Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use
Patients receiving immunosuppressive regimens involving combinations of drugs, including Myfortic, are at increased risk of developing lymphomas and other malignancies, particularly of the skin (see section 4.8). 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 minimise 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.

Patients receiving Myfortic should be instructed to immediately report any evidence of infection, unexpected bruising, bleeding or any other manifestation of bone marrow depression.

Patients treated with immunosuppressants, including Myfortic, are at increased risk for opportunistic infections (bacterial, fungal, viral and protozoal), fatal infections and sepsis (see section 4.8). Among the opportunistic infections are BK virus associated nephropathy and JC virus associated progressive multifocal leukoencephalopathy (PML). 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. Mycophenolic acid has a cytostatic effect on B- and T-lymphocytes, therefore an increased severity of COVID-19 may occur, and appropriate clinical action should be considered.

There have been reports of hypogammaglobulinaemia in association with recurrent infections in patients receiving Myfortic in combination with other immunosuppressants. In some of these cases, switching MPA derivatives to an alternative immunosuppressant resulted in serum IgG levels returning to normal. Patients on Myfortic who develop recurrent infections should have their serum immunoglobulins measured. In cases of sustained, clinically relevant hypogammaglobulinaemia, appropriate clinical action should be considered taking into account the potent cytostatic effects that mycophenolic acid has on T- and B-lymphocytes.

There have been reports of bronchiectasis in patients who received Myfortic in combination with other immunosuppressants. In some of these cases, switching MPA derivatives to another immunosuppressant, resulted in improvement in respiratory symptoms. The risk of bronchiectasis may be linked to hypogammaglobulinaemia or to a direct effect on the lung.
There have been also isolated reports of interstitial lung disease (see section 4.8). It is recommended that patients who develop persistent pulmonary symptoms, such as cough and dyspnoea, are investigated for any evidence of underlying interstitial lung disease.

Reactivation of hepatitis B (HBV) or hepatitis C (HCV) have been reported in patients treated with immunosuppressants, including the mycophenolic acid (MPA) derivatives Myfortic and mycophenolate mofetil (MMF). 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 (which include mycophenolate mofetil and mycophenolate sodium) in combination with other immunosuppressants. The mechanism for MPA derivatives induced PRCA is unknown. PRCA may resolve with dose reduction or cessation of therapy. Changes to Myfortic therapy should only be undertaken under appropriate supervision in transplant recipients in order to minimise the risk of graft rejection (see Section 4.8).

Patients receiving Myfortic should be monitored for blood disorders (e.g. neutropenia or anemia - see section 4.8), which may be related to MPA itself, concomitant medications, viral infections, or some combination of these causes.

Patients taking Myfortic 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 blood disorders occur (e.g. neutropenia with absolute neutrophil count <1.5 x 103/µl or anemia) it may be appropriate to interrupt or discontinue Myfortic.

Patients should be advised that during treatment with MPA vaccinations may be less effective and the use of live attenuated vaccines should be avoided (see section 4.5).

Influenza vaccination may be of value. Prescribers should refer to national guidelines for influenza vaccination.

Because MPA derivatives have been associated with an increased incidence of digestive system adverse events, including infrequent cases of gastrointestinal tract ulceration and haemorrhage and perforation, Myfortic should be administered with caution in patients with active serious digestive system disease.

It is recommended that Myfortic not be administered concomitantly with azathioprine because concomitant administration of these drugs has not been evaluated.

Mycophenolic acid (as sodium salt) and mycophenolate mofetil should not be indiscriminately interchanged or substituted because of their different pharmacokinetic profiles.

Myfortic has been administered in combination with corticosteroids and ciclosporin.

There is limited experience with its concomitant use with induction therapies such as anti-T- lymphocyte globulin or basiliximab. The efficacy and safety of the use of Myfortic with other immunosuppressive agents (for example, tacrolimus) have not been studied.
The concomitant administration of Myfortic and drugs which interfere with enterohepatic circulation, for example cholestyramine or activated charcoal, may result in sub-therapeutic systemic MPA exposure and reduced efficacy.

Myfortic 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.

Myfortic therapy should not be initiated until a negative pregnancy test has been obtained.
Effective contraception must be used before beginning Myfortic therapy, during therapy and for six weeks following therapy discontinuation (see section 4.6).

Teratogenic effects
Mycophenolate is a powerful human teratogen. Spontaneous abortion (rate of 45 to 49%) and congenital malformations (estimated rate of 23 to 27%) have been reported following mycophenolate mofetil exposure during pregnancy. Therefore, Myfortic is contraindicated in pregnancy unless there are no suitable alternative treatments to prevent transplant rejection.
Female patients of childbearing potential should be made aware of the risks and follow the recommendations provided in section 4.6 (e.g., contraceptive methods, pregnancy testing) prior to, during, and after therapy with Myfortic. Physicians should ensure that women 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 section 4.6)

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

Because of robust clinical evidence showing a high risk of abortion and congenital malformations when mycophenolate mofetil is used in pregnancy every effort to avoid pregnancy during treatment should be taken. Therefore, women with childbearing potential must use at least one form of reliable contraception (section 4.3) before starting Myfortic therapy, during therapy and for six weeks after stopping the therapy, unless abstinence is the chosen method of contraception. Two complementary forms of contraception simultaneously are preferred to minimise the potential for contraceptive failure and unintended pregnancy.

For contraception advice for men see section 4.6.

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 at least 90 days following discontinuation of mycophenolate.

Myfortic contains sodium. This medicinal product contains 13 / 26 mg of sodium per tablet of Myfortic 180 / 360 mg, equivalent to 0.65 / 1.3 % of the WHO recommended maximum daily intake of 2 g sodium for an adult.

Excipients with known effect:
Myfortic contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Effects on Driving

4.7    Effects on ability to drive and use machines

Myfortic has minor influence on the ability to drive and use machines.