Indications for use
In combination therapy with cyclosporine and corticosteroids: prophylaxis of kidney, heart, liver allograft rejection reaction.

List of information required before use
Contraindications
hypersensitivity to mycophenolate mofetil, mycophenolic acid or any of the drug components
Hypoxanthine-guanine phosphoribosyltransferase deficiency (Lesch-Nayen and Kelly-Siegmiller syndromes)
concomitant use with azathioprine
women of childbearing age who are not using highly effective contraceptive methods
women of childbearing age until a negative pregnancy test is obtained to exclude inadvertent use during pregnancy
pregnancy and lactation
children and adolescents under 18 years of age

Necessary precautions for use
Malignant neoplasms
As well as on the background of combined immunosuppression in general, and when the drug Mycop is administered as a component of an immunosuppressive regimen, there is an increased risk of lymphoma and other malignant neoplasms, especially of the skin. This risk appears to be related to the intensity and duration of immunosuppression rather than to the use of any drug per se. The standard recommendation for reducing the risk of skin cancer, is to limit exposure to sun and UV rays by wearing appropriate closed clothing and using sunscreens with a high protective factor value.
Infections
Patients receiving immunosuppressant drugs, including Mycop, are at increased risk for opportunistic infections (bacterial, fungal, viral, and protozoal), fatal infections, and sepsis. Among opportunistic infections, the most common are latent viral reactivations such as hepatitis B or C virus reactivation and infections caused by polyomaviruses (Human Polyomavirus 1 (HPV) associated with John Cunningham virus, which in turn is associated with progressive multifocal leukoencephalopathy (PML). Cases of hepatitis due to reactivation of hepatitis B virus or hepatitis C virus have been documented in carrier patients receiving immunosuppressants. These infections are often associated with excessive immune system suppression and may lead to serious or fatal conditions that should be considered by the clinician in the differential diagnosis of immunocompromised patients with impaired immune function, impaired renal function, or neurologic symptoms.
Cases of hypogammaglobulinemia due to recurrent infections have been reported in patients receiving mycophenolate mofetil in combination with other immunosuppressants. In some cases, switching from mycophenolate mofetil to an alternative immunosuppressant resulted in normalization of serum IgG levels. Patients who develop recurrent infections against the background of Mycop drug administration should measure the amount of immunoglobulins in serum. In cases of prolonged, clinically significant hypogammaglobulinemia, appropriate clinical measures should be considered, taking into account the cytostatic effect that mycophenolic acid has on T- and B-lymphocytes.
There have been published case reports of bronchiectasis in adults and children who have received mycophenolate mofetil in combination with other immunosuppressants. In some cases, switching from mycophenolate mofetil to another immunosuppressant resulted in improvement in respiratory symptoms. The risk of bronchiectasis may be associated with hypogammaglobulinemia or direct effects on the lungs. There have also been isolated reports of interstitial lung disease and pulmonary fibrosis, some of which have been fatal. It is recommended that patients who develop persistent pulmonary symptoms, such as cough and dyspnea, be evaluated.
Blood and immune system
Particular attention should be paid to the possibility of neutropenia in patients taking Mycop. Neutropenia may be associated with taking Mycop, as well as with the use of other drugs, viral infections or a combination of these causes. During treatment with mycophenolate mofetil it is necessary to determine the expanded blood formula during the first month - weekly, during the second and third months of treatment - 2 times a month, and then during the first year - monthly. In case of neutropenia (absolute neutrophil count less than 1.3×103/μl) it is necessary to interrupt treatment with Mycop or reduce the dose.
Cases of development of partial red cell aplasia (PRCA) have been observed in patients taking mycophenolate mofetil in combination with other immunosuppressive drugs. The mechanism of mycophenolate mofetil's effect on PKCA is unknown. The development of PKCA can be stopped by dose reduction or withdrawal of therapy with Mycop. Changes in Mycop therapy regimen should be made only under proper patient monitoring to minimize the risk of transplant rejection.
Patients receiving Mycop should be informed of the need to immediately report to the physician any signs of infection, bleeding, hemorrhage or other signs of bone marrow suppression.
Patients should be warned that during treatment with Mycop, vaccinations may be less effective and therefore the use of live attenuated vaccines should be avoided. Influenza vaccination may also affect therapy. Healthcare professionals prescribing the drug should refer to national guidelines for influenza vaccination.
Effect on the GI tract
Since administration of Mycop preparation may be accompanied by adverse reactions from GI tract, including rare adverse events such as ulceration of GI mucosa, gastrointestinal bleeding, GI perforations, caution should be exercised when prescribing Mycop preparation to patients with exacerbated digestive tract diseases.
Since mycophenolate mofetil is an inhibitor of inosine monophosphate dehydrogenase (IMPDH), from a theoretical point of view, it should not be prescribed to patients with rare genetically determined hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase (Lesch-Neien and Kelly-Siegmiller syndromes).
Interactions
Caution should be exercised when substituting combination therapy with immunosuppressants that interfere with intestinal hepatic recycling of IFC, e.g., cyclosporine for other drugs that do not have this effect, e.g., sirolimus, belatacept, or vice versa, which may result in altered IFC effects. Drugs of other classes that interfere with intestinal hepatic circulation of IFC, such as cholestyramine, should be used with caution because of their ability to reduce plasma IFC levels and efficacy.
It is not recommended to take Micop concomitantly with azathioprine, as such a combination has not been studied.
The benefit/risk ratio of mycophenolate mofetil in combination with tacrolimus or sirolimus has not been established.
Special Patient Groups
Elderly patients, compared with younger individuals, have an increased risk of adverse events such as infections (including invasive tissue cytomegalovirus infection), gastrointestinal bleeding, and pulmonary edema.
Teratogenic effects
Mycophenolate mofetil has strong teratogenic effects on humans. The drug Mycop is contraindicated in pregnancy, unless there are no alternative treatments to prevent graft rejection. Women and men of reproductive age should be aware of the risks and follow the recommendations given in the Contraception section. The physician should verify that women and men taking mycophenolate mofetil understand the risk of harm to the child, the need for effective contraception, and immediate consultation with their physician, in the event of possible pregnancy.
Additional Precautions
Patients should not donate blood during therapy and for 6 weeks after discontinuation of mycophenolate mofetil. Men may not be sperm donors during therapy or for 90 days after discontinuation of mycophenolate mofetil.

Interactions with other medicinal products
Acyclovir
Increased plasma concentrations of acyclovir have been observed with concomitant administration of acyclovir and mycophenolate mofetil compared to administration of the drugs separately. Changes in the pharmacokinetics of MFKG (phenolic glucuronide of MFKG) were minimal (8% increase in MFKG) and are not clinically significant. Since plasma concentrations of MPA are increased in renal failure, as are those of acyclovir, it is possible that the two drugs compete for tubular secretion, or their prodrugs such as valacyclovir, which may further increase concentrations of both drugs.
Antacids and Proton Pump Inhibitors (PPIs)
Exposure to MPA was reduced when mycophenolate mofetil (MMF) was co-administered with antacids such as magnesium and aluminum hydroxides and PPIs including lansoprazole and pantoprazole. There was no significant difference in the incidence of graft rejection or graft loss between patients receiving MMF and PPI and patients not taking PPI. This finding is supported by extrapolation of this result to all antacids, because the reduction in exposure with co-administration of MMF and magnesium and aluminum hydroxides is significantly less than with co-administration of MMF and PPI.
Cholestyramine
Following administration of a single dose of 1.5 g mycophenolate mofetil to healthy volunteers previously treated with 4 g cholestyramine 3 times daily for 4 days, a 40% decrease in MPA AUC was observed. Concomitant administration should be carried out with caution, as it may reduce the efficacy of mycophenolate mofetil.
Drugs affecting enterohepatic recirculation
Caution should be exercised with drugs that interfere with enterohepatic recirculation, due to the possible reduction in the efficacy of mycophenolate mofetil.
Cyclosporine A
Cyclosporin A (CsA) pharmacokinetics are not affected by mycophenolate mofetil.
However, when concomitant cyclosporine is discontinued, an approximately 30% increase in MPA AUC is possible. CsA interferes with the enterohepatic circulation of MPA, resulting in a 30-50% decrease in MPA exposure in renal transplant patients receiving mycophenolate mofetil and CsA compared to patients receiving sirolimus or belatacept and similar doses of mycophenolate mofetil. Conversely, a change in MPA exposure would be expected when patients are switched from CsA to one of the immunosuppressants that does not interfere with the enterohepatic circulation of MPA.
Telmisartan
Concomitant administration of telmisartan and mycophenolate mofetil resulted in an approximately 30% decrease in MPA concentrations. Telmisartan alters MPA clearance by increasing the synthesis of PPAR gamma (peroxisome proliferator-activated receptor gamma), which in turn increases the synthesis and activity of UGT1A9. No clinical implications for pharmacokinetic interactions were observed when comparing the incidence of graft rejection, graft loss, or adverse events between patients receiving mycophenolate mofetil with and without concomitant telmisartan.
Ganciclovir
Given the known effects of renal impairment on the pharmacokinetics of mycophenolate mofetil and ganciclovir, it is expected that coadministration of the two drugs (which compete for tubular secretion) would result in increased concentrations of MPA and ganciclovir. No significant change in the pharmacokinetics of MPA is expected, therefore, no dose adjustment of Mycop is required. If Mycop, ganciclovir and its analogues, such as valganciclovir, are prescribed to patients with renal insufficiency, the recommended dosage regimen for ganciclovir should be followed and patients should be closely monitored.
Oral contraceptives
Mycophenolate mofetil does not affect the pharmacokinetics and pharmacodynamics of oral contraceptives when administered concomitantly.
Rifampicin
In patients taking cyclosporine, concomitant administration of mycophenolate mofetil and rifampicin results in a decrease in MPA exposure (AUC0-12h) by 18% to 70%. It is recommended to monitor MPA levels and adjust mycophenolate mofetil doses, maintaining clinical efficacy when administered concomitantly with rifampicin.
Sevelamer
Concomitant use of sevelamer and mycophenolate mofetil decreased Cmax and AUC0-12 of MPA by 30% and 25%, respectively, without clinical consequences (i.e. transplant rejection). It is recommended to take Mycop at least one hour before or three hours after taking sevelamer to minimize the effect of MPA absorption. There are no data on the interaction of mycophenolate mofetil with other phosphate binders, not including sevelamer.
Trimethoprim/sulfamethoxazole
No effect on the bioavailability of MPA was observed.
Norfloxacin and metronidazole
In healthy volunteers, no significant interaction was observed when mycophenolate mofetil was taken simultaneously with norfloxacin and separately with metronidazole. However, co-administration of MPA with norfloxacin and metronidazole reduces MPA exposure by 30% after a single dose of mycophenolate mofetil.
Ciprofloxacin and amoxicillin in combination with clavulanic acid
In patients after kidney transplantation, a 50% decrease in the minimum concentration of MPA is observed in the days immediately after oral administration of ciprofloxacin or amoxicillin in combination with clavulanic acid. With continued antibacterial therapy, this effect decreases and disappears after discontinuation of therapy. Dose adjustment of MPA is not required unless there is an accurate understanding of the change in total MPA exposure. Thus, dose adjustment of Mycop is not required in the absence of clinical signs of graft dysfunction. However, clinical monitoring should be performed during and immediately after antibiotic therapy.
Tacrolimus
With co-administration, no effect on AUC and Cmax of MPA was observed in patients after liver transplantation. In patients after liver transplantation, the AUC of tacrolimus after multiple dosing with MPA at a dose of 1.5 g twice daily increased by approximately 20%. In patients after renal transplantation, administration of mycophenolate mofetil did not affect tacrolimus concentrations.
Other interactions
When probenecid and mycophenolate mofetil were co-administered to monkeys, the AUC of MPA in plasma increased by 3-fold. Thus, other drugs that undergo tubular secretion may compete with MPA, resulting in increased plasma concentrations of MPA or another drug that also undergoes tubular secretion.
Live vaccines
Should not be administered to patients with suppressed immunity. Antibody response to other vaccines may be reduced.

Special instructions
Contraception
Because of the genotoxic and teratogenic potential of mycophenolate mofetil, women of childbearing potential should use two reliable forms of contraception simultaneously before starting therapy with Mycop, during therapy, and for six weeks after stopping therapy; unless abstinence is the chosen method of contraception.
For sexually active men, it is recommended to use condoms during treatment and for at least 90 days after stopping treatment. Condom use applies to both reproductively healthy men and men after vasectomy due to the risks associated with the transmission of seminal fluid. In addition, female partners of men treated with Mycop are recommended to use highly effective contraception during treatment and for a total of 90 days after the last dose of Mycop.
Pregnancy
The use of Mycop during pregnancy is contraindicated and is possible only in cases where there is no more suitable alternative therapy. Mycop therapy should not be initiated unless pregnancy testing has been negative.
Women and men of childbearing potential should be advised of the increased risk of miscarriage and congenital malformations at the start of treatment and should be counseled on contraception and planning.
Before initiating Mycop therapy, women of childbearing potential should have a pregnancy test to rule out inadvertent exposure of the fetus to mycophenolate mofetil. Two serum or urine pregnancy tests with a sensitivity of at least 25 mIU/mL are recommended; the second test is performed 8 to 10 days after the first and immediately before starting mycophenolate mofetil. Pregnancy tests should be repeated if clinically necessary (e.g., after a break in contraception). The results of all pregnancy tests should be discussed with the patient. Patients should be instructed to contact their physician immediately if they become pregnant.
Peculiarities of the drug’s effect on the ability to drive a vehicle or operate potentially dangerous machinery
Patients who experience fatigue, drowsiness, or lethargy during treatment should avoid such activities.

Recommended Use
Dosage
Prevention of Kidney Transplant Rejection
Patients with a kidney transplant are recommended to take 1.0 g twice daily (daily dose 2 g) as part of combination therapy with cyclosporine and corticosteroids.
Prevention of Heart Transplant Rejection
The recommended dosage is 1.5 g twice daily (daily dose 3 g) as part of combination therapy with cyclosporine and corticosteroids.
Prevention of Liver Transplant Rejection
The recommended dosage is 1.5 g twice daily (daily dose 3 g) as part of combination therapy with cyclosporine and corticosteroids.
After kidney, heart or liver transplantation, the first dose of Mycop should be taken as soon as possible.
The duration of Mycop treatment is long, almost lifelong.
Dosage in special cases
In case of neutropenia (absolute neutrophil count < 1300 in 1 μl), it is necessary to interrupt treatment with Mycop or reduce its dose and carefully monitor the patient.
Elderly patients
In elderly patients who have undergone a kidney transplant, the recommended dose is 1 g twice a day, and after a heart or liver transplant – 1.5 g twice a day.
Patients with chronic renal impairment
In patients with severe chronic renal impairment (glomerular filtration rate less than 25 ml/min/1.73 m2) after kidney transplantation, doses higher than 1 g twice a day should be avoided, except for the immediate post-transplant period and the period after therapy for acute or refractory graft rejection. These patients should also be closely monitored.
No dosage adjustment is required for patients with postoperative delayed renal graft function. Data on the use of the drug in patients with renal insufficiency there are no recommendations for use in patients with severe liver failure, who have undergone a heart or liver transplant.
Patients with severe liver failure
No dose adjustment is required in patients with severe liver parenchyma who have undergone a kidney transplant. There are no data on the use of the drug in patients with severe liver parenchyma who have undergone a heart transplant.
Treatment of transplant rejection
Mycophenolic acid (MPA) is an active metabolite of mycophenolate mofetil. Kidney transplant rejection does not lead to changes in the pharmacokinetics of MPA, so dose reduction or discontinuation of therapy with Mycop is not required. There are no grounds for adjusting the dose of Mycop after cessation of transplant rejection. There are no pharmacokinetic data on liver transplant rejection.
Special instructions for use
Since mycophenolate mofetil showed a teratogenic effect in an experiment on rats and rabbits, the integrity of the Mycop capsules should not be violated. Avoid inhaling the powder contained in the capsules or allowing it to come into direct contact with the skin or mucous membranes. If this happens, wash the area thoroughly with soap and water, and wash the eyes with just water.
Any unused product and/or waste should be disposed of in accordance with local requirements.
Consult a healthcare professional for clarification on how to use the drug

Description of adverse reactions that occur with standard use of the drug and measures to take in this case (side effects)

Kidney transplant
Very common
bacterial infections, viral infections
anemia, leukopenia
hypercholesterolemia, hypophosphatemia
headache
arterial hypertension
cough, dyspnea
abdominal pain, constipation, diarrhea, dyspepsia, nausea, vomiting
hematuria
asthenia, edema, fever

Common
fungal infections
benign skin neoplasm, neoplasm, skin cancer
ecchymosis, leukocytosis, pancytopenia, thrombocytopenia
acidosis, hyperglycemia, hyperkalemia, hyperlipidemia, hypocalcemia, hypokalemia, hypomagnesemia, hyperuricemia, gout, weight loss
confusion, depression, insomnia, anxiety
dizziness, hypertonia, paresthesia, drowsiness, tremor, seizures
tachycardia
arterial hypotension, venous thrombosis, vasodilation
pleural effusion
abdominal distension, colitis, decreased appetite, esophagitis, flatulence, gastritis, gastrointestinal bleeding, gastrointestinal ulcer, gingival hyperplasia, intestinal obstruction, oral ulcers, stomatitis
alkaline phosphatase increased, lactate dehydrogenase increased, liver enzymes increased, hepatitis, hyperbilirubinemia
acne, alopecia, rash, skin hypertrophy
arthralgia, muscle weakness
increased blood creatinine, renal dysfunction
chills, hernia, malaise, pain

Uncommon
protozoal infections
lymphoma, lymphoproliferative disorder
partial red cell aplasia, bone marrow failure, pseudolymphoma
agitation, abnormal thinking
dysgeusia
lymphocele
bronchiectasis, interstitial lung disease
belching, pancreatitis
hypersensitivity, hypogammaglobulinemia
jaundice
blood urea increased

Very rare
pulmonary fibrosis

Liver transplant
Very common
bacterial infections, fungal infections, viral infections
anaemia, leukocytosis, leukopenia, thrombocytopenia
hyperglycaemia, hyperkalemia, hypocalcemia, hypokalemia, hypomagnesaemia, hypophosphatemia
confusion, depression, insomnia, anxiety
dizziness, headache pain, paresthesia, tremor
tachycardia
hypertension, hypotension
cough, dyspnea, pleural effusion
bloating, abdominal pain, constipation, decreased appetite, diarrhea, dyspepsia, flatulence, nausea, vomiting
increased liver enzymes, hepatitis, hyperbilirubinemia
rash
increased blood creatinine, increased blood urea, renal dysfunction
asthenia, chills, edema, hernia, pain, fever

Common
benign skin neoplasm, neoplasm
ecchymosis, pancytopenia
acidosis, hypercholesterolemia, hyperlipidemia, hyperuricemia, gout, weight loss
agitation, abnormal thinking
hypertonicity, drowsiness, seizures
venous thrombosis, vasodilation
colitis, esophagitis, gastritis, gastrointestinal bleeding, gastrointestinal ulcer, gingival hyperplasia, intestinal obstruction, oral ulcer, pancreatitis, stomatitis
hypersensitivity
alkaline phosphatase increased, jaundice
acne, alopecia, skin hypertrophy
arthralgia, muscle weakness
hematuria
malaise

Uncommon
protozoal infections
lymphoma, lymphoproliferative disorder, skin cancer
partial red cell aplasia, bone marrow failure, pseudolymphoma
dysgeusia
lymphocele
bronchiectasis, pulmonary fibrosis
belching
lactate dehydrogenase increased

Very rare
interstitial lung disease
hypogammaglobulinemia

Cardiac transport
Very common
bacterial infections, fungal infections, viral infections
anemia, ecchymosis, leukocytosis, leukopenia, thrombocytopenia
acidosis, hypercholesterolemia, hyperglycemia, hyperkalemia, hyperlipidemia, hypokalemia, hypomagnesemia, hyperuricemia, gout
confusion, depression, insomnia, agitation, anxiety
dizziness, headache, hypertonia, paresthesia, drowsiness, tremor
tachycardia
arterial hypertension, arterial hypotension, vasodilation
cough, dyspnea, pleural effusion
abdominal pain, constipation, decreased appetite, diarrhea, dyspepsia, flatulence, nausea, vomiting
increased lactate dehydrogenase activity, increased liver enzymes, hyperbilirubinemia
acne, rash, skin hypertrophy
arthralgia, muscle weakness
increased blood creatinine, increased blood urea, renal dysfunction
asthenia, chills, edema, hernia, pain, fever

Common
benign skin neoplasm, neoplasm, skin cancer
pseudolymphoma
hypocalcemia, hypophosphatemia, weight loss
abnormal thinking
convulsions, dysgeusia
venous thrombosis
bloating, colitis, esophagitis, eructation, gastritis, gastrointestinal bleeding, gastrointestinal ulcer, gingival hyperplasia, intestinal obstruction, oral ulcer, stomatitis
hypersensitivity
increased alkaline phosphatase, jaundice
alopecia
hematuria
malaise

Uncommon
protozoal infections
lymphoma, lymphoproliferative disease
partial red cell aplasia, bone marrow failure, pancytopenia
lymphocele
bronchiectasis, pulmonary fibrosis
pancreatitis
hepatitis

Very rare
interstitial lung disease
hypogammaglobulinemia

If adverse drug reactions occur, contact your health care provider, pharmacist, or directly to the Adverse Drug Reactions (Actions) Information Database, including reports of drug ineffectiveness
Republican State enterprise on the Right of Economic Management National Center for Expertise of Medicines and Medical Devices of the Committee for Medical and Pharmaceutical Control of the Ministry of Healthcare of the Republic of Kazakhstan
http://www.ndda.kz

Additional information

Composition of the medicinal product
One capsule contains the active substance - mycophenolate mofetil 250 mg, excipients: pregelatinized starch (starch 1500 LM) (partially pregelatinized corn starch), sodium croscarmellose (Ac-di-sol SD-711), povidone (K-90) (Plasdone K-90), magnesium stearate.

Capsule shell composition:
cap — dye FD & C Blue 2 (E132), titanium dioxide (E171), gelatin; body — iron oxide red (E172), iron oxide yellow (E172), titanium dioxide (E171), gelatin.

Description of appearance, smell, taste
Hard gelatin capsule size '1', with a brown body and a blue cap, with the inscription “H” on the cap and “M1” on the body.
Capsule contents — powder from white to almost white.

Release form and packaging
100 capsules are placed in a high-density polyethylene container.
1 container together with instructions for medical use in Kazakh and Russian languages ​​are placed in a cardboard pack.

Shelf life
3 years
Do not use after the expiration date.

Storage conditions
Store in a dry, dark place, at a temperature not exceeding 25 °C.
Keep out of reach of children!

Conditions of dispensing from pharmacies
On prescription