METOJECT PEN 25 mg INJECTABLE SOLUTION IN PRE-FILLED PEN

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 have severe liver or kidney disease or blood disorders,
• if you regularly drink large amounts of alcohol,
• if you have a severe infection, such as tuberculosis, HIV, or other immunodeficiency syndromes,
• if you have mouth ulcers, stomach ulcers, or intestinal ulcers,
• if you are pregnant or breastfeeding (see section "Pregnancy, breastfeeding, and fertility"),
• if you are receiving live vaccines at the same time.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Metoject PEN

• if you are elderly or generally feel unwell and weak,
• if you have liver problems,
• if you have dehydration problems (loss of fluids).
• if you have diabetes mellitus and are being treated with insulin.

Special precautions for treatment with Metoject PEN

Methotrexate temporarily affects the production of sperm and eggs, which is reversible in most cases. Methotrexate can cause abortions and severe birth defects. If you are a woman, you should avoid becoming pregnant while using methotrexate and for at least 6 months after stopping treatment. If you are a man, you should avoid fathering a child if you are receiving methotrexate and for at least 3 months after stopping treatment. See also section "Pregnancy, breastfeeding, and fertility".

Follow-up tests and recommended precautions

Even if methotrexate is used in low doses, serious side effects can occur. To detect them in time, your doctor will need to perform tests and laboratory tests.

Before starting treatment

Before starting treatment, you will have blood tests to check that you have enough blood cells. You will also have blood tests to check liver function and to find out if you have hepatitis. Additionally, serum albumin (a blood protein), hepatitis status (liver infection), and kidney function will be checked. Your doctor may also decide to perform other liver tests; some of these may involve imaging of the liver, and others may require taking a small tissue sample from the liver to examine it in more detail. Your doctor may also check if you have tuberculosis, and you may have a chest X-ray or a lung function test.

During treatment

Your doctor may perform the following tests:

• Examination of the oral cavity and pharynx to identify changes in the mucous membrane, such as inflammation or ulceration.
• Blood tests/blood cell counts with cell blood count and measurement of serum methotrexate levels.
• Blood tests to monitor liver function.
• Imaging tests to monitor liver function.
• Removal of a small tissue sample from the liver to examine it in more detail.
• Blood tests to monitor kidney function.
• Monitoring of the respiratory tract and, if necessary, a lung function test.

It is very important that you attend these scheduled tests.

If the results of any of these tests are abnormal, your doctor will adjust your treatment accordingly.

Elderly patients

Elderly patients treated with methotrexate should be closely monitored by a doctor to detect possible side effects as soon as possible.

The age-related decline in liver and kidney function and low body reserves of folic acid in the elderly require a relatively low dose of methotrexate.

Other precautions

Acute pulmonary hemorrhage has been reported with methotrexate in patients with underlying rheumatologic disease. If you notice blood when coughing or spitting, you should contact your doctor immediately.

Methotrexate can affect the immune system and vaccination results. It can also affect the results of immunological tests. It can reactivate chronic inactive infections (such as herpes zoster, tuberculosis, hepatitis B or C). During treatment with Metoject PEN, you should not receive live vaccines.

Methotrexate can make your skin more sensitive to sunlight. Avoid intense sunlight and do not use sunbeds or UV lamps without medical advice. To protect your skin from intense sunlight, wear suitable clothing or use a sunscreen with a high protection factor.

During treatment with methotrexate, radiation-induced dermatitis and sunburn (memory reactions) may recur. Psoriatic lesions may worsen during UV radiation and concurrent administration of methotrexate.

An increase in lymph node size (lymphoma) may occur, and in such cases, treatment should be discontinued.

Diarrhea can be a side effect of Metoject PEN and requires discontinuation of treatment. If you have diarrhea, talk to your doctor.

Certain brain disorders (encephalopathy/leukoencephalopathy) have been reported in cancer patients treated with methotrexate. It cannot be ruled out that these side effects may occur when methotrexate is used to treat other diseases.

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

Using Metoject PEN with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. Also, keep this in mind for medicines that you might take in the future.

The effect of treatment may be affected if Metoject PEN is administered at the same time as certain medicines:

• Antibiotics such as: tetracyclines, chloramphenicol, non-absorbable broad-spectrum antibiotics, penicillins, glycopeptides, sulfonamides, ciprofloxacin, and cefalotin (medicines to prevent or treat certain infections).
• Non-steroidal anti-inflammatory drugs (NSAIDs) or salicylates (medicines for pain or inflammation, such as acetylsalicylic acid, diclofenac, or ibuprofen, or pyrazolones).
• Metamizole (synonyms novaminsulfon and dipyrone) (medicine for severe pain and/or fever).
• Probenecid (medicine for gout).
• Weak organic acids such as loop diuretics.
• Medicines that can cause adverse effects on the bone marrow, such as trimethoprim-sulfamethoxazole (an antibiotic) and pyrimethamine.
• Other medicines used to treat rheumatoid arthritis, such as leflunomide, sulfasalazine, and azathioprine.
• Cyclosporin (to suppress the immune system).
• Mercaptopurine (a cytostatic medicine).
• Retinoids (medicines for psoriasis and other skin diseases).
• Theophylline (medicine for bronchial asthma and other lung diseases).
• Certain medicines for stomach discomfort, such as omeprazol and pantoprazol.
• Hypoglycemic agents (medicines used to lower blood sugar levels).

Vitamins containing folic acidmay alter the effect of your treatment and should only be taken when advised by your doctor.

Live vaccines should be avoided.

Using Metoject PEN with food, drinks, and alcohol

During treatment with Metoject PEN, you should avoid consuming alcohol and large amounts of coffee, caffeinated soft drinks, and black tea.

Pregnancy, breastfeeding, and fertility

Pregnancy

Do not use Metoject PEN during pregnancy or if you are planning to become pregnant. Methotrexate can cause birth defects, harm the fetus, or cause miscarriages. 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 administered to pregnant patients or those planning to become pregnant.

In women of childbearing age, any possibility of pregnancy should be excluded with appropriate measures, such as a pregnancy test before starting treatment.

You should avoid becoming pregnant while taking methotrexate and for at least 6 months after stopping treatment, using reliable contraceptive methods during this entire time (see also section "Warnings and precautions").

If you become pregnant during treatment or suspect that you may be pregnant, consult your doctor as soon as possible. You should be offered information about the risk of harmful effects on the child during treatment.

If you wish to become pregnant, consult your doctor, who may refer you to a specialist for information before the planned start of treatment.

Breastfeeding

Stop breastfeeding before and during treatment with Metoject PEN.

Male fertility

Available data do not indicate a higher risk of malformations or miscarriages if the father takes a dose of methotrexate less than 30 mg/week. However, this risk cannot be completely ruled out. Methotrexate can be genotoxic, which means it can cause genetic mutations. Methotrexate can affect sperm production and cause birth defects. Therefore, you should avoid fathering a child or donating sperm while taking methotrexate and for at least 3 months after stopping treatment.

Driving and using machines

Treatment with Metoject PEN can cause side effects that affect the central nervous system, such as fatigue and dizziness. Therefore, the ability to drive or use machines may be affected in certain cases. If you feel tired or drowsy, you should not drive or use machines.

Metoject PEN contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose;it is essentially "sodium-free".

3. How to use Metoject PEN

Important dosage warning for Metoject PEN (methotrexate):

Use Metoject PEN only once a weekfor the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis, and psoriatic arthritis, and Crohn's disease. Overuse of Metoject PEN (methotrexate) can be fatal. Read section 3 of this leaflet carefully. If you have any doubts, consult your doctor or pharmacist before using this medication.

Follow your doctor's instructions for administering this medication exactly. If you are unsure, consult your doctor or pharmacist again.

Your doctor will determine the dose, which will be adjusted individually. Normally, treatment takes between 4 and 8 weeks to take effect.

The injection of Metoject PEN is administered subcutaneously (under the skin) by or under the supervision of a doctor or healthcare professional only once a week. Along with your doctor, you will choose a day of the week that is suitable for you to receive the injection.

Use in children and adolescents

The doctor decides what dose is suitable for children and adolescents with polyarticular forms of juvenile idiopathic arthritis.

Metoject PEN is not recommended for use in children under 3 years of agebecause experience is limited in this age group.

Duration and method of administration

Metoject PEN is injected once a week!

The attending doctor will decide on the duration of treatment. Treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis vulgaris, psoriatic arthritis, and Crohn's disease with Metoject PEN is long-term treatment.

At the start of treatment, Metoject PEN may be injected by medical staff. However, your doctor may decide that you can learn to inject Metoject PEN yourself. You will receive the necessary training for this.

Under no circumstances should you attempt to inject yourselfunless you have been taught to do so.

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

Note that the entire contents must be used.

The handling and disposal of the medication and the pre-filled pen will be done in accordance with local regulations. Pregnant healthcare staff should not handle or administer Metoject PEN.

Methotrexate should not come into contact with the skin or mucous membranes. If it does come into contact, the affected area should 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, consult your doctor immediately.

If you suspect that you (or someone else) have administered too much Metoject PEN, contact your doctor or go to the nearest hospital immediately or consult the Toxicology Information Service, phone 91 562 04 20. They will decide what measures to take based on the severity of the poisoning. Bring the medication with you if you go to the doctor or hospital.

If you forget to use Metoject PEN

Do not use a double dose to make up for forgotten doses.

If you stop treatment with Metoject PEN

If you stop treatment with Metoject PEN, consult your doctor immediately.

If you feel that the effect of Metoject PEN is too strong or too weak, consult your doctor or pharmacist.

4. Possible side effects

Like all medications, this medication can cause side effects, although not everyone will experience them.

The frequency and severity of side effects will depend on the dose and frequency of administration. It is essential that your doctor performs regular checks, as serious side effects can occur even with the lowest doses. Your doctor will perform tests to detect abnormalitiesthat occur in the blood (such as low white blood cell count, low platelet count, or lymphoma) and changes in the kidneys and liver.

If you experience any of the following symptoms, contact your doctor immediately, as they may indicate a serious, potentially life-threatening side effect that requires urgent specific treatment:

• Dry cough, difficulty breathing, and fever; may be signs of lung inflammation [frequent]
• Blood when coughing or spitting; may be signs of pulmonary hemorrhage [unknown frequency]
• Symptoms of liver damage such as yellowing of the skin or whites of the eyes; methotrexate can cause chronic liver damage (liver cirrhosis), scarring of the liver (liver fibrosis), fatty liver degeneration [all infrequent], acute liver inflammation (hepatitis) [rare], and liver failure [very rare]
• Allergic symptoms such as skin rash, including itching, swelling of the hands, feet, ankles, face, lips, mouth, or throat (which can cause difficulty swallowing or breathing) and feeling of fainting;these may be signs of severe allergic reactions or anaphylactic shock [rare]
• Symptoms of kidney damage such as swelling of the hands, ankles, or feet, or changes in urination frequency or decreased (oliguria) or absent (anuria) urine;these may be signs of kidney failure [rare]
• Symptoms of infection, e.g., fever, chills, pain, sore throat;methotrexate can make you more prone to infections. Serious infections such as a certain type of pneumonia (Pneumocystis jirovecii pneumonia) or sepsis [rare] may occur
• Symptoms such as weakness on one side of the body (stroke) or pain, swelling, redness, and unusual heat in one leg (deep vein thrombosis);this can happen when a blood clot breaks loose and blocks a blood vessel(thromboembolic event) [rare]
• Fever and severe deterioration of your general condition, or sudden fever accompanied by sore throat or mouth pain, or urinary problems; methotrexate can cause a sharp drop in the number of 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 may be signs of a severe decrease in the number of platelets caused by severe bone marrow depression [very rare]
• Symptoms such as severe headache, often in combination with fever, stiff neck, nausea, vomiting, disorientation, and sensitivity to lightmay indicate inflammation of the membranes surrounding the brain (aseptic meningitis) [very rare]
• Certain brain disorders (encephalopathy/leukoencephalopathy) have been reported in cancer patients treated with methotrexate; these side effects cannot be ruled out when methotrexate treatment is used for other diseases; signs of this type of brain disorder may be altered mental state,movement disorders (ataxia), visual disorders, or memory disorders[unknown frequency]
• Severe skin rash or blistering of the skin (this can also affect the mouth, eyes, and genitals); these may be signs of a condition called Stevens-Johnson syndrome or toxic epidermal necrolysis [very rare]

The following are other side effects that may occur:

Very common:may affect more than 1 in 10 people

• Inflammation of the mouth lining, indigestion, nausea, loss of appetite, abdominal pain.
• Abnormal test results for liver function (ASAT, ALAT, bilirubin, alkaline phosphatase).

Common:may affect up to 1 in 10 people

• Mouth ulcers, diarrhea.
• Skin rash, redness of the skin, itching.
• Headache, fatigue, drowsiness.
• Decreased blood cell production with a decrease in the number of white blood cells, red blood cells, or platelets.

Uncommon:may affect up to 1 in 100 people

• Inflammation of the throat.
• Inflammation of the intestine, vomiting, pancreatitis, black or tarry stools, gastrointestinal ulcers, and bleeding.
• Reactions similar to sunburn due to increased skin sensitivity to sunlight, hair loss, increased number of rheumatoid nodules, skin ulcers, shingles, inflammation of blood vessels, herpes-like rash, hives.
• Onset of diabetes mellitus.
• Dizziness, confusion, depression.
• Decreased serum albumin.
• Decrease in the number of all blood cells and platelets.
• Inflammation and ulceration of the urinary bladder or vagina, decreased kidney function, urinary disorders.
• Pain in the joints, muscle pain, reduction in bone mass.

Rare:may affect up to 1 in 1,000 people

• Inflammation of the gum tissue.
• Increased skin pigmentation, acne, bruising on the skin due to bleeding from blood vessels (ecchymosis, petechiae), allergic inflammation of blood vessels.
• Decreased number of antibodies in the blood.
• Infection (including reactivation of inactive chronic infections), red eyes (conjunctivitis).
• Mood changes (mood alterations).
• Visual disturbances.
• Inflammation of the sac around the heart, accumulation of fluid in the sac around the heart, obstruction of heart filling due to fluid in the sac surrounding the heart.
• Low blood pressure.
• Scarring of lung tissue (pulmonary fibrosis), difficulty breathing, and asthma, accumulation of fluid in the sac surrounding the lung.
• Stress fracture.
• Electrolyte disturbances.
• Fever, altered wound healing.

Very rare:may affect up to 1 in 10,000 people

• Toxic and acute dilation of the intestine (toxic megacolon).
• Increased pigmentation of the nails, inflammation of the cuticles (acute paronychia), deep infection of the hair follicles (furunculosis), visible enlargement of small blood vessels.
• Pain, loss of strength, or sensation of numbness or tingling/sensitivity to stimuli less than normal, altered taste (metallic taste), seizures, paralysis, meningism.
• Visual disturbance, non-inflammatory eye disorder (retinopathy).
• Loss of sexual appetite, impotence, breast enlargement in men, altered sperm formation (oligospermia), menstrual disorders, vaginal discharge.
• Increased size of lymph nodes (lymphoma).
• Lymphoproliferative disorders (excessive increase in white blood cells).

Frequency not known:cannot be estimated from the available data

• Increased number of certain white blood cells.
• Nosebleeds.
• Protein in the urine.
• Feeling of weakness.
• Damage to the jawbone (secondary to an excessive increase in white blood cells).
• Destruction of tissue at the injection site.
• Redness and peeling of the skin.
• Swelling.

Subcutaneous administration of methotrexate is well-tolerated locally. Only mild local skin reactions (such as burning sensations, erythema, swelling, color change, severe itching, pain) were observed, which decreased during treatment.

Reporting of side effects

If you experience any side effects, consult your doctor or pharmacist, even if they are possible side effects not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medication.

5. Storage of Metoject PEN

Keep this medication out of the sight and reach of children.

Store below 25°C. Do not freeze.

Keep the pre-filled pens in the outer packaging to protect them from light.

Do not use this medication after the expiry date stated on the carton and on the pre-filled pen after EXP. The expiry date is the last day of the month indicated.

Medicines should not be disposed of via wastewater or household waste. Dispose of the packaging and any unused medication in the pharmacy's SIGRE collection point. If in doubt, ask your pharmacist how to dispose of the packaging and any unused medication. This will help protect the environment.

6. Container Contents and Additional Information

Metoject CompositionPEN

• The active ingredient is methotrexate.

1 pre-filled pen with 0.15 ml of solution contains 7.5 mg of methotrexate.

1 pre-filled pen with 0.2 ml of solution contains 10 mg of methotrexate.

1 pre-filled pen with 0.25 ml of solution contains 12.5 mg of methotrexate.

1 pre-filled pen with 0.3 ml of solution contains 15 mg of methotrexate.

1 pre-filled pen with 0.35 ml of solution contains 17.5 mg of methotrexate.

1 pre-filled pen with 0.4 ml of solution contains 20 mg of methotrexate.

1 pre-filled pen with 0.45 ml of solution contains 22.5 mg of methotrexate.

1 pre-filled pen with 0.5 ml of solution contains 25 mg of methotrexate.

1 pre-filled pen with 0.55 ml of solution contains 27.5 mg of methotrexate.

1 pre-filled pen with 0.6 ml of solution contains 30 mg of methotrexate.

• The other components are sodium chloride, sodium hydroxide, and hydrochloric acid to adjust the pH, and water for injectable preparations.

Appearance of the Product and Container Contents

This medicine is presented as an injectable solution in a pre-filled pen.

The solution is yellow-brown and transparent.

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

The Metoject PEN pre-filled pen is a two-step auto-injector with a translucent cap and a blue safety shield for the needle.

The following pack sizes are marketed:

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

Only some pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

medac Gesellschaft für klinische Spezialpräparate mbH

Theaterstr. 6

22880 Wedel

Germany

Tel.: +49 4103 8006-0

Fax: +49 4103 8006-100

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Laboratorios Gebro Pharma, S.A.

Avenida Tibidabo n° 29

08022 Barcelona

Spain

Tel. +34 93 205 86 86

This medicine is authorized in the Member States of the European Economic Areaand in the United Kingdom (Northern Ireland)with the following names:

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

Metoject PEN

Iceland, Sweden: Metojectpen

Germany: metex PEN

Estonia, Latvia, Lithuania, Norway: Metex

Poland, Portugal:

Metex PEN

Denmark:

Metex Pen

Belgium:

Metoject

Date of the Last Revision of this Leaflet:August2024.

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es

You can access detailed and updated information on how to administer this medicine by scanning the QR code included in the packaging with your mobile phone (smartphone). You can also access this information at the following internet addresses:

Metoject PEN 7.5 mg solution for injection in pre-filled pen:

https://cima.aemps.es/info/78639

Metoject PEN 10 mg solution for injection in pre-filled pen:

https://cima.aemps.es/info/78632

Metoject PEN 12.5 mg solution for injection in pre-filled pen:

https://cima.aemps.es/info/78633

Metoject PEN 15 mg solution for injection in pre-filled pen:

https://cima.aemps.es/info/78634

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

https://cima.aemps.es/info/78704

Metoject PEN 20 mg solution for injection in pre-filled pen:

https://cima.aemps.es/info/78638

Metoject PEN 22.5 mg solution for injection in pre-filled pen:

https://cima.aemps.es/info/78635

Metoject PEN 25 mg solution for injection in pre-filled pen:

https://cima.aemps.es/info/78636

Metoject PEN 27.5 mg solution for injection in pre-filled pen:

https://cima.aemps.es/info/78637

Metoject PEN 30 mg solution for injection in pre-filled pen:

https://cima.aemps.es/info/78631

Instructions for Use

Recommendations

• Read the following instructions carefully before starting to administer the injection.
• Always use the injection technique that your doctor, pharmacist, or nurse advises.

Additional Information

The handling and disposal of the medicine and the pre-filled pen will be carried out in accordance with local regulations. Pregnant healthcare personnel should not handle or administer Metoject PEN.

Methotrexate should not come into contact with the skin or mucous membranes. If it comes into contact, the affected area should be rinsed immediately with plenty of water.

Note

To avoid any injury, never insert your fingers into the opening of the protective tubethat covers the needle. Do not destroy the pen.

Who to Contact in Case of Need

• If you have any doubts or problems, contact your doctor, pharmacist, or nurse.

If you or someone around you is injured with the needle, consult your doctor immediately and throw away the Metoject PEN pre-filled pen.

INSTRUCTIONS FOR USE

The following "Instructions for Use" contain information on how to inject the Metoject PEN pre-filled pen.

Read these "Instructions for Use" to the end before using the pre-filled pen for subcutaneous injection. Read the "Instructions for Use" every time you receive a new prescription and keep them in case you need to consult them after the injection.

Every time you receive a new medicine or a different dose of the medicine, always make sure it matches what your doctor has prescribed. Before starting to use the pen, the healthcare professional will show you or your caregiver how to use it correctly.

Do notuse the pen unless the healthcare professional has shown you how to do it. If you or your caregiver have any questions, contact the healthcare professional.

Storage of the MetojectPEN

• Store below 25 °C.
• Transport and store the pen in the outer packaging to protect it from light.
• Keep the pen in a safe place out of sight and reach of children.

Do notfreeze.

Do notstore at a temperature above 25 °C.

MetojectPEN(FigureA)

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

FigureA

Material Needed for Injection (FigureB)

On the day of the weekly injection, look for a comfortable place and make sure the area is well-lit and that you have a flat and clean work surface (e.g., a table) to place all the necessary material for the injection.

You will need:

• the Metoject PEN pre-filled pen.

Make sure you have the following additional materials to administer the injection, as they are not included in the packaging:

• your calendar to check the day of the weekly injection,
• a skin cleaning product, such as an alcohol disinfectant; if you don't have one, you can use water and soap,
• a cotton ball or gauze to treat the injection site,
• a container for the disposal of medical waste in accordance with local regulations.

FigureB

1. Choose the injection site (Figure E)
   • The injection can be administered in:
   • • the upper part of the thighs,
     • the lower abdomen, except for the area within 5 cm around the navel.
   • If your caregiver is administering the injection, the upper outer arm can also be used.
   • Choose a different site each time you administer an injection.

When choosing the injection site:

Do notadminister the injection in other parts of the body.

Do notadminister the injection in areas where the skin is bruised, tender, scaly, red, or hardened.

Do notadminister the injection where you have moles, scars, or stretch marks.

Do notadminister the injection through clothing.

FigureE