Patient leaflet - Methotrexate injection 25 mg / ml
1. What Methotrexate is and what it is used for
Methotrexate is an anti‑metabolite medicine (medicine which affects how the body’s cells grow) and immunosuppressant (medicine which reduces the activity of the immune system). This medicine is used in large doses (on its own or in combination with other medicines) to treat certain types of cancer such as breast cancer. In smaller doses it can be used to treat severe psoriasis (a skin disease with thickened patches of inflamed red skin, often covered by silvery scales), when it has not responded to other treatments.
2. What you need to know before you use Methotrexate
Do not use Methotrexate if:
- you are allergic to Methotrexate or any of the other ingredients of this medicine (listed in section 6)
- you have significant kidney or liver problems
- you have been told you have (or think you have) a blood disorder such as low levels of white blood cells, red blood cells (anaemia) or platelets
- you have any infection
- your immune system is not working as well as it should
you are pregnant or breast‑feeding (see section
‘Pregnancy, breast‑feeding and fertility’)
Tell your doctor, pharmacist or nurse before you use this medicine if you think any of the above applies to you. Warnings and precautions
During treatment with this medicine, you will be carefully monitored by the doctor, pharmacist or nurse. Tell the doctor, pharmacist or nurse before using this medicine if:
- you have a stomach ulcer or ulcerative colitis (inflammation and ulceration of the gut)
- you have an infection (e.g. pneumonia)
- you have liver or kidney problems or blood disorders including anaemia
you have a medical condition which causes a build‑up of
fluid in the lining of your lungs and chest wall (pleural effusion) causing breathlessness or swelling of the abdomen (ascites)
- you have recently undergone or are undergoing radiation therapy (risk of tissue and bone damage may be increased)
- you are to have any vaccinations as they may not work fully
- you have a folate deficiency (vitamin B9)
- you have chronic liver infections (e.g. hepatitis B or C)
you develop nausea, vomiting, diarrhoea, fainting muscle cramps (tumour lysis syndrome)
Special care is also to be taken in children, the elderly and in those who are in poor physical condition.
Acute bleeding from the lungs in patients with underlying rheumatologic disease has been reported with methotrexate. If you experience symptoms of spitting or coughing up blood you should contact your doctor immediately.
If you, your partner or your caregiver notice new onset or worsening of neurological symptoms including headaches, back pain, fever, general muscle weakness, paralysis, coma,
stroke‑like episodes, disturbance of vision, changes in thinking, memory and orientation leading to confusion and personality changes contact your doctor immediately because these may be symptoms of a very rare, serious brain infection called progressive multifocal leukoencephalopathy (PML). This medicine temporarily affects sperm and egg production. It can cause miscarriage and severe birth defects. If you are a woman you should avoid having a baby if you are being given methotrexate at the time and for at least 6 months after the end of your treatment with methotrexate. If you are a man, you should avoid fathering a child if you are being given methotrexate at the time and for at least 3 months after the end of your treatment.
See also section ‘Pregnancy, breast‑feeding and fertility’. This medicine can cause serious skin reactions. Stop using Methotrexate and seek medical attention immediately if you notice any of the symptoms related to these serious skin reactions described in section 4.
This medicine may make your skin more sensitive to sunlight. Avoid intense sun and do not use sunbeds or a sunlamp without medical advice. To protect your skin from intense sun, wear adequate clothing or use a sunscreen with a high protection factor.
Recommended follow-up examinations and precautions
Even if methotrexate is used in low doses, serious side
effects can occur. In order to detect them in time, your doctor must perform monitoring examinations and laboratory tests. Prior to the start of therapy:
Before you start treatment, your blood will be checked to see if you have enough blood cells. Your blood will also be tested to check your liver function and to find out if you have hepatitis. Furthermore, serum albumin (a protein in the blood), status and kidney function will be checked. The doctor may also decide to run other liver tests, some of these may be images of your liver and others may need a small sample of tissue taken from the liver in order to examine it more closely. Your doctor may also check to see if you have tuberculosis, and they may X‑ray your chest or perform a lung function test.
During the treatment:
Your doctor may perform the following examinations: ‑ examination of the oral cavity and the pharynx for changes in the mucous membrane such as inflammation or ulceration ‑ blood tests/blood count with number of blood cells and measurement of serum methotrexate levels ‑ blood test to monitor liver function
‑ imaging tests to monitor liver condition
‑ small sample of tissue taken from the liver in order to examine it more closely
‑ blood test to monitor kidney function
‑ respiratory tract monitoring and, if necessary, lung
function test
It is very important that you appear for these scheduled examinations.
If the results of any of these tests are irregular, your doctor will adjust your treatment accordingly.
Children
Children will need to be closely monitored, in order to identify the best dose of this medicine and in order to reduce undesirable effects in a timely manner.
Elderly patients
Elderly patients under treatment with this medicine should be monitored closely by a doctor so that possible side effects can be detected as early as possible. Age‑related impairment of liver and kidney function as well as low body reserves of the vitamin folic acid in old age require a relatively low dosage of methotrexate.
Other medicines and Methotrexate
Tell your doctor, pharmacist or nurse if you are taking, have
recently taken, or might take any other medicines. Special care is needed if you are taking/using other medicines as some could interact with methotrexate, for example:
- non‑steroidal anti‑inflammatory medicines e.g. ibuprofen (medicines taken for pain relief)
- aspirin or similar medicines (known as salicylates)
- proton‑pump inhibitors e.g. omeprazole, esomeprazole and pantoprazole (medicines used to reduce the production of stomach acid)
- diuretics (e.g. triameterene ‑ water tablets)
- hypoglycaemics, medicines taken for diabetes (including insulin and tablets)
antibiotics such as ciprofloxacin, penicillins, sulphonamides,
co‑trimoxazole or trimethoprim/sulfamethoxazole, tetracycline, chloramphenicol, anti‑protozoal pyrimethamine
- para‑aminobenzoic acid (nutrient in the vitamin B complex)
phenytoin (medi
cine often used to treat epileps ents containing folic acid dicine used to treat gout) ed for general anaesthesia and
y)
- vitamin supplem
- probenecid (me
nitrous oxide (us Nitrous oxide inc lead to an increa number of blood
pain relief).
reases the effect of methotrex se in some side effects (such cells and platelets and inflam
ate and can as reduced mation of
mouth). Followin effect on your ne
g injection into the spine it can rvous system
have an
metamizole (syn (medicine again
onyms novaminsulfon and dip st severe pain and/or fever)
yrone)
•
retinoids, such as acitretin (a medicine used to trea psoriasis) or isotretinoin (used to treat severe acne other drugs that may cause damage to your kidney
t
)
•
s
•
other drugs that may cause damage to your liver e leflunomide, azathioprine, sulfasalazine, retinoids,
.g.,
alcohol
•
live virus vaccines
•
chemotherapeutic medicines e.g. mercaptopurine (medicine used in the treatment of blood cell cance
r),
cytarabine and L‑asparaginase
- theophylline (medicine used in the treatment of asthma)
amiodarone (medicine used to treat and prevent heart
rhythm disorders)
- leflunomide (medicine used in the treatment of rheumatoid arthritis)
- packed red blood cells (used for transfusions)
- psoralen plus ultraviolet light (PUVA) therapy Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
Methotrexate with food, drink and alcohol
Do not drink alcohol whilst being treated with this medicine as alcohol increases the risk of liver damage.
Pregnancy, breast-feeding and fertility
If you are pregnant or breast‑feeding, think you may be
pregnant or are planning to have a baby, ask your doctor or pharmacist, before this medicine is used.
Pregnancy
Do not use methotrexate during pregnancy except if your doctor has prescribed it for oncology treatment. This medicine can cause birth defects, harm the unborn child or cause miscarriage. It is associated with malformations of the skull, face, heart and blood vessels, brain, and limbs. It is therefore very important that methotrexate is not given to pregnant women
or to women who are planning to become pregnant unless used for oncology treatment.
For non‑oncological indications, in women of child‑bearing age the possibility of a pregnancy must be ruled out, e.g. by pregnancy tests, before treatment is started.
Female fertility
Do not use this medicine if you are trying to become pregnant. You must avoid becoming pregnant during treatment with methotrexate and for at least 6 months after the end of treatment.
Therefore, you must ensure that you are taking effective contraception for the whole of this period (see also section "Warnings and precautions").
If you become pregnant during treatment or suspect you might be pregnant, speak to your doctor as soon as possible. If you do become pregnant during treatment, you should be offered advice regarding the risk of harmful effects on the child through treatment.
If you want to become pregnant, you should speak with your doctor, who may refer you for specialist advice before the planned start of treatment.
Mothers should not breast‑feed whilst treatment with methotrexate is ongoing.
Male fertility
The available evidence does not indicate an increased risk of malformations or miscarriage if the father takes methotrexate less than 30 mg/week. However, a risk cannot be completely excluded and there is no information regarding higher methotrexate doses. Methotrexate can have a genotoxic effect. This means that the medicine can cause genetic mutations. Methotrexate can affect the production of sperm, which is associated with the possibility of birth defects.
You should avoid fathering a child or donating semen during treatment with methotrexate and for at least 3 months after the end of treatment. As treatment with methotrexate at higher doses commonly used in cancer treatment can cause infertility and
genetic mutations, it may
be advisable for male patients trea
ted with methotrexate dos
es higher than 30 mg/week to consider sperm preservation b
efore the beginning of treatment
(see also section "Warnings a
nd precautions").
Ask your doctor, pharmacist o
r nurse for advice before taking any medicine.
Driving and using mach
ines
Do not drive or use machines if you experience any side effect
(e.g. fatigue and drowsiness) which may lessen your ability to do so.
Methotrexate contains sodium
Methotrexate 50 mg/2 ml and 250 mg/10 ml contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially
‘sodium‑free’.
Methotrexate 500 mg/20 ml contains 41.1 mg sodium (main component of cooking/table salt) per vial. This is equivalent to 2.06% of the recommended maximum daily dietary intake of sodium for an adult.
Methotrexate 1 g/40 ml contains 82.2 mg sodium (main component of cooking/table salt) per vial. This is equivalent to 4.11% of the recommended maximum daily dietary intake of sodium for an adult.
3. How to use Methotrexate
This medicine may be given by injection into a vein (intravenous injection), into muscle (intramuscular injection), into an artery
(intraarterial injection) or into the spine (intrathecal injection)*. It may also be given by infusion (drip) into a vein. It may be diluted before it is given.
*Of the presentations available (see section 6) only the 50 mg/2 ml is suitable for intrathecal injection.
Recommended dose
Your doctor will work out the correct dose of this medicine for you and how often it must be given.
The following information is intended for medical or healthcare professionals only Methotrexate 25 mg/ml Injection methotrexate FOR FURTHER INFORMATION PLEASE REFER TO THE SUMMARY OF PRODUCT CHARACTERISTICS INSTRUCTIONS FOR USE
Only the 50 mg/2 ml presentation is suitable for intrathecal administration.
Single use only. Discard any unused contents. After dilution, chemical and physical in‑use stability has been demonstrated in dextrose 5% and sodium chloride 0.9% infusion solutions for 30 days at 4°C in PVC containers when protected from light.
From a microbiological point of view the product should be used immediately. If not used immediately, in‑use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2‑8°C, unless dilution has taken place in controlled and validated aseptic conditions.
INCOMPATIBILITIES
Immediate precipitation or turbidity results when combined with certain concentrations of droperidol, heparin sodium, metoclopramide hydrochloride, ranitidine hydrochloride in syringe.
The dose of medicine given to you will depend on the disease being treated, your medical condition, your age, your size and how well your kidneys are working.
Dose in severe psoriasis:
Take this medicine only once a week.
Important warning about the dose of Methotrexate:
Use Methotrexate only once aweek for the treatment of psoriasis. Using too much of Methotrexate may be fatal.
Please read section 3 of this leaflet very carefully. If you have any questions, please talk to your doctor or pharmacist before you take this medicine.
If you use more Methotrexate than you should
This medicine will be given to you in a hospital, under the supervision of a doctor. It is unlikely that you will be given too much or too little, however, tell your doctor, pharmacist or nurse if you have any concerns.
4. Possible side effects
Like all medicines, methotrexate can cause side effects, although not everybody gets them.
Methotrexate is a very toxic medicine and patients have died,
or become very ill, whilst being treated with it. During treatment you should watch for any side effects and report them to the doctor.
Stop using Methotrexate and seek medical attention immediately if you notice any of the following symptoms of serious skin reactions:
- severe skin erosions and skin peeling, often with painful sores affecting the mouth or mucous membrane (epidermal necrosis)
If any of the following happen, tell your doctor, pharmacist or nurse immediately:
severe allergic reaction ‑ you may experience a sudden itchy rash (hives), swelling of the hands, feet, ankles, face, lips,
mouth or throat (which may cause difficulty in swallowing or breathing), rash with fever (frequency not known) and you may feel you are going to faint (frequency uncommon)
- serious skin reactions, such as rash and ulceration of the skin, reddening, blisters, pustules, necrosis or desquamation of the skin (frequency uncommon)
- inflammation of the lung with breathlessness – you may develop a persistent cough, weakness and raised temperature and experience pain or difficulty breathing, or become breathless. This may be associated with changes in a particular type of white cell in your blood (frequency uncommon)
- diarrhoea (frequency uncommon)
weakness in the legs that spreads to the upper limbs and
the face, which may result in paralysis (frequency not known)
- miscarriage (frequency not known)
- extreme inflammation and distention of the colon (frequency rare)
- ulcer or bleeding of the stomach and intestine (frequency rare)
- diseases of the brain (frequency uncommon), nerve pain around spinal cord (frequency not known)
- paralysis of one side of the body (frequency uncommon)
- infection in the bloodstream (sepsis) (frequency rare)
- acute inflammation of the liver with yellowing of the skin and whites of the eyes (acute hepatitis) (frequency rare)
re‑activation of a pre‑existing infection with hepatitis B
(frequency not known)
- worsening of a pre‑existing infection with hepatitis C (frequency not known)
- increased tendency towards bone fracture, bone pain (osteoporosis) (frequency not known)
- appearance of unexpected bruises or broken blood vessels (haemorrhage) (frequency not known)
chest pain (frequency not known)
- blood tests showing elevated uric acid, potassium and phosphorus (frequency rare)
The following side effects have also been reported: Uncommon (may affect up to 1 in 100 people):
- reduction in the activity of the bone marrow that produces blood cells; reduction in the number of red blood cells (anaemia) and platelets in the blood
- blood cancer
- defects in unborn child
- reduced appetite, feeling or being sick
- fits (seizures)
- headaches
- accumulation of fluid around the lungs
- inflammation of the pancreas, vomiting, inflammation of the lining of the mouth
- hair loss in patches (alopecia)
- kidney failure, kidney damage
- increase in liver function test
- sunburn‑like reactions due to increased sensitivity of the skin to sunlight
Rare (may affect up to 1 in 1,000 people):
- inflammation of the nose and throat, inflammation of the gums
- high blood glucose level (diabetes mellitus)
- mood alterations
- effects on learning and memory
difficulty in spea communication
king, difficulty in language and
- blurred vision
serious alteratio
ns in vision
low blood press
ure (hypotension)
blood clot which
causes pain, swelling or redne ngs which causes shortness o flammation of small intestine
ss
scarring of the lu
f breath
- bloody stools, in
difficulty in the di
gestion or absorption of nutrient nction, liver damage (hepatoto
s from food xicity),
decline in liver fu
portal fibrosis
•
itching or the appearance of lightened patches on t bruises, skin rash painful detachment of thick scaly p skin ulcer, itchy rash, acne
he skin, atches,
•
joint pain, muscle pain difficulty urinating
•
•
irregular periods in women
•
abortion
•
formation of small lump
- tiny cracks in a bone
Very rare (may affect up to 1 in 10,000 people):
- boils
- severe reduction in blood cells which can cause weakness, bruising or make infections more likely, excessive growth of white blood cells
- reduction in certain antibodies (called "gamma globulin") in your immune system which protect you from viruses and bacteria that make you sick
- sensation of tingling, pins and needles, cranial nerve disorders*, total or partial loss of sensation in a part of your body
- eye infection (conjunctivitis)
- accumulation of fluid or inflammation of the membrane that surrounds the heart
- inflammation of blood vessels
- presence of blood in the vomit
- reduction in albumin levels in the blood
- dilation of some small blood vessels in the skin
- presence of blood in the urine, increase of blood urea nitrogen and serum creatine levels in a laboratory test
alteration of egg or sperm production, infertility, temporary reduction in spermatozoa concentration in the sperm and vaginal discharge
*optic nerve disorder
Not known (cannot be determined from the available data):
- infections caused by various microorganisms (e.g. bacteria, viruses, fungi, yeast) in different organs (e.g. lungs, liver), inflammation of bladder lining, inflammation, discharge, itching and pain in vagina
- severe reduction in blood cells, enlarged lymph nodes, increase in the number of a type of white blood cells eosinophils in the blood, reduction in red blood cell count
- other metabolic changes
- perforation of the intestine
- paralysis that mostly affects the movement of the lower body**, absence of reaction to stimuli, uncontrollable movements**, confusion, dizziness, difficulty in ability to think and remember
- ringing in the ears (tinnitus)
- inflammation of the pulmonary alveolus, cough, spitting or coughing of blood*, nausea
- liver problems, fatty liver
- aggravation of psoriatic lesions, swelling of the skin, epidermal necrolysis, redness and shedding of skin, sensation of numbness or tingling
- death, sudden death
- bone damage in the jaw (secondary to excessive growth of white blood cells)
- presence of protein in the urine
- genital problems and urinary tract problems, vaginal ulceration
- fever, chills, feeling unwell, fatigue, swelling with fluid retention, swelling inside the mouth
- injection site reaction, dark red or black patches of skin around the injection site, often accompanied with pain
- increased intracranial pressure**
*has been reported for methotrexate used patients with underlying rheumatologic disease
**h
ave followed intrathecal ad
ministration
Some different side eff
ects may occur following injection into the spine.
These are:
- headache
- back or shoulder pain
difficulty with bending your
head down
- fever
- temporary paralysis or weakness
- problems with a particular part of your brain, leading to shaking, abnormal balance or staggering
- irritability and confusion
- stiffness
- fits
- loss of memory
- sleepiness
- coma
- death
This medicine may lead to problems with your blood, liver and kidneys. Your doctor will take blood samples to check for these problems and may ask you to have an operation to have a small sample of your liver removed.
Effects on fertility
Treatment with this medicine may reduce fertility in men and women. Fertility is thought to go back to normal after the treatment with this medicine is stopped. Tell your doctor if you have concerns.
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects, you can help provide more information on the safety of this medicine.
5. How to store Methotrexate
Keep this medicine out of the sight and reach of children. Expiry date
Do not use this medicine after the expiry date which is stated on the vial label and carton after 'EXP'. Where only a month and year is stated, the expiry date refers to the last day of that month. Storage conditions
The vials should be kept in the outer carton, in order to protect from light.
Do not store above 25°C.
The vials should not be frozen.
Unused portions of opened vials must not be stored for later use. Prepared infusions should be used immediately, however, if this is not possible, they can, in certain circumstances, be stored for up to 30 days in a refrigerator provided they have been prepared in a way to exclude microbial contamination.
6. Contents of the pack and other information
What Methotrexate contains
The active substance is methotrexate. Each millilitre (ml) of solution contains 25 milligrams (mg) of methotrexate.
The other ingredients are sodium chloride, sodium hydroxide (see section 2 “Methotrexate contains Sodium”), hydrochloric acid (pH adjuster) and water for injection.
What Methotrexate looks like and contents of the pack
This medicine is a clear, yellow solution for injection which comes in glass containers called vials. It may be supplied in packs containing:
- 5 x 50 mg/2 ml vials
- 1 x 500 mg/20 ml vial
Not all packs may be marketed.
Methotrexate 25 mg/ml
PAA251489
Marketing Authorisation Holder
Hospira UK Limited, Walton Oaks, Walton‑On‑The‑Hill Dorking Road, Tadworth, Surrey, KT20 7NS, UK Manufacturer
Pfizer Service Company BV, Hermeslaan 11, 1932 Zaventem Belgium
This leaflet was last revised in 08/2026.
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