майфортик

Overdose

There have been anecdotal reports of deliberate or accidental overdoses with Майфортик, whereas not all patients experienced related adverse reactions.

In those overdose cases in which adverse reactions were reported, the reactions fall within the known safety profile of the class. Accordingly an overdose of Майфортик could possibly result in oversuppression of the immune system and may increase the susceptibility to infection including opportunistic infections, fatal infections and sepsis. If blood dyscrasias occur (e.g., neutropenia with absolute neutrophil count < 1.5 x 103/mcL or anemia), it may be appropriate to interrupt or discontinue Майфортик.

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.

General supportive measures and symptomatic treatment should be followed in all cases of overdosage. Although dialysis may be used to remove the inactive metabolite mycophenolic acid glucuronide (MPAG), it would not be expected to remove clinically significant amounts of the active moiety, mycophenolic acid, due to the 98% plasma protein binding of mycophenolic acid. By interfering with enterohepatic circulation of mycophenolic acid, activated charcoal or bile sequestrates, such as cholestyramine, may reduce the systemic mycophenolic acid exposure.

Contraindications

Майфортик is contraindicated in patients with a hypersensitivity to mycophenolate sodium, mycophenolic acid, mycophenolate mofetil, or to any of its excipients. Reactions like rash, pruritus, hypotension, and chest pain have been observed in clinical trials and post marketing reports.

Pharmaceutical form

Undesirable effects

The following adverse reactions are discussed in greater detail in other sections of the label.

• Embryofetal Toxicity
• Lymphomas and Other Malignancies
• Serious Infections
• New or Reactivated Viral Infections
• Blood Dyscrasias Including Pure Red Cell Aplasia
• Serious GI Tract Complications
• Rare Hereditary Deficiencies

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described below derive from two randomized, comparative, active-controlled, double-blind, double-dummy trials in prevention of acute rejection in de novo and converted stable kidney transplant patients.

In the de novo trial, patients were administered either Майфортик 1.44 grams per day (N=213) or MMF 2 grams per day (N=210) within 48 hours post-transplant for 12 months in combination with cyclosporine, USP MODIFIED and corticosteroids. Forty-one percent of patients also received antibody therapy as induction treatment. In the conversion trial, renal transplant patients who were at least 6 months post-transplant and receiving 2 grams per day MMF in combination with cyclosporine USP MODIFIED, with or without corticosteroids for at least two weeks prior to entry in the trial were randomized to Майфортик 1.44 grams per day (N=159) or MMF 2 grams per day (N=163) for 12 months.

The average age of patients in both studies was 47 years and 48 years (de novo study and conversion study, respectively), ranging from 22 to 75 years. Approximately 66% of patients were male; 82% were white, 12% were black, and 6% other races. About 40% of patients were from the United States and 60% from other countries.

In the de novo trial, the overall incidence of discontinuation due to adverse reactions was 18% (39/213) and 17% (35/210) in the Майфортик and MMF arms, respectively. The most common adverse reactions leading to discontinuation in the Майфортик arm were graft loss (2%), diarrhea (2%), vomiting (1%), renal impairment (1%), CMV infection (1%), and leukopenia (1%). The overall incidence of patients reporting dose reduction at least once during the 0 to 12 month study period was 59% and 60% in the Майфортик and MMF arms, respectively. The most frequent reasons for dose reduction in the Майфортик arm were adverse reactions (44%), dose reductions according to protocol guidelines (17%), dosing errors (11%) and missing data (2%).

The most common adverse reactions ( ≥ 20%) associated with the administration of Майфортик were anemia, leukopenia, constipation, nausea, diarrhea, vomiting, dyspepsia, urinary tract infection, CMV infection, insomnia, and postoperative pain.

The adverse reactions reported in ≥ 10% of patients in the de novo trial are presented in Table 2 below.

Table 2: Adverse Reactions (%) Reported in ≥ 10% of de novo Kidney Transplant Patients in Either Treatment Group

Table 3 summarizes the incidence of opportunistic infections in de novo transplant patients.

Table 3: Viral and Fungal Infections (%) Reported Over 0 to 12 Months

Lymphoma developed in 2 de novo patients (1%), (1 diagnosed 9 days after treatment initiation) and in 2 conversion patients (1%) receiving Майфортик with other immunosuppressive agents in the 12-month controlled clinical trials.

Nonmelanoma skin carcinoma occurred in 1% de novo and 12% conversion patients. Other types of malignancy occurred in 1% de novo and 1% conversion patients.

The adverse reactions reported in < 10% of de novo or conversion patients treated with Майфортик in combination with cyclosporine and corticosteroids are listed in Table 4.

Table 4: Adverse Reactions Reported in < 10% of Patients Treated with Майфортик in Combination with Cyclosporine* and Corticosteroids

The following additional adverse reactions have been associated with the exposure to mycophenolic acid (MPA) when administered as a sodium salt or as mofetil ester:

Gastrointestinal: Intestinal perforation, gastrointestinal hemorrhage, gastric ulcers, duodenal ulcers , colitis (including CMV colitis), pancreatitis, esophagitis, and ileus.

Infections: Serious life-threatening infections such as meningitis and infectious endocarditis, tuberculosis, and atypical mycobacterial infection.

Respiratory: Interstitial lung disorders, including fatal pulmonary fibrosis.

The following adverse reactions have been identified during post-approval use of Майфортик or other MPA derivatives. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• Congenital malformations including ear, facial, cardiac and nervous system malformations and an increased incidence of first trimester pregnancy loss have been reported following exposure to MMF during pregnancy.
• Infections
  • Cases of progressive multifocal leukoencephalopathy (PML), sometimes fatal.
  • Polyomavirus associated nephropathy (PVAN), especially due to BK virus infection, associated with serious outcomes, including deteriorating renal function and renal graft loss.
  • Viral reactivation in patients infected with HBV or HCV.
• Cases of pure red cell aplasia (PRCA) have been reported in patients treated with MPA derivatives in combination with other immunosuppressive agents.

The following additional adverse reactions have been identified during postapproval use of Майфортик: agranulocytosis, asthenia, osteomyelitis, lymphadenopathy, lymphopenia, wheezing, dry mouth, gastritis, peritonitis, anorexia, alopecia, pulmonary edema, Kaposi's sarcoma.

Therapeutic indications

Майфортик® (mycophenolic acid) is indicated for the prophylaxis of organ rejection in adult patients receiving a kidney transplant.

Майфортик is indicated for the prophylaxis of organ rejection in pediatric patients 5 years of age and older who are at least 6 months post kidney transplant.

Майфортик is to be used in combination with cyclosporine and corticosteroids.

Майфортик delayed-release tablets and mycophenolate mofetil (MMF) tablets and capsules should not be used interchangeably without physician supervision because the rate of absorption following the administration of these two products is not equivalent.

Майфортик price

Pharmacokinetic properties

Майфортик exhibits linear and dose-proportional pharmacokinetics over the dose-range (360 to 2160 mg) evaluated. The absolute bioavailability of Майфортик in stable renal transplant patients on cyclosporine was 72%. MPA is highly protein bound ( > 98% bound to albumin). The predominant metabolite of MPA is the phenolic glucuronide (MPAG) which is pharmacologically inactive. A minor metabolite AcMPAG which is an acyl glucuronide of MPAG is also formed and has pharmacological activity comparable to MPA. MPAG undergoes renal elimination. A fraction of MPAG also undergoes biliary excretion, followed by deconjugation by gut flora and subsequent reabsorption as MPA. The mean elimination half-lives of MPA and MPAG ranged between 8 and 16 hours, and 13 and 17 hours, respectively.

In vitro studies demonstrated that the enteric-coated Майфортик tablet does not release MPA under acidic conditions (pH < 5) as in the stomach but is highly soluble in neutral pH conditions as in the intestine. Following Майфортик oral administration without food in several pharmacokinetic studies conducted in renal transplant patients, consistent with its enteric-coated formulation, the median delay (Tlag) in the rise of MPA concentration ranged between 0.25 and 1.25 hours and the median time to maximum concentration (Tmax) of MPA ranged between 1.5 and 2.75 hours. In comparison, following the administration of MMF, the median Tmax ranged between 0.5 and 1.0 hours. In stable renal transplant patients on cyclosporine, USP MODIFIED based immunosuppression, gastrointestinal absorption and absolute bioavailability of MPA following the administration of Майфортик delayed-release tablet was 93% and 72%, respectively. Майфортик pharmacokinetics is dose proportional over the dose range of 360 to 2160 mg.

The mean (± SD) volume of distribution at steady state and elimination phase for MPA is 54 (± 25) L and 112 (± 48) L, respectively. MPA is highly protein bound to albumin, > 98%. The protein binding of mycophenolic acid glucuronide (MPAG) is 82%. The free MPA concentration may increase under conditions of decreased protein binding (uremia, hepatic failure, and hypoalbuminemia).

MPA is metabolized principally by glucuronyl transferase to glucuronidated metabolites. The phenolic glucuronide of MPA, mycophenolic acid glucuronide (MPAG), is the predominant metabolite of MPA and does not manifest pharmacological activity. The acyl glucuronide is a minor metabolite and has comparable pharmacological activity to MPA. In stable renal transplant patients on cyclosporine, USP MODIFIED based immunosuppression, approximately 28% of the oral Майфортик dose was converted to MPAG by presystemic metabolism. The AUC ratio of MPA:MPAG:acyl glucuronide is approximately 1:24:0.28 at steady state. The mean clearance of MPA was 140 (± 30) mL/min.

The majority of MPA dose administered is eliminated in the urine primarily as MPAG ( > 60%) and approximately 3% as unchanged MPA following Майфортик administration to stable renal transplant patients. The mean renal clearance of MPAG was 15.5 (± 5.9) mL/min. MPAG is also secreted in the bile and available for deconjugation by gut flora. MPA resulting from the deconjugation may then be reabsorbed and produce a second peak of MPA approximately 6 to 8 hours after Майфортик dosing. The mean elimination half-life of MPA and MPAG ranged between 8 and 16 hours, and 13 and 17 hours, respectively.

Compared to the fasting state, administration of Майфортик 720 mg with a high-fat meal (55 g fat, 1000 calories) had no effect on the systemic exposure (AUC) of MPA. However, there was a 33% decrease in the maximal concentration (Cmax), a 3.5-hour delay in the Tlag (range, -6 to 18 hours), and 5.0-hour delay in the Tmax (range, -9 to 20 hours) of MPA. To avoid the variability in MPA absorption between doses, Майфортик should be taken on an empty stomach.

Qualitative and quantitative composition

Special warnings and precautions for use

Included as part of the PRECAUTIONS section.

Use of Майфортик during pregnancy is associated with an increased risk of first trimester pregnancy loss and an increased risk of congenital malformations, especially external ear and other facial abnormalities including cleft lip and palate, and anomalies of the distal limbs, heart, esophagus, kidney, and nervous system.

Females of reproductive potential must be aware of the increased risk of first trimester pregnancy loss and congenital malformations and must be counseled regarding pregnancy prevention and planning. For recommended pregnancy testing and contraception methods.

Only physicians experienced in immunosuppressive therapy and management of organ transplant patients should prescribe Майфортик. Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physicians responsible for maintenance therapy should have complete information requisite for the follow-up of the patient.

Patients receiving immunosuppressants, including Майфортик, are at increased risk of developing lymphomas and other malignancies, particularly of the skin. The risk appears to be related to the intensity and duration of immunosuppression rather than to the use of any specific agent.

As usual for patients with increased risk for skin cancer, exposure to sunlight and UV light should be limited by wearing protective clothing and using a sunscreen with a high protection factor.

Post-transplant lymphoproliferative disorder (PTLD) has been reported in immunosuppressed organ transplant recipients. The majority of PTLD events appear related to Epstein Barr Virus (EBV) infection. The risk of PTLD appears greatest in those individuals who are EBV seronegative, a population which includes many young children.

Patients receiving immunosuppressants, including Майфортик, are at increased risk of developing bacterial, viral, fungal, and protozoal infections, and new or reactivated viral infections including opportunistic infections. These infections may lead to serious, including fatal outcomes. Because of the danger of oversuppression of the immune system which can increase susceptibility to infection, combination immunosuppressant therapy should be used with caution.

Polyomavirus associated nephropathy (PVAN), JC virus associated progressive multifocal leukoencephalopathy (PML), cytomegalovirus (CMV) infections, reactivation of hepatitis B (HBV) or hepatitis C (HCV) have been reported in patients treated with immunosuppressants, including the mycophenolic acid (MPA) derivatives Майфортик and MMF. Reduction in immunosuppression should be considered for patients who develop evidence of new or reactivated viral infections. Physicians should also consider the risk that reduced immunosuppression represents to the functioning allograft.

PVAN, especially due to BK virus infection, is associated with serious outcomes, including deteriorating renal function and renal graft loss. Patient monitoring may help detect patients at risk for PVAN.

PML, which is sometimes fatal, commonly presents with hemiparesis, apathy, confusion, cognitive deficiencies, and ataxia. Risk factors for PML include treatment with immunosuppressant therapies and impairment of immune function. In immunosuppressed patients, physicians should consider PML in the differential diagnosis in patients reporting neurological symptoms and consultation with a neurologist should be considered as clinically indicated.

The risk of CMV viremia and CMV disease is highest among transplant recipients seronegative for CMV at time of transplant who receive a graft from a CMV seropositive donor. Therapeutic approaches to limiting CMV disease exist and should be routinely provided. Patient monitoring may help detect patients at risk for CMV disease..

Viral reactivation has been reported in patients infected with HBV or HCV. Monitoring infected patients for clinical and laboratory signs of active HBV or HCV infection is recommended.

Cases of pure red cell aplasia (PRCA) have been reported in patients treated with MPA derivatives in combination with other immunosuppressive agents. The mechanism for MPA derivatives induced PRCA is unknown; the relative contribution of other immunosuppressants and their combinations in an immunosuppressive regimen is also unknown. In some cases PRCA was found to be reversible with dose reduction or cessation of therapy with MPA derivatives. In transplant patients, however, reduced immunosuppression may place the graft at risk. Changes to Майфортик therapy should only be undertaken under appropriate supervision in transplant recipients in order to minimize the risk of graft rejection.

Patients receiving Майфортик should be monitored for blood dyscrasias (e.g., neutropenia or anemia). The development of neutropenia may be related to Майфортик itself, concomitant medications, viral infections, or some combination of these reactions. Complete blood count should be performed weekly during the first month, twice monthly for the second and the third month of treatment, then monthly through the first year. If blood dyscrasias occur [neutropenia develops (ANC < 1.3 x 103/mcL) or anemia], dosing with Майфортик should be interrupted or the dose reduced, appropriate tests performed, and the patient managed accordingly.

Gastrointestinal bleeding (requiring hospitalization), intestinal perforations, gastric ulcers, and duodenal ulcers have been reported in patients treated with Майфортик. Майфортик should be administered with caution in patients with active serious digestive system disease.

The use of live attenuated vaccines should be avoided during treatment with Майфортик; examples include (but not limited to) the following: intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines.

Майфортик is an inosine monophosphate dehydrogenase inhibitor (IMPDH Inhibitor). Майфортик should be avoided in patients with rare hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) such as Lesch-Nyhan and Kelley-Seegmiller syndromes because it may cause an exacerbation of disease symptoms characterized by the overproduction and accumulation of uric acid leading to symptoms associated with gout such as acute arthritis, tophi, nephrolithiasis or urolithiasis and renal disease including renal failure.

See FDA-approved patient labeling (Medication Guide)

• Inform pregnant women and females of reproductive potential that use of Майфортик in pregnancy is associated with an increased risk of first trimester pregnancy loss and an increased risk of congenital malformations.
• In the event of a positive pregnancy test, discuss the risks and benefits of Майфортик with the patient. Encourage her to enroll in the pregnancy registry. (1-800-617-8191)..

• Discuss pregnancy testing, pregnancy prevention and planning with females of reproductive potential.
• Inform females of reproductive potential must use acceptable birth control during entire Майфортик therapy and for 6 weeks after stopping Майфортик, unless the patient chooses to avoid heterosexual sexual intercourse completely (abstinence).
• For patients who are considering pregnancy, discuss appropriate alternative immunosuppressants with less potential for embryofetal toxicity. Risks and benefits of Майфортик should be discussed with the patient.

Advise patients that they should not breastfeed during Майфортик therapy.

• Inform patients they are at increased risk of developing lymphomas and other malignancies, particularly of the skin, due to immunosuppression.
• Advise patients to limit exposure to sunlight and ultraviolet (UV) light by wearing protective clothing and use a sunscreen with a high protection factor.

Inform patients they are at increased risk of developing a variety of infections, including opportunistic infections, due to immunosuppression and to contact their physician if they develop any symptoms of infection.

Inform patients they are at increased risk for developing blood dyscrasias (e.g., neutropenia or anemia) and to immediately contact their healthcare provider if they experience any evidence of infection, unexpected bruising, bleeding, or any other manifestation of bone marrow suppression.

Inform patients that Майфортик can cause gastrointestinal tract complications including bleeding, intestinal perforations, and gastric or duodenal ulcers. Advise the patient to contact their healthcare provider if they have symptoms of gastrointestinal bleeding or sudden onset or persistent abdominal pain.

Inform patients that Майфортик can interfere with the usual response to immunizations and that they should avoid live vaccines.

Advise patients to swallow Майфортик tablets whole, and not crush, chew, or cut the tablets. Inform patients to take Майфортик on an empty stomach, 1 hour before or 2 hours after food intake.

Patients should be advised to report to their doctor the use of any other medications while taking Майфортик. The simultaneous administration of any of the following drugs with Майфортик may result in clinically significant adverse reactions:

Antacids with magnesium and aluminum hydroxides
Azathioprine
Cholestyramine
Hormonal Contraceptives (e.g., birth control pill, transdermal patch, vaginal ring, injection, and implant)

In a 104-week oral carcinogenicity study in rats, mycophenolate sodium was not tumorigenic at daily doses up to 9 mg per kg, the highest dose tested. This dose resulted in approximately 0.6 to 1.2 times the systemic exposure (based on plasma AUC) observed in renal transplant patients at the recommended dose of 1440 mg per day. Similar results were observed in a parallel study in rats performed with MMF. In a 104-week oral carcinogenicity study in mice, MMF was not tumorigenic at a daily dose level as high as 180 mg per kg (which corresponds to 0.6 times the recommended mycophenolate sodium therapeutic dose, based on body surface area).

The genotoxic potential of mycophenolate sodium was determined in five assays. Mycophenolate sodium was genotoxic in the mouse lymphoma/thymidine kinase assay, the micronucleus test in V79 Chinese hamster cells, and the in vivo mouse micronucleus assay. Mycophenolate sodium was not genotoxic in the bacterial mutation assay (Salmonella typhimurium TA 1535, 97a, 98, 100, and 102) or the chromosomal aberration assay in human lymphocytes.

Mycophenolate mofetil generated similar genotoxic activity. The genotoxic activity of mycophenolic acid (MPA) is probably due to the depletion of the nucleotide pool required for DNA synthesis as a result of the pharmacodynamic mode of action of MPA (inhibition of nucleotide synthesis).

Mycophenolate sodium had no effect on male rat fertility at daily oral doses as high as 18 mg per kg and exhibited no testicular or spermatogenic effects at daily oral doses of 20 mg per kg for 13 weeks (approximately 2 times the systemic exposure of MPA at the recommended therapeutic dose). No effects on female fertility were seen up to a daily dose of 20 mg per kg (approximately 3 times the systemic exposure of MPA at the recommended therapeutic dose).

For those females using Майфортик at any time during pregnancy and those becoming pregnant within 6 weeks of discontinuing therapy, the healthcare practitioner should report the pregnancy to the Mycophenolate Pregnancy Registry (1-800-617-8191). The healthcare practitioner should strongly encourage the patient to enroll in the pregnancy registry. The information provided to the registry will help the Health Care Community to better understand the effects of mycophenolate in pregnancy.

Following oral or intravenous (IV) administration, MMF is metabolized to mycophenolic acid (MPA), the active ingredient in Майфортик and the active form of the drug. Use of MMF during pregnancy is associated with an increased risk of first trimester pregnancy loss and an increased risk of congenital malformations, especially external ear and other facial abnormalities including cleft lip and palate, and anomalies of the distal limbs, heart, esophagus, kidney and nervous system. In animal studies, congenital malformations and pregnancy loss occurred when pregnant rats and rabbits received mycophenolic acid at dose multiples similar to and less than clinical doses.

Risks and benefits of Майфортик should be discussed with the patient. When appropriate, consider alternative immunosuppressants with less potential for embryofetal toxicity. In certain situations, the patient and her healthcare practitioner may decide that the maternal benefits outweigh the risks to the fetus. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

Human Data

In the National Transplantation Pregnancy Registry (NTPR), there were data on 33 MMF-exposed pregnancies in 24 transplant patients; there were 15 spontaneous abortions (45%) and 18 live-born infants. Four of these 18 infants had structural malformations (22%). In postmarketing data (collected from 1995 to 2007) on 77 women exposed to systemic MMF during pregnancy, 25 had spontaneous abortions and 14 had a malformed infant or fetus. Six of 14 malformed offspring had ear abnormalities. Because these postmarketing data are reported voluntarily, it is not always possible to reliably estimate the frequency of particular adverse outcomes. These malformations are similar to findings in animal reproductive toxicology studies. For comparison, the background rate for congenital anomalies in the United States is about 3%, and NTPR data show a rate of 4%-5% among babies born to organ transplant patients using other immunosuppressive drugs. There are no relevant qualitative or quantitative differences in the teratogenic potential of mycophenolate sodium and MMF.

Animal Data

In a teratology study performed with mycophenolate sodium in rats, at a dose as low as 1 mg per kg, malformations in the offspring were observed, including anophthalmia, exencephaly, and umbilical hernia. The systemic exposure at this dose represents 0.05 times the clinical exposure at the dose of 1440 mg per day Майфортик. In teratology studies in rabbits, fetal resorptions and malformations occurred at doses equal to or greater than 80 mg per kg per day, in the absence of maternal toxicity (which corresponds to about 1.1 times the recommended clinical dose, based on body surface area).

It is not known whether MPA is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Майфортик, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

The safety and effectiveness of Майфортик have been established in pediatric kidney transplant patients 5 to 16 years of age who were initiated on Майфортик at least 6 months post-transplant. Use of Майфортик in this age group is supported by evidence from adequate and well-controlled studies of Майфортик in a similar population of adult kidney transplant patients with additional pharmacokinetic data in pediatric kidney transplant patients. Pediatric doses for patients with BSA < 1.19 m² cannot be accurately administered using currently available formulations of Майфортик tablets.

The safety and effectiveness of Майфортик in de novo pediatric kidney transplant patients and in pediatric kidney transplant patients below the age of 5 years have not been established.

Clinical studies of Майфортик did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Of the 372 patients treated with Майфортик in the clinical trials, 6% (N=21) were 65 years of age and older and 0.3% (N=1) were 75 years of age and older. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Females of reproductive potential must be made aware of the increased risk of first trimester pregnancy loss and congenital malformations and must be counseled regarding pregnancy prevention and planning.

Females of reproductive potential include girls who have entered puberty and all women who have a uterus and have not passed through menopause. Menopause is the permanent end of menstruation and fertility. Menopause should be clinically confirmed by a patient's healthcare practitioner. Some commonly used diagnostic criteria include 1) 12 months of spontaneous amenorrhea (not amenorrhea induced by a medical condition or medical therapy), or 2) postsurgical from a bilateral oophorectomy.

To prevent unplanned exposure during pregnancy, females of reproductive potential should have a serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL immediately before starting Майфортик. Another pregnancy test with the same sensitivity should be done 8 to 10 days later. Repeat pregnancy tests should be performed during routine follow-up visits. Results of all pregnancy tests should be discussed with the patient.

In the event of a positive pregnancy test, females should be counseled with regard to whether the maternal benefits of mycophenolate treatment may outweigh the risks to the fetus in certain situations.

Females of reproductive potential taking Майфортик must receive contraceptive counseling and use acceptable contraception (see Table 5 for Acceptable Contraception Methods). Patients must use acceptable birth control during entire Майфортик therapy, and for 6 weeks after stopping Майфортик, unless the patient chooses abstinence (she chooses to avoid heterosexual intercourse completely).

Patients should be aware that Майфортик reduces blood levels of the hormones in the oral contraceptive pill and could theoretically reduce its effectiveness.

Table 5: Acceptable Contraception Methods for Females of Reproductive Potential
Pick from the following birth control options:

For patients who are considering pregnancy, consider alternative immunosuppressants with less potential for embryofetal toxicity. Risks and benefits of Майфортик should be discussed with the patient.

Dosage (Posology) and method of administration

The recommended dose of Майфортик is 720 mg administered twice daily (1440 mg total daily dose).

The recommended dose of Майфортик in conversion (at least 6 months post-transplant) pediatric patients age 5 years and older is 400 mg/m² body surface area (BSA) administered twice daily (up to a maximum dose of 720 mg administered twice daily).

Майфортик tablets should be taken on an empty stomach, 1 hour before or 2 hours after food intake.

Майфортик tablets should not be crushed, chewed, or cut prior to ingesting. The tablets should be swallowed whole in order to maintain the integrity of the enteric coating.

Pediatric patients with a BSA of 1.19 to 1.58 m² may be dosed either with three Майфортик 180 mg tablets, or one 180 mg tablet plus one 360 mg tablet twice daily (1080 mg daily dose). Patients with a BSA of > 1.58 m² may be dosed either with four Майфортик 180 mg tablets, or two Майфортик 360 mg tablets twice daily (1440 mg daily dose). Pediatric doses for patients with BSA < 1.19 m² cannot be accurately administered using currently available formulations of Майфортик tablets.