MYCOPHENOLATE MOFETIL

Treatment with Mycophenolate mofetil for infusion should be initiated and maintained by appropriately qualified transplant specialists. V. SOLUTION MUST NOT BE ADMINISTERED BY RAPID OR BOLUS INTRAVENOUS INJECTION. Posology Mycophenolate mofetil for infusion is an alternative dosage form to Mycophenolate mofetil oral forms (capsules, tablets and powder for oral suspension) that may be administered for up to 14 days.

The initial dose of Mycophenolate mofetil for infusion should be given within 24 hours following transplantation.

Renal transplant:

Tthe recommended dose in renal transplant patients is 1 g administered twice daily (2 g daily dose).

Hepatic transplant:

The recommended dose of Mycophenolate mofetil for infusion in hepatic transplant patients is 1 g administered twice daily (2 g daily dose). IV Mycophenolate mofetil for infusion should continue 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).

Use in special populations Paediatric population:

Safety and efficacy of mycophenolate mofetil in paediatric patients have not been established. No pharmacokinetic data with mycophenolate mofetil are available for paediatric renal transplant patients. No pharmacokinetic data are available for paediatric patients following hepatic transplants.

Elderly:

The recommended dose of 1 g administered twice a day for renal or hepatic transplant patients is appropriate for the elderly. 73 m-2), 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 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.

1%) were among the most common and/or serious adverse reactions associated with the administration of mycophenolate mofetil in combination with ciclosporin and corticosteroids. 4). Tabulated list of adverse reactions The adverse 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) and very rare (<1/10,000).

Due to the large differences observed in the frequency of certain adverse reactions across the different transplant indications, the frequency is presented separately for renal and hepatic transplant patients. Table 1 Adverse reactions Adverse drug reaction (MedDRA) System Organ Class Renal transplant Hepatic transplant Frequency Frequency Infections and infestations Bacterial infections Very Common Very Common Fungal infections Common Very Common Protozoal infections Uncommon Uncommon Viral infections Very Common Very Common Neoplasms benign, malignant and unspecified (including cysts and polyps) Benign neoplasm of skin Common Common Lymphoma Uncommon Uncommon Lymphoproliferative disorder Uncommon Uncommon Neoplasm Common Common Skin cancer Common Uncommon Blood and lymphatic system disorders Anemia Very Common Very Common Aplasia pure red cell Uncommon Uncommon Bone marrow failure Uncommon Uncommon Ecchymosis Common Common Leukocytosis Common Very Common Leukopenia Very Common Very Common Pancytopenia Common Common Pseudolymphoma Uncommon Uncommon Thrombocytopenia Common Very Common Metabolism and nutrition disorders Acidosis Common Common Hypercholesterolemia Very Common Common Hyperglycemia Common Very Common Hyperkalemia Common Very Common Hyperlipidemia Common Common Hypocalcemia Common Very Common Hypokalemia Common Very Common Hypomagnesemia Common Very Common Hypophosphatemia Very Common Very Common Hyperuricaemia Common Common Gout Common Common Weight decreased Common Common Psychiatric disorders Confusional state Common Very Common Depression Common Very Common Insomnia Common Very Common Agitation Uncommon Common Anxiety Common Very Common Thinking abnormal Uncommon Common Nervous system disorders Dizziness Common Very Common Headache Very Common Very Common Hypertonia Common Common Paresthesia Common Very Common Somnolence Common Common Tremor Common Very Common Convulsion Common Common Dysgeusia Uncommon Uncommon Cardiac disorders Tachycardia Common Very Common Vascular disorders Hypertension Very Common Very Common Hypotension Common Very Common Lymphocele Uncommon Uncommon Venous thrombosis Common Common Vasodilatation Common Common Respiratory, thoracic and mediastinal disorders Bronchiectasis Uncommon Uncommon Cough Very Common Very Common Dyspnea Very Common Very Common Interstitial lung disease Uncommon Very Rare Pleural effusion Common Very Common Pulmonary fibrosis Very Rare Uncommon Gastrointestinal disorders Abdominal distension Common Very Common Abdominal pain Very Common Very Common Colitis Common Common Constipation Very Common Very Common Decreased appetite Common Very Common Diarrhea Very Common Very Common Dyspepsia Very Common Very Common Esophagitis Common Common Eructation Uncommon Uncommon Flatulence Common Very Common Gastritis Common Common Gastrointestinal hemorrhage Common Common Gastrointestinal ulcer Common Common Gingival hyperplasia Common Common Ileus Common Common Mouth ulceration Common Common Nausea Very Common Very Common Pancreatitis Uncommon Common Stomatitis Common Common Vomiting Very Common Very Common Immune system disorders Hypersenstivity Uncommon Common Hypogammaglobulinaemia Uncommon Very Rare Hepatobiliary disorders Blood alkaline phosphatase increased Common Common Blood lactate dehydrogenase increased Common Uncommon Hepatic enzyme increased Common Very Common Hepatitis Common Very Common Hyperbilirubinaemia Common Very Common Jaundice Uncommon Common Skin and subcutaneous tissue disorders Acne Common Common Alopecia Common Common Rash Common Very Common Skin hypertrophy Common Common Musculoskeletal and connective tissue disorders Arthralgia Common Common Muscular weakness Common Common Renal and urinary disorders Blood creatinine increased Common Very Common Blood urea increased Uncommon Very Common Hematuria Very Common Common Renal impairment Common Very Common General disorders and administration site conditions Asthenia Very Common Very Common Chills Common Very Common Edema Very Common Very Common Hernia Common Very Common Malaise Common Common Pain Common Very Common Pyrexia Very Common Very Common de novo purine synthesis inhibitors- associated acute inflammatory syndrome Uncommon Uncommon Adverse reactions attributable to peripheral venous infusion were phlebitis and thrombosis, both observed at 4% in patients treated with mycophenolate mofetil.

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 for infusion 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.

1. 8). Mycophenolate mofetil for infusion is contraindicated in patients who are allergic to polysorbate 80. 6). 6). 6). 6.