Methotrexate parenteral vial/ampoule
- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Vials and ampoules containing methotrexate (information for pre-filled devices is held on separate monograph).
Severe psoriasis when other regimens unsuitable/ineffective
Treatment of neoplastic disease including; acute lymphocytic leukaemia, prophylaxis of meningeal leukaemia, non-hodgkin's lymphoma, osteogenic sarcoma, adjuvant and in advance disease of breast cancer, metastatic or recurrent head and neck cancer, choriocarcinoma and similar trophoblastic diseases, advanced cancer of urinary bladder.
Symptomatic treatment of severe recalcitrant disabling psoriasis, when other regimens are unsuitable or ineffective.
Crohn's disease - maintenance of remission
Severe Crohn's disease
Treatment of severe Crohn's disease and the maintenance of remission of Crohn's disease.
Treatment of autoimmune diseases, including severe active rheumatoid arthritis, juvenile idiopathic arthritis, juvenile dermatomyositis, vasculitis uveitis, systemic lupus erythematosus, localised scleroderma, and sarcoidosis.
Due to the complexity and specialist nature of dosage regimens for the treatment of malignant disease, specific dosing information for neoplastic disease is not included.
Doses may vary significantly if this agent is used as monotherapy or different combinations.
When using this agent, specialist literature, national guidelines, cancer network protocols and Trust chemotherapy protocols should be consulted.
Doses are calculated in terms of methotrexate not methotrexate sodium. Dosages are based on the patient's body weight or surface area except in the case of intrathecal administration when a single maximum dose is applied to all patients.
A test dose of 5mg to 10mg is recommended.
Initial dose: 7.5mg once weekly (some sources recommend starting range between 2.5mg to 10mg)
The usual maintenance dose is 10mg to 25mg once weekly either intramuscularly or intravenously. Titrate gradually (in 2.5mg steps) to a maximum of 30mg once weekly.
Severe Crohn's Disease (unlicensed)
Induction of remission
25mg once weekly by intramuscular injection.
Maintenance of remission
15mg once weekly by intramuscular injection.
Severe Active Rheumatoid Arthritis (unlicensed)
7.5mg once weekly by subcutaneous, intramuscular or intravenous injection. Titrate gradually (in 2.5mg steps) to a maximum of 25mg once weekly
Severe Crohn's Disease (unlicensed)
Children aged 7 to 18 years:
15mg/metre squared (maximum 25mg) once weekly by subcutaneous or intramuscular injection. Titrate to lowest effective dose for maintenance therapy.
Autoimmune Disease: Juvenile idiopathic arthritis, juvenile dermatomyositis, vasculitis, uveitis, systemic lupus erythematosus, localised scleroderma, and sarcoidosis (unlicensed)
Children aged 1 month to 18 years:
10mg to 15mg/metre squared (maximum 25mg per metre squared) once weekly by subcutaneous or intramuscular injection.
Patients with Renal Impairment
Creatinine clearance more than 50 ml per minute: No dose reduction required.
Creatinine clearance 20 to 50 ml per minute: Use 50% of dose.
Creatinine clearance less than 20 ml per minute: Contraindicated.
The renal drug handbook suggests a 50% dose reduction can be used in patients with a glomerular filtration rate between 10 and 50ml/minute.
For intramuscular, intravenous and intra-arterial routes of administration.
Some presentations are suitable for intrathecal use, ensure these preparations are isotonic and preservative-free.
Severe haematological disorder
Severe hepatic impairment
Severe renal impairment
Precautions and Warnings
Children under 18 years
Females of childbearing potential
History of high alcohol intake
History of radiotherapy
Significant pleural effusion
Administration of live vaccines is not recommended
Consider screening at risk patients for hepatitis B and/or C virus
Sodium content of formulation may be significant
Advise ability to drive/operate machinery may be affected by side effects
Ascites should be drained before treatment
Concurrent radiotherapy may increase risk of serious adverse effects
Consider calcium leucovorin rescue if systemic absorption of therapy likely
Consider use of folic acid supplement to improve tolerability
Give pre-treatment counselling and consideration of sperm cryopreservation
Maintain adequate hydration of patient prior / during treatment
Not all available brands are licensed for all indications
Not all available brands are licensed for all routes of administration
Pleural effusions should be drained before treatment
Treatment to be initiated and supervised by a specialist
Consult local policy on the safe use of anti-cancer drugs
Staff: Not to be handled by pregnant staff
Exclude pregnancy prior to initiation of treatment
Monitor full blood count and differential WBC before and during therapy
Monitor hepatic function before treatment and regularly during treatment
Monitor renal function before treatment and regularly during treatment
Perform chest X-ray prior to and periodically during treatment
Urinalysis required pre and post treatment
Consider liver biopsy after cumulative doses exceed 1.5g
Consider monitoring plasma drug levels
Elderly: Monitor renal function and consider dose modification
Examine mouth and throat for mucosal changes
Haemopoietic suppression may occur abruptly & with apparently safe dosages
If rash develops, consider possibility of Stevens-Johnson Syndrome
Monitor for drug induced pneumonitis at each visit
Monitor for hepatotoxicity which may occur without other signs of toxicity
Monitor haematocrit values
Monitor patients for signs of tumour lysis syndrome
Take chest X-ray if fever,cough,dyspnoea or other respiratory signs occur
Advise patient to report breathlessness or cough immediately
Advise patient to report symptoms of infection immediately
Advise patient to seek medical advice if severe skin reaction occurs
Advise patients to report signs of diarrhoea and stomatitis
Discontinue if hepatic enzymes (AST or ALT) become persistently raised
Discontinue if malignant lymphomas develop
Discontinue if patient develops respiratory symptoms
Discontinue treatment if profound drop in platelets or WBC occur
Interrupt treatment if diarrhoea or stomatitis occur
Consider dose reduction in hepatic impairment
Consider dose reduction in renal impairment
For high doses consider urinary alkalisation and high fluid throughput
Not licensed for all indications in all age groups
Advise patient not to take echinacea products concurrently
Advise patient to consult doctor before any self medication
Advise patients to avoid aspirin and NSAID use
Advise patient to avoid alcohol during treatment
Advise patient excessive dietary caffeine may adversely effect treatment
May cause impaired fertility
Male & female: Contraception required during & for 6 months after treatment
Advise patient to avoid exposure to sunlight and UV rays during treatment
The following tests should be carried out prior to and repeated every 1 to 2 weeks until treatment has stabilised, thereafter patients should be monitored every 2 to 3 months:
Complete blood count with differential blood count and platelets
Renal function tests
If liver dysfunction occurs, withhold for a minimum of 2 weeks before reintroduction.
In patients treated for psoriasis the need for liver biopsy should be considered on a case by case basis considering hepatic risk factors such as: Excessive prior alcohol consumption, persistent elevation of liver enzymes, anamnestic liver diseases, hereditary liver diseases, diabetes mellitus, obesity, history of significant exposure to hepatotoxic drugs, prolonged methotrexate treatment (cumulative dose of 1.5g or more).
Treatment should be withdrawn from patients with respiratory symptoms and a thorough investigation including chest X-ray should be carried out to exclude infection. Pneumonitis carnii should be considered in patients with respiratory conditions. If methotrexate induced lung disease is suspected initiate corticosteroids and methotrexate treatment should not be restarted.
Additional precautions relevant for intrathecal use
Always ensure that the methotrexate chosen to prepare intrathecal dosages is of an appropriate strength and licensed for intrathecal administration.
Systemic toxicity of methotrexate may occur following intrathecal administration and be enhanced in patients with renal dysfunction, ascites or other effusions due to prolongation of serum half-life.
Additional precautions for all routes
High doses may cause the precipitation of methotrexate or its metabolites in the renal tubules. A high fluid throughput and alkalisation of the urine to pH 6.5 to 7.0 is recommended as a preventative measure.
Folate deficiency states may increase methotrexate toxicity. Folic or folinic acid may be required, with some manufacturers advising it should be used for all doses over 100mg.
Some sources suggest caution should be used in patients with acute porphyria. However, NAPOS classifies methotrexate as probably not porphyrinogenic.
Pregnancy and Lactation
Methotrexate is contraindicated in pregnancy.
Abortion, foetal death and congenital abnormalities have occurred in pregnant women receiving methotrexate, especially during first trimester exposure.
Although methotrexate is known to persist in tissues for long periods, Briggs states that pregnancies after methotrexate is discontinued to not seem to be at an increased risk.
The effect of concurrent therapies must also be considered.
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 ).
Methotrexate is contraindicated in breastfeeding.
Methotrexate is excreted in human breast milk in concentrations strong enough that there is a risk to the infant.
The effect of concurrent therapies must also be considered.
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
Abnormal tissue cell changes
Amenorrhoea during and after treatment
Bone marrow depression
Elevation of liver enzymes
Exacerbation of psoriasis
Hepatic disorders (fatty changes)
Increased susceptibility to infection
Loss of libido
Precipitation of diabetes
Skin pigmentation changes
Sudden death reported
Transient cognitive dysfunction
Unusual cranial sensations
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 ).
Last Full Review Date: August 2018
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.
The Renal Drug Handbook. Fourth Edition (2014) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.
Summary of Product Characteristics: Methotrexate Injection 25mg/ml. Accord Healthcare. Revised June 2018.
Summary of Product Characteristics: Methotrexate Injection 100mg/ml. Accord Healthcare. Revised June 2018.
Summary of Product Characteristics: Methotrexate Injection 2.5mg/ml. Hospira UK Ltd. Revised July 2018.
Summary of Product Characteristics: Methotrexate Injection 5mg/2ml. Hospira UK Ltd. Revised July 2018.
Summary of Product Characteristics: Methotrexate Injection 25mg/ml. Hospira UK Ltd. Revised July 2018.
Summary of Product Characteristics: Methotrexate Injection 100mg/ml. Hospira UK Ltd. Revised July 2018.
Summary of Product Characteristics: Methotrexate Injection 100mg/ml. Medac GmbH. Revised March 2018.
The Norwegian Porphyria Centre (NAPOS).
Available at: https://www.drugs-porphyria.org
Last revised: 11 January 2012.
Last accessed: 28 September 2015.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 16 August 2018
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Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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