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 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mycophenolate mofetil (RS-61443), a derivative of mycophenolic acid, is a new immunosuppressive agent that inhibits de novo purine synthesis in activated lymphocytes. In a clinical trial of mycophenolate mofetil in the treatment of recurrent or persistent heart rejection, 17 patients 0.6 to 104 months (median 5.4 months) after transplantation received a daily oral dose of mycophenolate mofetil of 3000 mg, with seven patients increasing to 3500 mg daily. Azathioprine was routinely discontinued at the start of mycophenolate mofetil treatment. One patient in shock from acute rejection required retransplantation before starting mycophenolate mofetil and died 68 days later of cytomegalovirus sepsis. Another patient died 72 days after mycophenolate mofetil of protracted multisystem failure (present before mycophenolate mofetil). One patient required early cessation of mycophenolate mofetil, and the other 14 patients were alive and well 5 to 10 months after initiating mycophenolate mofetil treatment. Three patients required transient dose reduction and one patient required discontinuation of mycophenolate mofetil because of nausea, diarrhea, or abdominal cramps. No other clinical side effects were noted. Frequency of rejection decreased from 0.67 rejection episodes per patient per month before mycophenolate mofetil to 0.27 rejection episodes per patient per month after mycophenolate mofetil (p < 0.0001). Frequency of infection was unchanged after mycophenolate mofetil (p = 0.9). Renal function was not affected by mycophenolate mofetil (creatinine clearance 1.8 mg/dl before mycophenolate mofetil vs 1.7 mg/dl after mycophenolate mofetil; p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment of recurrent heart rejection with mycophenolate mofetil (RS-61443): initial clinical experience. 806 Oct 21

Mycophenolate mofetil, a pro-drug for mycophenolic acid, is an investigational immunosuppressive compound that is being developed for the treatment of rheumatoid arthritis (RA). The drug and its primary metabolite, mycophenolic acid, inhibit the de novo pathway of purine biosynthesis and have greater anti-proliferative effects on lymphocytes than on other rapidly dividing cells. Significant clinical improvement has been seen in many mycophenolate mofetil-treated RA patients who have been refractory to treatment with a variety of disease-modifying anti-rheumatic drugs (DMARDs). Treatment with mycophenolate mofetil reduces rheumatoid factor titres, immunoglobulin (IgG, IgM, and IgA) levels, and the total number of T cells (CD2) in RA patient peripheral blood; in addition, lymphocyte mitogen responses are inhibited and delayed hypersensitivity skin test reactivity is decreased. A dose of 2 g daily is more effective than lower doses, including several pulsing regimens. The most frequent adverse events reported by patients on mycophenolate mofetil are gastrointestinal, mainly nausea, vomiting, abdominal pain, and diarrhea. RA studies have demonstrated no clinically significant nephrotoxicity, hepatotoxicity, or bone marrow toxicity attributable to mycophenolate mofetil.
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PMID:Therapy of rheumatoid arthritis with mycophenolate mofetil. 832 35

Mycophenolate mofetil (MMF) is a new immunosuppressive drug that selectively inhibits de novo purine synthesis. It has been tested in three large double-blind controlled trials for the prevention of rejection in renal transplant patients. These studies indicate that the use of MMF dramatically decreases the incidence of biopsy-proven rejection, the use of multiple courses of steroids for rejection, and the use of antilymphocyte preparations for treatment of rejection. The drug was well tolerated with an acceptable safety profile. The main side effects were gastrointestinal (nausea, vomiting, diarrhea), but seldom resulted in the cessation of drug therapy. Hematologic side effects similar to those with azathioprine occurred and were reversible. There was a slight increase in CMV-invasive disease with the use of MMF, but no deaths. Rates of malignancy were within published ranges for transplant recipients. Mycophenolate mofetil is a safe and efficacious drug for prevention of rejection in kidney transplant recipients.
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PMID:Mycophenolate mofetil for maintenance therapy in kidney transplantation. 868 49

Despite limited understanding of therapeutic aetiopathogenesis of ulcerative colitis and Crohn's disease, there is a strong evidence base for the efficacy of pharmacological and biological therapies. It is equally important to recognise toxicity of the medical armamentarium for inflammatory bowel disease (IBD). Sulfasalazine consists of sulfapyridine linked to 5-aminosalicylic acid (5-ASA) via an azo bond. Common adverse effects related to sulfapyridine 'intolerance' include headache, nausea, anorexia, and malaise. Other allergic or toxic adverse effects include fever, rash, haemolytic anaemia, hepatitis, pancreatitis, paradoxical worsening of colitis, and reversible sperm abnormalities. The newer 5-ASA agents were developed to deliver the active ingredient of sulfasalazine while minimising adverse effects. Adverse effects are infrequent but may include nausea, dyspepsia and headache. Olsalazine may cause a secretory diarrhoea. Uncommon hypersensitivity reactions, including worsening of colitis, pancreatitis, pericarditis and nephritis, have also been reported. Corticosteroids are commonly prescribed for treatment of moderate to severe IBD. Despite short term efficacy, corticosteroids have numerous adverse effects that preclude their long term use. Adverse effects include acne, fluid retention, fat redistribution, hypertension, hyperglycaemia, psycho-neurological disturbances, cataracts, adrenal suppression, growth failure in children, and osteonecrosis. Newer corticosteroid preparations offer potential for targeted therapy and less corticosteroid-related adverse effects. Azathioprine and mercaptopurine are associated with pancreatitis in 3 to 15% of patients that resolves upon drug cessation. Bone marrow suppression is dose related and may be delayed. The adverse effects of methotrexate include nausea, leucopenia and, rarely, hypersensitivity pneumonia or hepatic fibrosis. Common adverse effects of cyclosporin include nephrotoxicity, hypertension, headache, gingival hyperplasia, hyperkalaemia, paresthesias, and tremors. These adverse effects usually abate with dose reduction or cessation of therapy. Seizures and opportunistic infections have also been reported. Antibacterials are commonly employed as primary therapy for Crohn's disease. Common adverse effects of metronidazole include nausea and a metallic taste. Peripheral neuropathy can occur with prolonged administration. Ciprofloxacin and other antibacterials may be beneficial in those intolerant to metronidazole. Newer immunosuppressive agents previously reserved for transplant recipients are under investigation for IBD. Tacrolimus has an adverse effect profile similar to cyclosporin, and may cause renal insufficiency. Mycophenolate mofetil, a purine synthesis inhibitor, has primarily gastrointestinal adverse effects. Biological agents targeting specific sites in the immunoinflammatory cascade are now available to treat IBD. Infliximab, a chimeric antibody targeting tumour necrosis factor-or has been well tolerated in clinical trials and early postmarketing experience. Additional trials are needed to assess long term adverse effects.
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PMID:Comparative tolerability of treatments for inflammatory bowel disease. 1108 48

Mycophenolate mofetil, the morpholinoethylester of mycophenolic acid, is an immunosuppressant used in combination with ciclosporin (cyclosporin) and corticosteroids to prevent organ rejection after heart and kidney transplantations. The drug seems also to be effective in dermal diseases after systemic administration. However, up to date mycophenolate mofetil can be only systemically administered and this is associated with several side effects such as nausea, leucopenia, sepsis, and diarrhoea. The aim of this study was to develop a topical formulation containing mycophenolate mofetil and to investigate in-vitro release and penetration into human skin ex-vivo. HPLC was applied to quantify mycophenolate mofetil after release studies from semisolid formulations using a dodecanol-collodion membrane as a lipophilic acceptor. Penetration studies with an amphiphilic cream using excised human breast skin were carried out in Franz-type diffusion cells. Mycophenolate mofetil and its active metabolite mycophenolic acid were detected by HPLC-MS after microsectioning in different skin layers. In this study the penetration of mycophenolate mofetil from an amphiphilic cream into excised human skin was shown. Additionally, the enzymatic hydrolysis of penetrated mycophenolate mofetil into mycophenolic acid was proven even under ex-vivo conditions. In-vivo a higher extent of metabolism of mycophenolate mofetil to mycophenolic acid would be expected because of the complete enzyme activity. This topical formulation might be a promising alternative to the usual systemic administration of mycophenolate mofetil in the treatment of skin diseases such as psoriasis.
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PMID:Investigation of the penetration behaviour of mycophenolate mofetil from a semisolid formulation into human skin ex-vivo. 1180 88

The treatment of severe lupus nephritis is based on the combination of steroids and cytotoxic drugs. Intravenous cyclophosphamide administered in "pulses" is effective in the induction of remission but other therapeutic alternatives are sought in refractory cases or severely relapsing patients. Mycophenolate mofetil, used in renal transplantation, also can be useful in severe lupus nephritis. We describe the evolution of 6 patients (5 women and 1 man; age 17-45 years) with severe lupus nephropathy who after achieving remission with intravenous cyclophosphamide and steroids (5 cases) or cyclosporin A (1 case) showed relapse of proteinuria and were treated with mycophenolate mofetil (dose 1000-2000 mg/day). Two patients have completed 24 months, 1 patient two cycles of 12 months, 2 patients 18 months and 1 patient 6 months. After this treatment, all patients have achieved remission (3 partial and 3 complete). There was no treatment failure and no one patient discontinued medication; however 1 case relapsed. There were no changes in leucocytes, haemoglobin, serum creatinine and serum albumin. ANA and alpha DNA antibodies decreased. Proteinuria (measured as protein/creatinine urine ratio: initial 3 and final 0.3) and dose of steroids (initial: 17.5 mg/d and final 5 mg/d) decreased significantly (p < 0.05 Wilcoxon t-test). The most common side effects were nausea and abdominal discomfort that improved without discontinuation of treatment. We conclude that mycophenolate mofetil is effective and a safe drug in severe relapsing lupus nephritis.
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PMID:[Mycophenolate mofetil in lupus nephritis]. 1198 81

Mycophenolate mofetil (MMF) is an immunosuppressive agent that is widely used in the management of liver transplant recipients. MMF inhibits the inosine monophosphate dehydrogenase that has been shown to have in vitro antiviral properties against flaviviruses, suggesting the possibility that it might also inhibit the hepatitis C virus (HCV). The goal of this short-term dose escalation study was to assess the antiviral effects of MMF on HCV replication. Patients with chronic hepatitis C who had not undergone liver transplantation were randomized to 8 weeks of treatment with one of four mycophenolate dose regimens (1000 mg orally twice daily, 500 mg orally twice daily, 250 mg orally twice daily, or a matched oral placebo twice daily). All groups were double-blinded. Quantitative HCV RNA levels and serum alanine aminotransferase were assessed at baseline, at weeks 2, 4, and 8 of dosing, and at weeks 4 and 8 of follow-up. Thirty patients met inclusion criteria, enrolled, and were randomized. HCV RNA levels did not change significantly during treatment. Specifically, no subject became virus negative or had a one-log decrease in virus level. Serum aminotransferase level did not normalize in any subject. The most common side effects were headache, nausea, and diarrhea. Mycophenolate alone does not appear to have a significant antiviral or biochemical effect in patients with chronic hepatitis C.
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PMID:Lack of antiviral effect of a short course of mycophenolate mofetil in patients with chronic hepatitis C virus infection. 1251 74

The management of nephrotic syndrome (NS) in children remains a clinical challenge for pediatricians and pediatric nephrologists. Especially, the treatment of patients with steroid-resistant (SR) and steroid-dependent (SD) nephrotic syndrome, because they are at risk for developing complications from prolonged exposure to steroids, CsA and alkylating agents. Mycophenolate mofetil (MMF) is a selective and reversible inhibitor of inosine monophosphate dehydrogenase used above all in transplantology and recently also in patients with nephrotic syndrome. The aim of this study was to tentatively assess the usefulness and the safety of MMF as an immunosuppressive agent in children with steroid-resistant NS, in whom remission was not obtained with previous treatment regimens, and those with steroid-dependent NS, in whom severe adverse reactions were observed in steroid and cyclosporine therapy. The study included 19 children with NS (11 girls, 8 boys) aged 7 to 19.5 years (a mean of 13.5), treated at the Deptartment of Pediatric Nephrology. The duration of disease was from 1 to 16 years (a mean of 9.3). The patients were divided into 3 groups: I--9 children with steroid-dependent NS; II--6 children with steroid-dependent NS and episodes of steroid-resistance; III--4 children with steroid-resistant NS. All patients in groups II and III required multi-drug therapy (prednisone, cyclosporine A, methylprednisolone, chlorambucil, cyclophosphamide) before MMF was introduced. MMF was administered orally: 180-600 mg/m2 body surface/dose, twice daily. The follow-up period lasted for 4 to 16 months (a mean of 7.7). The clinical outcome analysis included decrease or disappearance of proteinuria, clinical improvement and/or possibility of tapering therapy intensity, especially the dosage of steroids and/or CsA. Also, renal function was monitored with serum cystatine C concentration. Particular attention was paid to adverse effects of MMF upon the gastro- intestinal tract and/or opportunistic infections. All medication (apart from MMF) could be discontinued in 4 patients; in 15 cases, prednizone dose was reduced and in 9 cases CsA dose was reduced or discontinued. In group I (SD) steroid treatment could be reduced from a mean prednisone dose of 22.8 to 3.6 mg/m2/48 hours (p=0.018), in groups II and III, in spite of 50 % reduction of a mean prednisone dose, the difference did not reach statistical significance. During MMF therapy Csa treatment could be reduced from a mean CsA dose 4.3 to 2.9 mg/kg/24 hours (p=0.008). Improvement or preservation of stable renal function was observed in all patients--cystatin C levels decreased significantly from a mean 1.35 to 0.96 mg/l (p=0.007). Adverse reaction to MMF (abdominal pain) was observed in 2 patients (nausea, vomiting, diarrhoea in 1, CMV infection in 1). The initial clinical observation of MMF treatment in nephrotic patients shows its best effect in the group of patients with steroid-dependent NS. MMF can safely be used in children with NS. The introduction of MMF allows for reduction of other chronically used medications, especially CsA and steroids.
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PMID:[Mycophenolate mofetil in treatment of childhood nephrotic syndrome--preliminary report]. 1689 86

Mycophenolate mofetil (MMF) is an immunosuppressant drug being used for induction and maintenance of remission of lupus nephritis in systemic lupus erythematosus. Evidence about its use was sought from full publications and abstracts of randomised trials and cohort studies by using a variety of search strategies. Efficacy and adverse event outcomes were sought. Five randomised trials enrolled patients with World Health Organization (WHO) class III, IV, or V (mostly IV) lupus nephritis, predominantly comparing MMF (1 to 3 g daily) with cyclophosphamide and steroid. Complete response and complete or partial response was significantly more frequent with MMF than with cyclophosphamide, with numbers needed to treat of 8 (95% confidence interval 4.3 to 60) to induce one additional complete or partial response, with wide confidence intervals. Death was reported less frequently with MMF (0.7%, 1 death in 152 patients) than with cyclophosphamide (7.8%, 12 deaths in 154 patients), with a number needed to treat to prevent (NNTp) one death of 14 (8 to 48). Hospital admission was also lower with MMF (1.7% versus 15%; NNTp 7.4 [4.8 to 16]). Serious infections, leucopaenia, amenorrhoea, and hair loss were all significantly less frequent with MMF than with cyclophosphamide, but diarrhoea was significantly more common with MMF. Ten of 18 cohort studies enrolled only patients with lupus nephritis (author-defined or WHO class III to V). Seven of these 10 reported that complete or partial response with MMF (mostly 1 or 2 g daily) with steroid occurred in 121/151 (80%) and that treatment failure or no response occurred in 30/151 (20%). Adverse events were generally similar in cohort studies with and without only patients with lupus nephritis. In all 18 cohorts, gastrointestinal adverse events (diarrhoea, nausea, vomiting) occurred in 30%, infection in 23%, and serious infection in 4.3%. Adverse event discontinuations occurred in 14% and lack of efficacy occurred in 10%. There was a single death with MMF, a mortality rate over the course of 1 year of approximately 0.2%. The results form a basis on which to plan future studies and provide a guide for the use of MMF in lupus nephritis until results of larger studies are available. At least one such study is under way.
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PMID:Systematic review and meta-analysis of randomised trials and cohort studies of mycophenolate mofetil in lupus nephritis. 1716 90

Mycophenolate mofetil (MMF) is licensed as a prophylaxis in combination therapy to prevent renal transplant rejection. Gastrointestinal side effects are fairly common and include diarrhoea, abdominal discomfort, nausea, vomiting, gastritis and constipation. This drug has recently been described as causing villous atrophy, nutrient malabsorption and colonic mucosal changes. We present a case of reversible steatorrhoea occurring in a patient treated with MMF following an episode of infections diarrhoea.
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PMID:Steatorrhoea complicating post-infectious diarrhoea in a renal transplant patient on mycophenolate mofetil therapy. 1906 19


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