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METHOTREXATE 30 MG SOLUTION FOR INJECTION IN PRE-FILLED PEN

Active substance(s): METHOTREXATE

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PATIENT INFORMATION LEAFLET

2859, 2860,2861,2862,2863
07.06.16[2]

Metoject® PEN 17.5 mg solution for injection
in pre-filled pen
Metoject® PEN 20 mg solution for injection in
pre-filled pen
Metoject® PEN 22.5 mg solution for injection
in pre-filled pen
Metoject® PEN 25 mg solution for injection in
pre-filled pen
Metoject® PEN 30 mg solution for injection in
pre-filled pen
(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.
Your medicine is available using any of above names but will be referred
to as Metoject PEN throughout the leaflet. Metoject PEN is also available
in strengths other than those listed in Section 6.
What is in this leaflet
1. What Metoject PEN is and what it is used for
2. What you need to know before you use Metoject PEN
3. How to use Metoject PEN
4. Possible side effects
5. How to store Metoject PEN
6. Contents of the pack and other information
1. What Metoject PEN is and what it is used for
Metoject PEN 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.
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.
Psoriasis is a common chronic skin disease, characterised by red
patches covered by thick, dry, silvery, adherent scales.
Psoriatic arthritis is a kind of arthritis with psoriatric lesions of the skin
and nails, especially at the joints of fingers and toes.
Metoject PEN modifies and slows down the progression of the disease.
2. What you need to know before you use Metoject PEN
Do not use Metoject PEN if you
 are allergic to methotrexate or any of the other ingredients of this
medicine (listed in section 6).
 suffer from liver or severe kidney diseases or blood diseases.
 regularly drink large amounts of alcohol.
 suffer from a severe infection, such as tuberculosis, HIV or other
immunodeficiency syndromes.
 suffer from stomach ulcer or intestinal ulcer.
 are pregnant or breast-feeding.
 receive vaccinations with live vaccines at the same time.
Warnings and precautions
Talk to your doctor or pharmacist before taking Metoject PEN if you:
 are elderly or if you feel generally unwell and weak.
 have problems with the way your liver works.
 suffer from dehydration (water loss).
Recommended follow-up examinations and safety measures:
Even when Metoject PEN 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.
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.
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:
 Examination of the mouth and throat for changes of the mucosa.
 Blood tests.
 Check if your liver is working properly.
 Check if your kidneys are working properly.
 Check of respiratory system and if necessary lung function test.
Methotrexate may affect your immune system and vaccination results. It
may also affect the result of immunological tests.
Inactive, chronic infections (such as herpes zoster [shingles],
tuberculosis, hepatitis B or C) may flare up. During therapy with
Metoject PEN you must not be vaccinated with live vaccines.
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 if this is the case,
therapy must be stopped.

Diarrhoea can be a possible side effect of Metoject PEN and requires an
interruption of therapy. If you suffer from diarrhoea please speak to your
doctor.
Other medicines and Metoject PEN
Tell your doctor or pharmacist if you are taking, have recently taken or
might take any other medicines. Please note that this also applies to
medicines that you will take in the future.
The effect of the treatment may be affected if Metoject PEN is
administered at the same time as certain other medicines:
 Medicines harming the liver or the blood count, such as leflunomide.
 Antibiotics (medicines to prevent/fight certain infections) such as:
tetracyclines, chloramphenicol, and non-absorbable broad-spectrum
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
(such as acetylsalicylic acid, diclofenac and ibuprofen) and pyrazole
(e.g. metamizol for treating pain).
 Medicinal products, which may have adverse effects on the bone
marrow, such as 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).

Instructions for use
Recommendations
 Carefully read the instructions below before starting your injection.
 Always use the injection technique advised by your doctor, pharmacist
or nurse.
Additional information
The manner of handling and throwing away of the medicine and pre-filled
pen must be in accordance with local requirements. Pregnant healthcare
personnel should not handle and/or administer Metoject PEN.
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.
What you need in order to administer your injection using the
Metoject PEN pre-filled pen
You need:
 1 Metoject PEN pre-filled pen
 1 alcohol pad
Metoject PEN pre-filled pen components:

Injection button
Handling area

Transparent control zone
Cap

Vitamins containing folic acid may impair the effect of your treatment and
should only be taken when advised by your doctor.
Vaccination with live vaccine must be avoided.
Metoject PEN 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 PEN.
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.
Do not take Metoject PEN during pregnancy. Men and women should use
an effective method of birth control during treatment and during a further
six months after treatment with Metoject PEN has been discontinued.

Stop breast-feeding prior to and during treatment with Metoject PEN.

3. How to use Metoject PEN
Always take this medicine exactly as your doctor has told you.
Check with your doctor or pharmacist if you are not sure.
Your doctor decides on the dosage, which is adjusted individually to you.
Usually it takes 4 – 8 weeks before there is any effect of the treatment.
Metoject PEN is administered subcutaneously (under the skin) 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.
Use in children and adolescents
The doctor decides on the appropriate dose in children and adolescents
with polyarthritic forms of juvenile idiopathic arthritis.
Metoject PEN is not recommended in children less than 3 years of
age due to insufficient experience in this age group.
Method and duration of administration
Metoject PEN is injected once weekly!
The duration of the treatment is determined by the treating physician.
Treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis
vulgaris and psoriatic arthritis with Metoject PEN is a long-term treatment.
At the start of your therapy, Metoject PEN will be injected by medical
staff. However, your doctor may decide that you are able to learn how to
inject Metoject PEN under the skin yourself. You will then receive
appropriate training.
Under no circumstances should you try to inject Metoject PEN
yourself before you have received such training.

b)

After cap removal before injection

c)

After injection

If the Metoject PEN pre-filled pen
appears to be damaged do not use it.
Use another one and contact your doctor,
pharmacist or nurse.
In case a small air bubble is visible
through the transparent control zone, this
will not affect your dose nor will it harm
you.
If you are not able to see or to check the
system correctly prior to injection, ask
someone around you for assistance.

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. Men should seek advice about the possibility of
sperm preservation before starting therapy.

Metoject PEN contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per dose;
i.e. essentially “sodium-free”.

With cap before injection

What you need to do before administering your injection
1. Wash your hands very carefully.
2. Remove the system from its packaging.
3. Check the Metoject PEN pre-filled pen before using it:

In women of child-bearing age, any existing pregnancy must be excluded
with certainty by taking appropriate measures, such as pregnancy test,
prior to therapy.

Driving and using machines
Treatment with Metoject PEN may cause adverse reactions affecting the
central nervous system, such as 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 do not drive or use machines.

a)

4. Set the Metoject PEN pre-filled pen on a clean flat surface (such as a
table).
Where you should administer the injection
The most appropriate zones for your
injection are:
 upper thighs,
 abdomen except around the navel.
 If someone around you administers the
injection for you, the person may also
use the top of the zone at the back of
the arm, just below the shoulder.
 Change the injection area with each
injection. This will minimize any
reactions at the injection site.
 Never inject into areas where the skin is tender, bruised, red or hard or
where you have scars or stretch marks. If you have psoriasis, you
should not try to inject directly into any raised, thick, red or scaly skin
patches or lesions.
How to prepare the injection
5. Clean your skin in the chosen injection
zone using the enclosed alcohol pad.

6. Hold the Metoject PEN pre-filled pen
with one hand in the handling area.
 Do not remove the cap before you are
ready to administer the injection.

7. Use your other hand to pull the cap
straight off. The small needle shield
comes off with the cap automatically. If
not, use another pen and contact your
doctor, pharmacist or nurse.
 Do not press the button until you are
ready to inject.
 If you are unable to remove the cap, ask
someone around you for assistance.

Note: Once you have removed the cap, perform your injection
without delay.

8. With your free hand, build a skin fold
by gently squeezing the area of the
cleaned skin at the injection site.
 The fold must be held pinched until the
Metoject PEN pre-filled pen is
removed from the skin after the
injection.

You can also find guidance on how to use Metoject PEN in the section
“Instructions for use” at the end of this leaflet.
Please note that all of the contents have to be used.
The manner of handling and throwing away of the medicine and pre-filled
pen must be in accordance with local requirements. Pregnant health care
personnel should not handle and/or administer Metoject PEN.
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.

9. Position the uncapped transparent end
of Metoject PEN pre-filled pen
perpendicular to the fold of skin.
10.Without pressing the button, push
the Metoject PEN pre-filled pen firmly
onto your skin in order to unlock the
button.
 If you are unable to push the Metoject
PEN pre-filled pen to the stop-point,
ask someone around you for
assistance.
How to administer the injection:
11.While holding the Metoject PEN prefilled pen firmly against the skin,
now press the button with your thumb.
12.You will hear a click which indicates the
start of the injection.
Keep holding the pen against the raised
skin until all of the medicine is injected.
This can take up to 5 seconds.

Note:
Do not remove the Metoject PEN pre-filled pen from the skin before the
end of the injection to avoid incomplete injection.
If the injection is not triggered, release the button, make sure that the
Metoject PEN pre-filled pen is pressed firmly against the skin and push
hard on the button.
If you have troubles with your hearing, count 5 seconds from the moment
you have pressed the button and then lift the Metoject PEN pre-filled pen
from the injection site.
13.Remove the Metoject PEN pre-filled
pen from the injection site,
perpendicular to the skin (pull up).
14.The protective shield automatically
moves into place over the needle.
The protective shield is then locked
and the needle is protected.
15.In case of a slight bleeding use a
plaster.

Before throwing away the Metoject PEN pre-filled pen, check visually that
there is no liquid left in the pen, at the bottom of the transparent control
zone. If there is liquid left in the pen, not all of the medicine has been
injected correctly and you should consult your doctor.
Note
To avoid any injury, never insert your fingers in the opening of the
protective tube covering the needle. Do not destroy the pen.
Whom should you contact in case of need
 For any problem or question, contact your doctor, pharmacist or nurse.
 If you or someone around you is injured by the needle, consult your
doctor immediately and throw away the Metoject PEN pre-filled pen.

If you use more Metoject PEN than you should
If you use more Metoject PEN than you should, talk to your doctor
immediately.
If you forget to use Metoject PEN
Do not take a double dose to make up for a forgotten dose.
If you stop using Metoject PEN
If you stop using Metoject PEN, talk to your doctor immediately.
If you have the impression that the effect of Metoject PEN is too strong or
too weak, talk to your doctor or pharmacist.
4. Possible side effects
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.
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:
 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
 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)

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
 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)
Subcutaneous application of methotrexate is locally well tolerated. Only
mild local skin reactions (such as burning sensations, erythema, swelling,
discolouration, severe itching, pain) were observed, decreasing during
therapy.
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This
includes any possible side effects not listed in this leaflet. You can also
report side effects directly via the Yellow Card Scheme at:
www.mhra.gov.uk/yellowcard.
By reporting side effects, you can help provide more information on the
safety of this medicine.
5. How to store Metoject PEN
Keep out of the sight and reach of children.
Do not store above 25°C.
Keep the pre-filled pen in the outer carton in order to protect from light.
Do not use after the expiry date stated on the packaging. The expiry date
refers to the last day of that month.
Medicines should not be disposed via wastewater or household waste.
Ask your pharmacist how to dispose of medicines no longer required. The
measures will help to protect the environment.
If your pre-filled pen show any signs of deterioration, consult your doctor
or pharmacist who will tell you what to do.
6. Contents of the pack and other information
What Metoject PEN contains
 The active substance is methotrexate.
1 pre-filled pen with 0.35 ml solution contains 17.5 mg methotrexate.
1 pre-filled pen with 0.4 ml solution contains 20 mg methotrexate.
1 pre-filled pen with 0.45 ml solution contains 22.5 mg methotrexate.
1 pre-filled pen with 0.5 ml solution contains 25 mg methotrexate.
1 pre-filled pen with 0.6 ml solution contains 30 mg methotrexate.
The other ingredients are sodium chloride, sodium hydroxide and
hydrochloric acid (for pH adjustment), and water for injections.
What Metoject PEN looks like and contents of the pack
Pre-filled pen containing a clear, yellow-brown solution in pre-filled
colourless glass syringe with a plunger stopper of rubber and embedded
injection needle. The syringe is externally equipped with the device for
self-administration.
Metoject PEN is available in pack of 1 pre-filled pen.
Alcohol pads included in the package.
PRODUCT LICENCE HOLDER AND MANUFACTURER
Manufactured by medac Gesellschaft für klinische Spezialpräparate mbH,
Theaterstr. 6, 22880 Wedel, Germany and procured from within the EU
by Product Licence holder: Star Pharmaceuticals Ltd., 5 Sandridge Close,
Harrow, Middlesex HA1 1XD. Repackaged by Servipharm Ltd.
POM
17.5 mg
20 mg
22.5 mg
25 mg
30 mg

-

PL 20636/2859
PL 20636/2860
PL 20636/2861
PL 20636/2862
PL 20636/2863

In the following, please find the other side effects that may occur:
Leaflet issue and revision date (Ref): 07.06.16[2]
Very common: may affect more than 1 in 10 people
 Mouth inflammation, indigestion, nausea (feeling sick), loss of appetite
 Increase in liver enzymes
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, occlusion of a blood vessel by dislodged blood clot
(thromboembolic events)
 Lung fibrosis, shortness of breath and bronchial asthma, accumulation
of fluid in the sac around the lung
 Electrolyte disturbances

Metoject is trademark of medac Gesellschaft für klinische Spezialpräparate
mbH.

PATIENT INFORMATION LEAFLET

2859, 2860,2861,2862,2863
07.06.16[2]

Metex® PEN 17.5 mg solution for injection in
pre-filled pen
Metex® PEN 20 mg solution for injection in
pre-filled pen
Metex® PEN 22.5 mg solution for injection in
pre-filled pen
Metex® PEN 25 mg solution for injection in
pre-filled pen
Metex® PEN 30 mg solution for injection in
pre-filled pen
(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.
Your medicine is available using any of above names but will be referred
to as Metex PEN throughout the leaflet. Metex PEN is also available in
strengths other than those listed in Section 6.
What is in this leaflet
1. What Metex PEN is and what it is used for
2. What you need to know before you use Metex PEN
3. How to use Metex PEN
4. Possible side effects
5. How to store Metex PEN
6. Contents of the pack and other information
1. What Metex PEN is and what it is used for
Metex PEN 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.
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.
Psoriasis is a common chronic skin disease, characterised by red
patches covered by thick, dry, silvery, adherent scales.
Psoriatic arthritis is a kind of arthritis with psoriatric lesions of the skin
and nails, especially at the joints of fingers and toes.
Metex PEN modifies and slows down the progression of the disease.
2. What you need to know before you use Metex PEN
Do not use Metex PEN if you
 are allergic to methotrexate or any of the other ingredients of this
medicine (listed in section 6).
 suffer from liver or severe kidney diseases or blood diseases.
 regularly drink large amounts of alcohol.
 suffer from a severe infection, such as tuberculosis, HIV or other
immunodeficiency syndromes.
 suffer from stomach ulcer or intestinal ulcer.
 are pregnant or breast-feeding.
 receive vaccinations with live vaccines at the same time.
Warnings and precautions
Talk to your doctor or pharmacist before taking Metex PEN if you:
 are elderly or if you feel generally unwell and weak.
 have problems with the way your liver works.
 suffer from dehydration (water loss).
Recommended follow-up examinations and safety measures:
Even when Metex PEN 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.
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.
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:
 Examination of the mouth and throat for changes of the mucosa.
 Blood tests.
 Check if your liver is working properly.
 Check if your kidneys are working properly.
 Check of respiratory system and if necessary lung function test.
Methotrexate may affect your immune system and vaccination results. It
may also affect the result of immunological tests.
Inactive, chronic infections (such as herpes zoster [shingles],
tuberculosis, hepatitis B or C) may flare up. During therapy with Metex
PEN you must not be vaccinated with live vaccines.
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 if this is the case,
therapy must be stopped.

Diarrhoea can be a possible side effect of Metex PEN and requires an
interruption of therapy. If you suffer from diarrhoea please speak to your
doctor.
Other medicines and Metex PEN
Tell your doctor or pharmacist if you are taking, have recently taken or
might take any other medicines. Please note that this also applies to
medicines that you will take in the future.
The effect of the treatment may be affected if Metex PEN is administered
at the same time as certain other medicines:
 Medicines harming the liver or the blood count, such as leflunomide.
 Antibiotics (medicines to prevent/fight certain infections) such as:
tetracyclines, chloramphenicol, and non-absorbable broad-spectrum
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
(such as acetylsalicylic acid, diclofenac and ibuprofen) and pyrazole
(e.g. metamizol for treating pain).
 Medicinal products, which may have adverse effects on the bone
marrow, such as 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).

Instructions for use
Recommendations
 Carefully read the instructions below before starting your injection.
 Always use the injection technique advised by your doctor, pharmacist
or nurse.
Additional information
The manner of handling and throwing away of the medicine and pre-filled
pen must be in accordance with local requirements. Pregnant healthcare
personnel should not handle and/or administer Metex PEN.
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.
What you need in order to administer your injection using the Metex
PEN pre-filled pen
You need:
 1 Metex PEN pre-filled pen
 1 alcohol pad
Metex PEN pre-filled pen components:

Injection button
Handling area

Transparent control zone
Cap

Vitamins containing folic acid may impair the effect of your treatment and
should only be taken when advised by your doctor.
Vaccination with live vaccine must be avoided.
Metex PEN 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 Metex PEN.
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.
Do not take Metex PEN during pregnancy. Men and women should use
an effective method of birth control during treatment and during a further
six months after treatment with Metex PEN has been discontinued.

Stop breast-feeding prior to and during treatment with Metex PEN.

3. How to use Metex PEN
Always take this medicine exactly as your doctor has told you.
Check with your doctor or pharmacist if you are not sure.
Your doctor decides on the dosage, which is adjusted individually to you.
Usually it takes 4 – 8 weeks before there is any effect of the treatment.
Metex PEN is administered subcutaneously (under the skin) 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.
Use in children and adolescents
The doctor decides on the appropriate dose in children and adolescents
with polyarthritic forms of juvenile idiopathic arthritis.
Metex PEN is not recommended in children less than 3 years of age
due to insufficient experience in this age group.
Method and duration of administration
Metex PEN is injected once weekly!
The duration of the treatment is determined by the treating physician.
Treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis
vulgaris and psoriatic arthritis with Metex PEN is a long-term treatment.
At the start of your therapy, Metex PEN will be injected by medical staff.
However, your doctor may decide that you are able to learn how to inject
Metex PEN under the skin yourself. You will then receive appropriate
training.
Under no circumstances should you try to inject Metex PEN yourself
before you have received such training.

b)

After cap removal before injection

c)

After injection

If the Metex PEN pre-filled pen appears
to be damaged do not use it. Use
another one and contact your doctor,
pharmacist or nurse.
In case a small air bubble is visible
through the transparent control zone, this
will not affect your dose nor will it harm
you.
If you are not able to see or to check the
system correctly prior to injection, ask
someone around you for assistance.

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. Men should seek advice about the possibility of
sperm preservation before starting therapy.

Metex PEN contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per dose;
i.e. essentially “sodium-free”.

With cap before injection

What you need to do before administering your injection
1. Wash your hands very carefully.
2. Remove the system from its packaging.
3. Check the Metex PEN pre-filled pen before using it:

In women of child-bearing age, any existing pregnancy must be excluded
with certainty by taking appropriate measures, such as pregnancy test,
prior to therapy.

Driving and using machines
Treatment with Metex PEN may cause adverse reactions affecting the
central nervous system, such as 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 do not drive or use machines.

a)

4. Set the Metex PEN pre-filled pen on a clean flat surface (such as a
table).
Where you should administer the injection
The most appropriate zones for your
injection are:
 upper thighs,
 abdomen except around the navel.
 If someone around you administers the
injection for you, the person may also
use the top of the zone at the back of
the arm, just below the shoulder.
 Change the injection area with each
injection. This will minimize any
reactions at the injection site.
 Never inject into areas where the skin is tender, bruised, red or hard or
where you have scars or stretch marks. If you have psoriasis, you
should not try to inject directly into any raised, thick, red or scaly skin
patches or lesions.
How to prepare the injection
5. Clean your skin in the chosen injection
zone using the enclosed alcohol pad.

6. Hold the Metex PEN pre-filled pen with
one hand in the handling area.
 Do not remove the cap before you are
ready to administer the injection.

7. Use your other hand to pull the cap
straight off. The small needle shield
comes off with the cap automatically. If
not, use another pen and contact your
doctor, pharmacist or nurse.
 Do not press the button until you are
ready to inject.
 If you are unable to remove the cap, ask
someone around you for assistance.

Note: Once you have removed the cap, perform your injection
without delay.

8. With your free hand, build a skin fold
by gently squeezing the area of the
cleaned skin at the injection site.
 The fold must be held pinched until the
Metex PEN pre-filled pen is removed
from the skin after the injection.

You can also find guidance on how to use Metex PEN in the section
“Instructions for use” at the end of this leaflet.
Please note that all of the contents have to be used.
The manner of handling and throwing away of the medicine and pre-filled
pen must be in accordance with local requirements. Pregnant health care
personnel should not handle and/or administer Metex PEN.
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.

9. Position the uncapped transparent end
of Metex PEN pre-filled pen
perpendicular to the fold of skin.
10.Without pressing the button, push
the Metex PEN pre-filled pen firmly
onto your skin in order to unlock the
button.
 If you are unable to push the Metex
PEN pre-filled pen to the stop-point,
ask someone around you for
assistance.
How to administer the injection:
11.While holding the Metex PEN prefilled pen firmly against the skin,
now press the button with your thumb.
12.You will hear a click which indicates the
start of the injection.
Keep holding the pen against the raised
skin until all of the medicine is injected.
This can take up to 5 seconds.

Note:
Do not remove the Metex PEN pre-filled pen from the skin before the end
of the injection to avoid incomplete injection.
If the injection is not triggered, release the button, make sure that the
Metex PEN pre-filled pen is pressed firmly against the skin and push hard
on the button.
If you have troubles with your hearing, count 5 seconds from the moment
you have pressed the button and then lift the Metex PEN pre-filled pen
from the injection site.
13.Remove the Metex PEN pre-filled
pen from the injection site,
perpendicular to the skin (pull up).
14.The protective shield automatically
moves into place over the needle.
The protective shield is then locked
and the needle is protected.
15.In case of a slight bleeding use a
plaster.

Before throwing away the Metex PEN pre-filled pen, check visually that
there is no liquid left in the pen, at the bottom of the transparent control
zone. If there is liquid left in the pen, not all of the medicine has been
injected correctly and you should consult your doctor.
Note
To avoid any injury, never insert your fingers in the opening of the
protective tube covering the needle. Do not destroy the pen.
Whom should you contact in case of need
 For any problem or question, contact your doctor, pharmacist or nurse.
 If you or someone around you is injured by the needle, consult your
doctor immediately and throw away the Metex PEN pre-filled pen.

If you use more Metex PEN than you should
If you use more Metex PEN than you should, talk to your doctor
immediately.
If you forget to use Metex PEN
Do not take a double dose to make up for a forgotten dose.
If you stop using Metex PEN
If you stop using Metex PEN, talk to your doctor immediately.
If you have the impression that the effect of Metex PEN is too strong or
too weak, talk to your doctor or pharmacist.
4. Possible side effects
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.
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:
 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
 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)

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
 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)
Subcutaneous application of methotrexate is locally well tolerated. Only
mild local skin reactions (such as burning sensations, erythema, swelling,
discolouration, severe itching, pain) were observed, decreasing during
therapy.
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This
includes any possible side effects not listed in this leaflet. You can also
report side effects directly via the Yellow Card Scheme at:
www.mhra.gov.uk/yellowcard.
By reporting side effects, you can help provide more information on the
safety of this medicine.
5. How to store Metex PEN
Keep out of the sight and reach of children.
Do not store above 25°C.
Keep the pre-filled pen in the outer carton in order to protect from light.
Do not use after the expiry date stated on the packaging. The expiry date
refers to the last day of that month.
Medicines should not be disposed via wastewater or household waste.
Ask your pharmacist how to dispose of medicines no longer required. The
measures will help to protect the environment.
If your pre-filled pen show any signs of deterioration, consult your doctor
or pharmacist who will tell you what to do.
6. Contents of the pack and other information
What Metex PEN contains
 The active substance is methotrexate.
1 pre-filled pen with 0.35 ml solution contains 17.5 mg methotrexate.
1 pre-filled pen with 0.4 ml solution contains 20 mg methotrexate.
1 pre-filled pen with 0.45 ml solution contains 22.5 mg methotrexate.
1 pre-filled pen with 0.5 ml solution contains 25 mg methotrexate.
1 pre-filled pen with 0.6 ml solution contains 30 mg methotrexate.
The other ingredients are sodium chloride, sodium hydroxide and
hydrochloric acid (for pH adjustment), and water for injections.
What Metex PEN looks like and contents of the pack
Pre-filled pen containing a clear, yellow-brown solution in pre-filled
colourless glass syringe with a plunger stopper of rubber and embedded
injection needle. The syringe is externally equipped with the device for
self-administration.
Metex PEN is available in pack of 1 pre-filled pen.
Alcohol pads included in the package.
PRODUCT LICENCE HOLDER AND MANUFACTURER
Manufactured by medac Gesellschaft für klinische Spezialpräparate mbH,
Theaterstr. 6, 22880 Wedel, Germany and procured from within the EU
by Product Licence holder: Star Pharmaceuticals Ltd., 5 Sandridge Close,
Harrow, Middlesex HA1 1XD. Repackaged by Servipharm Ltd.
POM
17.5 mg
20 mg
22.5 mg
25 mg
30 mg

-

PL 20636/2859
PL 20636/2860
PL 20636/2861
PL 20636/2862
PL 20636/2863

In the following, please find the other side effects that may occur:
Leaflet issue and revision date (Ref): 07.06.16[2]
Very common: may affect more than 1 in 10 people
 Mouth inflammation, indigestion, nausea (feeling sick), loss of appetite
 Increase in liver enzymes
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, occlusion of a blood vessel by dislodged blood clot
(thromboembolic events)
 Lung fibrosis, shortness of breath and bronchial asthma, accumulation
of fluid in the sac around the lung
 Electrolyte disturbances

PATIENT INFORMATION LEAFLET

2859, 2860,2861,2862,2863
07.06.16[2]

Methotrexate 17.5 mg solution for injection in
pre-filled pen
Methotrexate 20 mg solution for injection in
pre-filled pen
Methotrexate 22.5 mg solution for injection in
pre-filled pen
Methotrexate 25 mg solution for injection in
pre-filled pen
Methotrexate 30 mg solution for injection in
pre-filled pen
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.
Your medicine is available using any of above names but will be referred
to as Methotrexate PEN throughout the leaflet. Methotrexate PEN is also
available in strengths other than those listed in Section 6.
What is in this leaflet
1. What Methotrexate PEN is and what it is used for
2. What you need to know before you use Methotrexate PEN
3. How to use Methotrexate PEN
4. Possible side effects
5. How to store Methotrexate PEN
6. Contents of the pack and other information
1. What Methotrexate PEN is and what it is used for
Methotrexate PEN 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.
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.

Diarrhoea can be a possible side effect of Methotrexate PEN and requires
an interruption of therapy. If you suffer from diarrhoea please speak to
your doctor.
Other medicines and Methotrexate PEN
Tell your doctor or pharmacist if you are taking, have recently taken or
might take any other medicines. Please note that this also applies to
medicines that you will take in the future.
The effect of the treatment may be affected if Methotrexate PEN is
administered at the same time as certain other medicines:
 Medicines harming the liver or the blood count, such as leflunomide.
 Antibiotics (medicines to prevent/fight certain infections) such as:
tetracyclines, chloramphenicol, and non-absorbable broad-spectrum
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
(such as acetylsalicylic acid, diclofenac and ibuprofen) and pyrazole
(e.g. metamizol for treating pain).
 Medicinal products, which may have adverse effects on the bone
marrow, such as 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).

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.
Do not take Methotrexate PEN 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 PEN has
been discontinued.

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. Men should seek advice about the possibility of
sperm preservation before starting therapy.

Warnings and precautions
Talk to your doctor or pharmacist before taking Methotrexate PEN if you:
 are elderly or if you feel generally unwell and weak.
 have problems with the way your liver works.
 suffer from dehydration (water loss).
Recommended follow-up examinations and safety measures:
Even when Methotrexate PEN 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.
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.
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:
 Examination of the mouth and throat for changes of the mucosa.
 Blood tests.
 Check if your liver is working properly.
 Check if your kidneys are working properly.
 Check of respiratory system and if necessary lung function test.
Methotrexate may affect your immune system and vaccination results. It
may also affect the result of immunological tests.
Inactive, chronic infections (such as herpes zoster [shingles],
tuberculosis, hepatitis B or C) may flare up. During therapy with
Methotrexate PEN you must not be vaccinated with live vaccines.
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 if this is the case,
therapy must be stopped.

What you need in order to administer your injection using the
Methotrexate PEN pre-filled pen
You need:
 1 Methotrexate PEN pre-filled pen
 1 alcohol pad
Methotrexate PEN pre-filled pen components:

Injection button
Handling area

Transparent control zone
Cap

Methotrexate PEN 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 Methotrexate PEN.

Psoriasis is a common chronic skin disease, characterised by red
patches covered by thick, dry, silvery, adherent scales.

2. What you need to know before you use Methotrexate PEN
Do not use Methotrexate PEN if you
 are allergic to methotrexate or any of the other ingredients of this
medicine (listed in section 6).
 suffer from liver or severe kidney diseases or blood diseases.
 regularly drink large amounts of alcohol.
 suffer from a severe infection, such as tuberculosis, HIV or other
immunodeficiency syndromes.
 suffer from stomach ulcer or intestinal ulcer.
 are pregnant or breast-feeding.
 receive vaccinations with live vaccines at the same time.

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.

Vaccination with live vaccine must be avoided.

In women of child-bearing age, any existing pregnancy must be excluded
with certainty by taking appropriate measures, such as pregnancy test,
prior to therapy.

Methotrexate PEN modifies and slows down the progression of the
disease.

Additional information
The manner of handling and throwing away of the medicine and pre-filled
pen must be in accordance with local requirements. Pregnant healthcare
personnel should not handle and/or administer Methotrexate PEN.

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

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 psoriatric lesions of the skin
and nails, especially at the joints of fingers and toes.

Instructions for use
Recommendations
 Carefully read the instructions below before starting your injection.
 Always use the injection technique advised by your doctor, pharmacist
or nurse.

Methotrexate PEN contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per dose;
i.e. essentially “sodium-free”.
3. How to use Methotrexate PEN
Always take this medicine exactly as your doctor has told you.
Check with your doctor or pharmacist if you are not sure.
Your doctor decides on the dosage, which is adjusted individually to you.
Usually it takes 4 – 8 weeks before there is any effect of the treatment.
Methotrexate PEN is administered subcutaneously (under the skin) 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.
Use in children and adolescents
The doctor decides on the appropriate dose in children and adolescents
with polyarthritic forms of juvenile idiopathic arthritis.
Methotrexate PEN is not recommended in children less than 3 years
of age due to insufficient experience in this age group.
Method and duration of administration
Methotrexate PEN is injected once weekly!
The duration of the treatment is determined by the treating physician.
Treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis
vulgaris and psoriatic arthritis with Methotrexate PEN is a long-term
treatment.
At the start of your therapy, Methotrexate PEN will be injected by medical
staff. However, your doctor may decide that you are able to learn how to
inject Methotrexate PEN under the skin yourself. You will then receive
appropriate training.
Under no circumstances should you try to inject Methotrexate PEN
yourself before you have received such training.

With cap before injection

b)

After cap removal before injection

c)

After injection

What you need to do before administering your injection
1. Wash your hands very carefully.
2. Remove the system from its packaging.
3. Check the Methotrexate PEN pre-filled pen before using it:
If the Methotrexate PEN pre-filled pen
appears to be damaged do not use it.
Use another one and contact your doctor,
pharmacist or nurse.
In case a small air bubble is visible
through the transparent control zone, this
will not affect your dose nor will it harm
you.
If you are not able to see or to check the
system correctly prior to injection, ask
someone around you for assistance.

Stop breast-feeding prior to and during treatment with Methotrexate PEN.
Driving and using machines
Treatment with Methotrexate PEN may cause adverse reactions affecting
the central nervous system, such as 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 do not drive or use
machines.

a)

4. Set the Methotrexate PEN pre-filled pen on a clean flat surface (such as
a table).
Where you should administer the injection
The most appropriate zones for your
injection are:
 upper thighs,
 abdomen except around the navel.
 If someone around you administers the
injection for you, the person may also
use the top of the zone at the back of
the arm, just below the shoulder.
 Change the injection area with each
injection. This will minimize any
reactions at the injection site.
 Never inject into areas where the skin is tender, bruised, red or hard or
where you have scars or stretch marks. If you have psoriasis, you
should not try to inject directly into any raised, thick, red or scaly skin
patches or lesions.
How to prepare the injection
5. Clean your skin in the chosen injection
zone using the enclosed alcohol pad.

6. Hold the Methotrexate PEN pre-filled
pen with one hand in the handling area.
 Do not remove the cap before you are
ready to administer the injection.

7. Use your other hand to pull the cap
straight off. The small needle shield
comes off with the cap automatically. If
not, use another pen and contact your
doctor, pharmacist or nurse.
 Do not press the button until you are
ready to inject.
 If you are unable to remove the cap, ask
someone around you for assistance.

Note: Once you have removed the cap, perform your injection
without delay.

8. With your free hand, build a skin fold
by gently squeezing the area of the
cleaned skin at the injection site.
 The fold must be held pinched until the
Methotrexate PEN pre-filled pen is
removed from the skin after the
injection.

You can also find guidance on how to use Methotrexate PEN in the
section “Instructions for use” at the end of this leaflet.
Please note that all of the contents have to be used.
The manner of handling and throwing away of the medicine and pre-filled
pen must be in accordance with local requirements. Pregnant health care
personnel should not handle and/or administer Methotrexate PEN.
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.

9. Position the uncapped transparent end
of Methotrexate PEN pre-filled pen
perpendicular to the fold of skin.
10.Without pressing the button, push
the Methotrexate PEN pre-filled pen
firmly
onto your skin in order to unlock the
button.
 If you are unable to push the
Methotrexate PEN pre-filled pen to the
stop-point, ask someone around you
for assistance.
How to administer the injection:
11.While holding the Methotrexate PEN
prefilled pen firmly against the skin,
now press the button with your thumb.
12.You will hear a click which indicates the
start of the injection.
Keep holding the pen against the raised
skin until all of the medicine is injected.
This can take up to 5 seconds.

Note:
Do not remove the Methotrexate PEN pre-filled pen from the skin before
the end of the injection to avoid incomplete injection.
If the injection is not triggered, release the button, make sure that the
Methotrexate PEN pre-filled pen is pressed firmly against the skin and
push hard on the button.
If you have troubles with your hearing, count 5 seconds from the moment
you have pressed the button and then lift the Methotrexate PEN pre-filled
pen from the injection site.
13.Remove the Methotrexate PEN prefilled
pen from the injection site,
perpendicular to the skin (pull up).
14.The protective shield automatically
moves into place over the needle.
The protective shield is then locked
and the needle is protected.
15.In case of a slight bleeding use a
plaster.

Before throwing away the Methotrexate PEN pre-filled pen, check visually
that there is no liquid left in the pen, at the bottom of the transparent
control zone. If there is liquid left in the pen, not all of the medicine has
been injected correctly and you should consult your doctor.
Note
To avoid any injury, never insert your fingers in the opening of the
protective tube covering the needle. Do not destroy the pen.
Whom should you contact in case of need
 For any problem or question, contact your doctor, pharmacist or nurse.
 If you or someone around you is injured by the needle, consult your
doctor immediately and throw away the Methotrexate PEN pre-filled
pen.

If you use more Methotrexate PEN than you should
If you use more Methotrexate PEN than you should, talk to your doctor
immediately.
If you forget to use Methotrexate PEN
Do not take a double dose to make up for a forgotten dose.
If you stop using Methotrexate PEN
If you stop using Methotrexate PEN, talk to your doctor immediately.
If you have the impression that the effect of Methotrexate PEN is too
strong or too weak, talk to your doctor or pharmacist.
4. Possible side effects
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.
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:
 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
 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)

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
 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)
Subcutaneous application of methotrexate is locally well tolerated. Only
mild local skin reactions (such as burning sensations, erythema, swelling,
discolouration, severe itching, pain) were observed, decreasing during
therapy.
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This
includes any possible side effects not listed in this leaflet. You can also
report side effects directly via the Yellow Card Scheme at:
www.mhra.gov.uk/yellowcard.
By reporting side effects, you can help provide more information on the
safety of this medicine.
5. How to store Methotrexate PEN
Keep out of the sight and reach of children.
Do not store above 25°C.
Keep the pre-filled pen in the outer carton in order to protect from light.
Do not use after the expiry date stated on the packaging. The expiry date
refers to the last day of that month.
Medicines should not be disposed via wastewater or household waste.
Ask your pharmacist how to dispose of medicines no longer required. The
measures will help to protect the environment.
If your pre-filled pen show any signs of deterioration, consult your doctor
or pharmacist who will tell you what to do.
6. Contents of the pack and other information
What Methotrexate PEN contains
 The active substance is methotrexate.
1 pre-filled pen with 0.35 ml solution contains 17.5 mg methotrexate.
1 pre-filled pen with 0.4 ml solution contains 20 mg methotrexate.
1 pre-filled pen with 0.45 ml solution contains 22.5 mg methotrexate.
1 pre-filled pen with 0.5 ml solution contains 25 mg methotrexate.
1 pre-filled pen with 0.6 ml solution contains 30 mg methotrexate.
The other ingredients are sodium chloride, sodium hydroxide and
hydrochloric acid (for pH adjustment), and water for injections.
What Methotrexate PEN looks like and contents of the pack
Pre-filled pen containing a clear, yellow-brown solution in pre-filled
colourless glass syringe with a plunger stopper of rubber and embedded
injection needle. The syringe is externally equipped with the device for
self-administration.
Methotrexate PEN is available in pack of 1 pre-filled pen.
Alcohol pads included in the package.
PRODUCT LICENCE HOLDER AND MANUFACTURER
Manufactured by medac Gesellschaft für klinische Spezialpräparate mbH,
Theaterstr. 6, 22880 Wedel, Germany and procured from within the EU
by Product Licence holder: Star Pharmaceuticals Ltd., 5 Sandridge Close,
Harrow, Middlesex HA1 1XD. Repackaged by Servipharm Ltd.
POM
17.5 mg
20 mg
22.5 mg
25 mg
30 mg

-

PL 20636/2859
PL 20636/2860
PL 20636/2861
PL 20636/2862
PL 20636/2863

In the following, please find the other side effects that may occur:
Leaflet issue and revision date (Ref): 07.06.16[2]
Very common: may affect more than 1 in 10 people
 Mouth inflammation, indigestion, nausea (feeling sick), loss of appetite
 Increase in liver enzymes
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, occlusion of a blood vessel by dislodged blood clot
(thromboembolic events)
 Lung fibrosis, shortness of breath and bronchial asthma, accumulation
of fluid in the sac around the lung
 Electrolyte disturbances

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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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