Mycophenolate mofetil oral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of mycophenolate mofetil.
Drugs List
Therapeutic Indications
Uses
Prophylaxis of acute organ rejection for allogeneic cardiac transplant
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 cardiac transplants in combination with ciclosporin and corticosteroids.
Prophylaxis of acute transplant rejection in patients receiving allogeneic hepatic transplants in combination with ciclosporin and corticosteroids.
Not all indications are licensed for all age groups.
Unlicensed Uses
Rheumatic and inflammatory conditions
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local protocols for the relevant indication should be consulted.
Adults
Renal transplant:
1g twice daily initiated within 72 hours of transplantation.
Cardiac transplant:
1.5g twice daily initiated within 5 days of transplantation.
Hepatic transplant:
The first four days of mycophenolate mofetil treatment are carried out using the intravenous infusion. This is then substituted with oral therapy at a dose of 1.5g twice a day as soon as it can be tolerated after the first four days.
Children
Renal transplant:
Children & adolescents (aged 2 years to 18 years)
600mg/square metre administered twice daily (up to a maximum 2g daily).
As some adverse reactions occur with greater frequency in this age group 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.
Alternative sources suggest the following unlicensed doses:
Renal transplant (unlicensed)
In combination with a corticosteroid and ciclosporin
Children aged 1 month to 2 years: 600mg/square metre twice daily (maximum 2g daily)
In combination with a corticosteroid and tacrolimus
Children aged 1 month to 18 years: 300mg/square metre twice daily (maximum 2g daily)
Hepatic transplantation in combination with a corticosteroid and ciclosporin or tacrolimus (unlicensed)
Children aged 1 month to 18 years: 10mg/kg twice daily, increased to 20mg/kg twice daily (maximum 2g daily)
Patients with Renal Impairment
In renal transplant patients with severe chronic renal impairment (GFR less than 25 ml/minute/1.73 square metre), outside of the immediate post transplant period, doses greater than 1g administered twice daily should be avoided. These patients should be carefully observed.
No dosage adjustments are required for patients experiencing delayed renal graft function post-operatively.
Additional Dosage Information
Concurrent antibiotics
Reduction in mycophenolate levels has been observed when antibiotics including ciprofloxacin, co-amoxiclav and norfloxacin combined with metronidazole have been given concomitantly with mycophenolate. Patients should be closely monitored during antibiotic treatment for early signs of graft dysfunction.
Administration
If required, the oral suspension can be administered through a nasogastric tube with a minimum size of 8 French (minimum 1.7 mm internal diameter).
Contraindications
Hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase
Neonates under 1 month
Breastfeeding
Pregnancy
Precautions and Warnings
Children 1 month to 18 years
Females of childbearing potential
Patients over 65 years
Hereditary fructose intolerance
Phenylketonuria
Renal impairment - glomerular filtration rate below 25ml/minute/1.73m sq
Severe gastrointestinal disorder
Administration of live vaccines is not recommended
Some formulations contain aspartame - caution in phenylketonuria
Advise ability to drive/operate machinery may be affected by side effects
Treatment to be initiated and supervised by a specialist
Oral liquid contains hydroxybenzoate: caution in hypersensitivity
Presentations with sorbitol unsuitable in hereditary fructose intolerance
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 signs of neurological toxicity
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
Reactivation of hepatitis B may occur in chronic carriers
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
Not licensed for all indications in all age groups
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
Patients should not donate blood during or for 6 weeks after treatment
Patients should not donate semen during or 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.
Prior to initiation female patients of child bearing potential are recommended to have pregnancy excluded using two serum or urine pregnancy tests with a sensitivity of at least 25 mIU/ml. The second test should be preformed 8-10 days after the first and be immediately prior to initiation of mycophenolate mofetil.
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
Anaemia
Anaphylactic reaction
Anorexia
Anxiety
Aplastic anaemia
Arthralgia
Asthenia
Benign skin neoplasms
BK virus associated with nephropathy
Blood urea increased
Bone marrow depression
Bronchiectasis
Chills
Colitis
Confusion
Constipation
Convulsions
Cough
Cytomegalovirus infection
Depression
Diarrhoea
Dizziness
Dysgeusia
Dyspepsia
Dyspnoea
Gastro-intestinal haemorrhage
Gastro-intestinal ulceration
Gingival hyperplasia
Headache
Hepatitis
Hyperbilirubinaemia
Hypercholesterolaemia
Hyperglycaemia
Hyperkalaemia
Hyperlipidaemia
Hypersensitivity reactions
Hypertension
Hypertonia
Hypocalcaemia
Hypogammaglobulinaemia
Hypokalaemia
Hypomagnesaemia
Hypophosphataemia
Hypotension
Ileus
Increase in alkaline phosphatase
Increase in lactate dehydrogenase
Increased risk of skin cancer
Increased susceptibility to development of lymphoma and other malignancies
Increased susceptibility to infection
Increases in hepatic enzymes
Insomnia
Interstitial lung disease
Intestinal villous atrophy
Jaundice
Leucocytosis
Leukopenia
Lymphoproliferative disorders
Malaise
Myasthenia gravis-like syndrome
Mycobacterial infection
Nausea
Neutropenia
Oedema
Oesophagitis
Pain - generalised
Pancreatitis
Pancytopenia
Paraesthesia
Pleural effusion
Progressive multifocal leukoencephalopathy (PML)
Pulmonary fibrosis
Pulmonary oedema
Pyrexia
Rash
Red cell aplasia
Renal impairment
Serum creatinine increased
Skin hypertrophy
Somnolence
Stomatitis
Tachycardia
Thrombocytopenia
Tremor
Vasodilatation
Vomiting
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, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Summary of Product Characteristics: Cellcept 250mg capsules. Roche Products Ltd. Revised March 2022.
Summary of Product Characteristics: Cellcept 500mg tablets. Roche Products Ltd. Revised March 2022.
Summary of Product Characteristics: Cellcept 1g/5ml powder for oral suspension. Roche Products Ltd. Revised September 2019.
Summary of Product Characteristics: Mycophenolate mofetil 250mg tablets. Accord Healthcare. Revised February 2014
Summary of Product Characteristics: Mycophenolate mofetil 500mg tablets. Accord Healthcare. Revised February 2014
Summary of Product Characteristics: Mycophenolate mofetil 250mg tablets. Actavis UK Ltd. Revised July 2013.
Summary of Product Characteristics: Mycophenolate mofetil 500mg tablets. Actavis UK Ltd. Revised October 2014.
Summary of Product Characteristics: Myfenax 250mg capsules. Teva Pharma. Revised October 2014.
Summary of Product Characteristics: Myfenax 500mg tablets. Teva Pharma. Revised October 2014.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 8 September 2017
MHRA Drug Safety Update January 2015
Available at: https://www.mhra.gov.uk
Last accessed: 22 January 2015
HPRA Medicines Safety notice - CellCept 11/11/2015
Available at: https://www.mhra.gov.uk
Last accessed: 18 November 2015
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