Drugs List

Therapeutic Indications

Uses

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.

Contraindications

Children under 18 years
Breastfeeding
Galactosaemia
Pregnancy

Precautions and Warnings

Elderly
Hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase
Drug induced neutropenia with cell count below 1.5 x 10 to the power of 9/L
Glucose-galactose malabsorption syndrome
Hepatitis
Lactose intolerance
Renal impairment- creatinine clearance below 25ml/minute/1.73 square metre
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 lactose
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 bone marrow depression
Monitor renal function in patients with renal impairment
Monitor serum immunoglobulins in patients with recurrent infections
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
Oversuppression of immune system may increase susceptibility to infection
Advise patient to seek advice at first indications of pregnancy
Discontinue or interrupt treatment if neutropenia develops
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

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 mycophenolic acid.

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

Mycophenolic acid 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

Mycophenolic acid is contraindicated in breastfeeding.

It is not known whether mycophenolic acid 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 distension
Acne
Agitation
Alopecia
Altered liver function tests
Anaemia
Anorexia
Arthralgia
Arthritis
Back pain
BK virus associated with nephropathy
Blood pressure changes
Blurred vision
Bronchiectasis
Colitis
Conjunctivitis
Contusion
Cough
Cytomegalovirus gastritis
Delusions
Diabetes mellitus
Dizziness
Dream abnormalities
Dry mouth
Duodenal ulcer
Dyspepsia
Dyspnoea
Electrolyte disturbances
Endocarditis
Eructation
Fatigue
Flatulence
Gastric ulceration
Gastritis
Gastro-intestinal disturbances
Gastro-intestinal haemorrhage
Gastro-intestinal perforation
Gastroesophageal reflux disease
Gingival hyperplasia
Haematuria
Halitosis
Headache
Hepatitis
Hypercholesterolaemia
Hyperlipidaemia
Hyperphosphataemia
Hypogammaglobulinaemia
Ileus
Impotence
Increased risk of skin cancer
Influenza-like syndrome
Insomnia
Interstitial lung disease
Jaundice
Kaposi's Sarcoma
Leukopenia
Lip ulceration
Lymphadenopathy
Lymphocele
Lymphopenia
Lymphoproliferative disorders
Meningitis
Muscle cramps
Mycobacterial infection
Nausea
Neutropenia
Oedema
Oesophagitis
Opportunistic infections
Osteomyelitis
Pain
Pancreatitis
Pancytopenia
Parotid duct obstruction
Peptic ulceration
Peritonitis
Progressive multifocal leukoencephalopathy (PML)
Pulmonary congestion
Pulmonary fibrosis
Pulmonary oedema
Pyrexia
Rash
Red cell aplasia
Renal tubular necrosis
Rigors
Sepsis
Serum creatinine increased
Skin papilloma
Soft or liquid stools
Sub-ileus
Tachycardia
Thirst
Thrombocytopenia
Tongue discolouration (reversible)
Tremor
Tuberculosis
Urethral stricture
Weakness
Wheezing

Presentation

Oral formulations of mycophenolic acid (as mycophenolate sodium).

Drugs List

Therapeutic Indications

Uses

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.

Dosage

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

Mycophenolic acid and mycophenolate mofetil should not be indiscriminately interchanged or substituted due to their different pharmacokinetic profiles.

The medication can be taken with or without food - the patient must chose the option and it should be adhered to.

Adults

Contraindications

Children under 18 years
Breastfeeding
Galactosaemia
Pregnancy

Precautions and Warnings

Elderly
Hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase
Drug induced neutropenia with cell count below 1.5 x 10 to the power of 9/L
Glucose-galactose malabsorption syndrome
Hepatitis
Lactose intolerance
Renal impairment- creatinine clearance below 25ml/minute/1.73 square metre
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 lactose
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 bone marrow depression
Monitor renal function in patients with renal impairment
Monitor serum immunoglobulins in patients with recurrent infections
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
Oversuppression of immune system may increase susceptibility to infection
Advise patient to seek advice at first indications of pregnancy
Discontinue or interrupt treatment if neutropenia develops
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

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 mycophenolic acid.

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

Mycophenolic acid 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

Mycophenolic acid is contraindicated in breastfeeding.

It is not known whether mycophenolic acid 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 distension
Acne
Agitation
Alopecia
Altered liver function tests
Anaemia
Anorexia
Arthralgia
Arthritis
Back pain
BK virus associated with nephropathy
Blood pressure changes
Blurred vision
Bronchiectasis
Colitis
Conjunctivitis
Contusion
Cough
Cytomegalovirus gastritis
Delusions
Diabetes mellitus
Dizziness
Dream abnormalities
Dry mouth
Duodenal ulcer
Dyspepsia
Dyspnoea
Electrolyte disturbances
Endocarditis
Eructation
Fatigue
Flatulence
Gastric ulceration
Gastritis
Gastro-intestinal disturbances
Gastro-intestinal haemorrhage
Gastro-intestinal perforation
Gastroesophageal reflux disease
Gingival hyperplasia
Haematuria
Halitosis
Headache
Hepatitis
Hypercholesterolaemia
Hyperlipidaemia
Hyperphosphataemia
Hypogammaglobulinaemia
Ileus
Impotence
Increased risk of skin cancer
Influenza-like syndrome
Insomnia
Interstitial lung disease
Jaundice
Kaposi's Sarcoma
Leukopenia
Lip ulceration
Lymphadenopathy
Lymphocele
Lymphopenia
Lymphoproliferative disorders
Meningitis
Muscle cramps
Mycobacterial infection
Nausea
Neutropenia
Oedema
Oesophagitis
Opportunistic infections
Osteomyelitis
Pain
Pancreatitis
Pancytopenia
Parotid duct obstruction
Peptic ulceration
Peritonitis
Progressive multifocal leukoencephalopathy (PML)
Pulmonary congestion
Pulmonary fibrosis
Pulmonary oedema
Pyrexia
Rash
Red cell aplasia
Renal tubular necrosis
Rigors
Sepsis
Serum creatinine increased
Skin papilloma
Soft or liquid stools
Sub-ileus
Tachycardia
Thirst
Thrombocytopenia
Tongue discolouration (reversible)
Tremor
Tuberculosis
Urethral stricture
Weakness
Wheezing

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: March 2018

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

MHRA Drug Safety Update November 2015
Available at: https://www.mhra.gov.uk
Last accessed: 14 March 2018

Summary of Product Characteristics: Ceptava 180mg Gastro-resistant Tablets. Sandoz Limited. Revised May 2018.

Summary of Product Characteristics: Ceptava 360mg Gastro-resistant Tablets. Sandoz Limited. Revised May 2018.

Summary of Product Characteristics: Myfortic 180mg gastro-resistant tablets. Novartis Pharmaceuticals UK. Revised August 2018.

Summary of Product Characteristics: Myfortic 360mg gastro-resistant tablets. Novartis Pharmaceuticals UK. Revised August 2018.

The Renal Drug Handbook. Fourth Edition (2014) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.