CellCept Special Precautions

General: Neoplasms: As in all patients receiving immunosuppressive regimens involving combinations of drugs, patients receiving Mycophenolate mofetil (CellCept) as part of an immunosuppressive regimen 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 with all patients at an 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.
Infections: Oversuppression of the immune system can also increase susceptibility to infection including opportunistic infections, fatal infections and sepsis (see Adverse Reactions). Such infections include latent viral reactivation, such as hepatitis B or hepatitis C reactivation, or infections caused by polyomaviruses. Cases of hepatitis due to reactivation of hepatitis B or hepatitis C have been reported in carrier patients treated with immunosuppressants. Cases of Progressive Multifocal Leukoencephalopathy (PML) associated with the JC virus, sometimes fatal, have been reported in Mycophenolate mofetil (CellCept) treated patients. The reported cases generally had risk factors for PML, including 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.
BK virus-associated nephropathy has been observed during the use of Mycophenolate mofetil (CellCept) in patients post renal transplant. This infection can be associated with serious outcomes, sometimes leading to renal graft loss. Patient monitoring may help detect patients at risk for BK virus-associated nephropathy. Due to the cytostatic effect of Mycophenolate mofetil (CellCept) on B- and T-lymphocytes, increased severity of COVID-19 may occur. Dose reduction or discontinuation of Mycophenolate mofetil (CellCept) should be considered for patients who develop evidence of BK virus-associated nephropathy, or in cases of clinically significant COVID-19.
Blood and immune system: Cases of pure red cell aplasia (PRCA) have been reported in patients treated with Mycophenolate mofetil (CellCept) in combination with other immunosuppressive agents. The mechanism for mycophenolate mofetil induced PRCA is unknown; the relative contribution of other immunosuppressants and their combinations in an immunosuppression regimen are also unknown. In some cases PRCA was found to be reversible with dose reduction or cessation of Mycophenolate mofetil (CellCept) therapy. In transplant patients however reduced immunosuppression may place the graft at risk.
Patients receiving Mycophenolate mofetil (CellCept) should be instructed to report immediately any evidence of infection, unexpected bruising, bleeding or any other manifestation of bone marrow depression.
Patients on Mycophenolate mofetil (CellCept) should have complete blood counts weekly during the first month of treatment, twice monthly for the second and third months, then monthly through the first year. In particular, patients receiving Mycophenolate mofetil (CellCept) should be monitored for neutropenia. The development of neutropenia may be related to Mycophenolate mofetil (CellCept), concomitant medications, viral infection or some combination of these causes (see Special Dosage Instructions under Dosage & Administration). If neutropenia develops (absolute neutrophil count <1.3 x 10³/μL), dosing with Mycophenolate mofetil (CellCept) should be interrupted or the dose should be reduced and the patient carefully observed (see Special Dosage Instructions under Dosage & Administration).
Blood Donation: Patients should not donate blood during therapy and for at least 6 weeks following discontinuation of Mycophenolate mofetil (CellCept).
Vaccination: Patients should be advised that during treatment with Mycophenolate mofetil (CellCept) 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: Mycophenolate mofetil (CellCept) has been associated with an increased incidence of digestive system adverse events, including infrequent cases of gastrointestinal tract ulceration, hemorrhage, and perforation. Mycophenolate mofetil (CellCept) should be administered with caution in patients with active digestive system disease.
Mycophenolate mofetil (CellCept) is an inosine monophosphate dehydrogenase (IMPDH) 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. tacrolimus, sirolimus, belatacept, or vice versa, as this might result in changes of MPA exposure (see Interactions). Therapeutic drug monitoring of MPA may be appropriate when switching combination therapy (e.g. from ciclosporin to tacrolimus or vice versa) or to ensure adequate immunosuppression in patients with high immunological risk (e.g. risk of rejection, treatment with antibiotics, addition or removal of an interacting medication).
Drugs which interfere with MPA's enterohepatic cycle (e.g. cholestyramine, sevelamer, antibiotics) should be used with caution due to their potential to reduce the plasma levels and efficacy of Mycophenolate mofetil (CellCept) (see Interactions). Sevelamer and other calcium free phosphate binders should be taken 2 hours after Mycophenolate mofetil (CellCept) intake to minimize the impact on the absorption of MPA.
It is recommended that Mycophenolate mofetil (CellCept) should not be administered concomitantly with azathioprine because both have the potential to cause bone marrow suppression and such concomitant administration has not been studied.
Special Populations: Semen Donation: Men should not donate semen during therapy and for 90 days following discontinuation of Mycophenolate mofetil (CellCept).
Drug Abuse and Dependence: There is no data available to show that Mycophenolate mofetil (CellCept) has the potential for drug abuse or dependence.
Ability to Drive and Use Machines: Mycophenolate mofetil (CellCept) may have a moderate influence on the ability to drive and use machines.
Patients should be advised to use caution when driving or using machines if they experience adverse drug reactions such as somnolence, confusion, dizziness, tremor, or hypotension during treatment with Mycophenolate mofetil (CellCept) (see Adverse Reactions).
Renal Impairment: See Dosage & Administration and Pharmacology: Pharmacokinetics under Actions.
Hepatic Impairment: See Dosage & Administration and Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions.
Use in Pregnancy & Lactation: Mycophenolate mofetil (CellCept) is contraindicated in pregnancy and during breastfeeding (see Pregnancy and Lactation under Use in Pregnancy & Lactation).
Use in Children: See Dosage & Administration, Adverse Reactions, and Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions.
Use in the Elderly: Geriatric patients may be at an increased risk of adverse events such as certain infections (including cytomegalovirus tissue invasive disease) and possibly gastrointestinal hemorrhage and pulmonary edema, compared with younger individuals (see Adverse Reactions).
See Dosage & Administration, previous text, Adverse Reactions, and Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions.