Myfortic Special Precautions

Patients with rare hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT): Myfortic is an IMPDH (inosine monophosphate dehydrogenase) inhibitor. On theoretical grounds, it should therefore be avoided in patients with a 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 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 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 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 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 taking Myfortic 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 Myfortic.
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 previously mentioned). 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 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, Myfortic should be administered with caution in patients with active serious digestive system disease.
Combination with other agents: 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 Myfortic with other immunosuppressants have not been studied.
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 mg of sodium per tablet of Myfortic 180 mg, equivalent to 0.65% of the WHO recommended maximum daily intake of 2 g sodium for an adult.
This medicinal product contains 26 mg of sodium per tablet of Myfortic 360 mg, equivalent to 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.
Use in Pregnancy, lactation, females and males of reproductive potential: 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 Use in Pregnancy & Lactation).
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 under Use in Pregnancy & Lactation (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 Use in Pregnancy & Lactation): Because of robust clinical evidence showing a high risk of abortion and congenital malformations when mycophenolate mofetil is used in pregnancy effort to avoid pregnancy during treatment should be taken. Therefore women with childbearing potential must use at least one form reliable contraception (see Contraindications) 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 Use in Pregnancy & Lactation.
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.