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Experimental and Clinical... Aug 2020The aim of this study was to evaluate recipient safety, tolerability, and pharmacokinetics of mycophenolate mofetil suspension compared with mycophenolate mofetil... (Comparative Study)
Comparative Study
OBJECTIVES
The aim of this study was to evaluate recipient safety, tolerability, and pharmacokinetics of mycophenolate mofetil suspension compared with mycophenolate mofetil capsules as part of induction therapy after living-donor liver transplant.
MATERIALS AND METHODS
Between July 2017 and April 2019, we retrospectively enrolled 20 adult primary living-donor liver transplant recipients. Recipients were divided into 3 groups: group 1 received mycophenolate mofetil suspension of 3000 mg (n = 6), group 2 received 3000 mg mycophenolate mofetil via opened capsules (n = 8), and group 3 received mycophenolate mofetil suspension of 2000 mg (n = 6). Administration was started on postoperative day 1, with tacrolimus administered on postoperative day 2 or day 3.
RESULTS
The values of area under the plasma concentration time curve for 0 to 12 hours were significantly higher in the 3000 mg/day mycophenolate mofetil suspension group than in the 2000 mg/day mycophenolate mofetil suspension group (P = .024) and in the 3000mg/day mycophenolate mofetil capsule group (P = .013). Significant positive correlations were shown between blood concentration at 8 hours after administration and the plasma concentration time curve for 0 to 12 hours (r2 = 0.96; P < .001) in patients in the suspension group. No patients required mycophenolate mofetil reduction because of leukopenia and diarrhea. Only 1 biopsy-proven acute cellular rejection was recognized in the mycophenolate mofetil suspension group (at 2000 mg/day). There were no significant differences in frequency of opportunistic infections among the 3 groups.
CONCLUSIONS
Mycophenolate mofetil suspension is useful as part of immunosuppressive induction therapy after living-donor liver transplant because its concentration increases greater than that of mycophenolate mofetil capsules and because of the low risk of rejection and adverse events.
Topics: Aged; Capsules; Drug Compounding; Drug Therapy, Combination; Female; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Liver Transplantation; Living Donors; Male; Middle Aged; Mycophenolic Acid; Pharmaceutical Solutions; Retrospective Studies; Time Factors; Treatment Outcome
PubMed: 32490763
DOI: 10.6002/ect.2020.0041 -
Clinical Transplantation 2006Liver transplantation (LTX) today has become a routine procedure granting curative treatment for various hepatic diseases with excellent survival rates. Constant... (Review)
Review
Liver transplantation (LTX) today has become a routine procedure granting curative treatment for various hepatic diseases with excellent survival rates. Constant improvement of immuno-suppressive regimens has led to significant reduction of rejection frequency and increased safety in long-term management. Calcineurin-inhibitors play the key role in most immunosuppressive protocols providing strong T-cell suppression yet often associated with numerous side-effects. Increasing renal insufficiency as well as hypertension, hyperglycaemia, hyperuricaemia, and increased risk of secondary malignancy account for the major problems in short- and long-term follow-up of LTX patients. Mycophenolate mofetil (MMF) as a purine-synthesis inhibitor has proved to be a potent immunosuppressive agent largely free of the CI-associated side-effects. MMF therefore has been used to modulate immunosuppressive protocols in order to both increase efficacy and to reduce CI-related side-effects such as nephrotoxicity. In recent years, MMF-monotherapy protocols have been suggested for LTX patients with renal insufficiency. This review provides an overview on the current role of MMF in immunosuppressive protocols after LTX and evaluates innovative therapeutic concepts.
Topics: Graft Rejection; Humans; Immunosuppressive Agents; Liver Transplantation; Mycophenolic Acid
PubMed: 17100705
DOI: 10.1111/j.1399-0012.2006.00604.x -
Transplantation Sep 2005Mycophenolate mofetil (MMF) is approved for prophylaxis of acute rejection after kidney, heart, and liver transplantation as well as for pediatric patients after kidney... (Review)
Review
Mycophenolate mofetil (MMF) is approved for prophylaxis of acute rejection after kidney, heart, and liver transplantation as well as for pediatric patients after kidney transplantation. MMF, a noncompetitive inhibitor of inosine monophosphate dehydrogenase (IMPDH), blocks de novo purine synthesis which leads to an effective inhibition of proliferation selectively in T and B lymphocytes, smooth muscle cells, and fibroblasts. MMF shows additional effects with inhibition of the expression of activating and adhesion molecules on the surface of lymphocytes. The beneficial safety profile with distinct side effects compared to calcineurin inhibitors (CNI) enable efficacious combination with ciclosporin or tacrolimus as de novo therapy after liver transplantation. Furthermore, recent studies show the possibility to reduce CNI induced toxicities by adding MMF to primary immunosuppression. MMF is also used to enable early steroid withdrawal after liver transplantation. MMF can increase efficacy of immunosuppressive therapy and thereby support the treatment of steroid resistant acute rejections, chronic rejections and chronic graft dysfunction.
Topics: Adrenal Cortex Hormones; Drug Administration Schedule; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Liver Transplantation; Mycophenolic Acid; Tacrolimus
PubMed: 16286893
DOI: 10.1097/01.tp.0000187133.53916.8f -
The New England Journal of Medicine Nov 2005
Topics: Cyclophosphamide; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Lupus Nephritis; Mycophenolic Acid; Remission Induction
PubMed: 16306526
DOI: 10.1056/NEJMe058256 -
Therapeutic Drug Monitoring Apr 2006A roundtable meeting to discuss the use of therapeutic drug monitoring (TDM) to guide immunosuppression with mycophenolate mofetil was held in New York in December 2004.... (Review)
Review
A roundtable meeting to discuss the use of therapeutic drug monitoring (TDM) to guide immunosuppression with mycophenolate mofetil was held in New York in December 2004. Existing recommendations for the initial months after transplantation were updated. After ensuring adequate levels of mycophenolic acid (MPA, the active metabolite of mycophenolate mofetil) immediately after transplantation, optimal efficacy may require only a few dose adjustments, because intrapatient variability in exposure seems low. Recommendations based on current knowledge were made for posttransplantation sampling time points and for target MPA concentrations. Algorithms for estimating MPA exposure using limited sampling strategies were presented, and a new assay for MPA discussed. It was agreed that because of interpatient variability and the influence of concomitant immunosuppressants, TDM might help optimize outcomes, especially in patients at higher risk of rejection. The value of TDM in the general transplant population will be assessed from large, ongoing, randomized studies.
Topics: Algorithms; Area Under Curve; Drug Monitoring; Graft Rejection; Humans; Immunosuppressive Agents; Mycophenolic Acid; Organ Transplantation; Practice Guidelines as Topic; Randomized Controlled Trials as Topic
PubMed: 16628123
DOI: 10.1097/01.ftd.0000199358.80013.bd -
Expert Opinion on Drug Safety May 2008Mycophenolate mofetil (MMF) has proved to be a major addition to the therapeutic options for the treatment of multisystem autoimmune disorders. The majority of the...
Mycophenolate mofetil (MMF) has proved to be a major addition to the therapeutic options for the treatment of multisystem autoimmune disorders. The majority of the autoimmune rheumatological diseases are more prevalent in women and they are often first diagnosed during childbearing age. MMF use during pregnancy is associated with an increased risk of malformations and first-trimester pregnancy loss. The most frequent malformations include external ear and other facial malformations such as cleft palate and lip. Therefore MMF should be avoided during pregnancy and safe contraceptive methods provided.
Topics: Abnormalities, Drug-Induced; Adult; Animals; Contraindications; Craniofacial Abnormalities; Female; Humans; Immunosuppressive Agents; Lupus Nephritis; Maternal-Fetal Exchange; Mycophenolic Acid; Organ Transplantation; Pregnancy; Pregnancy Complications; Pregnancy Outcome
PubMed: 18462179
DOI: 10.1517/14740338.7.3.219 -
AACN Clinical Issues Aug 1996The field of immunosuppression has entered a new era of sophistication, enabling investigators to selectively target specific pathways within the immune system. Recent... (Review)
Review
The field of immunosuppression has entered a new era of sophistication, enabling investigators to selectively target specific pathways within the immune system. Recent advances offer hope that rejection after transplantation may be prevented or treated more effectively than ever before. Expanded understanding of the intracellular activities produced by immunotherapy provides a crucial foundation for clinical practice in transplant medicine. More than 25 drugs are currently under investigation for treatment of rejection, with several already undergoing clinical trials. Because they have limited actions, it is unlikely that any single agent ever will be able to control all components of the immune response. Advantages of combination therapy are, therefore, well established. Paramount to the success of this approach is the ability to select drugs with complementary mechanisms of action and without excess toxicities and unfavorable interactions. Mycophenolate mofetil (CellCept), a novel immunosuppressant for treatment of acute rejection after renal transplantation, holds great promise toward producing successful outcomes.
Topics: Drug Interactions; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid
PubMed: 8826401
DOI: 10.1097/00044067-199608000-00007 -
The Annals of Pharmacotherapy Nov 2003To review the pharmacology, pharmacokinetics, efficacy, and safety of mycophenolate sodium. (Review)
Review
OBJECTIVE
To review the pharmacology, pharmacokinetics, efficacy, and safety of mycophenolate sodium.
DATA SOURCES
Primary literature was obtained via a MEDLINE search (1966-June 2003). Abstracts were obtained from the manufacturer and included in the analysis.
STUDY SELECTION AND DATA EXTRACTION
All studies and abstracts evaluating mycophenolate sodium in solid organ transplantation were considered for inclusion. English-language studies and abstracts were selected for inclusion, but were limited to those consisting of human subjects.
DATA SYNTHESIS
Mycophenolate sodium, a mycophenolic acid prodrug, is an inhibitor of T-lymphocyte proliferation. Mycophenolic acid reduces the incidence of acute rejection in renal transplantation. Mycophenolate sodium is enteric coated and has been suggested as a potential method to reduce the gastrointestinal adverse events seen with mycophenolate mofetil. Both mycophenolate mofetil and mycophenolate sodium have been shown to be therapeutically equivalent at decreasing the incidence of allograft rejection and loss. The frequency of adverse events is similar between both compounds, with the most common events being diarrhea and leukopenia.
CONCLUSIONS
Mycophenolate sodium is effective in preventing acute rejection in renal transplant recipients. At doses of 720 mg twice daily, the efficacy and safety profiles are similar to those of mycophenolate mofetil 1000 mg twice daily. Mycophenolate sodium has been approved in Switzerland; approval in the US is pending.
Topics: Adolescent; Adult; Aged; Child; Drug Interactions; Humans; Immunosuppressive Agents; Kidney Transplantation; Middle Aged; Mycophenolic Acid; Prodrugs; Randomized Controlled Trials as Topic; Tablets, Enteric-Coated
PubMed: 14565799
DOI: 10.1345/aph.1D063 -
Transplantation Proceedings Apr 1996Overall, the PK of MMF is reasonably straightforward and relatively unaffected by the complex pathophysiological changes involved in the management of renal transplant... (Review)
Review
Overall, the PK of MMF is reasonably straightforward and relatively unaffected by the complex pathophysiological changes involved in the management of renal transplant recipients. The ability to relate plasma MPA concentrations to efficacy through the PK/PD correlation implies that, unlike for many other drugs, plasma PK has direct relevance to the clinical outcome. These features should not only greatly help the exploration of immunosuppressive regiments using MMF but also the development of clinical use of MMF in situations other than renal transplantation.
Topics: Body Weight; Humans; Immunosuppressive Agents; Intestinal Absorption; Kidney Transplantation; Lymphocyte Activation; Mycophenolic Acid
PubMed: 8623466
DOI: No ID Found -
Current Drug Safety 2020Mycophenolate Mofetil (MMF) is an immunosuppressive drug usually used in kidney transplants to prevent rejection. It has various adverse effects such as leucopenia,...
INTRODUCTION
Mycophenolate Mofetil (MMF) is an immunosuppressive drug usually used in kidney transplants to prevent rejection. It has various adverse effects such as leucopenia, anemia, diarrhea but Mouth ulcers are rarely reported.
METHOD
We present a case report of MMF-induced mouth ulcers in an African patient.
CASE REPORT
A 41-year-old African-male patient has painful oral ulcers which developed 5 months after kidney transplantation. The immunosuppressive maintenance regimen comprised Steroids, Tacrolimus and MMF.
RESULT
These ulcers were firstly related to a fungic or viral infection so the patient was prescribed Fluconazole and Aciclovir without any improvement. Then, Tacrolimus blood level was checked and it was in a therapeutic range. Finally, we decide to stop MMF and the ulcers healed quickly.
DISCUSSION
Oral ulcers are frequently seen complications in immunosuppressant patient but are rarely described with MMF. These ulcers can become large and very painful and degrade patient's life quality. So when infections causes are excluded, we have to keep in mind that these ulcers can be a drug adverse effect.
Topics: Adult; Drug-Related Side Effects and Adverse Reactions; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Mycophenolic Acid; Oral Ulcer; Steroids; Tacrolimus; Transplant Recipients
PubMed: 31660841
DOI: 10.2174/1574886314666191011153609