Methotrexate 100 mg / ml injection – patient leaflet, side effects, dosage

1. What Methotrexate is and what it is used for

Methotrexate is an anti‑metabolite medicine (medicine which affects how the body’ cells grow) and immunosuppressant (medicine which reduces the activity of the immune system).

s

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

Methotrexate 100 mg/ml Injection must not be injected intrathecally (into the spine).

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 methotrexate if you think any o the above applies to you.

f

Warnings and precautions

During treatment with Methotrexate, you will be carefully monitored by the doctor, pharmacist or nurse.

Tell your doctor 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 problems 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 sun‑beds or a sun‑lamp 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), 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 perfo lung function test.

rm a

During the treatment:

Your doctor may perform the following examinations:

‑ examination of the oral cavity and the pharynx for changes in the muc

ous

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 ‑ blood test to monitor kidney function

closely

‑ respiratory tract monitoring and, if necessary, lun It is very important that you appear for these scheduled

g function test examinations.

If the results of any of these tests are irregular, your doct accordingly.

or will adjust your treatment

Children

Children will need to be closely monitored, in order to id

entify 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 and anti‑protozoal pyrimethamine

• para‑aminobenzoic acid (nutrient in the vitamin B complex)
• phenytoin (medicine often used to treat epilepsy)
• vitamin supplements containing folic acid
• probenecid (medicine used to treat gout)

• nitrous oxide (used for general anaesthesia and pain relief). Nitrous oxide

  increases the effect of methotrexate and can lead to an increase in some side effects (such as reduced number of blood cells and platelets and inflammation of mouth).

  • metamizole (synonyms novaminsulfon and dipyrone) (medicine against severe pain and /or fever)

  • retinoids, such as acitretin (a medicine used to treat psoriasis) or isotretinoin

    (used to treat severe acne)

  • other drugs that may cause damage to your kidneys
  • other drugs that may cause damage to your liver e.g., leflunomide, azathioprine, sulfasalazine, retinoids, alcohol
  • live virus vaccines
  • chemotherapeutic medicines e.g. mercaptopurine (medicine used in the treatment of blood cell cancer), 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.

Using 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

Tell your doctor if you are pregnant, trying to become 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‑oncolog a pregnancy mu

ical indications, in women of child‑bearing age the possibility of st be ruled out, e.g. by pregnancy tests, before treatment is started.

Female fertility Do not use this becoming pregn after the end of t

medicine if you are trying to becom ant during treatment with methotre reatment. Therefore, you must ens

e pregnant. You must avoid xate and for at least 6 months ure that you are taking effective contraception fo precautions"). If you become p to your doctor as

r the whole of this period (see also

section "Warnings and regnant during treatment or suspec soon as possible. If you do becom

t you might be pregnant, speak e pregnant during treatment, you should be offere through treatment. If you want to becom

d advice regarding the risk of harmful effects on the child e pregnant, you should speak with your doctor, who may refer you for specialist adv Mothers should not b Male fertility

ice before the planned start of treatment.

reast‑feed whilst treatment with methotrexate is ongoing.

The available eviden

ce does not indicate an increased risk of malformations or miscarriage if the fat

her takes methotrexate less than 30 mg/week. However, a risk cannot be completel

y 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 treated with methotrexate doses higher than 30 mg/week to consider sperm preservation before the beginning of treatment (see also section "Warnings and precautions"). Ask your doctor, pharmacist or nurse for advice before taking any medicine. Driving and using machines

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 1 g/10 ml contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially ‘sodium free’.

Methotrexate 5 g/50 ml contains 58.9 mg sodium (main component of cooking/table salt) per vial. This is equivalent to 2.95% of the recommended maximum daily dietary intake of sodium for an adult.

3. How to use Methotrexate

This medicine may be given by injection (using a syringe) into a vein (intravenously), into muscle (intramuscularly) or into an artery (intraarterially). This medicine must not be administered intrathecally (injected into the spinal cord). It may also be given by infusion (drip) into a vein. It may be diluted before it is given.

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 100 mg/ml Injection methotrexate

FOR FURTHER INFORMATION PLEASE REFER TO THE SUMMARY OF PRODUCT CHARACTERISTICS

INSTRUCTIONS FOR USE

This presentation of 100mg/ml is not 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.

Dose in severe psoriasis:

Take this medicine only once a week.

Important warning about the dose of Methotrexate:

Use Methotrexate only once a week 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.

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. 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, this medicine 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 known) and you may feel you are going to faint (frequency uncommon)

  not

• serious skin reactions, such as rash and ulceration of the skin, reddeni

  ng,

  blisters, pustules, necrosis or desquamation of the skin (frequency unco

  mmon) sistent

• inflammation of the lung with breathlessness – you may develop a per

  cough, weakness, raised temperature and experience pain or difficulty breathing, or become breathless. This may be associated with change

  s in a

  particular type of white cell in your blood (frequency uncommon)

• diarrhoea (frequency uncommon)
• miscarriage (frequency not known)
• extreme inflammation and distention of the colon (frequency rare)

• ulcer or bleeding of the stomach and intestine (fre

  quency rare)

• diseases of the brain (frequency uncommon), ner

  ve pain around spinal cord

  (frequency not known)

• paralysis of one side of the body (frequency unco

  mmon)

• infection in the bloodstream (sepsis) (frequency ra

  re)

• acute inflammation of the liver with yellowing of th

  e 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 to 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)

• sunburn‑like reactions due to increased sensitivity of the skin to sunlight

  (frequency uncommon)

• kidney failure, kidney damage
• increase in liver function test

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 speaking, difficulty in language and communication, sleepiness
  • blurred vision, serious alterations in vision
  • low blood pressure (hypotension)
  • blood clot which causes pain, swelling or redness
  • scarring of the lungs which causes shortness of breath
  • bloody stools, inflammation of small intestine
  • difficulty in the digestion or absorption of nutrients from food
  • decline in liver function, liver damage (hepatotoxicity), portal fibrosis
  • itching or the appearance of lightened patches on the skin, bruises, skin rash painful detachment of thick scaly patches, sensitivity of the skin to sun light, skin ulcer, itchy rash, acne
  • 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 le

  vels in a laboratory test

• alteration

  of egg or sperm production, infertili oa concentration in the sperm and rder

  ty, temporary reduction in vaginal discharge

  spermatoz *optic nerve diso Not known (can

  not be determined from the availab

  le data):

• infections

  caused by various microorganisms ifferent organs (e.g. lungs, liver), inf ion, discharge, itching and pain in v uction in blood cells, enlarged lym

  (e.g. bacteria, viruses, fungi, lammation of bladder lining, agina

  yeast) in d inflammat

• severe red

  ph nodes, increase in the number of a ty

  pe of white blood cells eosinophils in the blood, reduction in re

  d blood cell coun

  t

• other metaboli

  c changes

• perforation of t

  he intestine

• paralysis that

  mostly affects the movement of the lower body**, absence of uli, uncontrollable movements**, confusion, dizziness,

  reaction to stim

  difficulty in abil

  ity to think and remember

• ringing in the e

  ars (tinnitus)

• inflammation o

  f 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

**have followed intrathecal administration

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 of 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 100 milligrams (mg) of methotrexate.

The other ingredients are 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/orange solution for injection which comes in glass containers called vials.

It may be supplied in packs containing:

1 x 1 g/10 ml vial

1 x 5 g/50 ml vial

Not all packs may be marketed.

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.

Ref: gxME 32_0

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Methotrexate 100 mg/ml

Injection

PAA251490