Mycophenolate Mofetil

Mycophenolate Mofetil is indicated in combination with ciclosporin and corticosteroids for the prophylaxis of acute transplant rejection in adult and paediatric (1 to 18 years of age) patients receiving allogeneic renal, cardiac or hepatic transplants.

Treatment should be initiated and maintained by appropriately qualified transplant specialists. Posology Adults Renal transplant Treatment 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).

Cardiac transplant Treatment should be initiated within 5 days following transplantation. 5 g administered twice daily (3 g daily dose). Hepatic transplant Treatment of intravenous 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 (1 to 18 years) The paediatric dosing information in this section applies to all oral formulations within the range of mycophenolate mofetil products, as appropriate.

Different oral formulations should not be substituted without clinical supervision. The recommended mycophenolate mofetil initial dose for paediatric renal, cardiac and hepatic transplant patients is 600 mg/m2 (of body surface area (BSA)), administered orally, twice daily (initial total daily dose not to exceed 2 g, or 10 ml of the oral suspension).

The dose and product form should be individualised based on clinical assessment. If the recommended initial dose is well tolerated but does not achieve clinically adequate immunosuppression in paediatric cardiac and hepatic transplant patients, the dose can be increased to 900 mg/m2 BSA twice daily (maximum total daily dose of 3 g, or 15 ml of the oral suspension).

The recommended maintenance dose for paediatric renal transplant patients remains at 600 mg/m2 twice daily (maximum total daily dose of 2 g or 10 ml of the oral suspension). 25 m2 due to the increased risk of choking. 5 g daily dose).

5 m2 may be prescribed mycophenolate mofetil capsules or tablets 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.

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 Adults Mycophenolic acid (MPA) is the active metabolite of mycophenolate mofetil. Renal transplant rejection does not lead to changes in MPA pharmacokinetics; dose reduction or interruption of treatment is not required.

There is no basis for dose adjustment following cardiac transplant rejection. No pharmacokinetic data are available during hepatic transplant rejection. Paediatric population No data are available for treatment of first or refractory rejection in paediatric transplant patients.

Method of administration For oral use. Precautions to be taken before handling or administering the medicinal product. Because mycophenolate mofetil has demonstrated teratogenic effects in rats and rabbits, tablets should not be crushed to avoid inhalation or direct contact with skin or mucous membranes with powder.

If such contact occurs, wash thoroughly with soap and water; rinse eyes with plain water.

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), 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 adverse reactions across the different transplant indications, the frequency is presented separately for renal, hepatic and cardiac transplant patients. Table 1 Adverse reactions in studies investigating mycophenolate mofetil treatment in adults and adolescents, or through post-marketing surveillance Adverse reaction (MedDRA) System Organ Class Renal transplant Hepatic transplant Cardiac transplant 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 Anaemia 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 Immune system disorders Hypersenstivity Uncommon Common Common Hypogammaglobulinaemia Uncommon Very Rare Very Rare Anaphylactic reactions Not Known Not Known Not Known 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 Dyspnoea 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 Diarrhoea Very Common Very Common Very Common Dyspepsia Very Common Very Common Very Common Esophagitis Common Common Common Eructation Uncommon Uncommon Common Flatulence Common Very Common Very Common Gastritis Common Common Common Gastrointestinal haemorrhage 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 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 Uncommon Common Common Skin and subcutaneous tissue disorders Acne Common Common Very Common Alopecia Common Common Common Rash Common Very Common Very Common Skin hypertrophy Common Common Very Common Musculoskeletal and connective tissue disorders Arthralgia Common Common Very Common Muscular weakness Common Common Very Common Renal and urinary disorders Blood creatinine increased Common Very Common Very Common Blood urea increased Uncommon Very Common Very Common Haematuria Very Common Common Common Renal impairment Common Very Common Very Common General disorders and administration […]

1. 8). 6). 6). 6). 6).

JAMP-Mycophenolate Capsules (mycophenolate mofetil) is indicated for:

Adults  The prophylaxis of organ rejection in patients receiving allogeneic renal, cardiac or hepatic transplants. JAMP-Mycophenolate Capsules should be used concomitantly with cyclosporine and corticosteroids. 1 Pediatrics (2-18 years of age):  JAMP-Mycophenolate Capsules is indicated for the prophylaxis of organ rejection in pediatric patients (2 to 18 years) receiving allogeneic renal transplants.

JAMP - Mycophenolate Capsules should be used concomitantly with cyclosporine and corticosteroids. 2 Geriatrics  No data are available to Health Canada; therefore, Health Canada has not authorized an indication for geriatric use.

1 Dosing Considerations  JAMP-Mycophenolate Capsules (mycophenolate mofetil) should be used concomitantly with standard cyclosporine and corticosteroid therapy. JAMP-Mycophenolate Capsules  The initial oral dose of JAMP-Mycophenolate Capsules should be given as soon as possible following renal, cardiac or hepatic transplantation.

Food had no effect on MPA AUC, but has been shown to decrease MPA Cmax by 40%. It is recommended that JAMP- Mycophenolate Capsules be administered on an empty stomach. 2 Recommended Dose and Dosage Adjustment Adults Renal Transplantation A dose of 1 g administered orally twice a day (daily dose of 2 g) is recommended for use in renal transplant patients.

5 g administered twice daily (daily dose of 3 g) was used in clinical trials and was shown to be safe and effective, no efficacy advantage could be established for renal transplant patients. Patients receiving 2 g per day of mycophenolate mofetil in these trials demonstrated an overall better safety profile than did patients receiving 3 g per day of mycophenolate mofetil.

5 g twice daily oral (daily dose of 3 g) is recommended for use in adult cardiac transplant patients. 5 g twice daily oral (daily dose of 3 g) is recommended for use in adult hepatic transplant patients. 5 g daily dose). 5 m2 may be dosed with JAMP-Mycophenolate Capsules at a dose of 1 g twice daily (2 g daily dose).

73 m 2) outside the immediate post-transplant period, doses of JAMP-Mycophenolate Capsules greater than 1 g administered twice a day should be avoided. These patients should also be carefully observed. (See CLINICAL PHARMACOLOGY: Pharmacokinetics, Special Populations and Conditions, Renal Insufficiency) No data are available for cardiac or hepatic transplant patients with severe chronic renal impairment.

JAMP-Mycophenolate Capsules should be used for cardiac or hepatic transplant patients with severe chronic renal impairment if the potential benefits outweigh the potenti al risks. 3 x 103/μL), dosing with JAMP-Mycophenolate Capsules should be interrupted or the dose reduced, appropriate diagnostic tests performed, and the patient managed appropriately.

(See WARNINGS AND PRECAUTIONS: Immune, Monitoring and Laboratory Tests and ADVERSE REACTIONS) Delayed Renal Graft Function Post Transplant: No dose adjustment is recommended for these patients, however, they should be carefully observed.

4 Administration JAMP-Mycophenolate Capsules should be administered orally, and should be taken on an empty stomach (See CLINICAL PHARMACOLOGY: Absorption)

1 Adverse Reaction Overview The adverse event profile associated with the use of immunosuppressive drugs is often difficult to establish owing to the presence of underlying disease and the concurrent use of many other medications. The principal adverse reactions associated with the administration of JAMP- Mycophenolate Capsules include diarrhea, leukopenia, sepsis and vomiting, and there is evidence of a higher frequency of certain types of infections.

2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in JAMP-Mycophenolate Capsules (Mycophenolate Mofetil Capsules) Page 13 of 68 real-world use. Mycophenolate mofetil (oral) The incidence of adverse events for mycophenolate mofetil was determined in randomized comparative double-blind trials in prevention of rejection in renal (2 active, 1 placebo controlled trials), cardiac (1 active controlled trial) and hepatic (1 active controlled trial) transplant patients.

Safety data are summarized below for all active controlled trials in renal (2 trials), cardiac (1 trial) and hepatic (1 trial) transplant patients. Approximately 53% of renal patients, 65% of the cardiac patients and 45% of the hepatic patients have been treated for more than one year.

Adverse events, whether or not deemed to be causally associated with the study medication, reported in  10% of patients in treatment groups are presented below. 8 […]

 JAMP-Mycophenolate Capsules (mycophenolate mofetil) is contraindicated in patients with a known hypersensitivity to mycophenolate mofetil, mycophenolic acid or any component of the drug product. (See DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING).

 JAMP-Mycophenolate Capsules is contraindicated during pregnancy due to its mutagenic and teratogenic potential (see WARNINGS and PRECAUTIONS).  JAMP-Mycophenolate Capsules is contraindicated in women of childbearing potential not using highly effective contraceptive methods and without providing a pregnancy test result.

(see WARNINGS and PRECAUTIONS).  JAMP-Mycophenolate Capsules is contraindicated in women who are breastfeeding (see WARNINGS and PRECAUTIONS).

3) ], in combination with other immunosuppressants. Mycophenolate mofetil is an antimetabolite immunosuppressant indicated for the prophylaxis of organ rejection in adult and pediatric recipients 3 months of age and older of allogeneic kidney, heart or liver transplants, in combination with other immunosuppressants ( 1 )

4 ) Reduce or interrupt dosing in the event of neutropenia. 1 Important Administration Instructions Mycophenolate mofetil should not be used without the supervision of a physician with experience in immunosuppressive therapy. Mycophenolate Mofetil Capsules and Tablets Mycophenolate mofetil oral dosage forms (capsules or tablets) should not be used interchangeably with mycophenolic acid delayed-release tablets without supervision of a physician with experience in immunosuppressive therapy because the rates of absorption following the administration of mycophenolate mofetil oral dosage forms and mycophenolic acid delayed-release tablets are not equivalent.

Mycophenolate mofetil tablets should not be crushed and mycophenolate mofetil capsules should not be opened or crushed. Patients should avoid inhalation or contact of the skin or mucous membranes with the powder contained in mycophenolate mofetil capsules and oral suspension.

If such contact occurs, they must wash the area of contact thoroughly with soap and water. In case of ocular contact, rinse eyes with plain water. The initial oral dose of mycophenolate mofetil should be given as soon as possible following kidney, heart or liver transplant.

It is recommended that mycophenolate mofetil be administered on an empty stomach. 3) ] . Patients should be instructed to take a missed dose as soon as they remember, except if it is closer than 2 hours to the next scheduled dose; in this case, they should continue to take mycophenolate mofetil at the usual times.

2 Dosage Recommendations for Kidney Transplant Patients Adults The recommended dosage for adult kidney transplant patients is 1 g orally or intravenously infused over no less than 2 hours, twice daily (total daily dose of 2 g). The recommended dosage of mycophenolate mofetil oral suspension for pediatric kidney transplant patients 3 months and older is 600 mg/m 2 , administered twice daily (maximum total daily dose of 2 g or 10 mL of the oral suspension).

5 g orally twice daily (total daily dose of 3 g). 25 m 2 may be started on therapy with capsules or tablets as follows: Table 2 Pediatric Heart Transplant: Pediatric Starting Dosage Using Capsules or Tablets Body Surface Area Starting Dosage Maximum maintenance dose: 3 g total daily.

5 g administered orally twice daily (total daily dose of 3 g). 25 m 2 may be started on therapy with capsules or tablets as follows: Table 3 Pediatric Liver Transplant: Pediatric Starting Dosage Using Capsules or Tablets Body Surface Area Starting Dosage Maximum maintenance dose: 3 g total daily.

3) ] . 73 m 2 ), do not administer doses of mycophenolate mofetil greater than 1 g twice a day. 3) ] . 1) ] .

, opportunistic infection. 1 ) To report SUSPECTED ADVERSE REACTIONS, contact Accord Healthcare Inc. 1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

An estimated total of 1557 adult patients received mycophenolate mofetil during pivotal 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.

Patients in all study arms also received cyclosporine and corticosteroids. 3) ] . 3) ] . 5 g twice daily) with azathioprine (2 studies) or placebo (1 study) when administered in combination with cyclosporine (Sandimmune ® ) and corticosteroids to prevent acute rejection episodes.

One study also included anti-thymocyte globulin (ATGAM ®) induction therapy. 5 to 3 mg/kg/day (n=289), in combination with cyclosporine (Sandimmune ® or Neoral ® ) and corticosteroids as maintenance immunosuppressive therapy. 5 g twice daily orally or azathioprine 1 to 2 mg/kg/day intravenously followed by azathioprine 1 to 2 mg/kg/day orally, in combination with cyclosporine (Neoral ® ) and corticosteroids as maintenance immunosuppressive therapy.

The total number of patients enrolled was 565. Approximately 53% of the kidney transplant patients, 65% of the heart transplant patients, and 48% of the liver transplant patients were treated for more than 1 year. Adverse reactions reported in ≥ 20% of patients in the mycophenolate mofetil treatment groups are presented below.

The safety data of three kidney transplantation studies are pooled together. "-" Indicates that the incidence was below the cutoff value of 20% for inclusion in the table. "Edema" includes peripheral edema, facial edema, scrotal edema.

"Pain" includes musculoskeletal pain (myalgia, neck pain, back pain). 1 In the three de novo kidney studies, patients receiving 2 g/day of mycophenolate mofetil had an overall better safety profile than did patients receiving 3 g/day of mycophenolate mofetil.

2) ]. 1% of patients. Three-year safety data in kidney and heart transplant patients did not reveal any unexpected changes in incidence of malignancy compared to the 1-year data. 35% (2/148) by 12 months post-transplant. 3) ] . 5) ]. The most common opportunistic infections in patients receiving mycophenolate mofetil with other immunosuppressants were mucocutaneous candida, CMV viremia/syndrome, and herpes simplex.

5%. 3) ]. The most serious gastrointestinal disorders reported were ulceration and hemorrhage, which are known risks associated with mycophenolate mofetil. Mouth, esophageal, gastric, duodenal, and intestinal ulcers often complicated by hemorrhage, as well as hematemesis, melena, and hemorrhagic forms of gastritis and colitis were commonly reported during the pivotal clinical trials, while the most common gastrointestinal disorders were diarrhea, nausea and vomiting.

5) ] . The following adverse reactions were reported with 3% to <20% incidence in kidney, heart, and liver transplant patients treated with mycophenolate mofetil, in combination with cyclosporine and corticosteroids. Table 6 Adverse Reactions in Controlled Studies of De Novo Kidney, Heart or Liver Transplantation Reported in 3% to <20% of Patients Treated with Mycophenolate Mofetil in Combination with Cyclosporine and Corticosteroids Body System Adverse Reactions Body as a Whole cellulitis, chills, hernia, malaise Infections and Infestations fungal infections Hematologic and Lymphatic coagulation disorder, ecchymosis, pancytopenia Urogenital hematuria Cardiovascular hypotension Metabolic and Nutritional acidosis, alkaline phosphatase increased, hyperlipemia, hypophosphatemia, weight loss Digestive esophagitis, flatulence, gastritis, gastrointestinal hemorrhage, hepatitis, ileus, nausea and vomiting, stomach ulcer, stomatitis Neoplasm benign, malignant and unspecified neoplasm Skin and Appendages skin benign neoplasm, skin carcinoma Psychiatric confusional state Nervous hypertonia, paresthesia, somnolence Musculoskeletal arthralgia, myasthenia Pediatrics The type and frequency of adverse events in a clinical study for prevention of kidney allograft rejection in 100 pediatric patients 3 months to 18 years of age dosed with mycophenolate mofetil oral suspension 600 mg/m 2 twice daily (up to 1 g twice daily) were generally similar to those observed in adult patients dosed with mycophenolate mofetil capsules at a dose of 1 g twice daily with the exception of abdominal pain, fever, infection, pain, sepsis, diarrhea, vomiting, pharyngitis, respiratory tract infection, hypertension, leukopenia, and anemia, which were observed in a higher proportion in pediatric patients.

Safety information in pediatric heart transplant or pediatric liver transplant patients treated with mycophenolate mofetil is supported by an open-label study in pediatric liver transplant patients and publications; the type and frequency of the reported adverse reactions are consistent with those observed in pediatric patients following renal transplant and in adults.

1) ]. 2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of mycophenolate mofetil. 3) ].

Congenital malformations include:

Facial malformations: cleft lip, cleft palate, micrognathia, hypertelorism of the orbits Abnormalities of the ear and eye: abnormally formed or absent external/middle ear, coloboma, microphthalmos Malformations of the fingers: polydactyly, syndactyly, brachydactyly Cardiac abnormalities: atrial and ventricular septal defects Esophageal malformations: esophageal atresia Nervous system malformations: such as spina bifida .

Cardiovascular:

Venous thrombosis has been reported in patients treated with mycophenolate mofetil administered intravenously.

Digestive :

Colitis, pancreatitis. 4) ] .

Immune:

Hypersensitivity, hypogammaglobinemia. 3) ] .

Respiratory :

Bronchiectasis, interstitial lung disease, fatal pulmonary fibrosis, have been reported rarely and should be considered in the differential diagnosis of pulmonary symptoms ranging from dyspnea to respiratory failure in post-transplant patients receiving mycophenolate mofetil.

Vascular:

Lymphocele

4 CONTRAINDICATIONS Allergic reactions to mycophenolate mofetil have been observed; therefore, mycophenolate mofetil is contraindicated in patients with a hypersensitivity to mycophenolate mofetil (MMF), mycophenolic acid (MPA) or any component of the drug product.

Hypersensitivity to mycophenolate mofetil, mycophenolic acid or any component of the drug product ( 4 )

CellCept is indicated in combination with ciclosporin and corticosteroids for the prophylaxis of acute transplant rejection in adult and paediatric (1 to 18 years of age) patients receiving allogeneic renal, cardiac or hepatic transplants.

Treatment should be initiated and maintained by appropriately qualified transplant specialists. Posology Adults Renal transplant Treatment 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).

Cardiac transplant Treatment should be initiated within 5 days following transplantation. 5 g administered twice daily (3 g daily dose). Hepatic transplant Treatment of intravenous 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 (1 to 18 years) The paediatric dosing information in this section applies to all oral formulations within the range of mycophenolate mofetil products, as appropriate.

Different oral formulations should not be substituted without clinical supervision. The recommended mycophenolate mofetil initial dose for paediatric renal, cardiac and hepatic transplant patients is 600 mg/m2 (of body surface area (BSA)), administered orally, twice daily (initial total daily dose not to exceed 2 g, or 10 ml of the oral suspension).

3 The dose and product form should be individualised based on clinical assessment. If the recommended initial dose is well tolerated but does not achieve clinically adequate immunosuppression in paediatric cardiac and hepatic transplant patients, the dose can be increased to 900 mg/m2 BSA twice daily (maximum total daily dose of 3 g, or 15 ml of the oral suspension).

The recommended maintenance dose for paediatric renal transplant patients remains at 600 mg/m2 twice daily (maximum total daily dose of 2 g or 10 ml of the oral suspension). 25 m2 due to the increased risk of choking. 5 g daily dose).

5 m2 may be prescribed mycophenolate mofetil capsules or tablets 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.

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 Adults Mycophenolic acid (MPA) is the active metabolite of mycophenolate mofetil. Renal transplant rejection does not lead to changes in MPA pharmacokinetics; dose reduction or interruption of treatment is not required.

There is no basis for dose adjustment following cardiac transplant rejection. No pharmacokinetic data are available during hepatic transplant rejection. Paediatric population No data are available for treatment of first or refractory rejection in paediatric transplant patients.

Method of administration For oral use. Precautions to be taken before handling or administering the medicinal product. Because mycophenolate mofetil has demonstrated teratogenic effects in rats and rabbits, capsules should not be opened or crushed to avoid inhalation or direct contact with skin or mucous membranes of the powder contained in the capsules.

If such contact occurs, wash thoroughly with soap and water; rinse eyes with plain water. 4

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), 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 adverse reactions across the different transplant indications, the frequency is presented separately for renal, hepatic and cardiac transplant patients. Table 1 Adverse reactions in studies investigating mycophenolate mofetil treatment in adults and adolescents, or through post-marketing surveillance Adverse reaction (MedDRA) System Organ Class Renal transplant Hepatic transplant Cardiac transplant Frequency Frequency Frequency Infections and infestations Bacterial infections Very Common Very Common Very Common Fungal infections Common Very Common Very Common 12 Adverse reaction (MedDRA) System Organ Class Renal transplant Hepatic transplant Cardiac transplant 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 Anaemia 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 Hypercholesterolaemia Very Common Common Very Common Hyperglycaemia Common Very Common Very Common Hyperkalaemia Common Very Common Very Common Hyperlipidaemia Common Common Very Common Hypocalcaemia Common Very Common Common Hypokalaemia Common Very Common Very Common Hypomagnesaemia Common Very Common Very Common Hypophosphataemia 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 13 Adverse reaction (MedDRA) System Organ Class Renal transplant Hepatic transplant Cardiac transplant 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 Dyspnoea 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 Diarrhoea Very Common Very Common Very Common Dyspepsia Very Common Very Common Very Common Esophagitis Common Common Common Eructation Uncommon Uncommon Common Flatulence Common Very Common Very Common Gastritis Common Common Common Gastrointestinal haemorrhage 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 Hypersenstivity Uncommon Common Common 14 Adverse reaction (MedDRA) System Organ Class Renal transplant Hepatic transplant Cardiac transplant Anaphylactic reactions Not known Not known Not known Hypogammaglobulinaemia Uncommon Very Rare Very Rare 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 Uncommon Common Common Skin and subcutaneous tissue disorders Acne Common Common Very Common Alopecia Common Common Common Rash Common Very Common Very Common Skin hypertrophy Common Common Very Common Musculoskeletal and connective tissue disorders Arthralgia Common […]

1. 8). 6). 6). 6). 6).