Patient leaflet - Metoject pen 10 mg solution for injection in Pre-filled pen, Methotrexate 10 mg solution for injection in Pre-filled pen
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.
- moderate to severe psoriasis in adult patients, and severe psoriatic arthritis in adults.
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.
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 psoriatic 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.
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.
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).
if you suffer from liver or severe kidney diseases or blood
diseases.
- if you regularly drink large amounts of alcohol.
if you suffer from a severe infection, such as tuberculosis,
HIV or other immunodeficiency syndromes.
if you suffer from mouth ulcers, stomach ulcer or intestinal ulcer.
- if you are pregnant or breast-feeding (see section ‘’Pregnancy, breast-feeding and fertility’’).
- if you 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.
- you have problems with the way your liver works.
- you suffer from dehydration (water loss).
Special precautionary measures for treatment with
Metoject PEN
Methotrexate temporarily affects sperm and egg production, which is reversible in most cases. Methotrexate can cause miscarriage and severe birth defects. You must avoid becoming pregnant when using methotrexate and for at least six months after treatment has stopped. See also section “Pregnancy, breast-feeding and fertility”.
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 of liver function.
- Check of kidney function.
Check of respiratory system and if necessary lung
function test.
Acute bleeding from the lungs in patients with underlying
rheumatologic disease has been reported with methotrexate.
If you experience symptoms of spitting or coughing up
blood you should contact your doctor immediately.
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.
Certain brain disorders (encephalopathy/
leukoencephalopathy) have been reported in cancer
patients receiving methotrexate. Such side effects cannot
be excluded when methotrexate is used to treat other
diseases.
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:
Antibiotics such as: tetracyclines, chloramphenicol,
non-absorbable broad-spectrum antibiotics, penicillines,
glycopeptides, sulphonamides, ciprofloxacin and
cefalotin (medicines to prevent/fight certain infections).
Non-steroidal anti-inflammatory drugs or salicylates
(medicines against pain and/or inflammation such as
acetylsalicylic acid, diclofenac and ibuprofen or pyrazole).
- Probenecid (medicine against gout).
Weak organic acids like loop diuretics (“water tablets”).
Medicines, which may have adverse effects on the bone
marrow, such as trimethoprim-sulphamethoxazole (an
antibiotic) and pyrimethamine.
Other medicines used to treat rheumatoid arthritis
such as leflunomide, sulphasalazine and azathioprine.
- Mercaptopurine (a cytostatic medicine).
Retinoids (medicine against psoriasis and other
dermatological diseases).
Theophylline (medicine against bronchial asthma and
other lung diseases).
Some medicines against stomach trouble such as
omeprazole and pantoprazole.
Hypoglycaemics (medicines that are used to lower the
blood sugar).
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
Pregnancy
Do not use Metoject PEN during pregnancy or if you are trying to become pregnant. Methotrexate can cause birth defects, harm the unborn child or cause miscarriage. It is associated with malformations of the skull, face, heart and blood vessels, brain and limbs. Therefore, it is very important that methotrexate is not given to pregnant patients or patients planning to become pregnant.
In women of child-bearing age, any possibility of pregnancy
must be excluded with appropriate measures, e.g.
pregnancy test before starting treatment.
You must avoid becoming pregnant whilst taking
methotrexate and for at least 6 months after treatment is
stopped by using reliable contraception throughout this
time (see also section “Warnings and precautions”).
If you do become pregnant during treatment or suspect
you might be pregnant, speak to your doctor as soon as
possible. You should be offered advice regarding the risk
of harmful effects on the child through treatment.
If you wish to become pregnant you should consult your
doctor, who may refer you for specialist advice before the
planned start of treatment.
Breast-feeding
Stop breast-feeding prior to and during treatment with Metoject PEN.
Male fertility
The available evidence does not indicate an increased risk of malformations or miscarriage if the father takes methotrexate less than 30 mg/week. However, a risk cannot be completely excluded. Methotrexate may be genotoxic. This means that the medicine may cause genetic mutation. Methotrexate can affect sperm production with the potential to cause birth defects. Therefore, you should avoid fathering a child or to donate semen whilst taking methotrexate and for at least 6 months after treatment is stopped.
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.
Metoject PEN contains sodium
This medicine contains less than 1 mmol sodium
(23 mg) per dose; that is to say essentially “sodium-free”.
3. How to use Metoject PEN
Important warning about the dose of Metoject PEN (methotrexate):
Use Metoject PEN only once a week for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis and psoriatic arthritis, and Crohn’s disease. Using too much of Metoject PEN (methotrexate) may be fatal. Please read section 3 of this leaflet very carefully. If you have any questions, please talk to your doctor or pharmacist before you take this medicine.
Always use 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 dose, 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, psoriatic arthritis
and Crohn’s disease with Metoject PEN is a long-term
treatment.
At the start of your treatment, Metoject PEN may be injected by medical staff. However, your doctor may decide that you can learn how to inject Metoject PEN yourself. You will receive appropriate training for you to do this. Under no circumstances should you attempt to inject yourself, unless you have been trained to do so.
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 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.
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 [common]
spitting or coughing blood; these might be signs of
bleeding from the lungs [not known]
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 in the liver (liver fibrosis), fatty degeneration of
the liver [all uncommon], inflammation of the liver (acute
hepatitis) [rare] and liver failure [very rare]
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]
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
Metoject PEN pre-filled pen components:
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:
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.
- 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 minimise 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.
- • Do not remove the cap before you are ready to administer the injection.
- 6.
Hold the pen with one hand in the handling area with the cap pointing upwards. Use your other hand to gently pull the cap straight off (do not bend or twist the cap). The cap has a small needle shield that should come off with the cap automatically. If the needle shield does not come off, use another pen and contact your doctor, pharmacist or nurse.
- • 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.
- 7. 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.
- 8.
Position the uncapped transparent
end of Metoject PEN pre-filled pen
perpendicular to the fold of skin.
- 9. 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:
- 10. While holding the Metoject PEN pre-filled pen firmly against the skin, now press the button with your thumb.
- 11.
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.
- 12. Remove the Metoject PEN pre-filled pen from the injection site, perpendicular to the skin (pull up).
- 13.
The protective shield automatically
moves into place over the needle.
The protective shield is then locked and the needle is protected.
- 14. 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.
symptoms of kidney damage such as swelling of
the hands, ankles or feet or changes in frequency of
urination or decrease (oliguria) or absence of urine
(anuria); these may be signs of kidney failure [rare]
symptoms of infections, e.g. fever, chills, achiness,
sore throat; methotrexate can make you more
susceptible to infections. Severe infections like a certain
type of pneumonia (Pneumocystis jirovecii pneumonia) or
blood poisoning (sepsis) may occur [rare]
symptoms 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);
This may happen when a dislodged blood clot causes
a blockage of a blood vessel (thromboembolic event)
[rare]
fever and serious deterioration of your general
condition, or sudden fever accompanied by a sore
throat or mouth, or urinary problems; methotrexate
can cause a sharp fall in certain white blood cells
(agranulocytosis) and severe bone marrow suppression
[very rare]
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]
symptoms such as severe headache often in
combination with fever, neck stiffness, feeling sick,
vomiting, disorientation and sensitivity to light may
indicate an inflammation of the membranes of the brain
(acute aseptic meningitis) [very rare]
certain brain disorders (encephalopathy/
leukoencephalopathy) have been reported in cancer
patients receiving methotrexate. Such side effects cannot be excluded when methotrexate therapy is used to treat other diseases. Signs of this kind of brain disorders may be altered mental state, movement disorders (ataxia),
visual disturbances or disturbances of memory
[not known]
severe skin rash or blistering of the skin (this can
also affect your mouth, eyes and genitals); these may
be signs of conditions called Stevens Johnson syndrome
or burned skin syndrome (toxic epidermal necrolysis/
Lyell’s syndrome) [very rare]
In the following, please find the other side effects that may
occur:
Very common: may affect more than 1 in 10 people
Inflammation of the mouth lining, indigestion, feeling sick,
loss of appetite, abdominal pain.
Abnormal liver function test (ASAT, ALAT, bilirubin,
alkaline phosphatase).
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.
Uncommon: may affect up to 1 in 100 people
- Throat inflammation.
Inflammation of the bowels, vomiting, inflammation of
pancreas, black or tarry stools, gastrointestinal ulcers
and bleeding.
Increased sensitivity to light, loss of hair, increased
number of rheumatic nodules, skin ulcer, 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 all blood cells and platelets.
Inflammation and ulcer of the urinary bladder or vagina,
reduced kidney function, disturbed urination.
Joint pain, muscle pain, reduction of bone mass.
Rare: may affect up to 1 in 1,000 people
- Inflammation of gum tissue.
Increased skin pigmentation, acne, blue spots on the skin
due to vessel bleeding (ecchymosis, petechiae), allergic
inflammation of blood vessels.
- Decreased number of anti-bodies in the blood.
Infection (incl. reactivation of inactive chronic infection),
red eyes (conjunctivitis).
- Mood swings (mood alterations).
- Visual disturbances.
Inflammation of the sac around the heart, accumulation
of fluid in the sac around the heart, obstruction of cardiac
filling due to fluid in the sac around the heart.
- Low blood pressure.
- Formation of scar tissue in the lung (pulmonary fibrosis), shortness of breath and bronchial asthma, accumulation of fluid in the sac around the lung.
- Stress fracture.
- Electrolyte disturbances.
- Fever, wound-healing impairment.
Very rare: may affect up to 1 in 10,000 people
- Acute toxic dilatation of the gut (toxic megacolon).
Increased pigmentation of the nails, inflammation of the
cuticles (acute paronychia), deep infection of hair
follicles (furunculosis), visible enlargement of small blood
vessels.
Pain, loss of strength or sensation of numbness or
tingling/having less sensitivity to stimulation than normal, changes in taste (metallic taste),
convulsions, paralysis, meningism.
Impaired vision, non-inflammatory eye disorder
(retinopathy).
Loss of sexual drive, impotence, male breast
enlargement, defective sperm formation (oligospermia),
menstrual disorder, vaginal discharge.
- Enlargement of lymphatic nodes (lymphoma).
Lymphoproliferative disorders (excessive growth of
white blood cells).
Not known: frequency cannot be estimated from the
available data
- Increased number of certain white blood cells.
- Nosebleed.
- Proteins in urine.
- Feeling of weakness.
Bone damage in the jaw (secondary to excessive growth
of white blood cells).
- Tissue destruction at injection site.
- Redness and shedding of skin.
- Swelling.
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 or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects, you can help provide more information on the safety of this medicine.
5. How to store Metoject PEN
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the
carton and pre-filled pen after EXP. The expiry date refers
to the last day of that month.
Do not store above 25 °C.
Keep the pre-filled pens in the outer carton in order to
protect from light.
If the pen becomes damaged, or the solution becomes discoloured or shows any signs of deterioration, you should seek the advice of your pharmacist who will tell you what to do.
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.
6. Contents of the pack and other information
What Metoject PEN contains
The active substance is methotrexate.
Each pre-filled pen with 0.15 ml solution contains 7.5 mg methotrexate.
Each pre-filled pen with 0.2 ml solution contains 10 mg methotrexate.
Each pre-filled pen with 0.25 ml solution contains 12.5 mg methotrexate.
Each pre-filled pen with 0.3 ml solution contains 15 mg methotrexate.
- Also contains sodium chloride, sodium hydroxide (for pH adjustment) and water for injections.
What Metoject PEN looks like and contents of the pack
Metoject PEN is presented as a solution for injection in a pre-filled pen. The solution is clear, yellow-brown in appearance.
Metoject PEN is available in pack sizes 1, 6 or 12 pre-filled pens.
Not all pack sizes may be marketed.
Manufacturer
medac Gesellschaft für klinische Spezialpräparate mbH,
Theaterstr. 6,
22880 Wedel,
Germany.
Procured from within the EU.
Product Licence Holder, and repackaged by:
Cross Healthcare Ltd.,
Unit 2a, Bandeath Industrial Estate, Throsk, Stirling,
FK7 7NP, UK.
PL 20504/0007 Metoject® PEN 7.5 mg solution for injection in pre-filled pen
PL 20504/0008 Metoject® PEN 10 mg solution for injection in pre-filled pen
PL 20504/0009 Metoject® PEN 12.5 mg solution for injection in pre-filled pen
PL 20504/0010 Metoject® PEN 15 mg solution for injection in pre-filled pen
This leaflet was last revised: 06.03.2021
Metoject® is a registered trade mark of:
medac Gesellschaft für klinische Spezialpräparate mbH
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MLFMET0007CRDE-06/03/2021-R01
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