MYCOPHENOLATE MOFETIL TILLOMED

Treatment with Mycophenolate mofetil should be initiated and maintained by appropriately qualified transplant specialists. Posology Use in renal transplant Adults 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). Paediatric population 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).

25m2. 5 g daily dose). 5 m2 may be prescribed Mycophenolate mofetil at a dose of 1 g twice daily (2 g daily dose). 8) 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.

Paediatric population < 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 Mycophenolate mofetil should be initiated within 5 days following transplantation.

5 g administered twice daily (3 g daily dose). Paediatric population No data are available for paediatric cardiac transplant patients. Use in hepatic transplant Adults IV 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.

5 g administered twice daily (3 g daily dose). Paediatric population No data are available for paediatric hepatic transplant patients. 5 g twice a day for cardiac or hepatic transplant patients is appropriate for the elderly. 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. 2). No data are available for cardiac or hepatic transplant patients with severe chronic renal impairment. 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 Mycophenolic acid (MPA) 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.

Summary of safety profile An estimated total of 1557 patients received mycophenolate mofetil during five clinical trials in the prevention of acute organ rejection. Of these, 991 were included in the three renal studies, 277 were included in one hepatic study, and 289 were included in one cardiac study.

Azathioprine was the comparator used in the hepatic and cardiac studies and in two of the renal studies whilst the other renal study was placebo-controlled. Patients in all study arms also received cyclosporine and corticosteroids. 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.

1%) were among the most common and/or serious adverse drug reactions associated with the administration of mycophenolate mofetil in combination with ciclosporin and corticosteroids. 4). Tabulated list of adverse reactions The adverse drug reactions from clinical trials and post-marketing experience are listed in Table 1, by MedDRA system organ class (SOC) along with their frequencies.

The corresponding frequency category for each adverse reaction is based on the following convention: 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) and not known (cannot be estimated from the available data).

Due to the large differences observed in the frequency of certain ADRs across the different transplant indications, frequency is presented separately for renal, hepatic and cardiac transplant patients. Table 1 Adverse reactions Adverse drug reaction (MedDRA) System Organ Class Renal transplant n = 991 Hepatic transplant n = 277 Cardiac transplant n = 289 Frequency Frequency Frequency Infections and infestations Bacterial infections Very Common Very Common Very Common Fungal infections Common Very Common Very Common Protozoal infections Uncommon Uncommon Uncommon Viral infections Very Common Very Common Very Common Neoplasms benign, malignant and unspecified (including cysts and polyps) Benign neoplasm of skin Common Common Common Lymphoma Uncommon Uncommon Uncommon Lymphoproliferative disorder Uncommon Uncommon Uncommon Neoplasm Common Common Common Skin Cancer Common Uncommon Common Blood and lymphatic system disorders Anemia Very Common Very Common Very Common Aplasia pure red cell Uncommon Uncommon Uncommon Bone marrow failure Uncommon Uncommon Uncommon Ecchymosis Common Common Very Common Leukocytosis Common Very Common Very Common Leukopenia Very Common Very Common Very Common Pancytopenia Common Common Uncommon Pseudolymphoma Uncommon Uncommon Common Thrombocytopenia Common Very Common Very Common Metabolism and nutrition disorders Acidosis Common Common Very Common Hypercholesterolemia Very Common Common Very Common Hyperglycemia Common Very Common Very Common Hyperkalemia Common Very Common Very Common Hyperlipidemia Common Common Very Common Hypocalcemia Common Very Common Common Hypokalemia Common Very Common Very Common Hypomagnesemia Common Very Common Very Common Hypophosphatemia Very Common Very Common Common Hyperuricaemia Common Common Very Common Gout Common Common Very Common Weight decreased Common Common Common Psychiatric disorders Confusional state Common Very Common Very Common Depression Common Very Common Very Common Insomnia Common Very Common Very Common Agitation Uncommon Common Very Common Anxiety Common Very Common Very Common Thinking abnormal Uncommon Common Common Nervous system disorders Dizziness Common Very Common Very Common Headache Very Common Very Common Very Common Hypertonia Common Common Very Common Paresthesia Common Very Common Very Common Somnolence Common Common Very Common Tremor Common Very Common Very Common Convulsion Common Common Common Dysgeusia Uncommon Uncommon Common Cardiac disorders Tachycardia Common Very Common Very Common Vascular disorders Hypertension Very Common Very Common Very Common Hypotension Common Very Common Very Common Lymphocele Uncommon Uncommon Uncommon Venous thrombosis Common Common Common Vasodilatation Common Common Very Common Respiratory, thoracic and mediastinal disorders Bronchiectasis Uncommon Uncommon Uncommon Cough Very Common Very Common Very Common Dyspnea Very Common Very Common Very Common Interstitial lung disease Uncommon Very Rare Very Rare Pleural effusion Common Very Common Very Common Pulmonary fibrosis Very Rare Uncommon Uncommon Gastrointestinal disorders Abdominal distension Common Very Common Common Abdominal pain Very Common Very Common Very Common Colitis Common Common Common Constipation Very Common Very Common Very Common Decreased appetite Common Very Common Very Common Diarrhea Very Common Very Common Very Common Dyspepsia Very Common Very Common Very Common Esophagitis Common Common Common Eructation Uncommon Uncommon Uncommon Flatulence Common Very Common Very Common Gastritis Common Common Common Gastrointestinal hemorrhage Common Common Common Gastrointestinal ulcer Common Common Common Gingival hyperplasia Common Common Common Ileus Common Common Common Mouth ulceration Common Common Common Nausea Very Common Very Common Very Common Pancreatitis Uncommon Common Uncommon Stomatitis Common Common Common Vomiting Very Common Very Common Very Common Immune system disorders Hypersensitivity Uncommon Common Common Hypogammaglobulinaemia Uncommon Very Rare Very Rare Anaphylactic reactions Not Known Not Known Not Known Hepatobiliary disorders Blood alkaline phosphatase increased Common Common Common Blood lactate dehydrogenase increased Common Uncommon Very Common Hepatic enzyme increased Common Very Common Very Common Hepatitis Common Very Common Uncommon Hyperbilirubinaemia Common Very Common Very Common Jaundice […]

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.

8). 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.

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 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 action 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.

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