Metoject PEN 17.5 mg solution for injection in pre-filled pen

• 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.

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

• 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.

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 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.

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).

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.

Alcohol as well as large amounts of coffee, caffeine-containing soft drinks and black tea should be avoided during treatment with Metoject PEN.

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.

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.

This medicine contains less than 1 mmol sodium (23 mg) per dose; that is to say essentially “sodium-free”.

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.

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.

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, talk to your doctor immediately.

Do not take a double dose to make up for a forgotten dose.

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.

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.

• 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.

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

The solution is clear, yellow-brown.

<For packs containing BD pens only>

Metoject PEN pre-filled pen is a three-step auto-injector that has a yellow cap and a yellow injection button.

<For packs containing YpsoMate pens only>

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.

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

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 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).

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.

5. Choose an injection site and clean the area of and around the chosen injection site.

• 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.

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.

• 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.

When receiving a new medicine or a new dose of medicine always check that it matches what your doctor has prescribed you. Before using the pen, your healthcare provider should show you or your caregiver how to use it correctly.

Do not use the pen unless you have been taught how to use it by your healthcare provider. If you or your caregiver have any questions, contact your healthcare provider.

Pre-filled Pen

Inject with your Metoject PEN pre-filled pen once a week only, and always inject on the same day of the week.

Do not inject or handle the product if you are pregnant.

• Keep the pen in a secure location out of the sight and reach of children.
• If you have any contact with the medicine, wash the affected area with plenty of water right away.

Do not remove the protective cap until just before your injection.

Do not share your pen with another person.

Do not use the pen if:

• it has dropped onto a hard surface or appears damaged.
• the clear yellow solution got discoloured, looks cloudy or contains particles.
• it has been frozen or stored above 25 °C.
• the expiry date has passed.

If you are unsure, contact your healthcare provider.

• Store below 25 °C.
• Transport and keep the pen in the outer carton in order to protect it from light.
• Keep the pen in a secure location out of the sight and reach of children.

Do not freeze.

Do not store above 25 °C.

The Metoject PEN pre-filled pen is a two-step, fixed-dose, single-use disposable auto-injector. It is available in 10 different doses ranging from 7.5 mg to 30 mg.

At your weekly injection day find a comfortable place, ensure the area is well lit and you have a clean flat surface, such as a table to place your injection supplies.

You need:

• your Metoject PEN pre-filled pen.

Make sure you have the following additional supplies available to perform your injection as they are not included in the package:

• your calendar to check your once weekly injection day,
• skin cleansing like alcohol disinfection, if not available water and soap,
• cotton ball or gauze to treat your injection site,
• container for disposal in accordance with local requirements.

1. Wash your hands and unpack your pen (Figure C)

• Wash your hands with soap and water.
• Carefully take the pen out of the carton.

Do not remove the protective cap until you are ready to inject.

2. Check your pen before use (Figure D)

Carefully check the name and dose on the pen and verify that you have the correct medication. If you are not able to see well enough, ask someone for assistance.

• Check the expiry date on the label of the pen.
• Do not use the pen if it has expired.
• Check the medicine through the inspection window by turning it upside down or gently shaking it. The medicine inside the pen should look clear and yellow.
  • Do not inject if the solution looks cloudy or discoloured or contains particles.
  • It is normal to see one or more air bubbles. Do not try to remove them.
  • You may see a scale in the window; you do not need to consider that.
• Check that the pen is not damaged and that the cap is firmly on. Do not use the pen if it looks damaged or if the cap has been removed or is not firmly attached.

If the pen is expired, appears damaged, or does not look as expected, do not use it and contact your healthcare provider.

Carefully place the pen on a clean flat surface, such as a table before performing the next steps.

3. Choose your injection site (Figure E)

• You can inject yourself into your:
  • upper thighs,
  • lower part of the abdomen except within 5 cm around the belly button.
• If a caregiver administers the injection for you, the person may also use the area at the back of the upper arm.
• Use a different site than for your last injection.

When selecting an injection site:

Do not inject into other parts of the body.

Do not inject into skin that is bruised, tender, scaly, red or hard.

Do not inject into moles, scars or stretch marks.

Do not inject through clothing.

4. Clean your injection site (Figure F)

• Clean your injection site with alcohol disinfection; if not available you may use water and soap.
• Allow the skin to air dry.

Do not fan or blow on the clean area.

Do not touch your injection site again until you have finished your injection.

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.

6. Position your pen (Figure H)

• 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.
• 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.

7. Start your injection (Figure I)

• 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.
• A first "click" hereby indicates the start of the injection. The blue plunger rod will move down.
• 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.

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

• Continue holding the pen down against your skin.
• 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.

9. Finishing your injection (Figure K)

• Remove the pen by pulling it straight up from the injection site.
• The blue needle cover automatically moves into place over the needle. The blue needle cover is then locked.
• 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.

10. Treat your injection site (Figure L)

• 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.
• If needed, cover the injection site with a small bandage.

Do not rub your injection site.

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.