Included in the formulation
Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):VED
7 nosologies
АТХ:L.04.A.A Selective immunosuppressants
Pharmacodynamics:Immunodepressant; a selective noncompetitive reversible inhibitor of inosine monophosphate dehydrogenase, inhibits the synthesis of guanosine nucleotides de novo.To proliferate T and B lymphocytes, newly synthesized nucleotides are needed, while the remaining cells are able to use the guanosine nucleotides contained in the tissues. This determines the selectivity of the drug against lymphocytes.
Pharmacokinetics:Absorption is high, metabolized at the first passage through the liver, forming an active metabolite - mycophenolic acid (MFC). Bioavailability (active metabolite) - 94%; The concentration in the plasma is reduced by 40% when taken with food. The connection with plasma proteins is 97%. IFC is metabolized by glucuronyltransferase to form phenolic glucuronide, which does not have pharmacological activity. It is excreted mainly by kidneys in the form of an inactive metabolite (93%, 1% - unchanged), 6% is excreted with feces. In patients recently (less than 40 days ago) who underwent renal transplantation, Cmax active metabolite in plasma is 40% lower than in healthy individuals or in patients who have long since undergone transplantation.
Indications:Prevention and treatment of the reaction of refractory rejection after allotransplantation of organs - as part of combined therapy with cyclosporine and GCS.
XXI.Z80-Z99.Z94 Presence of transplanted organs and tissues
Contraindications:Hypersensitivity, pregnancy, breast-feeding.
Carefully:Diseases of the gastrointestinal tract (in the phase of exacerbation). High risk of opportunistic infection.
Pregnancy and lactation:Action category for the fetus by FDA - D
There is evidence of a risk of adverse effects on the fetus. Studies on animals demonstrated the ability of toxic effects on reproductive function with the development of congenital anomalies. MIt can be prescribed to pregnant women only in cases where the potential benefit to the mother exceeds the possible risk to the fetus.
Dosing and Administration:Prevention: inside, within the first 72 hours after the operation - 1 g 2 times / day (tolerability of a daily dose of 2 g is better than 3 g / day, while the effectiveness does not change significantly).
Treatment: 3 g 2 times / day for initial and maintenance therapy. For neutropenia (the number of neutrophils is <1300 / μL), the dose is reduced; in patients with severe renal failure (CC below 25 ml / min) - the maximum daily dose of 2 g in 2 divided doses. In case of delayed reactions of graft rejection, conventional doses are used.
Side effects:Very often (more than 1/10); often (more than 1/100 and less than 1/10); not often (more than 1/1000 and less than 1/100); rarely (more than 1/10000 and less than 1/1000); very rarely (less than 1/10000, including single cases).
From the cardiovascular system: often - tachycardia, hypotension (including orthostatic), hypertension.
From the nervous system and sensory organs: often - agitation, depression, anxiety, confused consciousness, convulsions, tremor, drowsiness, headache, paresthesia, dysgeusia.
From the digestive tract: very often - nausea, vomiting, diarrhea, abdominal pain; often - bleeding of the gastrointestinal tract, peritonitis, intestinal obstruction, colitis, ulceration of gastric mucosa and duodenum, gastritis, esophagitis, stomatitis, belching of the air, flatulence.
From the hematopoietic system: very often - leukopenia, thrombocytopenia, anemia; often - pancytopenia
Influence on metabolism: often - acidosis, hyperkalemia, hypokalemia, hyperglycemia, hypomagnesemia, hypocalcemia, hyperlipidemia, hyperuricemia, gout, loss of appetite.
Infectious complications: very often - sepsis, candidiasis of the mucous membranes of the gastrointestinal tract, herpetic and CMV infections; often - pneumonia, respiratory tract infection, GI tract infection, bronchitis, pharyngitis, fungal skin lesions.
Neoplasms: often - skin cancer, benign skin tumors.
Other side effects include nephrotoxicity, arthralgia, edema, chills, asthenia, malaise, increased levels of liver enzymes, lactate dehydrogenase, alkaline phosphatase, creatinine and urea.
Overdose:Symptoms: increased incidence of gastrointestinal and hematological (in particular neutropenia) side effects. Treatment: dose reduction or drug withdrawal. To accelerate excretion, the appointment of sequestrants of bile acids is possible. Small amounts of glucuronide can be removed by hemodialysis (mycophenolic acid not dialyzed).
Interaction:Antacids reduce the absorption of the drug, and therefore recommended their sporadic, but not chronic use; colestramine reduces the concentration of mycophenolate, which can lead to a decrease in its effectiveness; tubular secretion blockers increase the concentration of the inactive metabolite.
With simultaneous application of mycophenolate mofetil and acyclovir or ganciclovir, the concentration of drugs in the plasma is increased.
Cyclosporine and tacrolimus increase the concentration of drugs in the blood plasma.
Co-trimoxazole and oral contraceptives (single dose) do not affect the pharmacokinetic parameters.
Special instructions:In patients receiving mycophenolate mofetil as part of immunosuppressive therapy, the risk of developing lymphomas and other malignant tumors (particularly skin cancer) with prolonged treatment with high doses increases. To reduce the risk of skin cancer, patients should avoid ultraviolet radiation (including sunlight).
During therapy, it is necessary to monitor the picture of peripheral blood.
Due to the undesirable effects on the fetus of women of reproductive age, effective methods of contraception should be used before, during, and for 6 weeks after drug withdrawal.
Patients taking mycophenolate mofetil are not vaccinated with live vaccines.
During the reception of mycophenolate mofetil, breastfeeding should be discontinued.