves renal function and blood pressure levels in more than 50% of patients with chronic renal impairment and hypertension after OLT. Many of the side effects of MMF were mild; it was safe accompanied by a low incidence of rejection reactions.     

Early experience with enteric-coated mycophenolate sodium in de novo kidney transplant recipients

INTRODUCTION: We sought to evaluate the efficacy of enteric-coated mycophenolate sodium (EC-MPS) and the gastrointestinal (GI) adverse events in de novo kidney transplant recipients. METHODS: This noncontrolled, retrospective review includes 22 de novo kidney transplant recipients. All patients received a standard course of basiliximab and were maintained on triple-drug therapy with EC-MPS, cyclosporine microemulsion (CsA), and prednisolone. The follow-up lasted 7.9 +/- 1.2 months. The incidence of GI adverse effects were compared with those of historical mycophenolate mofetil (MMF) studies. RESULTS: The serum creatinine was maintained within 1.4 +/- 0.7 mg/dL. The 2-hour CsA postdose level was 1080 +/- 327 ng/mL initially and gradually tapered to 851 +/- 435 ng/mL. The daily EC-MPS dose was 1404 +/- 180 mg initially and gradually tapered to 1098 +/- 288 mg. The GI adverse effects at the daily dose of EC-MPS 1422 +/- 126 mg included dyspepsia 27%, acid regurgitation 18.2%, epigastralgia 9%, nausea 9%, vomiting 4.5%, and poor appetite 4.5%. In comparison those from historical MMF 2 g/d studies included dyspepsia 3.1% to 40%, epigastralgia 10%, nausea 3.7% to 34%, and vomiting 0.6% to 10.7%. CONCLUSION: Immunosuppression with CsA, EC-MPS, and steroids maintains stable graft functions. Minimal dose reduction of EC-MPS decreases GI adverse events but without significance. EC-MPC and MMF have respective GI side effects; they can be used alternatively in patients with individual GI intolerance.