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Background Chronic lung allograft dysfunction (CLAD), predominantly manifest as bronchiolitis obliterans syndrome (BOS), is the primary cause of morbidity and death after lung transplantation. We assessed the efficacy and safety of 2 de novo immunosuppression protocols to prevent BOS. Methods This was a multicenter, prospective, international, randomized (1:1) open-label superiority study of de novo enteric-coated mycophenolate sodium (MPS) vs delayed-onset everolimus (RAD), both arms in combination with cyclosporine (CsA) monitored by 2-hour post-dose (C 2 ) levels, and corticosteroids. Target C 2 levels were lower in the RAD group because RAD is known to potentiate CsA nephrotoxicity. Cytolytic induction therapy was not used. Patients were stratified at entry for cystic fibrosis. Confirmation of anastomotic healing was required for randomization. Primary efficacy was freedom from BOS Grade 1 on intention-to-treat (ITT) analysis. Secondary efficacy parameters were patient and graft survival and severity of rejection. Treatment failure was defined by graft loss, patient death, drug cessation, or need for other therapy. Results The 3-year freedom from BOS Grade 1 was 70% for MPS ( n = 80) vs 71% for RAD ( n = 84; p = 0.95 by log-rank) in ITT but was lower in the RAD arm of the per-protocol population ( p = 0.03). The 3-year survival was 84% (MPS) vs 76% (RAD; p = 0.19 by log-rank). Thirteen patients switched from MPS vs 31 from RAD ( p < 0.01). Days on MPS were greater than days on RAD ( p < 0.01). Rejection events proven by biopsy specimen were more common on MPS ( p = 0.02), as were leucopenia ( p < 0.01), diarrhea ( p < 0.01), and cytomegalovirus infection ( p = 0.04). Venous thromboembolism was more frequent on RAD ( p = 0.02). Creatinine at 3 years was 160 ± 112 μmol/1iter in MPS patients vs 152 ± 98 μmol/1iter in RAD patients ( p = 0.67). Conclusions This 3-year ITT analysis found no significant difference between arms but was underpowered to accept the null hypothesis that RAD and MPS have equivalent efficacy in preventing BOS or death after lung transplantation. [ABSTRACT FROM AUTHOR]

A renal allograft recipient developed cough with hemoptysis on the 1st postoperative day. A chest X-ray was performed which was suggestive of fluid overload. His fluid was restricted and diuretics were added. On the same day, his pulmonary infiltrates worsened and a computed tomography (CT) of the chest was carried out, which was suggestive of the right lower lobe consolidation and left pleural effusion. He underwent a bronchoscopy and the lavage was sent for cultures, which did not grow any infective organism. Besides routine antibiotics, treatment for possible cytomegalovirus, fungal infections, and pneumocystis infection was instituted. Noninvasive ventilation was started on day 8. A repeat CT of the chest on the postoperative day 8 showed further worsening of the pulmonary infiltrates. As all the initial cultures and serology were negative, a possibility of interstitial pneumonitis was considered. Mycophenolate sodium was considered as a possible cause of the lung infiltrates and was withdrawn. The patient showed progressive improvement. His antibiotics were withdrawn. He was discharged on day 14. A repeat CT 4 weeks post transplant showed significant improvement in his pulmonary pathology. The acute lung injury was considered to be a drug reaction secondary to mycophenolate sodium. In a renal allograft recipient with persistent pulmonary infiltrates, interstitial involvement secondary to drugs should be considered if the patient does not improve with the standard treatment measures. [ABSTRACT FROM AUTHOR]

Background/Aims: 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. Methods: 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. Results: 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. Conclusion: 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. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The efficacy and safety of everolimus ( EVR) in simultaneous pancreas and kidney transplantation ( SPKT) is unclear. We retrospectively evaluated 25 consecutive SPKT recipients at our center from November 2011 to March 2013. All patients received dual induction (Thymoglobulin/basiliximab) and low-dose tacrolimus plus corticosteroids. Nine patients who received EVR were compared with 14 patients who received enteric-coated mycophenolate sodium ( EC- MPS); two patients who received sirolimus were excluded from the analysis. With a median follow-up of 14 months, the pancreas graft survival rate was 100% in both groups, and the kidney graft survival rate was 100% and 93% in EVR and EC- MPS patients, respectively. One EC- MPS patient lost her kidney graft from proteinuric kidney disease. Another EC- MPS patient received treatment for clinically diagnosed pancreas and kidney graft rejection. No rejection was observed in EVR patients. Serum creatinine and HbA1c levels were similar between the groups. There was no significant difference of surgical or medical complications. In conclusion, EVR seems to provide comparable short-term outcome to EC- MPS when combined with low-dose tacrolimus/steroids and dual induction therapy. A larger study with a longer follow-up is required to further assess this combination. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Different associations between single nucleotide polymorphisms (SNPs) in cellular target, metabolism enzymes or transport proteins, and biopsy-proven acute rejection (BPAR) or adverse events have been reported in transplant patients receiving mycophenolate mofetil. This work aimed to study these in patients on enteric-coated mycophenolate sodium (EC-MPS).The study included 189 renal transplant patients from the DOMINOS trial. Fifteen SNPs in IMPDH2, IMPDH1, ABCC2, SLCO1B3, UGT1A8, UGT1A9, UGT2B7, CYP2C8, HUS1, and IL12A were genotyped in all patients. Associations between SNPs and the first event of BPAR or diarrhea were investigated using multivariate logistic regressions. Associations between SNPs and leukopenia or anemia at nine different visits between days 0 and 190 after transplantation were studied using time-dependent Cox proportional hazards regression models.Multivariate analyses showed that the CYP2C8 rs11572076 wild-type genotype was associated significantly with a lower risk of leukopenia [GG vs. GA: hazard ratio (95% confidence interval) 0.14 (0.03, 0.59), P=0.00783]. Higher EC-MPS doses and the UGT2B7 c.-840 G>A variant allele were associated with an increased risk of anemia [EC-MPS per unit dose increase: 1.004 (1.003, 1.005), P<0.0001; UGT2B7 GA vs. AA: 1.65 (1.12, 2.43), P=0.01043; GG vs. AA: 1.88 (1.23, 2.88), P=0.00343]. However, no significant association was found between any of the SNPs studied and diarrhea or BPAR.Two pharmacogenetic associations reported previously with mycophenolate mofetil were found in a population of 189 renal transplant patients treated with EC-MPS. [ABSTRACT FROM AUTHOR]

Aim: Mycophenolate is an immunosuppressive agent which has been used in systemic lupus erythematosus (SLE) patients who have failed conventional therapy. However, the use of mycophenolate sodium in extra-renal SLE involvement has yet to be established. This study aimed to assess the efficacy of mycophenolate sodium in extra-renal SLE. Methods: A total of 14 SLE patients without renal involvement were randomized either to receive mycophenolate sodium or other immunosuppressive agents. Patients were assessed monthly from baseline until week 16. Assessment parameters included SLE Disease Activity Index (SLEDAI) score, other organ-specific parameters and immunological parameters, including anti-double stranded DNA and C3. Steroid-sparing effect of mycophenolate sodium was also evaluated. Results: Mycophenolate sodium produced a significant reduction in SLEDAI scores (P < 0.05) after 16 weeks of treatment. Mixed responses were detected in terms of organ-specific clinical changes. A positive trend was observed in improvement of immunological parameters and steroid dose reduction. No major adverse events were reported in this study. Conclusion: Mycophenolate sodium is a safe alternative therapy in SLE patients with extra-renal involvement. The reduction in SLEDAI scores and the observation of no major safety concerns suggest that a larger prospective study of mycophenolate sodium in non-renal SLE is warranted. [ABSTRACT FROM AUTHOR]

Objective: Cyclophosphamide is considered the treatment of choice for interstitial lung disease (ILD) secondary to systemic sclerosis (SSc), albeit having a minimal effect. Although controlled evidence does not exist, mycophenolate is used increasingly in clinical practice as an alternative. We aimed to compare the long-term efficacy of these drugs. Methods: Patients from our SSc cohort who received mycophenolate for over 1 year for progressive ILD were 1:1 matched for age, gender, and baseline forced vital capacity (FVC ±3 %) with cyclophosphamide-treated patients. Changes in FVC, total lung capacity (TLC), diffusion capacity for carbon monoxide (DLCO), and high-resolution computed tomography (HRCT) scans were compared between groups. Changes in pulmonary function tests (PFTs) over at least 1 year in six unmatched control patients, who had denied mycophenolate or cyclophosphamide, also were examined. Results: FVC, TLC, and DLCO did not change significantly in either mycophenolate (from 79.0 ± 12.5 to 80.2 ± 8.1 to 81.2 ± 11.4, from 71.5 ± 16.1 to 74.3 ± 10.8 to 71.8 ± 13.0, from 56.8 ± 12.0 to 55.2 ± 9.9 to 50.6 ± 8.5, respectively) or cyclophosphamide group (from 77.3 ± 12.5 to 79.7 ± 10.3 to 82.5 ± 12.9, from 64.7 ± 14.9 to 68.6 ± 16.0 to 66.1 ± 15.5, from 53.1 ± 14.3 to 56.4 ± 13.5 to 56.3 ± 6.7, respectively), after 1 or 2 years of treatment. PFTs also remained stable in the control group. In either the mycophenolate or cyclophosphamide groups, six patients remained stable, three improved, and one deteriorated according to the definitions of the American Thoracic Society. However, and despite the fact that patients in the cyclophosphamide group had more extended ILD at baseline, a deterioration of lung HRCT findings at 2 years was noticed after mycophenolate (from 10.0 ± 8.9 to 12.7 ± 8.2, p = 0.039) but not after cyclophosphamide. Conclusions: Although these results derive from patients selected for receiving at least 1 year of treatment and therefore they do not represent an intention-to-treat cohort, an eagerness to replace cyclophosphamide by mycophenolate in SSc-associated ILD treatment is not supported. [ABSTRACT FROM AUTHOR]

Background: Mycophenolate mofetil (MMF) has enjoyed increasing popularity as an emerging immunosuppressant treatment for various autoimmune dermatologic conditions, including pyoderma gangrenosum (PG). Objective: The aim of this study was to examine the efficacy and safety of MMF as used in PG. Methods: A retrospective chart review was conducted for all patients with PG treated with MMF at our institution (Victoria, Australia) for the past 11 years (2001-2012). Results: We identified 26 patients, 14 female and 12 male. Nine patients (34.6%) had associated systemic conditions. All patients received prednisolone. MMF was used as a first-line steroid-sparing agent in 11 patients (42.3%), second-line in 14 (53.8%), and third-line in 1 (3.85%). The average duration of treatment was 12.1 months. Fourteen patients experienced side effects (53.8%), although most were mild (26.9%). One patient died after a sigmoid colon perforation (3.85%). Overall 22 patients demonstrated clinical improvement during MMF treatment (84.6%). Thirteen patients achieved complete ulcer healing (50%), 10 while taking MMF and 3 after ceasing it. Limitations: This is a retrospective study based on a single-center cohort. Conclusion: Our experience suggests that MMF is highly efficacious in PG together with prednisolone, or as part of combination therapy with other immunosuppressants. [Copyright &y& Elsevier]

Background/Aims: While there are drug exposure equation models based on limited sampling times for mycophenolate mofetil (MMF), there are few for enteric-coated mycophenolate sodium (EC-MPS), and none that studied Chinese individuals. Our objective is to generate the optimal model equations for estimation of the mycophenolic acid (MPA) area under the plasma concentration-time curve from 0 to 12 h (MPA-AUC0-12h) with a limited sampling strategy (LSS) for renal transplant recipients receiving EC-MPS. Methods: The pharmacokinetics in 31 Chinese renal allograft recipients treated with EC-MPS in combination with tacrolimus and steroids were determined. The model equations were generated by multiple stepwise regression analysis for estimation of the MPA-AUC. Results: A total of 31 patients with an average age and weight of 37.58 ± 10.9 years and 60.9 ± 10.7 kg, respectively, were included. Mean serum creatinine and glomerular filtration rate were 112.2 ± 17.7 μmol/l and 65.6 ± 14.6 ml/min, respectively. The mean values of AUC0-12h, pre-dose MPA trough concentration (C0), maximum concentrations (Cmax), and time to reach Cmax (Tmax) were 61.17 ± 26.39 mg·h/l (range 22.9-123.0 mg·h/l), 4.98 ± 4.65 mg/l (range 0.13-20.04 mg/l), 17.54 ± 10.67 mg/l (range 4.08-42.36 mg/l), and 5.0 ± 2.6 h (range 1.0-10.5 h), respectively. The best predictive equation for estimation of MPA-AUC0-12h was -3.63 + 8.35 × C4 + 17.04 × C7 + 13.74 × C12 (r2 = 0.7491), prediction bias (PE%) was 20.9 ± 20.37, and prediction precision (APE%) was 3.66 ± 29.20. Conclusions: This model provides an effective approach for estimation of full MPA-AUC0-12h in Chinese adult renal allograft recipients treated with EC-MPS and tacrolimus. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Several immunosuppressive drugs are used as steroid-sparing agents in pemphigus vulgaris ( PV) treatment, with the aim of reducing the cumulative dose of steroids and minimizing the side effects of long-term steroid treatment. The objective of this study is to evaluate the efficacy and safety of enteric-coated mycophenolate sodium ( EC- MPS) as a steroid-sparing agent in PV patients. We performed a retrospective study on PV patients who had attended our dermatology department between October 2004 and December 2010 and who had been treated with a combined therapy of systemic corticosteroids and EC- MPS. In the 16 enrolled patients, the introduction of EC- MPS allowed the tapering of systemic corticosteroids, and in 12 of these patients, complete remission was achieved in the time of observation, on average in 4.3 months. Corticosteroid withdrawal was possible in two patients, and EC- MPS was very well tolerated. No serious adverse events were recorded. EC- MPS is a valid therapeutic opportunity as a steroid-sparing agent in PV patients. [ABSTRACT FROM AUTHOR]

This study aims to determine the effectiveness of mycophenolate sodium (MS) in patients with scleroderma (SSc)-related interstitial lung disease (ILD). In a prospective observational study, we evaluated 14 consecutive SSc-ILD patients who were treated with MS for 12 months. The effect of MS on lung function was examined by using longitudinal data analytic methods. Wilcoxon rank-sum tests were used to examine the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and diffusing capacity of the lung for carbon monoxide (DLCO) by pulmonary function testing. As a group, the median values for FVC, FEV1 and DLCO did not change significantly after 12 months of MS therapy and fulfilled the definition of stable disease by the American Thoracic Society. Individually, after 12 months of treatment, 6 out of 14 patients showed a pulmonary improvement defined as an increase of more than 10% in FVC, and 5 out of 14 patients remained stable. By contrast, the median FVC had declined a non-significant 7.2% from the previous 12 months before MS initiation. No significant drug adverse effects were registered. These prospective data suggest that MS is a safe and well-tolerated therapy for SSc-ILD patients, and it is capable of preventing functional pulmonary deterioration. [ABSTRACT FROM AUTHOR]

Optimal therapy and prognosis of crescentic-IgA nephropathy (C-IgAN) are not known. Reported treatment options for C-IgAN include combination of corticosteroids and cyclophosphamide for 6 months. The role of mycophenolate sodium in C-IgAN is unknown. We report a case of C-IgAN that was successfully treated with combination immunosuppressive therapy. [ABSTRACT FROM AUTHOR]

Purpose: To assess the efficacy and tolerability of mycophenolate sodium (MPS) in patients with uveitis. Methods: Retrospective analysis including uveitis patients treated with MPS (Myfortic®) for at least 3 months duration. MPS was administered in a dose of 720 mg twice daily. Results: We analyzed 35 patients (65 affected eyes) with anterior ( n = 5), intermediate ( n = 23), posterior ( n = 6), and panuveitis ( n = 1). Previous treatment consisted of systemic corticosteroids in all patients and at least one immunomodulating agent in 15 patients. Mean duration of MPS therapy was calculated as 9.6 months (3–31 months). MPS was able to control intraocular inflammation without relapse in 30 patients (85.7%). Stabilization or improvement of visual acuity was achieved in 60 eyes (92.3%). Tolerability of MPS was good or moderate in 34 patients (97.1%). Conclusions: MPS was demonstrated as an effective and well-tolerated immunosuppressive drug for different forms of uveitis. [ABSTRACT FROM AUTHOR]

Linear IgA bullous dermatosis (LABD) is a rare, blistering autoimmune disease characterized by linear deposits of IgA at the basement membrane zone (BMZ), with the possible presence of circulating IgA anti-BMZ antibodies. LABD of childhood is usually self-healing, while in adults it follows a more prolonged course and refractory cases may rarely occur. The first-line treatment for LABD is dapsone in monotherapy or in combination with systemic corticosteroids, but various therapeutic approaches have been used in non-responder patients. We report two adult patients with refractory LABD successfully treated with enteric-coated mycophenolate sodium (EC-MPS), a recently introduced formulation of mycophenolic acid (MPA). MPA is an immunosuppressive agent that acts by inhibiting monophosphate dehydrogenase, a key enzyme in the novo synthesis of purines. Based on the present cases, we indicate EC-MPS as being a safe and effective adjuvant therapy in the treatment of LABD when dapsone or the other steroid-sparing drugs fail. It seems to offer an improved gastric side effect profile in comparison with the classic formulation of MPA, namely its ester mycophenolate mofetil (MMF). [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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 m2 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. Conclusion: Enteric-coated mycophenolate sodium was effective and well-tolerated in the treatment of active lupus nephritis. [ABSTRACT FROM AUTHOR]

Background Approximately 75–95% of patients with cutaneous lupus erythematosus respond to antimalarial therapy and/or topical glucocorticosteroids. Immunosuppressive agents are usually considered a second-line approach in patients with resistant disease. Objectives This was a prospective, nonrandomized, open pilot study to evaluate the efficacy of mycophenolate sodium monotherapy in patients with recalcitrant subacute cutaneous lupus erythematosus (SCLE). Methods Monotherapy with oral enteric-coated mycophenolate sodium 1440 mg daily was given for a total of 3 months. Treatment outcome was evaluated by means of a validated clinical score for cutaneous lupus erythematosus, the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), as well as 20-MHz ultrasound measurements and colorimetry. Safety assessment included the monitoring of adverse effects and clinical laboratory parameters. Results Ten patients with active SCLE resistant to at least one standard therapy were included in the trial. Mycophenolate sodium led to a remarkable improvement of skin lesions, resulting in a significant decrease of the mean ± SD CLASI from 10·8 ± 6·0 at the beginning to 2·9 ± 2·6 at the end of therapy. Clinical improvement was confirmed by ultrasonographic assessments and colorimetry. No serious side-effects were noted. Conclusions Mycophenolate sodium is beneficial and safe in the treatment of patients with SCLE that failed standard therapy. However, these preliminary data must be confirmed by randomized controlled trials including a larger sample size. [ABSTRACT FROM AUTHOR]

Purpose. The pharmacology, pharmacokinetics, drug interactions, clinical efficacy, adverse effects, monitoring, and dosage and administration of enteric-coated (EC) mycophenolate sodium are reviewed. Summary. EC mycophenolate sodium is the EC salt form of mycophenolic acid (MPA), the active component of the pro-drug, mycophenolate mofetil. EC mycophenolate sodium was developed to reduce the upper-gastrointestinal (GI) effects of mycophenolate mofetil. Unlike oral mycophenolate mofetil, which releases MPA in the stomach, EC mycophenolate sodium releases MPA in the small intestine. The absolute bioavailability of EC mycophenolate sodium is 72%. MPA undergoes hepatic metabolism by glucuronyl transferase to the inactive mycophenolic acid glucuronide (MPAG), the predominant metabolite. The majority of an administered dose of EC mycophenolate sodium is found as MPAG in the urine. The mean terminal half-life of MPA ranges from 8 to 16 hours. EC mycophenolate sodium and mycophenolate mofetil have equivalent mechanisms of action and drug interaction profiles. Thus far, EC mycophenolate sodium has demonstrated similar efficacy and safety to mycophenolate mofetil in two Phase III clinical trials of adult renal transplant recipients. One study demonstrated improved health-related quality of life in patients switched from mycophenolate mofetil to EC mycophenolate sodium. Ongoing Phase IV studies are trying to further determine advantages of the EC product. Conclusion. EC mycophenolate sodium is a safe and effective immunosuppressive agent approved for use in the prevention of acute rejection after renal transplantation. It offers an excellent addition to the current armamentarium of immunosuppressive drugs for transplant immunosuppression. [ABSTRACT FROM AUTHOR]

Mycophenolate mofetil is one of the most frequently used immunosuppressive drugs in solid organ transplantation. Although the adverse effect profile of mycophenolate mofetil is comparatively benign, gastrointestinal adverse effects are a major concern. The adverse effects may require a dose reduction or discontinuation, thus limiting its clinical efficacy. Enteric-coated (EC) mycophenolate sodium is a new formulation of mycophenolic acid (MPA) that delivers the active moiety MPA, the same active moiety delivered by mycophenolate mofetil. It has been developed to help protect the upper gastrointestinal tract. It is implied that a reduction of adverse drug effects as well as a reduction of dose may improve efficacy and compliance. Noncompliance is often underestimated in solid organ transplant recipients, and adverse drug effects increase medication nonadherence. Recent clinical trials comparing EC mycophenolate sodium and mycophenolate mofetil in kidney recipients reported similar rates of efficacy and adverse effects. It is noteworthy that systemic MPA exposure is higher with EC mycophenolate sodium than with mycophenolate mofetil, without increased gastrointestinal toxicity. This finding is quite surprising, because part of MPA-associated gastrointestinal toxicity is related to its antiproliferative effect on enterocytes. However, enteric coating of MPA did not markedly reduce the number of gastrointestinal adverse effects. Further studies focusing on dosage, therapeutic drug monitoring and immunosuppressive regimens may reveal benefits of EC mycophenolate sodium for optimal individualised immunosuppression and improved compliance. At present, EC mycophenolate sodium is an alternative immunosuppressant to mycophenolate mofetil in kidney transplant recipients with an almost identical efficacy and safety profile. [ABSTRACT FROM AUTHOR]

▴ Mycophenolate sodium delayed release is an enteric-coated formulation designed to release the active agent (mycophenolic acid) in the small intestine. ▴ Mycophenolate sodium delayed release was equivalent in efficacy to, and had a similar tolerability profile as, mycophenolate mofetil in de novo renal transplant patients treated with ciclosporin (cyclosporin) and corticosteroids in a well designed study of 12 month's duration. ▴ Maintenance renal transplant patients treated with ciclosporin and corticosteroids were converted from mycophenolate mofetil to mycophenolate sodium delayed release without any alteration in efficacy or tolerability in a well designed study of 12 month's duration. ▴ The incidence of gastrointestinal adverse events with mycophenolate sodium delayed release was similar to that with mycophenolate mofetil. [ABSTRACT FROM AUTHOR]