Melbex
Melbex - General Information
Melbex is an an immunosuppresant drug and potent anti-proliferative, and can be used in place of the older anti-proliferative azathioprine. It is usually used as part of triple therapy including a calcineurin inhibitor (ciclosporin or tacrolimus) and prednisolone. It is also useful in research for the selection of animal cells that express the E. coli gene coding for XGPRT (xanthine guanine phosphoribosyltransferase).
Pharmacology of Melbex
Melbex is an antibiotic substance derived from Penicillium stoloniferum. It blocks de novo biosynthesis of purine nucleotides by inhibition of the enzyme inosine monophosphate dehydrogenase. Melbex is important because of its selective effects on the immune system. It prevents the proliferation of T-cells, lymphocytes, and the formation of antibodies from B-cells. It also may inhibit recruitment of leukocytes to inflammatory sites.
Melbex for patients
It is recommended that Myfortic be administered on an empty stomach, one hour before or two hours after food intake.
In order to maintain the integrity of the enteric coating of the tablet, patients should be instructed not to crush, chew, or cut Myfortic tablets and to swallow the tablets whole. Patients should be informed of the need for repeated appropriate laboratory tests while they are receiving Myfortic. Patients should be given complete dosage instructions and informed of the increased risk of lymphoproliferative disease and certain other malignancies.
Women of childbearing potential should be instructed of the potential risks during pregnancy, and that they should use effective contraception before beginning Myfortic therapy, during therapy, and for 6 weeks after Myfortic has been stopped.
Melbex Interactions
Antacids: Absorption of a single dose of Myfortic was decreased when administered to 12 stable renal transplant patients also taking magnesium-aluminum containing antacids (30 mL): the mean Cmax and AUC(0-t) values for MPA were 25% and 37% lower, respectively, than when Myfortic was administered alone under fasting conditions. It is recommended that Myfortic and antacids not be administered simultaneously.
Cyclosporine: When studied in stable renal transplant patients, cyclosporine, USP (MODIFIED) pharmacokinetics were unaffected by steady state dosing of Myfortic.
Acyclovir/Ganciclovir: may be taken with Myfortic; however, during the period of treatment, physicians should monitor blood cell counts. Both acyclovir/ganciclovir and MPAG concentrations are increased in the presence of renal impairment, their coexistence may compete for tubular secretion and further increase in the concentrations of the two.
Azathioprine/Mycophenolate Mofetil: Given that azathioprine and mycophenolate mofetil inhibit purine metabolism, it is recommended that Myfortic not be administered concomitantly with azathioprine or mycophenolate mofetil.
Cholestyramine and Drugs that Bind Bile Acids: These drugs interrupt enterohepatic recirculation and reduce MPA exposure when coadministered with mycophenolate mofetil. Therefore, do not administer Myfortic with cholestyramine or other agents that may interfere with enterohepatic recirculation or drugs that may bind bile acids, for example bile acid sequestrates or oral activated charcoal, because of the potential to reduce the efficacy of Myfortic.
Oral Contraceptives: Given the different metabolism of Myfortic and oral contraceptives, no drug interaction between these two classes of drug is expected. However, in a drug-drug interaction study, mean levonorgesterol AUC was decreased by 15% when coadministered with mycophenolate mofetil. Therefore, it is recommended that oral contraceptives are co- administered with Myfortic with caution and additional birth control methods be considered.
Live Vaccines: During treatment with Myfortic, the use of live attenuated vaccines should be avoided and patients should be advised that vaccinations may be less effective. Influenza vaccination may be of value. Prescribers should refer to national guidelines for influenza vaccination.
Drugs that alter the gastrointestinal flora may interact with Myfortic by disrupting enterohepatic recirculation. Interference of MPAG hydrolysis may lead to less MPA available for absorption.
Melbex Contraindications
Myfortic is contraindicated in patients with a hypersensitivity to mycophenolate sodium, mycophenolic acid, mycophenolate mofetil, or to any of its excipients.
Additional information about Melbex
Melbex Indication: For the prophylaxis of organ rejection in patients receiving allogeneic renal transplants, administered in combination with cyclosporine and corticosteroids.
Mechanism Of Action: Melbex is a potent, selective, uncompetitive, and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), and therefore inhibits the de novo pathway of guanosine nucleotide synthesis without incorporation into DNA. Because T- and B-lymphocytes are critically dependent for their proliferation on de novo synthesis of purines, whereas other cell types can utilize salvage pathways, mycophenolic acid has potent cytostatic effects on lymphocytes. Melbex inhibits proliferative responses of T- and B-lymphocytes to both mitogenic and allospecific stimulation. Addition of guanosine or deoxyguanosine reverses the cytostatic effects of mycophenolic acid on lymphocytes. Melbex also suppresses antibody formation by B-lymphocytes. Melbex prevents the glycosylation of lymphocyte and monocyte glycoproteins that are involved in intercellular adhesion to endothelial cells and may inhibit recruitment of leukocytes into sites of inflammation and graft rejection.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Mycophenolic acid
Synonyms: Mycophenoic acid
Drug Category: Antibiotics, Antineoplastic; Enzyme Inhibitors
Drug Type: Small Molecule; Approved
Other Brand Names containing Mycophenolic acid: Myfortic; Melbex;
Absorption: Bioavailability following oral administration of Myfortic delayed-release tablet ranges from 70-95%
Toxicity (Overdose): Oral (LD50): Acute: 352 mg/kg [Rat], 1000 mg/kg [Mouse], and >6000 mg/kg [Rabbit]. Possible signs and symptoms of acute overdose could include the following: hematological abnormalities such as leukopenia and neutropenia, and gastrointestinal symptoms such as abdominal pain, diarrhea, nausea and vomiting, and dyspepsia.
Protein Binding: >98%
Biotransformation: Mycophenolic acid is metabolized mainly by glucuronyl transferase to glucuronidated metabolites, predominantly the phenolic glucuronide, mycophenolic acid glucuronide (MPAG). MPAG does not manifest pharmacological activity. The acyl glucuronide minor metabolite has pharmacological activity similar to mycophenolic acid. The AUC ratio of Mycophenolic acid:MPAG:acyl glucuronide is approximately 1:24:0.28 at steady state.
Half Life: The mean elimination half-life for mycophenolic acid ranges from 8-16 hours, while that of the MPAG metabolite ranges from 13-17 hours.
Dosage Forms of Melbex: Tablet, coated Oral
Chemical IUPAC Name: (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1H-2-benzofuran-5-yl)-4-methylhex-4-enoic acid
Chemical Formula: C17H20O6
Mycophenolic acid on Wikipedia: https://en.wikipedia.org/wiki/Mycophenolic_acid
Organisms Affected: Humans and other mammals
