Use of enteric‐coated mycophenolate sodium in liver transplant patients with intestinal intolerance caused by mycophenolate mofetil

Doria, Cataldo; Ramirez, Carlo B.; Frank, Adam M.; Vaccino, Silvia; Fraser, Natalie S.; Marino, Ignazio R.

doi:10.1111/j.1399-0012.2009.01019.x

Cited by 12 publications

(14 citation statements)

References 12 publications

(14 reference statements)

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“…A limitation of the current study is that the treatment group is composed of patients with mild to moderate GI symptoms as patients with severe GI disturbances who had previously discontinued MMF were not eligible to participate in this study. This study limitation also occurred in other MMF to EC‐MPS conversion studies (20, 23). A smaller study evaluated eight liver transplant patients who previously discontinued MMF due to GI symptom burden.…”

Section: Discussionmentioning

confidence: 93%

“…An area of concern with previous EC‐MPS conversion trials is the high rate of discontinuation of EC‐MPS. In one study, 35% of patients discontinued EC‐MPS during the study, although there was significant improvement in the GIQLI in the patients who remained on EC‐MPS (20). Another study showed 28% of patients with no‐change or worsening GI symptoms after conversion to EC‐MPS (22).…”

Section: Discussionmentioning

confidence: 99%

“…With appropriate dosing, EC‐MPS and MMF exhibit equivalent exposure to MPA, the active compound in both formulations (14). Clinical trials in both kidney and liver transplant recipients reveal that EC‐MPS is therapeutically equivalent to MMF, and that conversion may be completed safely and effectively (15–22).…”

mentioning

confidence: 99%

“…These differences persist up to one yr post‐conversion and are independent of concomitant CNI administration (23, 24). Several small studies have promising results in improving GI symptom burden in the majority of liver transplant patients converted to EC‐MPS (17, 18, 20–22, 25), while other series report that as many as one‐third of patients had to discontinue EC‐MPS due to GI toxicities (20). This trial was designed to test our hypothesis that conversion to EC‐MPS yields an improved quality of life for liver transplant recipients.…”

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confidence: 99%

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

Toledo

Hendrix

Buchholz

et al. 2011

Clinical Transplantation

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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.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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

Toledo

Hendrix

Buchholz

et al. 2011

Clinical Transplantation

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“…Mycophenolate mofetil is primarily absorbed from the stomach; the most common adverse effects associated with MMF are gastrointestinal (GI) disorders, including diarrhoea, abdominal pain, dyspepsia, nausea, vomiting, ulcers and other GI events. EC‐MPS delays the release of MPA into the small intestine, and several studies have reported that it improves the GI tolerability and has better antirejection efficacy . EC‐MPS was introduced to China several years ago and there is limited information about its use in Chinese patients.…”

Section: Introductionmentioning

confidence: 99%

Cyclosporine A and tacrolimus combined with enteric-coated mycophenolate sodium influence the plasma mycophenolic acid concentration - a randomised controlled trial in Chinese live related donor kidney transplant recipients

et al. 2014

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Combined with the same EC-MPS dosage (1440 mg/day), the MPA-AUC0-12 of the Tac group was higher than that of the CsA group, and the Tac group had a longer MRT after kidney transplantation. Our data indicate that the concentration of MPA should be monitored in clinical therapy when EC-MPS is combined with different calcineurin inhibitors to reduce acute allograft rejection and avoid adverse events.

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Pharmacology and toxicology of mycophenolate in organ transplant recipients: an update

2014

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This review aims to provide an update of the literature on the pharmacology and toxicology of mycophenolate in solid organ transplant recipients. Mycophenolate is now the antimetabolite of choice in immunosuppressant regimens in transplant recipients. The active drug moiety mycophenolic acid (MPA) is available as an ester pro-drug and an enteric-coated sodium salt. MPA is a competitive, selective and reversible inhibitor of inosine-5'-monophosphate dehydrogenase (IMPDH), an important rate-limiting enzyme in purine synthesis. MPA suppresses T and B lymphocyte proliferation; it also decreases expression of glycoproteins and adhesion molecules responsible for recruiting monocytes and lymphocytes to sites of inflammation and graft rejection; and may destroy activated lymphocytes by induction of a necrotic signal. Improved long-term allograft survival has been demonstrated for MPA and may be due to inhibition of monocyte chemoattractant protein 1 or fibroblast proliferation. Recent research also suggested a differential effect of mycophenolate on the regulatory T cell/helper T cell balance which could potentially encourage immune tolerance. Lower exposure to calcineurin inhibitors (renal sparing) appears to be possible with concomitant use of MPA in renal transplant recipients without undue risk of rejection. MPA displays large between- and within-subject pharmacokinetic variability. At least three studies have now reported that MPA exhibits nonlinear pharmacokinetics, with bioavailability decreasing significantly with increasing doses, perhaps due to saturable absorption processes or saturable enterohepatic recirculation. The role of therapeutic drug monitoring (TDM) is still controversial and the ability of routine MPA TDM to improve long-term graft survival and patient outcomes is largely unknown. MPA monitoring may be more important in high-immunological recipients, those on calcineurin-inhibitor-sparing regimens and in whom unexpected rejection or infections have occurred. The majority of pharmacodynamic data on MPA has been obtained in patients receiving MMF therapy in the first year after kidney transplantation. Low MPA area under the concentration time from 0 to 12 h post-dose (AUC0-12) is associated with increased incidence of biopsy-proven acute rejection although AUC0-12 optimal cut-off values vary across study populations. IMPDH monitoring to identify individuals at increased risk of rejection shows some promise but is still in the experimental stage. A relationship between MPA exposure and adverse events was identified in some but not all studies. Genetic variants within genes involved in MPA metabolism (UGT1A9, UGT1A8, UGT2B7), cellular transportation (SLCOB1, SLCO1B3, ABCC2) and targets (IMPDH) have been reported to effect MPA pharmacokinetics and/or response in some studies; however, larger studies across different ethnic groups that take into account genetic linkage and drug interactions that can alter a patient's phenotype are needed before any clinical recommendations based on patient genotype can b...

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Use of enteric‐coated mycophenolate sodium in liver transplant patients with intestinal intolerance caused by mycophenolate mofetil

Abstract: OLT recipients who develop GI side effects caused by MMF can be safely converted to EC-MPS with improvement to their QoL.

Cited by 12 publications

References 12 publications

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

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

Cyclosporine A and tacrolimus combined with enteric-coated mycophenolate sodium influence the plasma mycophenolic acid concentration - a randomised controlled trial in Chinese live related donor kidney transplant recipients

Pharmacology and toxicology of mycophenolate in organ transplant recipients: an update

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