Metoject PEN 27.5 mg solution for injection in pre-filled pen – patient leaflet, side effects, dosage

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 th e 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).
• you have diabetes mellitus and are being treated with insulin.

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 6 months after treatment has stopped if you are a woman. If you are a man you should avoid fathering a child if you are being given methotrexate at the time and for at least 3 months after the end of your treatment. See also section “Pregnancy, breast-feeding and fertility”.

Recommended follow-up examinations and precautions Even if methotrexate is used in low doses, serious side effects can occur. In order to detect them in time, your doctor must perform monitoring examinations and laboratory tests.

Prior to the start of therapy

Before you start treatment, your blood will be checked to see if you have enough blood cells. Your blood will also be tested to check your liver function and to find out if you have hepatitis. Furthermore, serum albumin (a protein in the blood), hepatitis (liver infection) status and kidney function will be checked. The doctor may also decide to run other liver tests, some of these may be images of your liver and others may need a small sample of tissue taken from the liver in order to examine it more closely. Your doctor may also check to see if you have tuberculosis and they may X-ray your chest or perform a lung function test.

During the treatment

Your doctor may perform the following examinations:

• Examination of the oral cavity and the pharynx for changes in the

  mucous membrane such as inflammation or ulceration.

• Blood tests/blood count with number of blood cells and measurement

  of serum methotrexate levels.

• Blood test to monitor liver function.
• Imaging tests to monitor liver condition.

• Small sample of tissue taken from the liver in order to examine

  it more closely.

• Blood test to monitor kidney function.
• Respiratory tract monitoring and, if necessary, lung function test.

It is very important that you appear for these scheduled examinations. If the results of any of these tests are conspicuous, your doctor will adjust your treatment accordingly.

Elderly patients

Elderly patients under treatment with methotrexate should be monitored closely by a physician so that possible side effects can be detected as early as possible.

Age-related impairment of liver and kidney function as well as low body reserves of the vitamin folic acid in old age require a relatively low dosage of methotrexate.

Other precautions

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.

Methotrexate may make your skin more sensitive to sunlight. Avoid intense sun and do not use sun-beds or a sun-lamp without medical advice. To protect your skin from intense sun, wear adequate clothing or use a sunscreen with a high protection factor.

Radiation-induced dermatitis and sunburn 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 dia rrhoea, 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.

If you, your partner or your caregiver notice new onset or worsening of neurological symptoms including general muscle weakness, disturbance of vision, changes in thinking, memory and orientation leading to confusion and personality changes contact your doctor immediately because these may be symptoms of a very rare, serious brain infection called progressive multifocal leukoencephalopathy (PML).

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, penicillins, 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).

• Metamizole (synonyms novaminsulfon and dipyrone) (medicine

  against severe pain and/or fever).

• 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.

• Cyclosporine (for suppressing the immune system).
• 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 while 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 while taking methotrexate and for at least 3 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.

Read the Instructions for Use at the end of this leaflet to find guidance on how to correctly use Metoject PEN.

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.

Metoject PEN

solution for injection in pre-filled pen

95300-VBGB

BA

Metoject PEN

solution for injection in pre-filled pen

95300-VBGB

BA

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]

• 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.

• Sunburn-like reactions due to increased sensitivity of the skin to

  sunlight, 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.

Store below 25 °C. Do not freeze.

Keep the pre-filled pens in the outer carton in order to protect from light.

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 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.

  1 pre-filled pen with 0.15 ml solution contains 7.5 mg methotrexate. 1 pre-filled pen with 0.2 ml solution contains 10 mg methotrexate. 1 pre-filled pen with 0.25 ml solution contains 12.5 mg methotrexate. 1 pre-filled pen with 0.3 ml solution contains 15 mg 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 0.55 ml solution contains 27.5 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

This medicinal product is presented as a solution for injection in pre-filled pen.

The solution is clear, yellow-brown.

Metoject PEN pre-filled pen is a two-step auto-injector with a translucent protective cap and a blue needle cover.

The following pack sizes are available:

Metoject PEN is available in packs of 1, 2, 4, 5, 6, 10, 11, 12, 14, 15, and 24 pre-filled pens.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

medac

Gesellschaft für klinische Spezialpräparate mbH

Theaterstr. 6

22880 Wedel

Germany

Tel.: +49 4103 8006-0

Fax: +49 4103 8006-100

This medicine is authorised in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Austria, Czech Republic, Finland, Greece, Hungary, Netherlands, Slovak Republic, Slovenia, Spain, United Kingdom (Northern Ireland): Metoject PEN

Iceland, Sweden:

Metojectpen

Germany:

metex PEN

Estonia, Latvia, Lithuania, Norway:

Metex

Poland, Portugal:

Metex PEN

Denmark:

Metex Pen

Belgium:

Metoject

This leaflet was last revised in 08/2024.

Inject your dose

1. 5. Remove the cap (Figure G)

Only remove the protective cap when you are ready to inject.

Do not try to put the cap back on the pen once it is removed.

• Hold the pen with the cap

  pointing upwards and firmly pull the cap straight off.

  Do not bend or twist the cap

  while pulling off.

• Dispose of the cap right away.

• You may notice small droplets of

  the medicine. This is normal.

• Perform your injection

  immediately after removing the cap.

Do not touch the blue needle cover with your fingers. Touching the blue needle cover may accidentally trigger the injection and cause injury.

1. 6. Position your pen (Figure H)
2. •

   Position the uncapped blue needle

   cover at a 90 degree angle against the skin with the inspection window facing towards you so you can see it.

3. •

   You may feel more comfortable

   when grabbing a skin pinch by gently squeezing the area around the injection site with your thumb and forefingers before injecting, but this is not necessary for this pen.

4. 7. Start your injection (Figure I)
5. •

   To start your injection, push the

   pen down all the way. This will slide the blue needle cover up into the pen and the injection will start automatically.

6. •

   A first “click” hereby indicates the

   start of the injection. The blue plunger rod will move down.

7. •

   Keep holding the pen against the

   skin until all of the medicine is injected.

Do not change the position of the pen once the injection has started.

1. 8. Hold the pen in place to complete your injection (Figure J)
2. •

   Continue holding the pen down

   against your skin.

3. •

   Your injection is complete when

   either:

   • you hear a second “click”,

     shortly after the first

   • or: the blue plunger rod has

     stopped moving and fills the inspection window

   • or: 5 seconds have passed.

Do not remove the pen until at least 5 seconds have passed.

1. 9. Finishing your injection (Figure K)
2. •

   Remove the pen by pulling

   it straight

   up from the injection site.

3. •

   The blue needle cover

   automatically moves into place over the needle.

   The blue needle cover is then locked.

4. •

   Check the inspection window for

   any leftover yellow medicine inside.

If you still see yellow medicine inside the window you may not have received the full dose. If this happens or if you have any other concerns, contact your healthcare provider.

Do not touch the blue needle cover after injection. This may cause injury.

After your injection

1. 10. Treat your injection site (Figure L)
2. •

   You may notice a small drop

   of blood at the injection site.

   This is normal. Press a cotton ball or gauze on the area, if necessary.

3. •

   If needed, cover the injection site

   with a small bandage.

Do not rub your injection site.

1. 11. Dispose of your pen (Figure M)

Each pen can only be used once.

Do not recap the pen.

Keep your used pen and protective cap out of the sight and reach of children.

• Dispose of the cap and your pen

  right away after use.

  The manner of throwing away the

  medicine and the pre-filled pen must be in accordance with local requirements.

• Throw away the used supplies

  in your household trash. The paper carton can be recycled.

Safely dispose of Metoject PEN pre-filled pens that are expired, no longer needed, or otherwise unusable. Figure G

Figure H

Figure I

Figure J

Figure K

Figure L

Figure M

Metoject YM PEN · 95300-VBGB · BA · 08.24 · DMC-Code: 95300-VBGB