Drugs List

Therapeutic Indications

Uses

Prophylaxis of acute organ rejection for allogeneic hepatic transplant
Prophylaxis of acute organ rejection for allogeneic renal transplant

Prophylaxis of acute transplant rejection in patients receiving allogeneic renal transplants in combination with ciclosporin and corticosteroids.

Prophylaxis of acute transplant rejection in patients receiving allogeneic hepatic transplants in combination with ciclosporin and corticosteroids.

Administration

Administer only by slow intravenous infusion over a period of 2 hours.

Contraindications

Children under 18 years
Hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase
Breastfeeding
Pregnancy

Precautions and Warnings

Patients over 65 years
Renal impairment - glomerular filtration rate below 25ml/minute/1.73m sq
Severe gastrointestinal disorder

Administration of live vaccines is not recommended
Advise ability to drive/operate machinery may be affected by side effects
Treatment to be initiated and supervised by a specialist
Contains polysorbate
Exclude pregnancy prior to initiation of treatment
Consider immunosuppressant adjustment in the event of PML
If dyspnoea occurs, investigate for signs of progressive pulmonary disorder
Monitor FBC monthly from 4th month for the 1st year of treatment
Monitor FBC weekly for 1st month then fortnightly for 2nd and 3rd month
Monitor for and manage hepatitis reactivation during treatment
Monitor for signs of neurological toxicity
Monitor renal function
Monitor serum immunoglobulins in patients with recurrent infections
Advise patient to report headaches, seizures, confusion, visual disturbance
Advise patient to report persistent cough
Advise patient to report symptoms of infection immediately
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Consider immunosuppressant adjustment if BK virus nephropathy develops
If pure red cell aplasia is diagnosed reduce dose or discontinue treatment
Immunosuppressive drugs may increase risk of malignancy
May reduce effectiveness of vaccinations during treatment
Risk of developing opportunistic infections
Advise patient to seek advice at first indications of pregnancy
Review therapy if neutrophil count <1.3 x 10 to the power of 9/L
Female: Contraception required before, during & for 6 weeks after treatment
Female: Two reliable methods of contraception should be used simultaneously
Male: Use barrier contraception during and for 3 months after treatment
Advise patient to avoid exposure to sunlight and UV rays during treatment
Male: Contraception required for partners for 3 months after treatment

Elderly patients may generally be at increased risk of adverse drug reactions due to immunosuppression, including certain infections and possibly gastrointestinal haemorrhage and pulmonary oedema.

Cases of pure red cell aplasia (PRCA) have been reported in patients treated with mycophenolate mofetil in combination with other immunosuppressants. Although the mechanism is unknown mycophenolate mofetil induced PRCA may resolve with dose reduction or cessation of therapy. However changes to therapy should only be undertaken under appropriate supervision in transplant recipients in order to minimise the risk of graft rejection.

Cases of hypogammaglobulinaemia have been reported in association with recurrent infections. Patients with recurrent infections should have their immunoglobulins measured and patients with sustained hypogammaglobulinaemia should be treated appropriately considering the potent cytostatic effects of mycophenolic acid on T and B lymphocytes.

Cases of bronchiectasis have been reported in patients treated with mycophenolate mofetil in combination with other immunosuppressants. The risk may be linked to hypogammaglobulinaemia or direct effects on the lungs. Patients with persistent pulmonary symptoms such as cough and dyspnoea should be investigated for progressive pulmonary disorders.

Consider therapeutic drug monitoring of mycophenolate levels when starting or stopping concomitant ciclosporin.

Progressive Multifocal Leukoencephalopathy Syndrome (PML)
Progressive multifocal leukoencephalopathy syndrome (PML) has been reported in some patients treated with this agent. If patients present with symptoms indicating PML such as worsening neurological, cognitive or behavioural signs or symptoms, an MRI should be performed. If PML is diagnosed immunosuppressant treatment should be permanently discontinued.

Pregnancy and Lactation

Pregnancy

Mycophenolate mofetil is contraindicated in pregnancy.

Use in the first trimester is associated with spontaneous abortions and major birth defects. Malformations include external ear, facial anomalies and defects in the heart, oesophagus and kidney.

Animal studies have shown reproductive toxicity.

Schafer concludes that the use of the drug in pregnancy does not require termination of pregnancy. A detailed ultrasound should be offered to confirm normal morphological development in cases of first trimester exposure.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Mycophenolate mofetil is contraindicated in breastfeeding.

It is not known whether mycophenolate mofetil is excreted in human milk although its presence has been shown in the milk of lactating rats. The molecular weight is low enough that it is likely to be present in human breast milk. A risk to neonates cannot be excluded.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Abnormal thinking
Acidosis
Acne
Agitation
Agranulocytosis
Alopecia
Anaphylactic reaction
Angioneurotic oedema
Anorexia
Aplastic anaemia
Asthenia
BK virus associated with nephropathy
Blood disorders
Bone marrow depression
Bronchiectasis
Bronchitis
Candidiasis
Chills
Colitis
Convulsions
Cough
Cytomegalovirus infection
Depression
Duodenal ulcer
Dyspepsia
Dyspnoea
Electrolyte disturbances
Endocarditis
Flatulence
Gastric ulceration
Gastritis
Gastro-enteritis
Gastro-intestinal disturbances
Gastro-intestinal haemorrhage
Gingival hyperplasia
Headache
Hepatitis
Herpes infections
Hypercholesterolaemia
Hyperglycaemia
Hyperkalaemia
Hyperlipidaemia
Hypersensitivity reactions
Hypertension
Hypertonia
Hypocalcaemia
Hypogammaglobulinaemia
Hypokalaemia
Hypomagnesaemia
Hypophosphataemia
Hypotension
Ileus
Increase in alkaline phosphatase
Increase in lactate dehydrogenase
Increased susceptibility to development of lymphoma and other malignancies
Increases in hepatic enzymes
Infections
Influenza
Insomnia
Interstitial lung disease
Intestinal villous atrophy
Jaundice
Lymphoproliferative disorders
Malaise
Meningitis
Mycobacterial infection
Nausea
Neutropenia
Oedema
Oesophagitis
Pain - generalised
Pancreatitis
Paraesthesia
Peritonitis
Pharyngitis
Phlebitis
Pleural effusion
Pneumonia
Progressive multifocal leukoencephalopathy (PML)
Pulmonary fibrosis
Pulmonary oedema
Pyrexia
Rash
Red cell aplasia
Renal impairment
Respiratory tract infection
Rhinitis
Sepsis
Serum creatinine increased
Sinusitis
Somnolence
Stomatitis
Tachycardia
Thrombosis
Tremor
Tuberculosis
Urinary tract infections
Vasodilatation
Weight loss

Presentation

Infusions of mycophenolate mofetil (as hydrochloride)

Drugs List

Therapeutic Indications

Uses

Prophylaxis of acute organ rejection for allogeneic hepatic transplant
Prophylaxis of acute organ rejection for allogeneic renal transplant

Prophylaxis of acute transplant rejection in patients receiving allogeneic renal transplants in combination with ciclosporin and corticosteroids.

Prophylaxis of acute transplant rejection in patients receiving allogeneic hepatic transplants in combination with ciclosporin and corticosteroids.

Dosage

Whilst the doses stated below are those recommended by the manufacturer, local protocols for the relevant indication should be consulted.

Mycophenolate mofetil infusion may be administered as an alternative to oral formulations for up to 14 days post transplant. The initial dose should be given within 24 hours after transplantation.

Adults

Elderly

Patients with Renal Impairment

Additional Dosage Information

Administration

Administer only by slow intravenous infusion over a period of 2 hours.

Contraindications

Children under 18 years
Hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase
Breastfeeding
Pregnancy

Precautions and Warnings

Patients over 65 years
Renal impairment - glomerular filtration rate below 25ml/minute/1.73m sq
Severe gastrointestinal disorder

Administration of live vaccines is not recommended
Advise ability to drive/operate machinery may be affected by side effects
Treatment to be initiated and supervised by a specialist
Contains polysorbate
Exclude pregnancy prior to initiation of treatment
Consider immunosuppressant adjustment in the event of PML
If dyspnoea occurs, investigate for signs of progressive pulmonary disorder
Monitor FBC monthly from 4th month for the 1st year of treatment
Monitor FBC weekly for 1st month then fortnightly for 2nd and 3rd month
Monitor for and manage hepatitis reactivation during treatment
Monitor for signs of neurological toxicity
Monitor renal function
Monitor serum immunoglobulins in patients with recurrent infections
Advise patient to report headaches, seizures, confusion, visual disturbance
Advise patient to report persistent cough
Advise patient to report symptoms of infection immediately
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Consider immunosuppressant adjustment if BK virus nephropathy develops
If pure red cell aplasia is diagnosed reduce dose or discontinue treatment
Immunosuppressive drugs may increase risk of malignancy
May reduce effectiveness of vaccinations during treatment
Risk of developing opportunistic infections
Advise patient to seek advice at first indications of pregnancy
Review therapy if neutrophil count <1.3 x 10 to the power of 9/L
Female: Contraception required before, during & for 6 weeks after treatment
Female: Two reliable methods of contraception should be used simultaneously
Male: Use barrier contraception during and for 3 months after treatment
Advise patient to avoid exposure to sunlight and UV rays during treatment
Male: Contraception required for partners for 3 months after treatment

Elderly patients may generally be at increased risk of adverse drug reactions due to immunosuppression, including certain infections and possibly gastrointestinal haemorrhage and pulmonary oedema.

Cases of pure red cell aplasia (PRCA) have been reported in patients treated with mycophenolate mofetil in combination with other immunosuppressants. Although the mechanism is unknown mycophenolate mofetil induced PRCA may resolve with dose reduction or cessation of therapy. However changes to therapy should only be undertaken under appropriate supervision in transplant recipients in order to minimise the risk of graft rejection.

Cases of hypogammaglobulinaemia have been reported in association with recurrent infections. Patients with recurrent infections should have their immunoglobulins measured and patients with sustained hypogammaglobulinaemia should be treated appropriately considering the potent cytostatic effects of mycophenolic acid on T and B lymphocytes.

Cases of bronchiectasis have been reported in patients treated with mycophenolate mofetil in combination with other immunosuppressants. The risk may be linked to hypogammaglobulinaemia or direct effects on the lungs. Patients with persistent pulmonary symptoms such as cough and dyspnoea should be investigated for progressive pulmonary disorders.

Consider therapeutic drug monitoring of mycophenolate levels when starting or stopping concomitant ciclosporin.

Progressive Multifocal Leukoencephalopathy Syndrome (PML)
Progressive multifocal leukoencephalopathy syndrome (PML) has been reported in some patients treated with this agent. If patients present with symptoms indicating PML such as worsening neurological, cognitive or behavioural signs or symptoms, an MRI should be performed. If PML is diagnosed immunosuppressant treatment should be permanently discontinued.

Pregnancy and Lactation

Pregnancy

Mycophenolate mofetil is contraindicated in pregnancy.

Use in the first trimester is associated with spontaneous abortions and major birth defects. Malformations include external ear, facial anomalies and defects in the heart, oesophagus and kidney.

Animal studies have shown reproductive toxicity.

Schafer concludes that the use of the drug in pregnancy does not require termination of pregnancy. A detailed ultrasound should be offered to confirm normal morphological development in cases of first trimester exposure.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Mycophenolate mofetil is contraindicated in breastfeeding.

It is not known whether mycophenolate mofetil is excreted in human milk although its presence has been shown in the milk of lactating rats. The molecular weight is low enough that it is likely to be present in human breast milk. A risk to neonates cannot be excluded.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Abnormal thinking
Acidosis
Acne
Agitation
Agranulocytosis
Alopecia
Anaphylactic reaction
Angioneurotic oedema
Anorexia
Aplastic anaemia
Asthenia
BK virus associated with nephropathy
Blood disorders
Bone marrow depression
Bronchiectasis
Bronchitis
Candidiasis
Chills
Colitis
Convulsions
Cough
Cytomegalovirus infection
Depression
Duodenal ulcer
Dyspepsia
Dyspnoea
Electrolyte disturbances
Endocarditis
Flatulence
Gastric ulceration
Gastritis
Gastro-enteritis
Gastro-intestinal disturbances
Gastro-intestinal haemorrhage
Gingival hyperplasia
Headache
Hepatitis
Herpes infections
Hypercholesterolaemia
Hyperglycaemia
Hyperkalaemia
Hyperlipidaemia
Hypersensitivity reactions
Hypertension
Hypertonia
Hypocalcaemia
Hypogammaglobulinaemia
Hypokalaemia
Hypomagnesaemia
Hypophosphataemia
Hypotension
Ileus
Increase in alkaline phosphatase
Increase in lactate dehydrogenase
Increased susceptibility to development of lymphoma and other malignancies
Increases in hepatic enzymes
Infections
Influenza
Insomnia
Interstitial lung disease
Intestinal villous atrophy
Jaundice
Lymphoproliferative disorders
Malaise
Meningitis
Mycobacterial infection
Nausea
Neutropenia
Oedema
Oesophagitis
Pain - generalised
Pancreatitis
Paraesthesia
Peritonitis
Pharyngitis
Phlebitis
Pleural effusion
Pneumonia
Progressive multifocal leukoencephalopathy (PML)
Pulmonary fibrosis
Pulmonary oedema
Pyrexia
Rash
Red cell aplasia
Renal impairment
Respiratory tract infection
Rhinitis
Sepsis
Serum creatinine increased
Sinusitis
Somnolence
Stomatitis
Tachycardia
Thrombosis
Tremor
Tuberculosis
Urinary tract infections
Vasodilatation
Weight loss

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: January 2015

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 8th edition (2008) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. Accessed on 8 December 2014.

Martindale: The Complete Drug Reference, 35th edition (2007) ed. Sweetman, S. Pharmaceutical Press, London.

Paediatric Formulary Committee. BNF for Children (online) London: BMJ Group, Pharmaceutical Press, and RCPCH Publications. Accessed on 8 December 2014.

Summary of Product Characteristics: Cellcept 500mg powder for concentrate for solution for infusion. Roche Products Ltd. Revised March 2022.
Summary of Product Characteristics: Mycophenolate Mofetil 500mg Powder for concentrate for solution for infusion. Roche Products Ltd. Revised March 2015.

MHRA Drug Safety Update January 2015
Available at: https://www.mhra.gov.uk
Last accessed: 22 January 2015