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METHOTREXATE 25MG/ML SOLUTION FOR INJECTION OR INFUSION

Active substance(s): METHOTREXATE

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Methotrexate 25mg/ml
Solution for Injection or 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.
• 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. This includes any
possible side effects not listed in
this leaflet.
• The full name of this medicine
is Methotrexate 25mg/ml
Solution for Injection or Infusion
but within the leaflet it will be
referred to as Methotrexate
Solution.
In this leaflet:
1 What Methotrexate Solution
is and what it is used for
2 What you need to know
before you use
3 How to use
4 Possible side effects
5 How to store
6 Contents of the pack and
other information
1 What Methotrexate Solution

is and what it is used for

Methotrexate Solution is a substance
with the following properties:
• it interferes with the growth of
tumour cells in the body that
reproduce quickly (anti-tumour
agent)
• it reduces undesired reactions of
the body’s own defence mechanism
(immunosuppressant)
• it has anti-inflammatory effects.
Methotrexate Solution is used to treat
cancer, such as:
• lymphatic leukaemia (disease of
the blood or bone marrow with
increased number of white blood
cells)
• breast cancer
• bone cancer (osteosarcoma)
• head and neck cancer
• gynaecologic cancer
(choriocarcinoma, throphoblastic
disease – tumour development
directly associated with pregnancy)
• cancer of the lymphatic system
(Non-Hodgkin’s lymphoma).

2 What you need to know

before you use

Do not use Methotrexate
Solution if you

• are
 allergic to methotrexate or
any of the other ingredients of this
medicine (listed in section 6)
• you have significant kidney
disease
• you have significant liver disease
• have disorders of the bloodforming system
• have increased alcohol
consumption
• have severe or existing infections
• have gastro-intestinal ulcers or
ulcers of the oral cavity
• are pregnant or breast-feeding
(see section “Pregnancy and breastfeeding”).
You should not be given live vaccines
during treatment with Methotrexate
Solution.
Tell your doctor before you use
Methotrexate Solution if you think any
of the above applies to you.

Warning and precautions

Take special care with Methotrexate
Solution if you
• have/had any liver or kidney
disease
• have problem with your lung
function
• have abnormal accumulation
of liquid in the abdomen or in the
cavity between the lungs and chest
wall (ascites, pleural effusions)
• are dehydrated or suffer from
conditions leading to dehydration
(vomiting, diarrhoea, stomatitis)
• have diabetes mellitus treated with
insulin
• have inactive, prolonged infections
(e.g. tuberculosis, hepatitis B or C,
shingles (herpes zoster))
• experience any sign or symptoms
suggestive of infection, e.g. fever.
Inform your doctor in case any of the
above applies to you.

Methotrexate may be genotoxic. This
means that the medicine may cause
genetic mutation. Methotrexate can
affect sperm and egg production with
the potential to cause birth defects.
You and your partner must avoid
conception (becoming pregnant
or fathering children) if currently
receiving methotrexate and for at least
six months after your treatment with
methotrexate has stopped. See also
section “Pregnancy and lactation”. Since
treatment with methotrexate may lead
to infertility, it might be advisable for
male patients to look into the possibility
of sperm preservation before starting
treatment.
Even if methotrexate is administered
at low dosage, severe side effects can
occur. In order to diagnose them early,
regular monitoring by the doctor at
short-term intervals is necessary.
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.
If the results of any of these tests are
abnormal, treatment will only be
resumed when all readings are back to
normal.

Other medicines and
Methotrexate Solution

Tell your doctor or pharmacist if
you are taking, have recently taken
or might take any other medicines,
including medicines obtained without
a prescription and herbal or natural
medicinal products. Remember to
tell your doctor about your treatment
with Methotrexate Solution, if you are
prescribed another medicine while the
treatment is still ongoing. It is especially
important to tell your doctor if you are
using:
• other treatments for rheumatoid
arthritis or psoriasis such as
leflunomide, sulphasalazine (also
used for ulcerative colitis), salicylates
such as acetylsalicylic acid,
phenylbutazone, or amidopyrine
• alcohol (should be avoided)
• live vaccinations
• azathioprine (used to prevent
rejection after an organ transplant)
• retinoids (used to treat skin
disorders)
• anticonvulsant drugs (prevent fits)
• cancer treatments
• barbiturates (sleeping injection)
• tranquillisers
• oral contraceptives
• probenecid (for gout)
• antibiotics
• pyrimethamine (used to prevent
and treat malaria)
• vitamin preparations, which contain
folic acid
• proton-pump inhibitors (used to
treat severe heartburn or ulcers)
• theophylline (used to treat asthma).

Methotrexate Solution with food,
drink and alcohol
During Methotrexate Solution
treatment you should avoid any alcohol
consumption as well as excessive
consumption of coffee, caffeinecontaining beverages or black tea. Also
make sure you drink plenty of liquids
during treatment with Methotrexate
Solution because dehydration
(reduction in body water) can increase
the toxicity of Methotrexate Solution.

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 for advice before taking this
medicine.
You must not use Methotrexate
Solution during pregnancy. Men and
women should use an effective method
of birth control during treatment
and during a further six months after
treatment with Methotrexate Solution
has been discontinued.
In women of child-bearing age, any
existing pregnancy must be excluded
with certainty by taking appropriate
measures e.g. pregnancy test, prior to
therapy.
As methotrexate can be genotoxic, all
women who wish to become pregnant
are advised to consult a genetic
counselling centre, if possible already
prior to therapy, and men should seek
advice about the possibility of sperm
preservation before starting therapy,
see also section “Take special care with
Methotrexate Solution”.
Methotrexate passes into breast milk.
Breast‑feeding should be stopped
prior to and during treatment with
Methotrexate Solution.

Driving and using machines

Tiredness and dizziness can occur
during treatment. If affected you should
not drive or operate machinery.

You should avoid solarium and direct
sun light during treatment, as the skin is
more sensitive.
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AAAF3865

!
The following information is intended for medical or healthcare professionals only:

Methotrexate 25mg/ml Solution for Injection or Infusion
Instructions

WARNINGS
The dose must be adjusted carefully
depending on the body surface area if
methotrexate is used for the treatment
of tumour diseases. Fatal cases of
intoxication have been reported after
administration of incorrect calculated
doses.

Handling and disposal

• H
 andling must be in accordance with
local requirements. Cytostatics handling
should only be carried out by specially
trained staff and should only take place
in locations fitted for this purpose.
Work surfaces should be covered by
plastified absorbant paper, which can be
discarded after use.
• Protective gloves and glasses should be
used in order to avoid potential contact
with eyes, skin or mucosa. In the event
of contact with the eyes, irrigate with
copious amounts of water or sodium
chloride 0.9%. Seek medical evaluation.
Methotrexate is not blister forming and
should therefore not cause damage to

skin. However, if the compound should
get in contact with the skin or mucosa,
the affected area should still be rinsed
immediately with plenty of water.
Transient stinging can be treated with
a mild cream. If there is a danger that
larger quantities of methotrexate have
been absorbed (regardless of absorption
method), treatment with leucovorin
should be carried out.
• Adequate procedures should be in place
for accidental contamination due to
spillage; staff exposure to antineoplastic
agents should be recorded and
monitored.
• Cytostatics should not be handled by
pregnant staff.
• All contaminated waste materials
(including sharps, container, absorbent
materials, unused solution) should be
placed in a designated sealed and
labelled impervious waste disposal bag
or rigid waste container, and incinerated
in accordance with local procedures for
destruction for hazardous waste.

continued on top of next column
AAAF3865

continued over page

Methotrexate 25mg/ml PIL UK_EIRE

approved for print/date

colours/plates:
1. Black

item no: AAAF3865

dimensions: 130 x 600mm

print proof no: 01

pharmacode:

origination date: 17-05-2013

min pt size: 9pt

2.
3.
4.
5.
6.

originated by: MH
revision date:

Technical Approval

revised by:

date sent: 17-05-2013

supplier: Sindan

technically app. date: 20-05-2013

Non Printing Colours
1.
2.
3.

Methotrexate Solution contains

The medicinal product contains
0.192mmol sodium per ml solution
(4.425mg/ml). Doses less than 5ml
contain less than 1 mmol sodium
(23mg) per dose and are i.e. essentially
“sodium-free“, but to be taken into
consideration by patients on a
controlled sodium diet in case the dose
exceeds 5ml.

3 How to use
Treatment with methotrexate should
be initiated by or in consultation with
a doctor with considerable experience
in cancer treatment. The dose is usually
calculated based on various factors e.g.
the patient general health and body
surface area and the type of disease.
The overall duration of treatment and
intervals between administrations is
decided by the physician.
Methotrexate can be given
intramuscularly (in a muscle),
intravenously (in a vein), intra-arterially
(in an artery and intra-thecally.
Higher doses are usually given as an
infusion over 24 h, either alone or in
combination with other medicinal
products used to treat cancer.
Your doctor may instruct you to take
sodium bicarbonate or acetazolamide
tablets while receiving your medicine
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.
Use in children: This medicine should
be used with caution in children
and in line with standard therapy
recommendations.
Methotrexate should not come into
contact with the surface of the skin or
mucosa. In the event of contamination,
the affected area must be rinsed
immediately with plenty of water.

If you use more Methotrexate
Solution than you should

Your doctor decides on the dosage,
which is given by healthcare staff.
Overdose is therefore unlikely.
An overdose of methotrexate can lead
to severe toxic reactions. Overdose
symptoms may include easy bruising
or bleeding, unusual weakness, mouth
sores, nausea, vomiting, vomiting blood
or black or bloody stools. The antidote
in case of an overdose is calcium
folinate.

If you forget or stop using
Methotrexate Solution

You should not interrupt or discontinue
Methotrexate Solution treatment,
unless you have discussed this with
your doctor. In case you forget your
appointment for next dose, contact
your doctor as soon as possible to
schedule a new appointment. If you
suspect severe side effects, contact
your doctor immediately for advice.
If you have any further questions on the
use of this product, ask your doctor or
pharmacist.

4 Possible side effects
Like all medicines, Methotrexate
Solution can cause side effects,
although not everybody gets them.
Tell your doctor straight away if you
get any sudden wheeziness, difficulty
in breathing, swelling of the eyelids,
face or lips, rash or itching (especially
affecting your whole body).

Serious side effects

If you develop any of the following
side effects, contact your doctor
immediately:
• lung complaints (symptoms may be
general illness; dry, irritating cough;
shortness of breath, breathlessness
at rest, chest pain, or fever)
• severe peeling or blistering of the
skin
• unusual bleeding (including
vomiting blood) or bruising
• severe diarrhoea
• ulcers in mouth
• black or tarry stools
• blood in the urine or stools
• tiny red spots on the skin
• fever
• yellowing of the skin (jaundice)
• pain or difficulty in passing urine
• thirst and/or frequent urination
• fits (convulsions)
• loss of consciousness
• blurred or decreased vision.
The following side effects have also
been reported:
Very common (more than 1 in 10):
Inflammation of the mouth,
indigestion, loss of appetite, nausea
(feeling sick), vomiting, tummy pain,
inflammation and ulcers in the mouth
and throat. Increase in liver enzymes
(can be detected by a test carried out
by a doctor).
Common (between 1 in 100 and
1 in 10):
Changes in the number of blood cells
and platelets (can be detected by a test
carried out by a doctor). Headache,
tiredness, sleepiness. Diarrhoea.
Measles-like rash (alone), redness, and
itching.

continued on top of next column
AAAF3865

Uncommon (between 1 in 1,000 and
1 in 100):
Spinning sensation, confusion,
depression, fits. Brain disorder
(leukoencephalopathy/
encephalopathy). Lung damage.
Ulcers and bleeding in the digestive
tract. Liver disorders (can be detected
by a test carried out by a doctor),
diabetes, decreased blood protein
(can be detected by a test carried
out by a doctor). Nettle rash (alone),
light sensitivity, brown skin, hair loss,
increase of rheumatic nodules (lumps
of tissues), shingles, painful psoriasis.
Joint or muscle pain, brittle bones,
inflammation. Ulcers in the bladder
(possibly with blood in the urine),
painful urination. Severe allergic
reactions. Inflammation and ulcers of
the vagina.
Rare (between 1 in 1,000 and 1 in
10,000):
Inflammation of the lining of the
heart, fluid around the heart. Severely
visual disturbance, mood alterations.
Low blood pressure, blood clots. Sore
throat, interruption of breathing,
asthma. Inflammation of the digestive
tract, bloody stools, inflamed gums,
abnormal digestion. Changed colour
of nails, acne, red or purple spots. Bone
fracture. Kidney failure, little or no urine
produced, waste products in the blood.
Very rare (less than 1 in 10,000 and
unknown):
Infections. Severe failure of the bone
marrow (can be detected by a test
carried out by a doctor). Swollen glands.
Sleeplessness. Pain, muscle weakness,
pins and needles, changes in sense of
taste (metallic taste), inflammation of
the lining of the brain causing paralysis
or vomiting. Red eyes, damage to the
retina of the eye. Fluid on the lungs.
Vomiting blood. Cold sores. Protein in
the urine (can be detected by a test
carried out by a doctor). Loss of sex
drive, problems having an erection,
low sperm production, abnormal
periods, vaginal discharge, infertility.
Infection around a fingernail, severe
complication of the digestive tract,
fungal infections, boils, dilated small
blood vessels in the skin, damage to the
blood vessels of the skin. Lumps in the
armpit or groin. Slow wound healing.
Other: After injection into a muscle,
there may be a burning sensation or
damage at the injection site.
If you get any side effects, talk to your
doctor. This includes any side effects
not listed in this leaflet.

5 How to store
Keep this medicine out of the sight and
reach of children.
Do not use this medicine after the
expiry date which is stated on the label
and carton after EXP. The expiry date
refers to the last day of the month.
Use immediately after first opening.
Store in the original package in order to
protect from light.
Store below 25°C.
You must not use Methotrexate
Solution, if the solution is not clear and
contains particles.
This medicine and its packaging must
not be disposed of via wastewater or
household waste. Ask your pharmacist
how to dispose of medicines or
packaging no longer required. These
measures will help to protect the
environment.

6 Contents of the pack and

other information

What Methotrexate Solution
contains

• T he active substance is:
Methotrexate. 1ml of solution
for injection contains 25mg
methotrexate.
2ml vial contains 50mg
methotrexate; 10ml vial contains
250mg methotrexate; 20ml vial
contains 500mg methotrexate; 40ml
vial contains 1,000mg methotrexate.
• The other ingredients are: sodium
chloride, sodium hydroxide (for
pH adjustment), hydrochloric acid
(for pH adjustment) and water for
injections.

What Methotrexate Solution
looks like and contents of the
pack
Methotrexate Solution is a clear,
yellowish solution for injection.
Pack sizes:
1 x 2ml vial
1 x 20ml vial
1 x 40ml vial
Marketing Authorisation Holder
Actavis Group PTC ehf.
Reykjavíkurvegi 76-78
220 Hafnarfjörður
Iceland
Manufacturer
S.C. Sindan- Pharma S.R.L
11 Ion Mihalache Blvd
011171 Bucharest
Romania
This leaflet was last revised in
May 2013.

Actavis, Barnstaple, EX32 8NS, UK
Actavis Ireland, Euro Hs, Little Island, Cork

!
The solution is to be visually inspected
prior to use. Only clear solutions practically
free from particles should be used.

Incompatibilities

Strong oxidants and acids. Precipitation
or formation of a cloudy solution has
been seen during combinations with
chlorpromazine hydrochloride, droperidol,
idarubicin, metoclopramide hydrochloride,
heparin solution, prednisolone
sodium phosphate and promethazine
hydrochloride.
Parenteral methotrexate preparations
can be prepared with the following
intravenous solutions for infusion: 9mg/
ml (0.9%) sodium chloride, 50mg/ml (5%)
glucose. Other pharmaceuticals should not
be mixed with Methotrexate Solution in
the same infusion container.

Storage and shelf-life after first
opening/dilution

Vials before opening: Store below 25°C.
Store in the original package in order to
protect from light.
Vials after first opening: Use immediately.
continued on top of next column
AAAF3865

Solution after dilution: Chemical and
physical in-use stability have been
demonstrated for solutions containing
either 4.0 or 8.0mg/ml methotrexate in
9mg/ml (0.9%) sodium chloride and in
50mg/ml (5%) glucose for 30 days at 2-8°C
protected from light and at 25°C under
normal lighting conditions. Chemical
and physical in-use stability have been
demonstrated for solution containing
0.1mg/ml methotrexate in 9mg/ml (0.9%)
sodium chloride and in 50mg/ml (5%)
glucose for 30 days at 2-8°C protected
from light and for 5 days at 25°C, under
normal lighting conditions.
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 to 8°C, unless dilution has taken
place in controlled and validated aseptic
conditions.

Actavis, Barnstaple, EX32 8NS, UK
Actavis Ireland, Euro Hs, Little Island, Cork

Methotrexate 25mg/ml PIL UK_EIRE

approved for print/date

colours/plates:
1. Black

item no: AAAF3865

dimensions: 130 x 600mm

print proof no: 01

pharmacode:

origination date: 17-05-2013

min pt size: 9pt

2.
3.
4.
5.
6.

originated by: MH
revision date:

Technical Approval

revised by:

date sent: 17-05-2013

supplier: Sindan

technically app. date: 20-05-2013

Non Printing Colours
1.
2.
3.

Expand view ⇕

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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