Enteric-Coated Mycophenolate Sodium can be Safely Administered in Maintenance Renal Transplant Patients: Results of a 1-Year Study

Budde, Klemens; Curtis, John J.; Knoll, Greg; Chan, Lawrence; Neumayer, Hans‐Hellmut; Seifu, Yodit; Hall, Michael

doi:10.1046/j.1600-6143.2003.00321.x

Cited by 240 publications

(171 citation statements)

References 10 publications

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“…[60][61][62][63][64][65][66][67] Though designed specifically to improve GI adverse events, prospective randomized controlled studies did not find significant differences between the EC-MPS and MMF formulations. 60,65 However, MMF to EC-MPS conversion studies that implemented PRO measures consistently reported a significant improvement in patient-reported GI symptoms, [72][73][74] and in one study, increased numbers of patients were maintained on the maximum recommended EC-MPS dose. 74 These results could potentially translate into improved long-term patient and allograft outcomes, as MPA dose reduction has consistently demonstrated higher rates of rejection and graft loss.…”

Section: Resultsmentioning

confidence: 97%

“…65 The study included 322 renal transplant recipients. All patients received MMF 1000 mg twice daily in combination with cyclosporine, with or without corticosteroid for 14 days during the run-in period.…”

Section: Conversion From Mmf To Ec-mpsmentioning

confidence: 99%

“…Early studies comparing therapeutic equivalence of EC-MPS with MMF in de novo renal transplant patients, and a conversion study from MMF to EC-MPS, did not show any significant differences in GI toxicity. 60,65 However, 3 clinical studies that used a validated patient-reported outcome (PRO) instrument demonstrated improvement in GI adverse events following conversion from MMF to EC-MPA. [72][73][74] In a prospective, open-label, multicenter study, Chan and colleagues evaluated the benefit of converting renal transplant patients who experienced GI-related symptoms from MMF to EC-MPS utilizing the same patient-reported outcome measures.…”

Section: Patient-focused Perspectivementioning

confidence: 99%

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Mycophenolic acid agents: is enteric coating the answer?

Manitpisitkul¹,

Lee²,

Cooper³

2011

TRRM

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Addition of mycophenolate mofetil (MMF) to calcineurin-based immunosuppressive therapy has led to a significant improvement in graft survival and reduction of acute rejection in renal transplant recipients. However, in clinical practice, MMF dose reduction, interruption, or discontinuation due to hematological and gastrointestinal (GI) side-effects occurred in up to 50% of the patients. Large retrospective analyses have demonstrated that patients requiring MMF dose manipulation due to adverse events experienced a higher rate of rejection and graft loss. Enteric-coated mycophenolate sodium (EC-MPS) was developed with the goal of improving upper GI side-effects. Here, we review the efficacy and safety of EC-MPS in de novo kidney transplant recipient, and in stable renal transplant patients who were converted from MMF. The changes in GI-related adverse events using patient-reported outcome instruments are also reviewed.

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Section: Resultsmentioning

confidence: 97%

Section: Conversion From Mmf To Ec-mpsmentioning

confidence: 99%

Section: Patient-focused Perspectivementioning

confidence: 99%

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Mycophenolic acid agents: is enteric coating the answer?

Manitpisitkul¹,

Lee²,

Cooper³

2011

TRRM

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“…It is therefore not surprising that randomized, doubleblinded clinical studies in renal transplantation using equimolar dosage of MPA have failed to demonstrate any reduction of side effects after converting MMF to EC-MPS. 4 Enteric coating of drugs aims to release the active compound after passing the stomach, via a pHdependent dissolution. Thus, EC-MPS is solely intestinally resorbed with a delay compared to MMF depending on gastric emptying.…”

Section: Mmf To Ec-mpsmentioning

confidence: 99%

MMF to EC-MPS conversion: What makes the difference?

Schmidt

Brockmann

2007

Liver Transpl

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TO THE EDITORS:Dumortier et al. report on the prospective evaluation of converting stable liver transplant patients from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS). 1 Among their liver transplant patients since January 2003, they identified 36 patients with MMF-associated gastrointestinal (GI) symptoms, who remained symptomatic even after dosage reductions of MMF. Dosage of EC-MPS was adapted according to the dosage of the active compound mycophenolate acid (MPA) within MMF. Median blood trough level for MPA was 2.7 mg/L (range 0.74-3.91) before conversion. Blood trough levels were not reported after conversion. GI symptoms resolved in 20 patients (55%) and improved in an additional 6 patients (17%) in this pilot study. The authors conclude that this therapeutic strategy can improve GI symptoms. They speculate on the relevance of this conversion as a potential best therapeutic option in liver transplant patients who present with MMF-associated GI symptoms.In medicine, many 1-way conversion trials have been reported to be successful, but clear evidence was only demonstrated in a small proportion of these studies after well-designed studies using control groups were performed. This study lacks any control group or any cross-over design.Interestingly, the authors refer to the development of EC-MPS with a goal to reduce GI symptoms due to its enteric coating. MMF as a prodrug is readily absorbed in the upper GI tract and rapidly hydrolyzed to the active compound MPA. 2 The well-documented efficacy and the potential side effects of MMF result from MPA and its metabolites. There is accumulating evidence that MPA-associated GI side effects result after, but not before, GI resorption. Pescovitz et al. demonstrated that both intravenous and oral use of MMF result in similar side effects, including GI symptoms. 3 Thus, once equimolar dosage of MPA is administered as reported in this study, identical systemic MPA exposure should result both in identical efficacy and symptoms. It is therefore not surprising that randomized, doubleblinded clinical studies in renal transplantation using equimolar dosage of MPA have failed to demonstrate any reduction of side effects after converting MMF to EC-MPS. 4 Enteric coating of drugs aims to release the active compound after passing the stomach, via a pHdependent dissolution. Thus, EC-MPS is solely intestinally resorbed with a delay compared to MMF depending on gastric emptying. There are many medical and nutritional reasons that interfere with gastric passage and pH-dependent release in patients, such as diabetic enteropathy, use of proton pump inhibitors, and consuming fatty meals. Coadministering EC-MPS with a meal containing 55 g fat and 1000 calories is reported to delay t lag and t max by 3-5 hours for MPA (t max range up to 20 hours). 5 Therefore, EC-MPS is recommended to be administered apart from meals, and twice per day rather than more often.The most interesting question in the article of Dumortier et al. concerns the blood trough levels of M...

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“…6 Mycophenolate sodium may cause less gastric disorders because it is administered as an enteric-coated tablet and is mainly absorbed in the small intestine without being released in the stomach. 9 Calcineurin inhibitors are the cornerstone of modern immunosuppressive therapy after solidorgan transplant. Tacrolimus has been associated with an increased risk of diarrhea (odds ratio of 1.7; 95% confidence interval, 1.4-2.0) and constipation (odds ratio of 1.3; 95% confidence interval, 1.1-1.6).…”

Section: Introductionmentioning

confidence: 99%

Untitled

Królikowski

Pawłowicz²,

Budzisz³

et al. 2016

Exp Clin Transplant

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Objectives: Although immunosuppressive drugs have been recognized as leading causes of gastrointestinal symptoms after kidney transplant, other widely used medications such as proton-pump inhibitors recently have been implicated. Our aim was to study the effects of chronic proton-pump inhibitor therapy on gastrointestinal symptoms in clinically stable patients late after kidney transplant. Materials and Methods:The study comprised 100 kidney transplant recipients (66 men and 34 women, mean age of 49 ± 12 y, mean time after transplant of 56 ± 46 mo). All patients completed the Gastrointestinal Symptoms Rating Scale and the Quality of Life Questionnaire SF-8 surveys. Results:The most commonly reported symptoms included borborygmus (27%), flatulence (23%), abdominal distension (18%), urgent need of defecation (17%), and heartburn, acid reflux, and eructation (13%). Proton-pump inhibitors were chronically used by 50% of patients and sporadically by 33%. Gastrointestinal Symptoms Rating Scale scores were higher in patients who used proton-pump inhibitors (mean score of 7.8 ± 5.5 vs 4.6 ± 3.0; P = .013). Total score of items representing diarrhea in the Gastrointestinal Symptoms Rating Scale (increased passage of stools, loose stools, urgent need of defecation, incomplete evacuation) was higher in patients treated with proton-pump inhibitors than in those not treated (2.3 ± 2.2 vs 1.3 ± 1.9; P = .04). Conclusions: Chronic use of proton-pump inhibitors may increase the prevalence of gastrointestinal symptoms, particularly diarrhea, in patients late after kidney transplant.

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Enteric-Coated Mycophenolate Sodium can be Safely Administered in Maintenance Renal Transplant Patients: Results of a 1-Year Study

Cited by 240 publications

References 10 publications

Mycophenolic acid agents: is enteric coating the answer?

Mycophenolic acid agents: is enteric coating the answer?

MMF to EC-MPS conversion: What makes the difference?

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