Myfortic Special Precautions

Patients with rare hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT): Mycophenolic acid (Myfortic) is an IMPDH (inosine monophosphate dehydrogenase) inhibitor. On theoretical grounds, it should therefore be avoided in patients with rare hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) such as Lesch-Nyhan and Kelley-Seegmiller syndrome.
Malignancies: Patients receiving immunosuppressive regimens involving combinations of drugs, including mycophenolic acid (Myfortic), 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 of skin cancer, exposure to sunlight and UV light should be limited by wearing protective clothing and using a high protection factor sunscreen.
Infections: Patients receiving mycophenolic acid (Myfortic) should be instructed to immediately report any evidence of infection, unexpected bruising, bleeding or any other manifestation of bone marrow depression.
Oversuppression of the immune system increases the susceptibility to infection including opportunistic infections, fatal infections and sepsis (see ADVERSE REACTIONS).
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 MMF. Monitoring infected patients for clinical and laboratory signs of active HBV or HCV infection is recommended.
Cases of progressive multifocal leukoencephalopathy (PML), sometimes fatal, have been reported in patients treated with MPA derivatives which include mycophenolate mofetil and mycophenolate sodium (see ADVERSE REACTIONS). The reported cases generally had risk factors for PML, including immunosuppressant therapies and impairment of immune functions. 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. Polyomavirus associated nephropathy (PVAN), especially due to BK virus infection, should be included in the differential diagnosis in immunosuppressed patients with deteriorating renal function (see ADVERSE REACTIONS). Consideration should be given to reducing the total immunosuppression in patients who develop PML or PVAN. In transplant patients, however, reduced immunosuppression may place the graft at risk.
Blood dyscrasias: Patients receiving mycophenolic acid (Myfortic) should be monitored for blood dyscrasias (e.g. neutropenia or anemia - see ADVERSE REACTIONS), which may be related to MPA itself, comedication, viral infections, or some combination of these causes. Patients should have complete blood cell counts weekly during the first month, twice monthly for the second and third months of treatment, then monthly throughout the first year. If blood dyscrasias occur (e.g. neutropenia with absolute neutrophil count <1.5 x 103 / micro L or anemia) it may be appropriate to interrupt or discontinue mycophenolic acid.
Cases of pure red cell aplasia (PRCA) have been reported in patients treated with MPA derivatives in combination with other immunosuppressants (see ADVERSE REACTIONS). 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. However, MPA derivatives may cause blood dyscrasias (see previous text). 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 mycophenolic acid (Myfortic) therapy should only be undertaken under appropriate supervision in transplant recipients in order to minimize the risk of graft rejection.
Vaccinations: Patients should be advised that vaccinations may be less effective during treatment with MPA and the use of the live attenuated vaccines should be avoided (see INTERACTIONS). Influenza vaccination may be of value. Prescribers should refer to national guidelines for influenza vaccination.
Gastrointestinal disorders: As MPA derivatives have been associated with an increased incidence of digestive system adverse events, including infrequent cases of gastrointestinal tract ulceration, hemorrhage and perforation, Mycophenolic acid should be administered with caution in patients with active serious digestive system disease.
Combination with other agents: Mycophenolic acid (Myfortic) has been administered in combination with the following agents in clinical trials: antithymocyte globulin, basiliximab, ciclosporin for microemulsion and corticosteroids. The efficacy and safety of the use of mycophenolic acid (Myfortic) with other immunosuppressants have not been studied.
Use in Pregnancy & Lactation: Use of mycophenolic acid during pregnancy is associated with an increased risk of pregnancy loss including spontaneous abortion and/or congenital malformations. Mycophenolic acid (Myfortic) therapy should not be initiated in females of reproductive potential until a negative pregnancy test has been obtained. For information on use in pregnancy and contraceptive requirements (see USE IN PREGNANCY & LACTATION).
Mycophenolic acid should not be used during breast-feeding (see USE IN PREGNANCY & LACTATION).