METHOTREXATE 100 MG/ML CONCENTRATE FOR SOLUTION FOR INFUSION

Active substance: METHOTREXATE

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recognise these in good time, your doctor must
carry out check-ups and laboratory tests.
Package Leaflet: Information For The User

Methotrexate 100 mg/ml
Concentrate for Solution
for Infusion
Methotrexate

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

1. What Methotrexate is and
what it is used for
Methotrexate contains the active substance
methotrexate. Methotrexate is a cytostatic that
inhibits cell growth. Methotrexate has its greatest
effect on cells which increase frequently like
cancer cells, bone marrow cells and skin cells.
Methotrexate is used in the treatment of the
following types of cancer:
- acute lymphocytic leukaemia,
- non-Hodgkin’s lymphomas,
- 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.

2. What you need to know before
you take Methotrexate
Do not use Methotrexate
- If you are allergic (hypersensitive) to
methotrexate or any of the other ingredients of
this medicine (listed in section 6).
- If you have severe liver or kidney disease .
- If you have increased alcohol consumption.
- If you have disorders of the blood-forming system.
- If you have severe or existing infection such as
tuberculosis and HIV.
- If you have ulcers in the mouth and throat or
ulcers in the stomach and gut.
- If you are pregnant or breastfeeding (see
section Pregnancy, breast-feeding and fertility).
You should not be given live vaccines during
treatment with Methotrexat Accord.
Warnings and precautions
- Methotrexate can cause serious and sometimes
life-threatening undesirable effects. Your doctor
will talk to you about the advantage and risks of
the treatment and what the early signs and
symptoms of undesirable effects are.
- Methotrexate has been reported to cause foetal
death and/or congenital malformations.
Pregnancy should be avoided if you or your
partner is being treated with Methotrexate (see
Pregnancy and breast-feeding and fertility).
- Your skin or eyes can be extremely sensitive to
sunlight or other forms of light during the
treatment with Methotrexate. Therefore sunlight
and solarium should be avoided.
- Methotrexate can cause decrease in cells
responsible for providing immunity, carrying
oxygen, and those responsible for normal blood
clotting, thereby increasing chances of you
getting the infections (e.g pneumonia) or
increased bleedings.
Talk to your doctor, pharmacist or nurse before
taking Methotrexate
- If you are to undergo radiotherapy at the same
time as the Methotrexate treatment. The risk of
tissue and bone damage can increase with
simultaneous treatment.
- If you are having treatment in your spine
(intrathecally) or in a vein (intravenously) this
can cause a potentially life-threatening
inflammation in the brain.
Methotrexate 100 mg/ml must not be
administered in your spine (intrathecally).
- If you have a medical condition that means that
fluid is retained in your body, for example in the
lungs or in the stomach.
- If you have impaired kidney function.
- If you have impaired liver function.
- If you have an infection.
- If you need to be vaccinated. Methotrexate can
reduce the effect of the vaccines.
- If you have insulin dependent diabetes,
Methotrexate treatment should be carefully
monitored.
Recommended follow-up examinations and
precautions:
Even when methotrexate is used at low doses,
serious side effects can occur. In order to

The following information is intended for
medical or healthcare professional only
Instruction on how to prepare, handle and
dispose of Methotrexate 100 mg/ml
concentrate for solution for infusion
The solution should be visually inspected prior to
use. Only clear solution practically free from
particles should be used.
Methotrexate injection may be further diluted with
an appropriate preservative-free medium such as
glucose solution (5%) or sodium chloride solution
(0.9%). Chemical and physical stability of the
diluted solution have been demonstrated in

Before the start of treatment:
Before treatment is started your doctor may carry
out blood tests, and also to check how well your
kidneys and liver are working. You may also have
a chest X-ray. Further tests may also be done
during and after treatment. Do not miss
appointments for blood tests.
Other medicines and Methotrexate
Tell your doctor or pharmacist if you are taking,
have recently taken or might take any other
medicines, Methotrexate affects or is affected by
certain other medicinal products against:
- Pain and inflammation (so called NSAIDs and
salicylates)
- Cancer (cisplatin, cytarabine, mercaptopurine)
- Infections (ciprofloxacin and antibiotics such as
penicillins, tetracycline and chloramphenicol)
- Asthma (theophylline)
- Vitamin preparations containing folic acid or
substances like folic acid
- Rheumatism (leflunomide)
- High blood pressure (furosemide)
- Gout (probenicide)
- Radiotherapy
- Stomach ulcers, heartburn, reflux (such as
omeprazole, pantoprazole, lansoprazole)
- Epilepsy (phenytoin)
- Psoriasis or severe acne (retinoids, such as
acitretin ot isotretinoin)
- Rheumatoid arthritis or bowel disease
(sulfasalazine)
- Rejection after an organ transplant
(azathioprine)
- If you need to be vaccinated with a live
vaccination
Methotrexate with food, drink and alcohol
During treatment with Methotrexate, you should not
drink any alcohol and you should avoid excessive
consumption of coffee, soft drinks containing
caffeine and black tea. Also make sure you drink
plenty of liquids during treatment with Methotrexate
because dehydartion (reduction in body water) can
increase the toxicity of Methotrexate.
Pregnancy, breast-feeding and fertility
If you are pregnant or breast-feeding or think you
may be pregnant or are planning to have a baby,
tell your doctor for advice before taking this
medicine.
Methotrexate has been reported to cause foetal
death and/or congenital malformations. Therefore
do not use Methotrexate during pregnancy
except with an explicit prescription from a doctor.
Tell your doctor immediately if you think you are
pregnant.
Pregnancy should be avoided if you or your
partner is being treated with Methotrexate, as
treatment with Methotrexate of both male and
female can affect the foetus. How long you and
your partner should wait before you/your partner
try to get pregnant after completing treatment is
not known. The recommendations vary from
three months to one year.
Methotrexate is excreted breast milk in such
quantities that there are risks of affecting the
baby. Breast-feeding should therefore be
suspended during treatment with Methotrexate.
Methotrexate can cause genetic changes. It can
affect the sperm and egg production, which leads
to deformities. Treatment with methotrexate can
leads to infertility. Male patients are exploring the
possibility to preserve sperm before starting
treatment.
Driving and using machines
Undesirable effects such as tiredness and
dizziness may occur. If you feel tired or dizzy do
not drive and do not use machines.
Methotrexate contains sodium
Methotrexate contains 194 mg of sodium per
meximum daily dose.To be taken into consideration
by patients on a controlled sodium diet.

3. How to take Methotrexate
Methotrexate is given to you by healthcare
professionals.
The dose you receive and how often you receive
the dose, depend on the disease you are being
treated for your state of health and your age,
weight and body surface. Methotrexate can be
given in a muscle (intramuscularly), in a vein
(intravenously), or in an artery (intra-arterially).
If you have any further questions on the use of
this medicine, ask your doctor or pharmacist.

4. Possible side effects
Like all medicines, this medicine can cause side
effects, although not everybody gets them.
Methotrexate can have undesirable effects which
may be dangerous or life-threatening. During the
treatment you should be alert to signs of
undesirable effects and report them to your
doctor.
Contact a doctor immediately if you notice any of
the following undesirable effects. You may need
immediate medical care.

glucose solution (5%) and sodium chloride
solution (0.9%) at concentrations of 5mg/ml and
20mg/ml for 36 hours at 20-25°C and 35 days at
2-8°C. Diluted product is stable in both diluents at
both concentrations for 36 hours at 20-25°C and
35 days at 2-8°C. For microbial point of view, the
product should be used immediately. If not used
immediately, in-use storage times and condition
prior to use are the responsibility of the user and
would not longer than 24 hours at 2 to 8°C,
unless dilution has taken place in controlled
validated aseptic condition.
With respect to the handling the following general
recommendations should be considered: The

• Unexplained breathlessness, dry cough or
wheezing (symptoms of lung problems).
• Sudden itching, skin rash (urticaria), swollen
hands, feet, ankles, face, lips, mouth or throat
(which can make it hard to breathe and
swallow). It can also feel as if you are going to
faint (symptoms of a severe allergic reaction).
• Vomiting, diarrhoea or stomatitis and peptic
ulcers (Symptoms of effect on gastrointestinal
track).
• Yellowing of the skin or eyes, dark coloured
urine (symptoms of effect on the liver)
• Fever, shivering, aching body and sore throat
(symptoms of infection).
• Unexpected bleeding (for example bleeding
gums, dark urine, blood in the urine or vomit) or
unexpected bruising, black, tar-like faeces – this
can be due to a reduced coagulation capacity or
bleeding from the stomach or gut).
• Skin rashes with flaking or blistering and effects
on mucous membranes e.g. in the nose
(symptoms of Stevens-Johnsons syndrome, toxic
epidermal necrolysis and erythema multiforme).
• Abnormal behaviour, transient blindness and
generalised seizures (Symptoms of effect on
central nervous system).
• Paralysis (paresis).
A list of undesirable effects that have been
reported in treatment with Methotrexate is set out
below according to how common they are.
Very common (may affect more than 1 in 10
people):
• Loss of appetite, nausea, vomiting, abdominal
pain, impaired digestion, dyspepsia
• Inflammation and ulceration in mouth and throat
• Increase in level of liver enzyme
Common (may affect up to 1 in 10 people):
• Herpes zoster
• Effects on the blood e.g. anaemia, leukopenia,
thrombocytopenia
• Diarrhoea
• Dry cough, shortness of breath, chest pain,
fever
• Rashes, redness and itching
• Headache, Tiredness, drowsiness
Uncommon (may affect up to 1 in 100 people)
• Pancytopenia, agranulocytosis
• Inflammation of blood vessels
• Anaphylactoid reactions and allergic vasculitis
• Vertigo, confusion, depression
• Convulsions, encephalopathy
• Lymphoma (tumour in lymph tissue)
• Pulmonary fibrosis
• Bleeds and ulcers in the stomach and intestinal
tract
• Inflammation of pancreas
• Diabetic complications
• Reduced level of albumin
• Enhanced pigmentation of the skin
• Loss of hair, painful lesions of scaly patches
caused by psoriasis
• Increase of rheumatic nodules (lumps of tissues)
• Effects on skin and mucous membrane,
sometimes serious (Stevens-Johnsons
syndrome, toxic epidermal necrolysis)
• Skin becoming hypersensitive to sunlight, urticaria
• Brittle bones (osteoporosis), arthralgia, myalgia
• Liver fibrosis and cirrhosis, fatty liver
• Inflammation and ulceration of urinary bladder,
haematuria, dysuria
• Inflammation and ulceration of vagina
Rare (may affect up to 1 in 1,000 people)
• Pericarditis, pericarditis effusion and tamponade
• Megaloblastic anaemia
• Mood swings
• Paresis
• Effects on speech including dysarthria and
aphasia
• Myelopathy
• Visual disturbance, blurred vision
• Thrombosis (cerebral, deep vein and retinal
vein)
• Low blood pressure
• Diabetes
• Pharyngitis apnoea , bronchial asthma, gingivitis
• Inflammation in the small intestine
• Blood in the faeces
• Malabsorption
• Acne, sores on the skin, pigment changes of
the nails, bruises
• Fractures
• Renal failure, oliguria, azotaemia and anuria
• Hyperuricemia
• Elevated serum creatinine and urea level
• Liver damage.
• Abnormal development of mammary glands
Very rare (may affect up to1 in 10,000 people)
• Infections, sepsis opportunistic infections
• Severe failure of the bone marrow, anaemia
due to the fact that the bone marrow cannot
produce blood cells (aplastic anaemia)
Lymphadenopathy, lymphoproliferative disorder,
eosinophilia, neutropenia and
hypogammaglobulinaemia
• Immunosuppression
• Insomnia
• Impaired intellectual functions such as thinking,
remembering and reasoning
• Joint and/or muscle pain, lack of strength
• Myasthenia (muscle weakness)
• Meningism (paralysis, vomiting), acute aseptic
meningitis
• Abnormal sensations, changes in sense of taste
(metallic taste)
• Conjunctivitis, retinopathy, loss of vision, puffy
eye
• Inflammation eye follicles epiphora and
photophobia

product should be used and administered only by
trained personnel; the mixing of the solution should
take place in designated areas, designed to protect
personnel and the environment (e.g safety cabins);
protective clothing should be worn (including
gloves, eye protection, and masks if necessary).
Pregnant healthcare personnel should not handle
and/or administer Methotrexate.
Methotrexate should not come into contact with the
skin or mucosa. In the event of contamination, the
affected area must be irrigated immediately with
copious quantities of water at least ten minutes.
For single use only. Any unused solution should be

• Tumour lysis syndrome
• Allergic vasculitis, hidradentis
• Problem with lung function, shortness of breath,
pneumonia
• Infections of lungs
• Pleural effusion
• Dilation of colon (Toxic megacolon), blood in
vomit
• Reactivation of chronic hepatitis, acute liver
degeneration, herpes simplex hepatitis, liver
insufficiency
• Painful swelling of skin around nail
• Expansion of small blood vessels in the skin
(paronychia)
• Proteinuria
• Loss of libido impotence
• Menstrual disorder
• Discharge from the vagina
• Infertility
• Fever, impaired wound healing
Not known (frequency cannot be estimated from
the available data):
• Bleeding, blood outside of vessels
• Psychosis
• Accumulation of fluid in brain and lungs
• Metabolic disorder
• Skin necrosis, exfoliative dermatitis
Methotrexate must not be given in the spine as it
may cause very serious side effects.
Reporting of side effects
If you get any side effects, talk to your doctor,
pharmacist or nurse. This includes any side
effects not listed in this leaflet. You can also
report side effects directly (see details below). By
reporting side effects you can help provide more
information on the safety of this medicine.
United Kingdom
Yellow Card Scheme
Website:www.mhra.gov.uk/yellowcard
Ireland
HPRA Pharmacovigilance
Earlsfort Terrace
IRL - Dublin 2
Tel: +353 1 6764971
Fax: +353 1 6762517
Website: www.hpra.ie
e-mail: medsafety@hpra.ie
Malta
ADR Reporting
The Medicines Authority
Post-Licensing Directorate
203 Level 3, Rue D'Argens
GŻR-1368 Gżira
Website: www.medicinesauthority.gov.mt
e-mail: postlicensing.medicinesauthority@gov.mt

5. How to store Methotrexate
Keep this medicines out of the sight and reach of
children.
Do not use this medicine after the expiry date
which is stated on the label/carton after EXP. The
expiry date refers to the last day of the month.
Do not store above 30°C.
Do not throw away any medicines via
wastewater or household waste. Ask your
pharmacist how to throw away medicines no
longer required. These measures will help to
protect the environment.

6. Contents of the pack and
other information
What Methotrexatecontains
- The active substance is methotrexate.
- 1 ml solution contains 100 mg methotrexate
The other ingredients are sodium hydroxide and
water for injection.
What Methotrexatelooks like and contents of
the pack
The medicinal product is a clear yellow solution.
Package size:
1 vial in carton for 5 ml, 10 ml and 50 ml pack size
5 vials in a carton for 5 ml, 10 ml & 50 ml pack size
Not all pack sizes may be marketed.
Marketing Authorisation Holder and
Manufacturer
Marketing Authorisation Holder:
Accord Healthcare Limited
Sage House, 319 Pinner Road, North Harrow,
Middlesex, HA1 4HF, United Kingdom
Manufacturer:
Accord Healthcare Limited
Sage House, 319 Pinner Road, North Harrow,
Middlesex, HA1 4HF, United Kingdom
Wessling Hungary Kft
Fòti ùt 56., Budapest, 1047, Hungary
This leaflet was last revised in 07/2014

discarded. Waste should be disposed of carefully
in suitable separate containers, clearly labelled as
to their contents (as the patient's body fluids and
excreta may also contain appreciable amounts of
antineoplastic agents and it has been suggested
that they, and material such as bed linen
contaminated with them, should also be treated as
hazardous waste). Any unused product or waste
should be disposed of in accordance with local
requirements by incineration
Adequate procedures should be in place for
accidental contamination due to spillage; staff
exposure to antineoplastic agents should be
recorded and monitored.

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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.

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