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METOJECT 50 MG/ML SOLUTION FOR INJECTION

Active substance(s): METHOTREXATE

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Metoject 50 mg/ml · 90303-VOGB · DA · 10.14 · Pharma-Code: 941
Format: 600 x 490 mm · HKS 44 · Corrective action: KV01_jem_26.09.14

Other medicines and Metoject 50 mg/ml
Tell your doctor or pharmacist if you are taking, have recently taken
or might take any other medicines.
The effect of the treatment may be affected if Metoject 50 mg/ml is
administered at the same time as certain other drugs:
Package leaflet: Information for the user

Metoject 50 mg/ml
solution for injection
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 signs of illness are the same
as yours.
• If you get any side effects, talk to your doctor or pharmacist. This
includes any possible side effects not listed in this leaflet. See section 4.
What is in this leaflet
1. What Metoject 50 mg/ml is and what it is used for
2. What you need to know before you use Metoject 50 mg/ml
3. How to use Metoject 50 mg/ml
4. Possible side effects
5. How to store Metoject 50 mg/ml
6. Contents of the pack and other information
1. What Metoject 50 mg/ml is and what it is used for
Metoject contains methotrexate as active substance.
Methotrexate is a substance with the following properties:
• it interferes with the growth of certain cells in the body
that reproduce quickly
• it reduces the activity of the immune system
(the body’s own defence mechanism)
• it has anti-inflammatory effects
Metoject 50 mg/ml is indicated for the treatment of
• active rheumatoid arthritis in adult patients.
• polyarthritic forms of severe, active juvenile idiopathic arthritis,
when the response to nonsteroidal anti-inflammatory drugs (NSAIDs)
has been inadequate.
• severe recalcitrant disabling psoriasis, which is not adequately
responsive to other forms of therapy such as phototherapy, PUVA,
and retinoids, and severe psoriatic arthritis in adult patients.
• mild to moderate Crohn’s Disease in adult patients when adequate
treatment with other medicines is not possible.
Rheumatoid arthritis (RA) is a chronic collagen disease, characterised
by inflammation of the synovial membranes (joint membranes). These
membranes produce a fluid which acts as a lubricant for many joints.
The inflammation causes thickening of the membrane and swelling
of the joint.
Juvenile arthritis concerns children and adolescents less than 16 years.
Polyarthritic forms are indicated if 5 or more joints are affected within the
first 6 months of the disease.
Psoriatic arthritis is a kind of arthritis with psoriatic lesions of the skin
and nails, especially at the joints of fingers and toes.
Psoriasis is a common chronic skin disease, characterised by
red patches covered by thick, dry, silvery, adherent scales.

Metoject 50 mg/ml
solution for injection

90303-VOGB
DA

Metoject 50 mg/ml
solution for injection

90303-VOGB
DA

Metoject 50 mg/ml modifies and slows down the progression
of the disease.

• Medicines harming the liver or the blood count, e.g. leflunomide
• Antibiotics (medicines to prevent/fight certain infections) such
as: tetracyclines, chloramphenicol, and non-absorbable broadspectrum antibiotics, penicillines, glycopeptides, sulphonamides
(sulphur containing medicines that prevent/fight certain infections),
ciprofloxacin and cefalotin
• Non-steroidal anti-inflammatory drugs or salicylates
(medicines against pain and/or inflammation)
• Probenecid (medicine against gout)
• Weak organic acids like loop diuretics (“water tablets”) or some
medicines used for treatment of pain and inflammatory diseases
(e.g. acetylsalicylic acid, diclofenac and ibuprofen) and pyrazole
(e.g. metamizol for treating pain)
• Medicinal products, which may have adverse effects on the bone
marrow, e.g. trimethoprim-sulphamethoxazole (an antibiotic) and
pyrimethamine
• Sulphasalazine (antirheumatic medicine)
• Azathioprine (an immunosuppressive agent sometimes used
in severe forms of rheumatoid arthritis)
• Mercaptopurine (a cytostatic agent)
• Retinoids (medicine against psoriasis and other
dermatological diseases)
• Theophylline (medicine against bronchial asthma and other
lung diseases)
• Proton-pump inhibitors (medicines against stomach trouble)
• Hypoglycaemics (medicines that are used to lower the blood sugar)

1 pre-filled syringe of 0.15 ml contains 7.5 mg methotrexate.
1 pre-filled syringe of 0.20 ml contains 10 mg methotrexate. .
1 pre-filled syringe of 0.25 ml contains 12.5 mg methotrexate.
1 pre-filled syringe of 0.30 ml contains 15 mg methotrexate.
1 pre-filled syringe of 0.35 ml contains 17.5 mg methotrexate.
1 pre-filled syringe of 0.40 ml contains 20 mg methotrexate.
1 pre-filled syringe of 0.45 ml contains 22.5 mg methotrexate.
1 pre-filled syringe of 0.50 ml contains 25 mg methotrexate.
1 pre-filled syringe of 0.55 ml contains 27.5 mg methotrexate.
1 pre-filled syringe of 0.60 ml contains 30 mg methotrexate.
For the full list of excipients, see section 6.1.
3.

PHARMACEUTICAL FORM

Solution for injection, in pre-filled syringe.
Clear, yellow-brown solution.

Use in patient with a third distribution space (pleural effusions, ascitis):
As the half-life of Methotrexate can be prolonged to 4 times the normal
length in patients who possess a third distribution space dose reduction
or, in some cases, discontinuation of methotrexate administration may
be required (see section 5.2 and 4.4).
Duration and method of administration:
The medicine is for single use only.
Metoject 50 mg/ml solution for injection can be given by intramuscular,
intravenous or subcutaneous route (in children and adolescents only
subcutaneous or intramuscular).
The overall duration of the treatment is decided by the physician.
Note:
If changing from oral to parenteral administration a reduction of the dose
may be required due to the variable bioavailability of methotrexate after
oral administration.
Folic acid supplementation may be considered according to current
treatment guidelines.

Metoject 50 mg/ml is indicated for the treatment of

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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 for advice before
taking this medicine.
You must not take Metoject 50 mg/ml during pregnancy. There is a risk
of harm to the foetus and miscarriage. Men and women should use an
effective method of birth control during treatment and for a further six
months after treatment with Metoject 50 mg/ml 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.
Breast-feeding should be stopped prior to and during treatment
with Metoject 50 mg/ml.
Driving and using machines
Treatment with Metoject 50 mg/ml may cause adverse reactions
affecting the central nervous system, e.g. tiredness and dizziness.
Thus the ability to drive a vehicle and/or to operate machines may,
in certain cases, be compromised. If you feel tired or drowsy you
should not drive or use machines.
Metoject 50 mg/ml contains sodium
This medicinal product contains less than 1 mmol sodium (23 mg) per
dose, i.e. essentially “sodium-free”.

Warnings and precautions
Talk to your doctor or pharmacist before taking Metoject 50 mg/ml if:
• you are elderly or if you feel generally unwell and weak.
• your liver function is impaired.
• you suffer from dehydration (water loss).

The doctor decides on the appropriate dose in children and adolescents
with polyarthritic forms of juvenile idiopathic arthritis.
Metoject is not recommended in children less than 3 years of age due to
insufficient experience in this age group.

As there is very little data about giving the medicine intravenously in
children and adolescents, it must only be injected under the skin or into
a muscle.

Method and duration of administration
Metoject is injected once weekly!
The duration of the treatment is determined by the treating physician.
Treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis
vulgaris, psoriatic arthritis and Crohn’s disease with Metoject is a longterm treatment.
At the start of your therapy, Metoject may be injected by medical staff.
In certain cases your doctor may decide to instruct you how to inject
Metoject under the skin yourself. You will then receive appropriate
training.
Under no circumstances should you try to inject Metoject yourself
before you have received such training.
Please refer to the instructions for use at the end of the leaflet.
The manner of handling and disposal must be consistent with that of
other cytostatic preparations in accordance with local requirements.
Pregnant health care personnel should not handle and/or administer
Metoject 50 mg/ml.
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.

Methotrexate may affect your immune system and vaccination results.
It may also affect the result of immunological tests. Inactive, chronic
infections (e.g. herpes zoster [shingles], tuberculosis, hepatitis B or C)
may flare up. During therapy with Metoject 50 mg/ml you must not be
vaccinated with live vaccines.

If you have the impression that the effect of Metoject 50 mg/ml is too
strong or too weak, you should talk to your doctor or pharmacist.

Radiation induced dermatitis and sun-burn can reappear under
methotrexate therapy (recall-reaction). Psoriatic lesions can exacerbate
during UV-irradiation and simultaneous administration of methotrexate.
Enlarged lymph nodes (lymphoma) may occur and therapy must then
be stopped.

Like all medicines, this medicine can cause side effects, although not
everybody gets them.
The frequency as well as the degree of severity of the side effects
depends on the dosage level and the frequency of administration. As
severe side effects may occur even at low dosage, it is important that
you are monitored regularly by your doctor. Your doctor will do tests to
check for abnormalities developing in the blood (such as low white
blood cells, low platelets, lymphoma) and changes in the kidneys and
the liver.

Encephalopathy (a brain disorder) / leukoencephalopathy (a special
disorder of the white brain substance) have been reported in cancer
patients receiving methotrexate therapy and cannot be excluded for
methotrexate therapy in other diseases.

1 ml of solution contains 50 mg methotrexate
(as methotrexate disodium).

Metoject 50 mg/ml with food, drink and alcohol
Alcohol as well as large amounts of coffee, caffeine-containing
soft drinks and black tea should be avoided during treatment with
Metoject 50 mg/ml.

Metoject 50 mg/ml is administered by or under the supervision of a
physician or healthcare staff as an injection once a week only. Together
with your doctor you decide on a suitable weekday each week on
which you receive your injection. Metoject 50 mg/ml may be injected
intramuscularly (in a muscle), intravenously (in a vein) or subcutaneously
(under the skin).

Diarrhoea can be a toxic effect of Metoject 50 mg/ml and requires
an interruption of therapy. If you suffer from diarrhoea please speak
to your doctor.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Metoject 50 mg/ml is contraindicated in the case of

Do not use Metoject 50 mg/ml if you
• are allergic to methotrexate or any of the other ingredients
of this medicine (listed in section 6).
• suffer from severe liver or kidney diseases or blood diseases.
• regularly drink large amounts of alcohol.
• suffer from a severe infection, e.g. tuberculosis, HIV or other
immunodeficiency syndromes.
• suffer from ulcers in the mouth, stomach ulcer or intestinal ulcer.
• are pregnant or breast-feeding.
• receive vaccinations with live vaccines at the same time.

Examination of the mouth and throat for alterations of the mucosa
Blood tests
Check of liver function
Check of kidney function
Check of respiratory system and if necessary lung function test

2.

4. Possible side effects

Tell your doctor immediately if you experience any of the following
symptoms, as these may indicate a serious, potentially life-threatening
side effect, which require urgent specific treatment:

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CLINICAL PARTICULARS

active rheumatoid arthritis in adult patients,
polyarthritic forms of severe, active juvenile idiopathic arthritis,
when the response to nonsteroidal anti-inflammatory drugs
(NSAIDs) has been inadequate,
severe recalcitrant disabling psoriasis, which is not adequately
responsive to other forms of therapy such as phototherapy, PUVA,
and retinoids, and severe psoriatic arthritis in adult patients.
mild to moderate Crohn’s disease either alone or in combination
with corticosteroids in adult patients refractory or intolerant to
thiopurines.

4.2 Posology and method of administration

-

hypersensitivity to the active substance or to any of the excipients
listed in section 6.1,
severe liver impairment (see section 4.2),
alcohol abuse,
severe renal impairment (creatinine clearance less than 20 ml/min.,
see section 4.2 and section 4.4),
pre-existing blood dyscrasias, such as bone marrow hypoplasia,
leukopenia, thrombocytopenia, or significant anaemia,
serious, acute or chronic infections such as tuberculosis,
HIV or other immunodeficiency syndromes,
ulcers of the oral cavity and known active gastrointestinal
ulcer disease,
pregnancy, breast-feeding (see section 4.6),
concurrent vaccination with live vaccines.

4.4 Special warnings and precautions for use

Dosage in adult patients with rheumatoid arthritis:
The recommended initial dose is 7.5 mg of methotrexate once weekly,
administered either subcutaneously, intramuscularly or intravenously.
Depending on the individual activity of the disease and tolerability by the
patient, the initial dose may be increased gradually by 2.5 mg per week.
A weekly dose of 25 mg should in general not be exceeded. However,
doses exceeding 20 mg/week are associated with significant increase
in toxicity, especially bone marrow suppression. Response to treatment
can be expected after approximately 4 – 8 weeks. Upon achieving the
therapeutically desired result, the dose should be reduced gradually to
the lowest possible effective maintenance dose.

Recommended examinations and safety measures

Dosage in children and adolescents below 16 years with polyarthritic
forms of juvenile idiopathic arthritis
The recommended dose is 10-15 mg/m² body surface area (BSA)/
once weekly. In therapy-refractory cases the weekly dosage may be
increased up to 20mg/m2 body surface area/once weekly. However,
an increased monitoring frequency is indicated if the dose is increased.
Due to limited data availability about intravenous use in children and
adolescents, parenteral administration is limited to subcutaneous and
intramuscular injection.
Patients with JIA should always be referred to a rheumatology specialist
in the treatment of children/adolescents.

1.

Examination of the mouth and throat for mucosal changes

2.

Complete blood count with differential blood count and platelets.
Haemopoietic suppression caused by methotrexate may occur
abruptly and with apparently safe dosages. Any profound drop
in white-cell or platelet counts indicates immediate withdrawal
of the medicinal product and appropriate supportive therapy.
Patients should be advised to report all signs and symptoms
suggestive of infection. Patients taking simultaneous administration
of haematotoxic medicinal products (e.g. leflunomide) should be
monitored closely with blood count and platelets.

Use in children < 3 years of age is not recommended as insufficient data
on efficacy and safety is available for this population. (see section 4.4).

3.

Patients must be clearly informed that the therapy has to be applicated
once a week, not every day.
Patients undergoing therapy should be subject to appropriate
supervision so that signs of possible toxic effects or adverse reactions
may be detected and evaluated with minimal delay. Therefore
methotrexate should be only administered by, or under the supervision
of physicians whose knowledge and experience includes the use of
antimetabolite therapy. Because of the possibility of severe or even fatal
toxic reactions, the patient should be fully informed by the physician of
the risks involved and the recommended safety measures.
Use in children < 3 years of age is not recommended as insufficient data
on efficacy and safety are available for this population (see section 4.2).

Before beginning or reinstituting methotrexate therapy after a rest period:
Complete blood count with differential blood count and platelets, liver
enzymes, bilirubin, serum albumin, chest x-ray and renal function tests.
If clinically indicated, exclude tuberculosis and hepatitis.
During therapy (at least once a month during the first six months and
every three months thereafter):
An increased monitoring frequency should be considered also when the
dose is increased.

Dosage in patients with psoriasis vulgaris and psoriatic arthritis:
It is recommended that a test dose of 5 – 10 mg should be administered
parenterally, one week prior to therapy to detect idiosyncratic adverse
reactions. The recommended initial dose is 7.5 mg of methotrexate
once weekly, administered either subcutaneously, intramuscularly or
intravenously. The dose is to be increased gradually but should not,
in general, exceed a weekly dose of 25 mg of methotrexate. Doses
exceeding 20 mg per week can be associated with significant increase
in toxicity, especially bone marrow suppression. Response to treatment
can generally be expected after approximately 2 – 6 weeks. Upon
achieving the therapeutically desired result, the dose should be reduced
gradually to the lowest possible effective maintenance dose.
The dose should be increased as necessary but should in general not
exceed the maximum recommended weekly dose of 25 mg. In a few
exceptional cases a higher dose might be clinically justified, but should
not exceed a maximum weekly dose of 30 mg of methotrexate as toxicity
will markedly increase.

Liver function tests: Particular attention should be given to the
appearance of liver toxicity. Treatment should not be instituted
or should be discontinued if any abnormality of liver function
tests, or liver biopsy, is present or develops during therapy. Such
abnormalities should return to normal within two weeks after which
treatment may be recommenced at the discretion of the physician.
There is no evidence to support use of a liver biopsy to monitor
hepatic toxicity in rheumatological indications.
For psoriasis patients the need for a liver biopsy prior to and during
therapy is controversial. Further research is needed to establish
whether serial liver chemistry tests or propeptide of type III collagen
can detect hepatotoxicity sufficiently. The evaluation should be
performed case by case and differentiate between patients with no
risk factors and patients with risk factors such as excessive prior
alcohol consumption, persistent elevation of liver enzymes, history
of liver disease, family history of inheritable liver disease, diabetes
mellitus, obesity, and history of significant exposure to hepatotoxic
drugs or chemicals and prolonged Methotrexate treatment or
cumulative doses of 1.5 g or more.
Check of liver-related enzymes in serum: Temporary increases in
transaminases to twice or three times of the upper limit of normal
have been reported by patients at a frequency of 13 – 20 %. In the
case of a constant increase in liver-related enzymes, a reduction
of the dose or discontinuation of therapy should be taken into
consideration.

Dosage in patients with Crohn’s Disease:

Induction treatment:
25 mg/week administered either subcutaneously, intravenously or
intramuscularly.
Response to treatment can be expected after approximately
8 to 12 weeks.

Maintenance treatment:
15 mg/week administered either subcutaneously, intravenously or
intramuscularly.

Due to its potentially toxic effect on the liver, additional hepatotoxic
medicinal products should not be taken during treatment with
methotrexate unless clearly necessary and the consumption of
alcohol should be avoided or greatly reduced (see section 4.5).
Closer monitoring of liver enzymes should be exercised in patients
taking other hepatotoxic medicinal products concomitantly (e.g.
leflunomide). The same should be taken into account with the
simultaneous administration of haematotoxic medicinal products
(e.g. leflunomide).

There is not sufficient experience in the paediatric population to
recommend Metoject 50 mg/ml for the treatment of Crohn’s Disease
in this population.

See section 4.3.

6.

Methotrexate may, due to its effect on the immune system,
impair the response to vaccination results and affect the result
of immunological tests. Particular caution is also needed in
the presence of inactive, chronic infections (e.g. herpes zoster,
tuberculosis, hepatitis B or C) for reasons of eventual activation.
Vaccination using live vaccines must not be carried out under
methotrexate therapy.

Malignant lymphomas may occur in patients receiving low dose
methotrexate, in which case therapy must be discontinued. Failure of
the lymphoma to show signs of spontaneous regression requires the
initiation of cytotoxic therapy.
Concomitant administration of folate antagonists such as trimethoprim/
sulphamethoxazole has been reported to cause an acute megaloblastic
pancytopenia in rare instances.
Radiation induced dermatitis and sun-burn can reappear under
methotrexate therapy (recall-reaction). Psoriatic lesions can exacerbate
during UV-irradiation and simultaneous administration of methotrexate.

4.3 Contraindications

Metoject 50 mg/ml should only be prescribed by physicians, who are
familiar with the various characteristics of the medicinal product and its
mode of action. The administration should routinely be done by health
professionals. If the clinical situation permits the treating physician can,
in selected cases, delegate the subcutaneous administration to the
patient her/himself. In these cases, detailed administration instructions
from the physician are obligate. Metoject 50 mg/ml is injected once
weekly.
The patient is to be explicitly informed about the fact of administration
once weekly. It is advisable to determine a fixed, appropriate weekday
as day of injection.
Methotrexate elimination is reduced in patients with a third distribution
space (ascites, pleural effusions). Such patients require especially careful
monitoring for toxicity, and require dose reduction or, in some cases,
discontinuation of methotrexate administration (see section 5.2 and 4.4).

Patients with renal impairment:
Metoject 50 mg/ml should be used with caution in patients with impaired
renal function. The dose should be adjusted as follows:
Creatinine clearance (ml/min) Dose
> 50
100 %
20 – 50
50 %
< 20
Metoject 50 mg/ml must not be used

Assessment of respiratory system: Alertness for symptoms of
lung function impairment and, if necessary lung function test.
Pulmonary affection requires a quick diagnosis and discontinuation
of methotrexate. Pulmonary symptoms (especially a dry, nonproductive cough) or a non-specific pneumonitis occurring during
methotrexate therapy may be indicative of a potentially dangerous
lesion and require interruption of treatment and careful investigation.
Acute or chronic interstitial pneumonitis, often associated with
blood eosinophilia, may occur and deaths have been reported.
Although clinically variable, the typical patient with methotrexateinduced lung disease presents with fever, cough, dyspnoea,
hypoxemia, and an infiltrate on chest X-ray, infection needs to
be excluded. Pulmonary affection requires a quick diagnosis and
discontinuation of methotrexate therapy. This lesion can occur
at all dosages.

Use in elderly patients:
Dose reduction should be considered in elderly patients due to reduced
liver and kidney function as well as lower folate reserves which occur
with increased age.

4.1 Therapeutic indications

Your doctor decides on the dosage, which is adjusted individually.
Usually it takes 4 – 8 weeks before there is any effect of the treatment.







Metoject 50 mg/ml solution for injection

5.

For a full list of contraindications, see section 4.3.

Vaccination with live vaccine should be avoided.

2. What you need to know before you use Metoject 50 mg/ml

During therapy:
You will have the following tests at least once a month during the first
six months and at least every three months thereafter:

NAME OF THE MEDICINAL PRODUCT

4.

3. How to use Metoject 50 mg/ml

Before therapy:
Before starting the treatment, blood samples will be taken in order
to check that you have enough blood cells, tests to check your liver
function, serum albumin (a protein in the blood) and kidney function.
Your doctor will also check if you suffer from tuberculosis (infectious
disease in combination with little nodules in the affected tissue) and
a chest X-ray will be taken.

1.

Patients with hepatic impairment:
Methotrexate should be administered with great caution, if at all,
to patients with significant current or previous liver disease, especially
if due to alcohol. If bilirubin is > 5 mg/dl (85.5 μmol/l), methotrexate is
contraindicated.

Vitamins containing folic acid may impair the effect of your treatment
and should only be taken when advised by your doctor.

Crohn’s Disease is a type of inflammatory bowel disease that may
affect any part of the gastrointestinal tract causing symptoms such as
abdominal pain, diarrhoea, vomiting or weight loss.

Recommended follow-up examinations and safety measures:
Even when Metoject 50 mg/ml is administered in low doses, severe
side effects can occur. In order to detect them in time, check-ups and
laboratory tests have to be carried out by your doctor.

SUMMARY OF PRODUCT CHARACTERISTICS

4.

Renal function should be monitored by renal function tests and
urinanalysis (see sections 4.2 and 4.3).
As methotrexate is eliminated mainly by renal route, increased
serum concentrations are to be expected in the case of renal
impairment, which may result in severe undesirable effects.
Where renal function may be compromised (e.g. in the elderly),
monitoring should take place more frequently. This applies in
particular, when medicinal products are administered concomitantly,
which affect the elimination of methotrexate, cause kidney damage
(e.g. non-steroidal anti-inflammatory medicinal products) or which
can potentially lead to impairment of blood formation. Dehydration
may also intensify the toxicity of methotrexate.

Methotrexate elimination is reduced in patients with a third distribution
space (ascites, pleural effusions). Such patients require especially careful
monitoring for toxicity, and require dose reduction or, in some cases,
discontinuation of methotrexate administration. Pleural effusions and
ascites should be drained prior to initiation of methotrexate treatment
(see section 5.2).
Diarrhoea and ulcerative stomatitis can be toxic effects and require
interruption of therapy, otherwise haemorrhagic enteritis and death
from intestinal perforation may occur.
Vitamin preparations or other products containing folic acid, folinic acid
or their derivatives may decrease the effectiveness of methotrexate.
For the treatment of psoriasis, methotrexate should be restricted
to severe recalcitrant, disabling psoriasis which is not adequately
responsive to other forms of therapy, but only when the diagnosis has
been established by biopsy and/or after dermatological consultation.
Encephalopathy / leukoencephalopathy have been reported in oncologic
patients receiving methotrexate therapy and cannot be excluded for
methotrexate therapy in non-oncologic indications.
This medicinal product contains less than 1 mmol sodium (23 mg) per
dose, i.e. essentially “sodium-free”.
The absence of pregnancy should be confirmed before Metoject 50 mg/ml
is administered. Methotrexate causes embryotoxicity, abortion and
foetal defects in humans. Methotrexate affects spermatogenesis
and oogenesis during the period of its administration which may
result in decreased fertility. These effects appear to be reversible on
discontinuing therapy. Effective contraception in men and women should
be performed during treatment and for at least six months thereafter.
The possible risks of effects on reproduction should be discussed with
patients of childbearing potential and their partners should be advised
appropriately (see section 4.6).
4.5 Interaction with other medicinal products and other forms
of interaction
Alcohol, hepatotoxic medicinal products, haematotoxic medicinal
products
The probability of methotrexate exhibiting a hepatotoxic effect is
increased by regular alcohol consumption and when other hepatotoxic
medicinal products are taken at the same time (see section 4.4).
Patients taking other hepatotoxic medicinal products concomitantly
(e.g. leflunomide) should be monitored with special care. The same
should be taken into account with the simultaneous administration
of haematotoxic medicinal products (e.g. leflunomide, azathioprine,
retinoids, sulfasalazine). The incidence of pancytopenia and hepatotoxicity
can be increased when leflunomide is combined with methotrexate.
Combined treatment with methotrexate and retinoids like acitretin
or etretinate increases the risk of hepatotoxicity.
Oral antibiotics
Oral antibiotics like tetracyclines, chloramphenicol, and non-absorbable
broad-spectrum antibiotics can interfere with the enterohepatic
circulation, by inhibition of the intestinal flora or suppression of the
bacterial metabolism.
Antibiotics
Antibiotics, like penicillines, glycopeptides, sulfonamides, ciprofloxacin
and cefalotin can, in individual cases, reduce the renal clearance of
methotrexate, so that increased serum concentrations of methotrexate
with simultaneous haematological and gastro-intestinal toxicity may
occur.
Medicinal products with high plasma protein binding
Methotrexate is plasma protein bound and may be displaced by other
protein bound drugs such as salicylates, hypoglycaemics, diuretics,
sulphonamides, diphenylhydantoins, tetracyclines, chloramphenicol
and p-aminobenzoic acid, and the acidic anti-inflammatory agents,
which can lead to increased toxicity when used concurrently.
Probenecid, weak organic acids, pyrazoles and non-steroidal antiinflammatory agents
Probenecid, weak organic acids such as loop diuretics, and pyrazoles
(phenylbutazone) can reduce the elimination of methotrexate and higher
serum concentrations may be assumed inducing higher haematological
toxicity. There is also a possibility of increased toxicity when low dose
methotrexate and non steroidal anti-inflammatory medicinal products or
salicylates are combined.
Medicinal products with adverse reactions on the bone marrow
In the case of medication with medicinal products, which may
have adverse reactions on the bone marrow (e.g. sulphonamides,
trimethoprim-sulphamethoxazole, chloramphenicol, pyrimethamine);
attention should be paid to the possibility of pronounced impairment
of blood formation.
Medicinal products which cause folate deficiency
The concomitant administration of products which cause folate
deficiency (e.g. sulphonamides, trimethoprim-sulphamethoxazole) can
lead to increased methotrexate toxicity. Particular care is therefore
advisable in the presence of existing folic acid deficiency.
Products containing folic acid or folinic acid
Vitamin preparations or other products containing folic acid, folinic acid
or their derivatives may decrease the effectiveness of methotrexate.
Other antirheumatic medicinal products
An increase in the toxic effects of methotrexate is, in general, not to
be expected when Metoject 50 mg/ml is administered simultaneously
with other antirheumatic medicinal products (e.g. gold compounds,
penicillamine, hydroxychloroquine, sulphasalazine, azathioprine,
ciclosporin).

Metoject 50 mg/ml · 90303-VOGB · DA · 10.14 · Pharma-Code: 941
Format: 600 x 490 mm · HKS 44 · Corrective action: KV01_jem_26.09.14

Sulphasalazine
Although the combination of methotrexate and sulphasalazine can
cause an increase in efficacy of methotrexate and as a result more
undesirable effects due to the inhibition of folic acid synthesis through
sulphasalazine, such undesirable effects have only been observed
in rare individual cases in the course of several studies.
Mercaptopurine
Methotrexate increases the plasma levels of mercaptopurine.
The combination of methotrexate and mercaptopurine may therefore
require dose adjustment.
Proton-pump inhibitors
A concomitant administration of proton-pump inhibitors like omeprazole
or pantoprazole can lead to interactions: Concomitant administration
of methotrexate and omeprazole has led to delayed renal elimination
of methotrexate. In combination with pantoprazole inhibited renal
elimination of the metabolite 7-hydroxymethotrexate with myalgia and
shivering was reported in one case.
Theophylline
Methotrexate may decrease the clearance of theophylline; theophylline
levels should be monitored when used concurrently with methotrexate.
Caffeine- or theophylline-containing beverages
An excessive consumption of caffeine- or theophylline-containing
beverages (coffee, caffeine-containing soft drinks, black tea) should be
avoided during methotrexate therapy.
4.6 Fertility, pregnancy and lactation
Pregnancy
Metoject 50 mg/ml is contraindicated during pregnancy (see section 4.3).
In animal studies, methotrexate has shown reproductive toxicity
(see section 5.3). Methotrexate has been shown to be teratogenic to
humans; it has been reported to cause foetal death and/or congenital
abnormalities. Exposure of a limited number of pregnant women (42)
resulted in an increased incidence (1:14) of malformations (cranial,
cardiovascular and extremital). If methotrexate is discontinued prior to
conception, normal pregnancies have been reported. Women must not
get pregnant during methotrexate therapy. In case of women getting
pregnant during therapy medical counselling about the risk of adverse
reactions for the child associated with methotrexate therapy should be
sought. Therefore, patients of a sexually mature age (women and men)
must use effective contraception during treatment with Metoject 50 mg/ml
and at least 6 months thereafter (see section 4.4).
In women of child-bearing age, any existing pregnancy must be excluded
with certainty by taking appropriate measures, e.g. pregnancy test, prior
to initiating therapy.

Rare:
Very rare:

Musculoskeletal and connective tissue disorders
Uncommon:
Arthralgia, myalgia, osteoporosis.

Fertility
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.
4.7 Effects on ability to drive and use machines
Central nervous symptoms such as tiredness and dizziness can occur
during treatment, Metoject 50 mg/ml has minor or moderate influence
on the ability to drive and use machines.

6.

PHARMACEUTICAL PARTICULARS

6.1 List of excipients
Sodium chloride
Sodium hydroxide for pH adjustment
Water for injections

Renal and urinary disorders
Uncommon:
Inflammation and ulceration of the urinary bladder,
renal impairment, disturbed micturition.
Rare:
Renal failure, oliguria, anuria, electrolyte disturbances.

6.2 Incompatibilities

Reproductive system and breast disorders
Uncommon:
Inflammation and ulceration of the vagina.
Very rare:
Loss of libido, impotence, gynaecomastia, oligospermia,
impaired menstruation, vaginal discharge.

6.3 Shelf-life

In the absence of compatibility studies, this medicinal product must not
be mixed with other medicinal products.

2 years.
6.4 Special precautions for storage

General disorders and administration site conditions
Rare:
Allergic reactions, anaphylactic shock, allergic vasculitis,
fever, conjunctivitis, infection, sepsis, wound-healing
impairment, hypogammaglobulinaemia.
Very rare:
Local damage (formation of sterile abscess,
lipodystrophy) of injection site following intramuscular
or subcutaneous administration.
The appearance and degree of severity of undesirable effects depends
on the dosage level and the frequency of administration. However,
as severe undesirable effects can occur even at lower doses, it is
indispensable that patients are monitored regularly by the doctor
at short intervals.
When methotrexate is given by the intramuscular route, local undesirable
effects (burning sensation) or damage (formation of sterile abscess,
destruction of fatty tissue) at the site of injection can occur commonly.
Subcutaneous application of methotrexate is locally well tolerated. Only
mild local skin reactions were observed, decreasing during therapy.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation
of the medicinal product is important. It allows continued monitoring
of the benefit/risk balance of the medicinal product. Healthcare
professionals are asked to report any suspected adverse reactions
via www.mhra.gov.uk/yellowcard.
4.9 Overdose
a)
b)

Breast-feeding
Methotrexate is excreted in breast milk in such concentrations that
there is a risk for the infant, and accordingly, breast-feeding should be
discontinued prior to and throughout administration.

Increased pigmentation, acne, ecchymosis.
Stevens-Johnson syndrome, toxic epidermal necrolysis
(Lyell’s syndrome), increased pigmentary changes of the
nails, acute paronychia, furunculosis, telangiectasia.

Symptoms of overdosage
Toxicity of methotrexate mainly affects the haematopoietic system.
Treatment measures in the case of overdosage
Calcium folinate is the specific antidote for neutralising the toxic
undesirable effects of methotrexate.

In cases of accidental overdose, a dose of calcium folinate equal to or
higher than the offending dose of methotrexate should be administered
intravenously or intramuscularly within one hour and dosing continued
until the serum levels of methotrexate are below 10-7 mol/l.
In cases of massive overdose, hydration and urinary alkalisation may be
necessary to prevent precipitation of methotrexate and/or its metabolites
in the renal tubules. Neither haemodialysis nor peritoneal dialysis has
been shown to improve methotrexate elimination. Effective clearance of
methotrexate has been reported with acute, intermittent haemodialysis
using a high flux dialyser.
5.

PHARMACOLOGICAL PROPERTIES

Store below 25 °C. Keep the pre-filled syringes in the outer carton
in order to protect from light.
6.5 Nature and contents of container
Nature of container:
Pre-filled syringes of colourless glass (type I) of 1 ml capacity with
attached injection needle. Plunger stoppers of chlorobutyl rubber (type I)
and polystyrene rods inserted on the stopper to form the syringe plunger
or
Pre-filled syringes of colourless glass (type I) of 1 ml capacity with
enclosed injection needle.Plunger stoppers of chlorobutyl rubber (type I)
and polystyrene rods inserted on the stopper to form the syringe plunger.
Pack sizes:
Pre-filled syringes containing 0.15 ml, 0.20 ml, 0.25 ml, 0.30 ml, 0.35 ml,
0.40 ml, 0.45 ml, 0.50 ml, 0.55 ml or 0.60 ml solution are available in
packs of 1, 4, 5, 6, 10, 11, 12 and 24 syringes with attached s.c. injection
needle and alcohol pads.
and
Pre-filled syringes containing 0.15 ml, 0.20 ml, 0.25 ml, 0.30 ml, 0.35 ml,
0.40 ml, 0.45 ml, 0.50 ml, 0.55 ml or 0.60 ml solution are available in
packs of 1, 4, 5, 6, 10, 11, 12 and 24 syringes with enclosed s.c. injection
needle and alcohol pads.
For i.m and i.v use, a needle suitable for these routes of administration
must be used: The needle enclosed in the pack is suitable for s.c. use
only.

In the following, please find the other side effects that may occur:

All pack sizes are available with graduation marks.

Very common: may affect more than 1 in 10 people
• Mouth inflammation, indigestion, nausea (feeling sick), loss of appetite
• Increase in liver enzymes

Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
The manner of handling and disposal must be consistent with that of
other cytotoxic preparations in accordance with local requirements.
Pregnant health care personnel should not handle and/or administer
Metoject 50 mg/ml.
Methotrexate should not come into contact with the skin or mucosa.
In the event of contamination, the affected area must be rinsed
immediately with ample amount of water.
For single use only.

4.8 Undesirable effects
5.1 Pharmacodynamic properties
The most relevant undesirable effects are suppression of the
haematopoietic system and gastrointestinal disorders.
The following headings are used to organise the undesirable effects
in order of frequency:
Very common (≥ 1/10), common (≥ 1/100 to < 1/10),
uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000),
very rare (< 1/10,000), not known (cannot be estimated from the
available data)
Neoplasms benign, malignant and unspecified
(including cysts and polyps)
Very rare:
There have been reports of individual cases of lymphoma
which subsided in a number of cases once treatment with
methotrexate had been discontinued. In a recent study,
it could not be established that methotrexate therapy
increases the incidence of lymphomas.
Blood and lymphatic system disorders
Common:
Leukopenia, anaemia, thrombopenia.
Uncommon:
Pancytopenia.
Very rare:
Agranulocytosis, severe courses of bone marrow
depression.
Metabolism and nutrition disorders
Uncommon:
Precipitation of diabetes mellitus.
Nervous system disorders
Common:
Headache, tiredness, drowsiness.
Uncommon:
Dizziness, confusion, depression.
Very rare:
Impaired vision, pain, muscular asthenia or paraesthesia
in the extremities, changes in sense of taste (metallic
taste), convulsions, meningism, paralysis.
Unknown:
Leukoencephalopathy.
Eye disorders
Rare:
Visual disturbances.
Very rare:
Retinopathy.
Cardiac disorders
Rare:
Pericarditis, pericardial effusion, pericardial tamponade.
Vascular disorders
Rare:
Hypotension, thromboembolic events.
Respiratory, thoracic and mediastinal disorders
Common:
Pneumonia, interstitial alveolitis/pneumonitis often
associated with eosinophilia. Symptoms indicating
potentially severe lung injury (interstitial pneumonitis) are:
dry, not productive cough, short of breath and fever.
Rare:
Pulmonary fibrosis, Pneumocystis carinii pneumonia,
shortness of breath and bronchial asthma, pleural
effusion.
Gastrointestinal disorders
Very common: Stomatitis, dyspepsia, nausea, loss of appetite.
Common:
Oral ulcers, diarrhoea.
Uncommon:
Pharyngitis, enteritis, vomiting.
Rare:
Gastrointestinal ulcers.
Very rare:
Haematemesis, haematorrhea, toxic megacolon.
Hepatobiliary disorders (see section 4.4)
Very common: Elevated transaminases.
Uncommon:
Cirrhosis, fibrosis and fatty degeneration of the liver,
decrease in serum albumin.
Rare:
Acute hepatitis.
Very rare:
Hepatic failure.
Skin and subcutaneous tissue disorders
Common:
Exanthema, erythema, pruritus.
Uncommon:
Photosensitisation, loss of hair, increase in rheumatic
nodules, herpes zoster, vasculitis, herpetiform eruptions
of the skin, urticaria.

Pharmacotherapeutic group: Folic acid analogues, ATC code: L01BA01
Antirheumatic medicinal product for the treatment of chronic,
inflammatory rheumatic diseases and polyarthritic forms of juvenile
idiopathic arthritis. Immunomodulating and anti-inflammatory agent for
the treatment of Crohn’s disease.

Any unused medicinal product or waste material should be disposed of
in accordance with local requirements.
Instructions for subcutaneous use
The best places for the injection are:
upper thighs,
abdomen except around the navel.

Mechanism of action
Methotrexate is a folic acid antagonist which belongs to the class of
cytotoxic agents known as antimetabolites. It acts by the competitive
inhibition of the enzyme dihydrofolate reductase and thus inhibits DNA
synthesis. It has not yet been clarified, as to whether the efficacy of
methotrexate, in the management of psoriasis, psoriasis arthritis, chronic
polyarthritis and Crohn’s disease, is due to an anti-inflammatory or
immunosuppressive effect and to which extent a methotrexate-induced
increase in extracellular adenosine concentration at inflamed sites
contributes to these effects.

1.

International clinical guidelines reflect the use of methotrexate as a
second choice for Crohn’s disease patients that are intolerant or have
failed to respond to first-line immunomodulating agents as azathioprine
(AZA) or 6-mercaptopurine (6-MP).

7.

The adverse events observed in the studies performed with methotrexate
for Crohn’s disease at cumulative doses have not shown a different
safety profile of methotrexate than the profile it is already known.
Therefore, similar cautions must be taken with the use of methotrexate
for the treatment of Crohn’s disease as in other rheumatic and nonrheumatic indications of methotrexate (see sections 4.4 and 4.6).

2.
3.
4.
5.
6.

Clean the area around the chosen injection site (e.g. by using the
enclosed alcohol pad).
Pull the protective plastic cap straight off.
Build a skin fold by gently squeezing the area at the injection site.
The fold must be held pinched until the syringe is removed from the
skin after the injection.
Push the needle fully into the skin at a 90-degree angle.
Push the plunger down slowly and inject the liquid underneath the
skin. Remove the syringe from the skin at the same 90-degree angle.
MARKETING AUTHORISATION HOLDER

medac
Gesellschaft für klinische Spezialpräparate mbH
Theaterstr. 6
22880 Wedel
Germany
8.

MARKETING AUTHORISATION NUMBER

PL 11587/0046
5.2 Pharmacokinetic properties
Distribution
Following oral administration, methotrexate is absorbed from the
gastrointestinal tract. In case of low-dosed administration (dosages
between 7.5 mg/m² and 80 mg/m² body surface area), the mean
bioavailability is approx. 70 %, but considerable interindividual and
intraindividual deviations are possible (25 – 100 %). Maximum serum
concentrations are achieved after 1 – 2 hours.

9.

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION

Date of first authorisation: 21/11/2008
Date of latest renewal: 02/10/2013
10. DATE OF REVISION OF THE TEXT

Biotransformation
Bioavailability of subcutaneous, intravenous and intramuscular injection
is comparable and nearly 100 %.
Elimination
Approximately 50 % of methotrexate is bound to serum proteins. Upon
being distributed into body tissues, high concentrations in the form of
polyglutamates are found in the liver, kidneys and spleen in particular,
which can be retained for weeks or months. When administered in
small doses, methotrexate passes into the liquor in minimal amounts.
The terminal half-life is on average 6 – 7 hours and demonstrates
considerable variation (3 – 17 hours). The half-life can be prolonged to
4 times the normal length in patients who possess a third distribution
space (pleural effusion, ascites).
Approx. 10 % of the administered methotrexate dose is metabolised
intrahepatically. The principle metabolite is 7-hydroxymethotrexate.
Excretion takes places, mainly in unchanged form, primarily renal via
glomerular filtration and active secretion in the proximal tubulus.
Approx. 5 – 20 % methotrexate and 1 – 5 % 7-hydroxymethotrexate
are eliminated biliary. There is pronounced enterohepatic circulation.
In the case of renal impairment, elimination is delayed significantly.
Impaired elimination with regard to hepatic impairment is not known.

• persistent dry, non-productive cough, shortness of breath and
fever; these may be signs of an inflammation of the lungs (pneumonia)
[common — may affect up to 1 in 10 people]
• symptoms of liver damage such as yellowing of the skin and
whites of the eyes; methotrexate can cause chronic liver damage
(liver cirrhosis), formation of scar tissue of the liver (liver fibrosis),
fatty degeneration of the liver [all uncommon — may affect up to 1 in
100 people], inflammation of the liver (acute hepatitis) [rare — may
affect up to 1 in 1,000 people] and liver failure [very rare — may affect
up to 1 in 10,000 people]
• allergy symptoms such as skin rash including red itchy skin,
swelling of the hands, feet, ankles, face, lips, mouth or throat
(which may cause difficulty in swallowing or breathing) and
feeling you are going to faint; these may be signs of severe allergic
reactions or an anaphylactic shock [rare — may affect up to 1 in
1,000 people]
• symptoms of kidney damage such as swelling of the hands,
ankles or feet or changes in frequency of urination or decrease or
absence of urine; these may be signs of kidney failure [rare — may
affect up to 1 in 1,000 people]
• symptoms of infections, e.g. fever, chills, achiness, sore throat;
methotrexate can make you more susceptible to infections. Rarely
[may affect up to 1 in 1,000 people] severe infections like a certain
type of pneumonia (Pneumocystis carinii pneumonia) or blood
poisoning (sepsis) may occur
• severe diarrhoea, vomiting blood and black or tarry stools; these
symptoms may indicate a rare [may affect up to 1 in 1,000 people]
severe complication of the gastrointestinal system caused by
methotrexate e.g. gastrointestinal ulcers
• symptoms associated with the blockage (occlusion) of a blood
vessel by a dislodged blood clot (thromboembolic event) such
as weakness of one side of the body (stroke) or pain, swelling,
redness and unusual warmth in one of your legs (deep vein
thrombosis); methotrexate can cause thromboembolic events
[rare - may affect up to 1 in 1,000 people]
• fever and serious deterioration of your general condition, or
sudden fever accompanied by a sore throat or mouth, or urinary
problems; methotrexate can very rarely [may affect up to 1 in
10,000 people] cause a sharp fall in white blood cells (agranulocytosis)
and severe bone marrow suppression
• unexpected bleeding, e.g. bleeding gums, blood in the urine,
vomiting blood or bruising, these can be signs of a severely reduced
number of blood platelets caused by severe courses of bone marrow
depression [very rare — may affect up to 1 in 10,000 people]
• severe skin rash or blistering of the skin (this can also affect your
mouth, eyes and genitals); these may be signs of the very rare [may
affect up to 1 in 10,000 people] conditions called Stevens Johnson
syndrome or burned skin syndrome (toxic epidermal necrolysis)

15/10/2014

Common: may affect up to 1 in 10 people
• Mouth ulcers, diarrhoea
• Rash, reddening of the skin, itching
• Headache, tiredness, drowsiness
• Reduced blood cell formation with decrease in white and/or red blood
cells and/or platelets (leukopenia, anaemia, thrombocytopenia)
Uncommon: may affect up to 1 in 100 people
• Throat inflammation, inflammation of the bowels, vomiting
• Increased sensitivity to light, loss of hair, increased number of
rheumatic nodules, shingles, inflammation of blood vessels,
herpes-like skin rash, hives
• Onset of diabetes mellitus
• Dizziness, confusion, depression
• Decrease in serum albumin
• Decrease in the number of blood cells and platelets
• Inflammation and ulcer of the urinary bladder or vagina, reduced
kidney function, disturbed urination
• Joint pain, muscle pain, osteoporosis (reduction of bone mass)
Rare: may affect up to 1 in 1,000 people
• Increased skin pigmentation, acne, blue spots due to vessel bleeding
• Allergic inflammation of blood vessels, fever, red eyes, infection, woundhealing impairment, decreased number of anti-bodies in the blood
• Visual disturbances
• Inflammation of the sac around the heart, accumulation of fluid
in the sac around the heart
• Low blood pressure
• Lung fibrosis, shortness of breath and bronchial asthma,
accumulation of fluid in the sac around the lung
• Electrolyte disturbances
Very rare: may affect up to 1 in 10,000 people
• Profuse bleeding, toxic megacolon (acute toxic dilatation of the gut)
• Increased pigmentation of the nails, inflammation of the cuticles,
furunculosis (deep infection of hair follicles), visible enlargement
of small blood vessels
• Local damage (formation of sterile abscess, changes in the fatty
tissue) of injection site following administration into a muscle or
under the skin
• Impaired vision, pain, loss of strength or sensation of numbness
or tingling in arms and legs, changes in taste (metallic taste),
convulsions, paralysis, severe headache with fever
• Retinopathy (noninflammatory eye disorder)
• Loss of sexual drive, impotence, male breast enlargement
(gynaecomastia), defective sperm formation, menstrual disorder,
vaginal discharge
• Enlargement of lymphatic nodes (lymphoma)
Not known: frequency cannot be estimated from the available data
• Leukoencephalopathy (a disease of the white brain substance)
When methotrexate is given by the intramuscular route, local undesirable
effects (burning sensation) or damage (formation of sterile abscess,
destruction of fatty tissue) at the site of injection can occur commonly.
Subcutaneous application of methotrexate is locally well tolerated. Only
mild local skin reactions were observed, decreasing during therapy.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes
any possible side effects not listed in this leaflet. You can also report side
effects directly via www.mhra.gov.uk/yellowcard. By reporting side effects
you can help provide more information on the safety of this medicine.

The following pack sizes are available:
Pre-filled syringes with attached sc. injection needles, graduation and
alcohol pads containing 0.15 ml, 0.20 ml, 0.25 ml, 0.30 ml, 0.35 ml,
0.40 ml, 0.45 ml, 0.50 ml, 0.55 ml and 0.60 ml solution for injection in
packs of 1, 4, 5, 6, 10, 11, 12, and 24 pre-filled syringes.
Pre-filled syringes with enclosed sc. injection needles, graduation and
alcohol pads containing 0.15 ml, 0.20 ml, 0.25 ml, 0.30 ml, 0.35 ml,
0.40 ml, 0.45 ml, 0.50 ml, 0.55 ml and 0.60 ml solution for injection in
packs of 1, 4, 5, 6, 10, 11, 12, and 24 pre-filled syringes.
For i.m and i.v use, a needle suitable for these routes of administration
must be used: The needle enclosed in the pack is suitable for s.c. use only.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
medac Gesellschaft für klinische Spezialpräparate mbH
Theaterstr. 6
22880 Wedel
Germany
Phone: +49 4103 8006-0
Fax:
+49 4103 8006-100
This medicinal product is authorised in the Member States of the
EEA under the following names:
Austria, Belgium, Bulgaria, Czech Republic, Finland, Greece, Hungary,
Iceland, Netherlands, Romania, Slovak Republic, Slovenia, Spain,
Sweden, United Kingdom: Metoject
Denmark, Estonia, Latvia, Lithuania, Norway, Poland and Portugal: Metex
Germany: metex
Italy: Reumaflex
This leaflet was last revised in October 2014.

Instructions for use
Carefully read the instructions below before starting your injection,
and always use the injection technique advised by your doctor,
pharmacist or nurse.
For any problem or question, contact your doctor, pharmacist or nurse.
Preparation
Select a clean, well-lit and flat working surface.
Collect necessary items before you begin:
• 1 Metoject pre-filled syringe
• 1 alcohol pad (provided in the packaging)
Wash your hands carefully. Before use, check the Metoject syringe
for visual defects (or cracks).
Injection site
Areas for
The best sites for injection are:
subcutaneous injection - upper thighs,
- abdomen except around the navel.
• If someone is helping you with the injection,
he/she may also give the injection into the
back of your arms, just below the shoulder.
• Change the injection site with each
injection. This may reduce the risk of
developing irritations at the injection site.
• Never inject into skin that is tender, bruised,
red, hard, scarred or where you have
stretch marks. If you have psoriasis, you
should try not to inject directly into any
raised, thick, red or scaly skin patches or
lesions.

Abdomen

Thigh

Injecting the solution
1. Unpack the methotrexate pre-filled syringe and read the package
leaflet carefully. Remove the pre-filled syringe from the packaging
at room temperature.
2. Disinfection
Choose an injection site and disinfect it with
a swab soaked in disinfectant.
Allow at least 60 seconds for the disinfectant
to dry.

3. Remove the protective plastic cap
Carefully remove the grey protective plastic cap
by pulling it straight off the syringe. If the cap is
very stiff, turn it slightly with a pulling movement.
Important: Do not touch the needle of the prefilled syringe!

4. Inserting the cannula
Using two fingers, pinch up a fold of skin and
quickly insert the needle into the skin at a
90-degree angle.

5. Injection
Insert the needle fully into the fold of skin.
Push the plunger down slowly and inject the liquid
underneath your skin. Hold the skin securely until
the injection is completed.
Carefully pull the needle straight out.

5. How to store Metoject 50 mg/ml
Keep this medicine out of the sight and reach of children.
Store below 25 °C.
Keep the pre-filled syringes in the outer carton in order to protect
from light.
Do not use this medicine after the expiry date which is stated on the
packaging. The expiry date refers to the last day of that month.
Do not throw away any medicines via wastewater or household waste.
Ask your pharmacist how to throw away medicines you no longer use.
These measures will help protect the environment.

5.3 Preclinical safety data
Animal studies show that methotrexate impairs fertility, is embryo- and
foetotoxic and teratogenic. Methotrexate is mutagenic in vivo and in
vitro. As conventional carcinogenicity studies have not been performed
and data from chronic toxicity studies in rodents are inconsistent,
methotrexate is considered not classifiable as to its carcinogenicity
to humans.

What Metoject 50 mg/ml looks like and contents of the pack
Metoject 50 mg/ml pre-filled syringes contain a clear, yellow-brown
solution.

6. Contents of the pack and other information
What Metoject 50 mg/ml contains
• The active substance is methotrexate. 1 ml of solution contains
methotrexate disodium corresponding to 50 mg methotrexate.
• The other ingredients are sodium chloride, sodium hydroxide,
water for injections.

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 or someone around you is injured by the needle, consult your
doctor immediately and do not use this pre-filled syringe.
Disposal and other handling
The manner of handling and throwing away of the medicine and pre-filled
syringe must be in accordance with local requirements. Pregnant
healthcare personnel should not handle and/or administer Metoject.

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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