Micocept

Micocept

mycophenolic acid

Manufacturer:

Sandoz

Distributor:

Zuellig
Full Prescribing Info
Contents
Mycophenolate mofetil.
Description
Each capsule contains 250 mg of mycophenolate mofetil.
Each film-coated tablet contains 500 mg of mycophenolate mofetil.
Excipients/Inactive Ingredients: Cap 250 mg: Capsule content: Pregelatinised starch, Croscarmellose sodium, Povidone (K-90F), Magnesium stearate.
Capsule shell: Gelatine, Red iron oxide (E172), Yellow iron oxide (E172), Titanium dioxide (E171), FD&C Blue #2 (E132).
FC Tab 500 mg: Core content: Microcrystalline Cellulose, Povidone, Talc, Magnesium stearate, Croscarmellose sodium.
Coating content: Hypromellose, Hydroxypropyl cellulose, Titanium dioxide (E171), Macrogol (400), Iron Oxide Black (E172), Iron Oxide Red (E172).
Indications/Uses
Mycophenolate is indicated in combination with ciclosporin and corticosteroids for the prophylaxis of acute transplant rejection in patients receiving allogeneic renal, cardiac or hepatic transplants.
Dosage/Direction for Use
Treatment with Mycophenolate should be initiated and maintained by appropriately qualified transplant specialists.
Use in renal transplant: Adults: oral mycophenolate mofetil should be initiated within 72 hours following transplantation. The recommended dose in renal transplant patients is 1 g administered twice daily (2 g daily dose).
Children and adolescents (aged 2 to 18 years): the recommended dose of mycophenolate mofetil is 600 mg/m2 administered orally twice daily (up to a maximum of 2 g daily). Mycophenolate mofetil should only be prescribed to patients with a body surface area of at least 1.25 m2. Patients with a body surface area of 1.25 to 1.5 m2 may be prescribed mycophenolate mofetil at a dose of 750 mg twice daily (1.5 g daily dose). Patients with a body surface area greater than 1.5 m2 may be prescribed mycophenolate mofetil at a dose of 1 g twice daily (2 g daily dose). Mycophenolate mofetil 500 mg tablets should only be prescribed to patients with a body surface area greater than 1.5 m2, at a dose of 1 g twice daily (2 g daily dose). As some adverse reactions occur with greater frequency in this age group (see Adverse Reactions) compared with adults, temporary dose reduction or interruption may be required; these will need to take into account relevant clinical factors including severity of reaction.
Children (< 2 years): there are limited safety and efficacy data in children below the age of 2 years. These are insufficient to make dosage recommendations and therefore use in this age group is not recommended.
Use in cardiac transplant: Adults: oral mycophenolate mofetil should be initiated within 5 days following transplantation. The recommended dose in cardiac transplant patients is 1.5 g administered twice daily (3 g daily dose).
Children: no data are available for paediatric cardiac transplant patients.
Use in hepatic transplant: Adults: Intravenous mycophenolate mofetil should be administered for the first 4 days following hepatic transplant, with oral mycophenolate mofetil initiated as soon after this as it can be tolerated. The recommended oral dose in hepatic transplant patients is 1.5 g administered twice daily (3 g daily dose).
Children: no data are available for paediatric hepatic transplant patients.
Use in elderly (≥ 65 years): the recommended dose of 1 g administered twice a day for renal transplant patients and 1.5 g twice a day for cardiac or hepatic transplant patients is appropriate for the elderly.
Use in renal impairment: in renal transplant patients with severe chronic renal impairment (glomerular filtration rate < 25 ml/min/1.73 m2), outside the immediate post-transplant period, doses greater than 1 g administered twice a day should be avoided. These patients should also be carefully observed.
No dose adjustments are needed in patients experiencing delayed renal graft function post-operatively. No data are available for cardiac or hepatic transplant patients with severe chronic renal impairment.
Use in severe hepatic impairment: no dose adjustments are needed for renal transplant patients with severe hepatic parenchymal disease. No data are available for cardiac transplant patients with severe hepatic parenchymal disease.
Treatment during rejection episodes: MPA (mycophenolic acid) is the active metabolite of mycophenolate mofetil. Renal transplant rejection does not lead to changes in MPA pharmacokinetics; dosage reduction or interruption of mycophenolate mofetil is not required. There is no basis for mycophenolate mofetil dose adjustment following cardiac transplant rejection. No pharmacokinetic data are available during hepatic transplant rejection.
Method of administration: Oral administration.
Precautions to be taken before handling or administering the medicinal product: Because mycophenolate mofetil has demonstrated teratogenic effects in rats and rabbits.
Mycophenolate mofetil capsules should not be opened or crushed to avoid inhalation or direct contact with skin or mucous membranes of the powder contained in Mycophenolate mofetil capsules. If such contact occurs, wash thoroughly with soap and water; rinse eyes with plain water.
Mycophenolate tablets should not be crushed.
Overdosage
Reports of overdoses with mycophenolate mofetil have been received from clinical trials and during post-marketing experience. In many of these cases, no adverse events were reported. In those overdose cases in which adverse events were reported, the events fall within the known safety profile of the medicinal product.
It is expected that an overdose of mycophenolate mofetil could possibly result in oversuppression of the immune system and increase susceptibility to infections and bone marrow suppression (see Precautions). If neutropenia develops, dosing with mycophenolate mofetil should be interrupted or the dose reduced (see Precautions).
Haemodialysis would not be expected to remove clinically significant amounts of MPA or MPAG. Bile acid sequestrants, such as cholestyramine, can remove MPA by decreasing the enterohepatic recirculation of the drug.
Contraindications
Mycophenolate mofetil should not be given to patients with hypersensitivity to mycophenolate mofetil, mycophenolic acid or to any of the excipients listed in Description. Hypersensitivity reactions to mycophenolate mofetil have been observed (see Adverse Reactions).
Mycophenolate mofetil should not be given to women of childbearing potential who are not using highly effective contraception (see Use in Pregnancy & Lactation).
Mycophenolate mofetil treatment should not be initiated in women of child bearing potential without providing a pregnancy test result to rule out unintended use in pregnancy (see Use in Pregnancy & Lactation).
Mycophenolate mofetil should not be used in pregnancy unless there is no suitable alternative treatment to prevent transplant rejection (see Use in Pregnancy & Lactation).
Mycophenolate mofetil should not be given to women who are breastfeeding (see Use in Pregnancy & Lactation).
Special Precautions
Neoplasms: Patients receiving immunosuppressive regimens involving combinations of medicinal products, including mycophenolate mofetil, are at increased risk of developing lymphomas and other malignancies, particularly of the skin (see Adverse Reactions). The risk appears to be related to the intensity and duration of immunosuppression rather than to the use of any specific agent. As general advice to minimize the 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.
Infections: Patients treated with immunosuppressants, including mycophenolate mofetil, are at increased risk for opportunistic infections (bacterial, fungal, viral and protozoal), fatal infections and sepsis (see Adverse Reactions). Such infections include latent viral reactivation, such as hepatitis B or hepatitis C reactivation and infections caused by polyomaviruses (BK virus associated nephropathy, JC virus associated progressive multifocal leukoencephalopathy (PML). Cases of hepatitis due to reactivation of hepatitis B or hepatitis C have been reported in carrier patients treated with immunosuppressants. These infections are often related to a high total immunosuppressive burden and may lead to serious or fatal conditions that physicians should consider in the differential diagnosis in immunosuppressed patients with deteriorating renal function or neurological symptoms.
There have been reports of hypogammaglobulinaemia in association with recurrent infections in patients receiving mycophenolate mofetil in combination with other immunosuppressants. In some of these cases switching mycophenolate mofetil to an alternative immunosuppressant resulted in serum IgG levels returning to normal. Patients on mycophenolate mofetil who develop recurrent infections should have their serum immunoglobulins measured. In cases of sustained, clinically relevant hypogammaglobulinaemia, appropriate clinical actions should be considered taking into account the potent cytostatic effects that mycophenolic acid has on T- and B-lymphocytes.
There have been published reports of bronchiectasis in adults and children who received mycophenolate mofetil in combination with other immunosuppressants. In some of these cases switching mycophenolate mofetil to another immunosuppressant resulted in improvements in respiratory symptoms. The risk of bronchiectasis may be linked to hypogammaglobulinaemia or to a direct effect on the lung. There have also been isolated reports of interstitial lung disease and pulmonary fibrosis, some of which were fatal. It is recommended that patients who develop persistent pulmonary symptoms, such as cough and dyspnoea, are investigated.
Blood and immune system: Patients receiving mycophenolate mofetil should be monitored for neutropenia, which may be related to mycophenolate mofetil itself, concomitant medications, viral infections, or some combination of these causes. Patients taking mycophenolate mofetil should have complete blood counts weekly during the first month, twice monthly for the second and third months of treatment, then monthly through the first year. If neutropenia develops (absolute neutrophil count < 1.3 x 103/μl) it may be appropriate to interrupt or discontinue mycophenolate mofetil.
Cases of pure red cell aplasia (PRCA) have been reported in patients treated with mycophenolate mofetil in combination with other immunosuppressants. The mechanism for mycophenolate mofetil induced PRCA is unknown. PRCA may resolve with dose reduction or cessation of mycophenolate mofetil therapy. Changes to mycophenolate mofetil therapy should only be undertaken under appropriate supervision in transplant recipients in order to minimise the risk of graft rejection (see Adverse Reactions).
Patients receiving mycophenolate mofetil should be instructed to report immediately any evidence of infection, unexpected bruising, bleeding or any other manifestation of bone marrow depression.
Patients should be advised that during treatment with mycophenolate mofetil vaccinations may be less effective and the use of live attenuated vaccines should be avoided (see Interactions).
Influenza vaccination may be of value. Prescribers should refer to national guidelines for influenza vaccination.
Gastro-intestinal: Because mycophenolate mofetil has been associated with an increased incidence of digestive system adverse events, including infrequent cases of gastrointestinal tract ulceration, haemorrhage and perforation, mycophenolate mofetil should be administered with caution in patients with active serious digestive system disease.
Mycophenolate mofetil is an IMPDH (inosine monophosphate dehydrogenase) inhibitor. Therefore, it should be avoided in patients with rare hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) such as Lesch-Nyhan and Kelley-Seegmiller syndrome.
Interactions: Caution should be exercised when switching combination therapy from regimens containing immunosuppressants, which interfere with MPA enterohepatic recirculation e.g. ciclosporin to others devoid of this effect e.g. sirolimus, belatacept, or vice versa, as this might result in changes of MPA exposure. Drugs of other classes which interfere with MPA's enterohepatic cycle e.g. cholestyramine should be used with caution due to their potential to reduce the plasma levels and efficacy of mycophenolate mofetil (see Interactions).
It is recommended that mycophenolate mofetil not be administered concomitantly with azathioprine because such concomitant administration has not been studied.
FC tab 500 mg: In view of the significant reduction in the AUC of MPA by colestyramine, caution should be used in the concomitant administration of mycophenolate mofetil with medicinal products that interfere with enterohepatic recirculation because of the potential to reduce the efficacy of mycophenolate mofetil.
The risk: benefit of mycophenolate mofetil in combination with tacrolimus or sirolimus has not been established (see Interactions).
Special populations: Elderly patients may be at an increased risk of adverse events such as certain infections (including cytomegalovirus tissue invasive disease) and possibly gastrointestinal haemorrhage and pulmonary oedema, compared with younger individuals (see Adverse Reactions).
Teratogenic effects: Mycophenolate is a powerful human teratogen. Spontaneous abortion (rate of 45-49%) and congenital malformations (estimated rate of 23-27%) have been reported following MMF exposure during pregnancy. Therefore mycophenolate mofetil is contraindicated in pregnancy unless there are no suitable alternative treatments to prevent transplant rejection. Female and male patients of reproductive potential should be made aware of the risks and follow the recommendations provided in Use in Pregnancy & Lactation (e.g. contraceptive methods, pregnancy testing) prior to, during, and after therapy with mycophenolate mofetil. Physicians should ensure that women and men taking mycophenolate understand the risk of harm to the baby, the need for effective contraception, and the need to immediately consult their physician if there is a possibility of pregnancy.
Contraception (see Use in Pregnancy & Lactation): Because of the genotoxic and teratogenic potential of mycophenolate mofetil, women with childbearing potential should use two reliable forms of contraception simultaneously before starting mycophenolate mofetil therapy, during therapy, and for six weeks after stopping the therapy; unless abstinence is the chosen method of contraception (see Interactions).
Sexually active men are recommended to use condoms during treatment and for at least 90 days after cessation of treatment. Condom use applies for both reproductively competent and vasectomized men, because the risks associated with the transfer of seminal fluid also apply to men who have had a vasectomy. In addition, female partners of male patients treated with mycophenolate mofetil are recommended to use highly effective contraception during treatment and for a total of 90 days after the last dose of mycophenolate mofetil.
Additional precautions: Patients should not donate blood during therapy or for at least 6 weeks following discontinuation of mycophenolate. Men should not donate semen during therapy or for 90 days following discontinuation of mycophenolate.
Effects on ability to drive and use machines: No studies on the effects on the ability to drive and use machines have been performed.
The pharmacodynamic profile and the reported adverse reactions indicate that an effect is unlikely.
Cap 250 mg: Educational materials: In order to assist patients in avoiding foetal exposure to mycophenolate and to provide additional important safety information, the Marketing Authorisation holder will provide educational materials to healthcare professionals. The educational materials will reinforce the warnings about the teratogenicity of mycophenolate, provide advice on contraception before therapy is started and guidance on the need for pregnancy testing. Full patient information about the teratogenic risk and the pregnancy prevention measures should be given by the physician to women of childbearing potential and, as appropriate, to male patients.
Use In Pregnancy & Lactation
Contraception in males and females: Mycophenolate mofetil is contraindicated in women of childbearing potential who are not using highly effective contraception.
Because of the genotoxic and teratogenic potential of mycophenolate mofetil, women with childbearing potential should use two reliable forms of contraception simultaneously before starting and during therapy, and for six weeks after stopping the therapy; unless abstinence is the chosen method of contraception (see Interactions).
Sexually active (including vasectomized) men are recommended to use condoms during treatment, and for at least 90 days after cessation of treatment. Condom use applies for both reproductively competent and vasectomized men, because the risks associated with the transfer of seminal fluid also apply to men who have had a vasectomy. In addition, female partners of male patients treated with mycophenolate mofetil are also recommended to use highly effective contraception for the same period and for a total of 90 days after the last dose of mycophenolate mofetil.
Pregnancy: The use of mycophenolate mofetil is contraindicated during pregnancy unless there is no suitable alternative treatment to prevent transplant rejection.
Treatment should not be initiated without providing a negative pregnancy test result to rule out unintended use in pregnancy (see Contraindications).
Female and male patients of reproductive potential must be made aware of the increased risk of pregnancy loss and congenital malformations at the beginning of the treatment and must be counseled regarding pregnancy prevention and planning.
Before starting mycophenolate mofetil treatment, women of child bearing potential should undergo pregnancy testing in order to exclude unintended exposure of the embryo to mycophenolate. Two serum or urine pregnancy tests with a sensitivity of at least 25 mIU/mL are recommended; the second test should be performed 8-10 days after the first one and immediately before starting mycophenolate. Pregnancy tests should be repeated as clinically required (e.g. after any gap in contraception is reported). Results of all pregnancy tests should be discussed with the patient. Patients should be instructed to consult their physician immediately should pregnancy occur.
Mycophenolate is a powerful human teratogen, with an increased risk of spontaneous abortions and congenital malformations in case of exposure during pregnancy.
Spontaneous abortions have been reported in 45 to 49% of pregnant women exposed to mycophenolate mofetil, compared to a reported rate of between 12 and 33% in solid organ transplant patients treated with immunosuppressants other than mycophenolate mofetil.
Based on literature reports, malformations occurred in 23 to 27% of live births in women exposed to mycophenolate mofetil during pregnancy (compared to 2 to 3 % of live births in the overall population and approximately 4 to 5% of live births in solid organ transplant recipients treated with immunosuppressants other than mycophenolate mofetil).
Congenital malformations, including reports of multiple malformations, have been observed post-marketing in children of patients exposed to mycophenolate mofetil in combination with other immunosuppressants during pregnancy. The following malformations were most frequently reported: Abnormalities of the ear (e.g. abnormally formed or absent external/middle ear), external auditory canal atresia; Congenital heart disease such as atrial and ventricular septal defects; Facial malformations such as cleft lip, cleft palate, micrognathia and hypertelorism of the orbits; Abnormalities of the eye (e.g. coloboma); Malformations of the fingers (e.g. polydactyly, syndactyly); Tracheo-Oesophageal malformations (e.g. oesophageal atresia); Nervous system malformations such as spina bifida; Renal abnormalities.
In addition there have been isolated reports of the following malformations: Microphthalmia; congenital choroid plexus cyst; septum pellucidum agenesis; olfactory nerve agenesis.
Studies in animals have shown reproductive toxicity (see Pharmacology under Actions).
Breast-feeding: Mycophenolate mofetil has been shown to be excreted in the milk of lactating rats. It is not known whether this substance is excreted in human milk. Because of the potential for serious adverse reactions to mycophenolate mofetil in breast-fed infants, mycophenolate mofetil is contraindicated in nursing mothers (see Contraindications).
Adverse Reactions
The following undesirable effects cover adverse reactions from clinical trials: The principal adverse reactions associated with the administration of mycophenolate mofetil in combination with ciclosporin and corticosteroids include diarrhoea, leucopenia, sepsis and vomiting and there is evidence of a higher frequency of certain types of infections (see Precautions).
Malignancies: Patients receiving immunosuppressive regimens involving combinations of medicinal products, including mycophenolate mofetil, are at increased risk of developing lymphomas and other malignancies, particularly of the skin (see Precautions). Lymphoproliferative disease or lymphoma developed in 0.6% of patients receiving mycophenolate mofetil (2 g or 3 g daily) in combination with other immunosuppressants in controlled clinical trials of renal (2 g data), cardiac and hepatic transplant patients followed for at least 1 year. Non-melanoma skin carcinomas occurred in 3.6% of patients; other types of malignancy occurred in 1.1% of patients. Three-year safety data in renal and cardiac transplant patients did not reveal any unexpected changes in incidence of malignancy compared to the 1-year data. Hepatic transplant patients were followed for at least 1 year, but less than 3 years.
Opportunistic infections: All transplant patients are at increased risk of opportunistic infections; the risk increased with total immunosuppressive load (see Precautions). The most common opportunistic infections in patients receiving mycophenolate mofetil (2 g or 3 g daily) with other immunosuppressants in controlled clinical trials of renal (2 g data), cardiac and hepatic transplant patients followed for at least 1 year were candida mucocutaneous, CMV viraemia/syndrome and Herpes simplex. The proportion of patients with CMV viraemia/syndrome was 13.5%.
Paediatric population (children and adolescents [aged 2 to 18 years]): The type and frequency of adverse reactions in a clinical study, which recruited 92 paediatric patients aged 2 to 18 years who were given 600 mg/m2 mycophenolate mofetil orally twice daily, were generally similar to those observed in adult patients given 1 g mycophenolate mofetil twice daily. However, the following treatment-related adverse events were more frequent in the paediatric population, particularly in children under 6 years of age, when compared to adults: diarrhoea, sepsis, leucopenia, anaemia and infection.
Elderly patients (≥65 years): Elderly patients (≥65 years) may generally be at increased risk of adverse reactions due to immunosuppression. Elderly patients receiving mycophenolate mofetil as part of a combination immunosuppressive regimen may be at increased risk of certain infections (including cytomegalovirus tissue invasive disease) and possibly gastrointestinal haemorrhage and pulmonary oedema, compared to younger individuals.
Other adverse reactions: Adverse reactions, probably or possibly related to mycophenolate mofetil, reported in ≥1/10 and in ≥1/100 to <1/10 of patients treated with mycophenolate mofetil in the controlled clinical trials of renal (2 g data), cardiac and hepatic transplant patients are listed in the following table.
Adverse Reactions, Probably or Possibly Related to Mycophenolate mofetil, Reported in Patients Treated with Mycophenolate mofetil in Renal, Cardiac and Hepatic Clinical Trials when Used in Combination with Ciclosporin and Corticosteroids.
Within the system organ classes, undesirable effects are listed under heading of frequency, using the following categories: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to<1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. (See Table.)

Click on icon to see table/diagram/image

The following undesirable effects cover adverse reactions from post-marketing experience: The types of adverse reactions reported during post-marketing with mycophenolate mofetil are similar to those seen in the controlled renal, cardiac and hepatic transplant studies. Additional adverse reactions reported during post-marketing are described below with the frequencies reported within brackets if known.
Gastrointestinal: gingival hyperplasia (≥1/100 to <1/10), colitis including cytomegalovirus colitis (≥1/100 to <1/10), pancreatitis (≥1/100 to <1/10) and intestinal villous atrophy.
Infections: serious life-threatening infections including meningitis, endocarditis, tuberculosis and atypical mycobacterial infection. Cases of BK virus associated nephropathy, as well as cases of JC virus associated progressive multifocal leucoencephalopathy (PML), have been reported in patients treated with immunosuppressants, including mycophenolate mofetil.
Agranulocytosis (≥1/1,000 to <1/100) and neutropenia have been reported; therefore, regular monitoring of patients taking mycophenolate mofetil is advised (see Precautions). There have been reports of aplastic anaemia and bone marrow depression in patients treated with mycophenolate mofetil, some of which have been fatal.
Blood and lymphatic system disorder: Cases of pure red cell aplasia (PRCA) have been reported in patients treated with mycophenolate mofetil (see Precautions).
Isolated cases of abnormal neutrophil morphology, including the acquired Pelger-Huet anomaly, have been observed in patients treated with mycophenolate mofetil. These changes are not associated with impaired neutrophil function. These changes may suggest a 'left shift' in the maturity of neutrophils in haematological investigations, which may be mistakenly interpreted as a sign of infection in immunosuppressed patients such as those that receive mycophenolate mofetil.
Hypersensitivity: Hypersensitivity reactions, including angioneurotic oedema and anaphylactic reaction, have been reported.
Pregnancy, puerperium and perinatal conditions: Cases of spontaneous abortions have been reported in patients exposed to mycophenolate mofetil, mainly in the first trimester, see Use in Pregnancy & Lactation.
Congenital disorders: Congenital malformations have been observed post-marketing in children of patients exposed to mycophenolate mofetil in combination with other immunosuppressants, see Use in Pregnancy & Lactation.
Respiratory, thoracic and mediastinal disorders: There have been isolated reports of interstitial lung disease and pulmonary fibrosis in patients treated with mycophenolate mofetil in combination with other immunosuppressants, some of which have been fatal. There have also been reports of bronchiectasis in children and adults (frequency not known).
Immune system disorders: Hypogammaglobulinaemia has been reported in patients receiving mycophenolate mofetil in combination with other immunosuppressants (frequency not known).
Drug Interactions
Aciclovir: Higher aciclovir plasma concentrations were observed when mycophenolate mofetil was administered with aciclovir in comparison to the administration of aciclovir alone. The changes in MPAG (the phenolic glucuronide of MPA) pharmacokinetics (MPAG increased by 8%) were minimal and are not considered clinically significant. Because MPAG plasma concentrations are increased in the presence of renal impairment, as are aciclovir concentrations, the potential exists for mycophenolate mofetil and aciclovir, or its prodrugs, e.g. valaciclovir, to compete for tubular secretion and further increases in concentrations of both substances may occur.
Antacids and proton pump inhibitors (PPIs): Decreased mycophenolic acid (MPA) exposure has been observed when antacids, such as magnesium and aluminium hydroxides, and PPIs, including lansoprazole and pantoprazole, were administered with mycophenolate mofetil. When comparing rates of transplant rejection or rates of graft loss between mycophenolate mofetil patients taking PPIs vs. mycophenolate mofetil patients not taking PPIs, no significant differences were seen. These data support extrapolation of this finding to all antacids because the reduction in exposure when mycophenolate mofetil was co-administered with magnesium and aluminium hydroxides is considerably less than when mycophenolate mofetil was co-administered with PPIs.
Colestyramine: Following single dose administration of 1.5 g of mycophenolate mofetil to normal healthy subjects pre-treated with 4 g TID (three times a day) of colestyramine for 4 days, there was a 40% reduction in the AUC of MPA (see Precautions). Caution should be used during concomitant administration because of the potential to reduce efficacy of mycophenolate mofetil.
Medicinal products that interfere with enterohepatic circulation: Caution should be used with medicinal products that interfere with enterohepatic circulation because of their potential to reduce the efficacy of mycophenolate mofetil.
Ciclosporin A: Ciclosporin A (CsA) pharmacokinetics are unaffected by mycophenolate mofetil. In contrast, if concomitant ciclosporin treatment is stopped, an increase in MPA AUC of around 30% should be expected. CsA interferes with MPA enterohepatic recycling, resulting in reduced MPA exposures by 30-50% in renal transplant patients treated with mycophenolate mofetil and CsA compared with patients receiving sirolimus or belatacept and similar doses of mycophenolate mofetil (see Precautions). Conversely, changes of MPA exposure should be expected when switching patients from CsA to one of the immunosuppressants which does not interfere with MPA's enterohepatic cycle.
Telmisartan: Concomitant administration of telmisartan and mycophenolate mofetil resulted in an approximately 30% decrease of MPA concentrations. Telmisartan changes MPA's elimination by enhancing PPAR gamma (peroxisome proliferator-activated receptor gamma) expression, which in turn results in an enhanced UGT1A9 expression and activity. When comparing rates of transplant rejection, rates of graft loss or adverse event profiles between mycophenolate mofetil patients with and without concomitant telmisartan medication, no clinical consequences of the pharmacokinetic drug-drug interaction were seen.
Ganciclovir: Based on the results of a single dose administration study of recommended doses of oral mycophenolate and IV ganciclovir and the known effects of renal impairment on the pharmacokinetics of mycophenolate mofetil (see Dosage & Administration) and ganciclovir, it is anticipated that co-administration of these agents (which compete for mechanisms of renal tubular secretion) will result in increases in MPAG and ganciclovir concentration. No substantial alteration of MPA pharmacokinetics is anticipated and mycophenolate mofetil dose adjustment is not required. In patients with renal impairment in which mycophenolate mofetil and ganciclovir or its prodrugs, e.g. valganciclovir, are co-administered the dose recommendations for ganciclovir should be observed and patients monitored carefully.
Oral contraceptives: The pharmacokinetics and pharmacodynamics of oral contraceptives were unaffected by coadministration of mycophenolate mofetil (see Pharmacology under Actions).
Rifampicin: In patients not also taking ciclosporin, concomitant administration of mycophenolate mofetil and rifampicin resulted in a decrease in MPA exposure (AUC0-12h) of 18% to 70%. It is recommended to monitor MPA exposure levels and to adjust mycophenolate mofetil doses accordingly to maintain clinical efficacy when rifampicin is administered concomitantly.
Sevelamer: Decrease in MPA Cmax and AUC0-12h by 30% and 25%, respectively, were observed when mycophenolate mofetil was concomitantly administered with sevelamer without any clinical consequences (i.e. graft rejection). It is recommended, however, to administer mycophenolate mofetil at least one hour before or three hours after sevelamer intake to minimise the impact on the absorption of MPA. There is no data on mycophenolate mofetil with phosphate binders other than 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 concomitantly administered with norfloxacin and metronidazole separately. However, norfloxacin and metronidazole combined reduced the MPA exposure by approximately 30% following a single dose of mycophenolate mofetil.
Ciprofloxacin and amoxicillin plus clavulanic acid: Reductions in pre-dose (trough) MPA concentrations of about 50% have been reported in renal transplant recipients in the days immediately following commencement of oral ciprofloxacin or amoxicillin plus clavulanic acid. This effect tended to diminish with continued antibiotic use and to cease within a few days of their discontinuation. The change in predose level may not accurately represent changes in overall MPA exposure. Therefore, a change in the dose of mycophenolate mofetil should not normally be necessary in the absence of clinical evidence of graft dysfunction. However, close clinical monitoring should be performed during the combination and shortly after antibiotic treatment.
Tacrolimus: in hepatic transplant patients initiated on mycophenolate mofetil and tacrolimus, the AUC and Cmax of MPA, the active metabolite of mycophenolate mofetil, were not significantly affected by coadministration with tacrolimus. In contrast, there was an increase of approximately 20% in tacrolimus AUC when multiple doses of mycophenolate mofetil (1.5 g BID) were administered to patients taking tacrolimus. However, in renal transplant patients, tacrolimus concentration did not appear to be altered by mycophenolate mofetil (see Precautions).
Other interactions: co-administration of probenecid with mycophenolate mofetil in monkeys raises plasma AUC of MPAG by 3-fold. Thus, other substances known to undergo renal tubular secretion may compete with MPAG and thereby raise plasma concentrations of MPAG or the other substance undergoing tubular secretion.
Live vaccines: live vaccines should not be given to patients with an impaired immune response. The antibody response to other vaccines may be diminished (see Precautions).
Paediatric population: Interaction studies have only been performed in adults.
MIMS Class
ATC Classification
L04AA06 - mycophenolic acid ; Belongs to the class of selective immunosuppressive agents. Used to induce immunosuppression.
Presentation/Packing
Cap 250 mg (blue opaque cap-orange opaque body containing white to off white coloured powder) x 50's. FC tab 500 mg (lavender coloured, biconvex, plain on both sides) x 50's.
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