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Active substance(s): METHOTREXATE

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Patient information leaflet

Read all of this patient information leaflet carefully before it is administered to you because it contains important
information for you.
• Keep this leaflet. You may need to read it again.
• If you have further questions, ask your doctor, pharmacist or nurse.
• This product has been prescribed for you only. Do not pass it on to others. It may harm them even if their signs of illness
are the same as yours.
• If you get any side effects talk to your doctor, pharmacist or nurse. This includes any possible side effects not list in this
leaflet, See section 4.
What is in this leaflet:
1. What Methotrexate 25 mg/ml solution for injection is and what it is used for
2. What you need to know before receiving Methotrexate 25 mg/ml solution for injection
3. How Methotrexate 25 mg/ml solution for injection is administered
4. Possible side effects
5. How to store Methotrexate 25 mg/ml solution for injection
6. Contents of the pack and other information

Methotrexate 25 mg/ml solution for injection
1. What Methotrexate 25 mg/ml solution for injection
is and what it is used for
Methotrexate is one of a group of medicines known as
antimetabolites. It is used in the treatment of cancer as
well as psoriasis including psoriatic arthritis. It stops a
substance called dihydrofolate reductase from working.
This substance is an enzyme, which is important in “cell
growth (replication)”. By inhibiting the enzyme, cancer
cells will eventually “die”.
Methotrexate helps patients with psoriasis by killing the
cells in the skin that are growing too fast. It is these rapidly
growing cells that cause the raised patches of skin in
2. What you need to know before
Methotrexate 25 mg/ml solution for injection
2.1 Do NOT use Methotrexate 25 mg/ml solution for
• if you have ever had any allergic reaction to methotrexate
or any of the ingredients of this product
• if you have severe problems with your kidneys
• if you have severe problems with your liver, including
alcoholic liver disease, abnormal blood counts, fibrosis,
cirrhosis or recent active hepatitis
• if you suffer from alcoholism
• if you have any serious blood disorders (anaemia, a
reduction in white cell number (leucopenia) or platelet
number (thrombocytopenia))
• if you have an active infection
• if you have a medical condition, or are receiving
medication, which lowers your resistance to infection
• if you are pregnant or intend to become pregnant, or are
breast-feeding, as the drug can harm unborn and breastfed infants.
2.2 Warnings and precautions
Talk to your doctor, pharmacist or nurse before using
Methotrexate 25 mg/ml solution for injection
• if you have impaired respiratory function
• if you have mild to moderate kidney or liver problems, or
a mild to moderate blood disorder
• if you have diarrhoea
• if you have ulcers in your mouth, stomach or intestine
(large bowel)
• if you have ascites (collection of liquid in the free
abdominal cavity) and/or pleural effusions (collection of
liquid in the pleural cavity)
• if you are receiving or intend to receive any vaccine, as
methotrexate can reduce their effect
• if you have had radio- or chemotherapy before (especially
of the pelvis), or are receiving radiotherapy concurrently
• if you have an impaired general condition (if you feel
weak or infirm)
• if you are of advanced age
• if Methotrexate 25 mg/ml solution for injection is given to
very young children.
Please consult your doctor, even if these statements were
applicable to you at any time in the past.
2.3 Other medicines and Methotrexate 25 mg/ml
solution for injection
Tell your doctor, pharmacist or nurse if you are taking,
have recently taken, or might take any other medicines,
including medicines obtained without a prescription.
Medications which can be influenced by or can
influence the effect of methotrexate negatively:
• pain-killers such as salicylates (e.g. aspirin), amidopyrine
derivatives, phenylbutazone and leflunomide
• diphenylhydantoins (e.g. phenytoin, an antiepileptic
• barbiturates and tranquillisers (sedative agents)
• antibiotics
tetracyclines, penicillins, chloramphenicol, cotrimoxazole
and sulphonamides
• cytostatics (medication against cancer), e.g. cytarabine,
doxorubicin, mercaptopurine, procarbazine, cisplatin,

L-asparaginase and 5-fluorouracil
• Disease-modifying antirheumatic drugs (DMARD; drugs
that are used to treat rheumatoid arthritis)
• probenecid (uricosuric agent used in the prophylaxis of
• p-aminobenzoic acid (used in sun creams)
• non-steroidal
medications against "rheumatism", e.g. indomethacin,
• anti-folate drugs (e.g. nitrous oxide or co-trimoxazole)
• p-aminohippuric acid (substance to check kidney
• pyrimethamine (medication against malaria)
• cholestyramine (lipid-lowering agent)
• acitretin or other retinoids (for psoriasis or skin disorders)
• theophylline (used mainly in bronchial asthma)
• erythrocyte concentrates (for blood transfusion)
• nitrous oxide-based anaesthetics
• Proton pump inhibitors (used in the therapy of gastric
ulcers) e.g. omeprazole, esomeprazole, lansoprazole,
pantoprazole and rabeprazole
• sulphasalazine (for ulcerative colitis)
• tetrahydrofolic acid preparations
• oral antidiabetics (medications to treat diabetes) and
diuretics (increase urine output)
• hypoglycaemics (lower blood sugar levels)
• other medicinal products with nephrotoxic and
hepatotoxic potential (incl. alcohol)
• vaccinations
• azathioprine (an immunosuppressive drug)
• vitamin preparations containing folic acid or its derivates
Please note that these statements may also apply to
products used some time ago or at some time in the future.
2.4 Pregnancy and breast-feeding
Do not take Methotrexate 25 mg/ml solution for injection
if you are pregnant because it causes a variety of
malformations or even the death of the foetus. Women
must not get pregnant during treatment with Methotrexate
mg/ml solution for injection. If you get pregnant
during treatment with Methotrexate 25 mg/ml solution for
injection, please inform your doctor immediately!
Special indications for contraception:
Methotrexate temporarily influences sperm and egg
production. During treatment and up to 6 months
after treatment is stopped, you must practice effective
contraception. In this respect, it is of no importance
whether the male or the female partner takes Methotrexate
25 mg/ml solution for injection!
Do not take Methotrexate 25 mg/ml solution for injection
during breast-feeding, since methotrexate is excreted into
the breast milk. Methotrexate can seriously harm breastfed infants.
3. How Methotrexate 25 mg/ml solution for injection
is administered
Your doctor or nurse will give you Methotrexate 25 mg/
ml solution for injection injecting it either into the
central nervous system (intraventricular or intrathecal
administration only for the 2 ml vial), into one of your veins
(e.g. as bolus or infusion), arteries, or a muscle.
During your treatment, you will have a number of tests,
such as regular blood tests to check that appropriate
blood levels of methotrexate are attained and that your
kidneys are eliminating excess drug properly. Other tests
are performed routinely at the start and during the course
of therapy (e.g. chest X-ray, liver function test, full blood
count and urinalysis).
Your doctor may instruct you to take sodium bicarbonate
or acetazolamide tablets while receiving your injections to
help make sure that methotrexate is not concentrated in the
kidneys. If you receive methotrexate in high doses, you will
receive calcium folinate as well to lessen the side effects
of methotrexate. Your doctor will decide on a suitable dose

for you. Doses vary considerably and will depend on the
underlying disease. It is possible that you will only get
methotrexate. In the case of cancer, it is also possible that
you will receive so-called combination therapy in which
you must take several medications. Your body weight, age,
general condition of health, your response to the drug and
whether other medicines are required at the same time will
also influence the dose you receive.
4. Possible Side Effects
Like all medicines Methotrexate 25 
mg/ml solution for
injection can have side effects:
Methotrexate has the potential for serious, sometimes fatal
toxicity. Because the toxic reactions can occur at any time
during therapy, your doctor should observe you closely and
must inform you of early signs and symptoms of toxicity.
If you think you have an infection, a sore throat, fever
or chills during treatment, you should tell your doctor
The most common undesirable effects are ulcerative
stomatitis, leucopenia, nausea, and abdominal discomfort.
Unwanted effects of Methotrexate 25 mg/ml solution
for injection are
• Blood picture changes - e.g. your vulnerability for
infections may increase, you may suffer from unusual
bleeding or bruising and you may observe signs of
anaemia (weakness, tiredness, difficulties in breathing)
• disorders of the mouth, stomach and intestines like
mucositis (mucus membrane inflammation, e.g.
inflammation of the gums, tongue, throat, mouth,
intestines as well as ulcerations), lack of appetite,
feeling sick, vomiting, diarrhoea, unusual bleeding from
the mouth, stomach and intestines, inflammation of the
pancreas, increased risk of perforation, melaena (red to
black stools), malabsorption (disturbances of uptake of
nutrition with consequences such as body weight loss),
and toxic megacolon (severe complication with massive
dilatation of the colon and severe pain, for example)
• renal failure, impairment of renal function, inflammation
of the urinary bladder, blood in the urine, reduced or
faulty formation of sperm and egg cells, menstrual
dysfunction (periods may become less frequent or even
stop completely), infertility, abortion, malformations of
the foetus and pain or difficulty in passing urine
• damage to the liver such as fibrosis (increase in the
connective tissue), cirrhosis (transformation of the tissue
with hardening and abolition of the normal structure of
the organ), hepatitis (inflammation of the liver), acute
liver cell death, fatty degeneration of the liver or other
histologic (tissue) changes in the liver
• damage to the lungs such as inflammation and fibrosis
(increase in the connective tissue); the pulmonary
toxicity may manifest as fever, cough (especially dry and
nonproductive), difficulties or increase in the frequency of
breathing, chest pain, hypoxaemia (lack of oxygen in the
blood), and/or abnormal findings on chest radiography
and/or tests of respiratory function, and infections.
• adverse reactions of the skin such as formation of
blisters, becoming red and inflamed, loss of skin tissue,
vasculitis (inflammation of blood vessels), rash, itching,
nettle rash, photosensitivity, pigmentary changes
(discolouration of the skin), telangiectasia (expansion
of small superficial blood vessels in the skin), acne,
formation of boils, point-like or small flat bleeding, an
increase in rheumatic nodules, loss of hair, worsening
of psoriasis (with concomitant UV therapy), increased
colouration or inflammation or detachment of the nails, a
"recall" of radiation dermatitis (inflammation of the skin)
and sunburn
• leucoencephalopathy (inflammation of the brain),
manifested by ventricular enlargement (expansion of
the fluid spaces inside the brain), confusion, shaking,
irritability, sleepiness, ataxia (disturbance of balance
and co-ordination), dementia, feeling sick, fever, and
occasionally seizures or coma, significant intellectual
deficit, headache, drowsiness, speech disorder,
incomplete palsy affecting one or both sides of the
body, fits, dizziness, vomiting, mental disturbance, pain,
muscle weakness, paraesthesia (pins-and-needles
sensation), subtle cognitive dysfunction (easily disturbed
attention), mood swings, unusual sensations in the head,
and even death
• unwanted reactions of the eyes like swelling,
inflammation of the eyelid edges, conjunctivitis
(inflammation of the eye conjunctiva), unusual formation
of tears, photophobia, and impairment of vision
• allergic reactions, cerebral oedema (swelling of the
brain), haematoma, nodulosis (formation of nodules
under the skin), loss of interest in sex / impotence,
chills, fever without any detectable cause, decreased
resistance to infection, upper respiratory tract infection,
abnormal tissue cell changes, metabolic disorders,
hyperuricaemia (increased blood levels of uric acid,
possibly leading to gout), diabetes, osteoporosis and
other bone disorders, including aseptic necrosis of the
femoral head (loss of bone tissue in the hip joint), pains
in the joints, muscle pain, malaise and undue fatigue,

development of the breast gland in males, ringing in
the ears, sweating, vaginal discomfort, in rare cases
pericarditis (inflammation of the outer lining of the heart),
pericardial effusion and tamponing (collection of fluid
and blood, respectively, in the space between the outer
lining of the heart and the heart muscle), low blood
pressure, complications resulting from the formation of
blood clots in veins and arteries, tumour lysis syndrome
(renal failure due to massive destruction of rapidly
growing tumour cells) and even sudden death
• in cases of acute lymphocytic leukaemia, methotrexate
can cause pain in the left epigastric region (the area
overlying the stomach, below the left lower border of the
rib cage; inflammation of the space above the spleen
due to destruction of the leukaemic cells)
• other possible complications from administration into
the central nervous system include Guillain-Barré
syndrome (inflammation of the central nervous system),
nerve palsies, and cerebellar dysfunction, arachnoiditis
(inflammation of one of the membranes surrounding the
spinal cord) manifested as headache, back pain, neck
stiffness, and/or fever, subacute myelopathy (disorder
affecting the spinal cord) manifested as complete or
incomplete palsy of the lower limbs (paraparesis or
There have been reports on the manifestation of
lymphomas which were, in some cases, reversible after
discontinuing methotrexate therapy. The potential of
trexate to produce other cancers in humans has
been evaluated in several studies, but the results do not
confirm a cancerogenic risk.
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 also report side effects directly via
the Yellow Card Scheme – website:
yellowcard. Alternatively you can call Freephone 0808
100 3352 (available from 10 a.m. to 2 p.m. Mondays to
Fridays) or fill in a paper form available from your local
pharmacy. By reporting side effects you can help provide
more information on the safety of this medicine.
Storing Methotrexate 25 
mg/ml solution for
• Keep the medicine out of the reach and sight of children.
• Keep the vial in the outer carton in order to protect from
• Do not store above 25°C.
• For single dose use only. Discard any unused solution
immediately and safely after initial use.
• This medicine should only be administered by a
medically qualified person, e.g. a doctor.
• Methotrexate 25 mg/ml solution for injection should not
be used after the expiry date printed on the label.
• Any unused product or waste should be disposed of
in accordance with local requirements for example by
Remember this medicine is for you only. Only a doctor or a
nurse can give you the injection.
6. Contents of the pack and other information
What Methotrexate 25 mg/ml solution for injection
The active substance is methotrexate.
Each 1 ml of this sterile solution for injection contains
25 milligrams methotrexate.
The other ingredients are sodium hydroxide, sodium
chloride, water for injections, and nitrogen.
What Methotrexate 25 mg/ml solution for injection
looks like and contents of the pack
Methotrexate 25 mg/ml solution for injection is a yellow
and sterile solution in clear glass vials.
Pack sizes:
The solution for injection is available in
• packs of 1, 5 or 10 vial(s) containing 2 ml solution. This
corresponds to 50 mg of active substance methotrexate
per vial.
• packs of 1, 5 or 10 vial(s) containing 20 ml solution.
This corresponds to 500 mg of active substance
methotrexate per vial.
• packs of 1 or 5 vial(s) containing 40 ml solution.
This corresponds to 1,000 mg of active substance
methotrexate per vial.
• a pack of 1 vial containing 200 ml solution. This
corresponds to 5,000 mg of active substance
methotrexate per vial
Marketing Authorisation Holder
hameln pharmaceuticals ltd
Gloucester, United Kingdom
Haupt Pharma Wolfratshausen GmbH
Pfaffenrieder Str. 5, 82515 Wolfratshausen, Grmany
This leaflet was last approved in December 2014.

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.