Metoject 27.5 mg/0.55 ml solution for injection in pre-filled syringe

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Metoject 7.5 mg/0.15 ml solution for injection in pre-filled syringe

Metoject 10 mg/0.20 ml solution for injection in pre-filled syringe

Metoject 12.5 mg/0.25 ml solution for injection in pre-filled syringe

Metoject 15 mg/0.30 ml solution for injection in pre-filled syringe

Metoject 17.5 mg/0.35 ml solution for injection in pre-filled syringe

Metoject 20 mg/0.40 ml solution for injection in pre-filled syringe

Metoject 22.5 mg/0.45 ml solution for injection in pre-filled syringe

Metoject 25 mg/0.50 ml solution for injection in pre-filled syringe

Metoject 27.5 mg/0.55 ml solution for injection in pre-filled syringe

Metoject 30 mg/0.60 ml solution for injection in pre-filled syringe

methotrexate

Read all of this leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you. It could harm them.
• If you experience any side effects, talk to your doctor or pharmacist, even if it is a side effect not listed in this leaflet. See section 4.

Contents of the leaflet

1. What Metoject is and what it is used for
2. What you need to know before using Metoject
3. How to use Metoject
4. Possible side effects
5. How to store Metoject
6. Contents of the pack and other information

1. What Metoject is and what it is used for

Metoject contains methotrexate as the active substance.

Methotrexate is a substance with the following properties:

• interferes with the growth of certain rapidly dividing cells in the body,
• reduces the activity of the immune system (the body's natural defense mechanism),
• has anti-inflammatory effects.

Metoject is indicated for the treatment of:

• active rheumatoid arthritis in adult patients,
• polyarticular-course forms of active severe juvenile idiopathic arthritis, when the response to non-steroidal anti-inflammatory drugs (NSAIDs) has been inadequate,
• severe recalcitrant disabling psoriasis that does not respond adequately to other treatments such as phototherapy, PUVA, and retinoids, and severe psoriatic arthritis in adult patients,
• mild to moderate Crohn’s disease in adult patients when adequate treatment with other medications is not possible.

Rheumatoid arthritis (RA) is a chronic collagen disease characterized by inflammation of the synovial membranes (joint membranes). These membranes produce a fluid that acts as a lubricant in many joints. Inflammation causes thickening of the membrane and joint swelling.

Juvenile arthritis affects children and adolescents under 16 years of age. Polyarticular forms are defined by involvement of five or more joints within the first six months of the disease.

Psoriatic arthritis is a type of arthritis associated with psoriatic skin and nail lesions, particularly affecting the joints of the fingers and toes.

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

Metoject modifies and slows 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, diarrhea, vomiting, or weight loss.

2. What you need to know before using Metoject

Do not use Metoject:

• if you are allergic to methotrexate or to 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 consume large amounts of alcohol,
• if you have a severe infection, such as tuberculosis, HIV, or other immunodeficiency syndromes,
• if you have mouth ulcers, gastric ulcer, or intestinal ulcer,
• if you are pregnant or breastfeeding (see section "Pregnancy, breastfeeding, and fertility"),
• if you are receiving vaccines made with attenuated microorganisms at the same time.

Warnings and precautions

Talk to your doctor or pharmacist before starting to use Metoject if:

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

Special precautionary measures for treatment with Metoject

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

Follow-up tests and recommended precautions

Even when methotrexate is used at low doses, serious adverse reactions may occur. To detect them early, your doctor will need to perform regular examinations and laboratory tests.

Before starting treatment

Before starting treatment, blood tests will be performed to ensure you have sufficient blood cells. Blood tests will also be done to check liver function and to determine whether you have hepatitis. In addition, serum albumin (a blood protein), hepatitis status (liver infection), and kidney function will be monitored. Your doctor may also decide to perform additional liver tests; some of these may involve imaging of the liver, while others may require taking a small sample of liver tissue for more detailed examination. Your doctor may also check for tuberculosis, and you may be given a chest X-ray or a lung function test.

During treatment

Your doctor may perform the following examinations:

• Examination of the oral cavity and pharynx to identify changes in the mucous membrane, such as inflammation or ulceration.

• Blood tests / blood counts to measure blood cell counts and serum levels of methotrexate.

• Blood tests to monitor liver function.

• Imaging tests to monitor liver function.

  • Taking a small sample of liver tissue for more detailed examination.

• 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 examinations.

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

Elderly patients

Elderly patients receiving methotrexate should be closely monitored by a doctor to detect possible adverse effects as early as possible.

Age-related decline in liver and kidney function and low body stores 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 rheumatic disease. If you notice blood when coughing or spitting, contact your doctor immediately.

Methotrexate may affect the immune system and the results of vaccinations. It may also affect the results of immunological tests. It may reactivate chronic latent infections (e.g., herpes zoster ["shingles"], tuberculosis, hepatitis B or C). During treatment with Metoject, you must not receive vaccines made with attenuated microorganisms.

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

Radiation-induced dermatitis and sunburns (recall reactions) may reappear during methotrexate treatment. Psoriatic lesions may worsen during UV radiation and simultaneous administration of methotrexate.

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

Diarrhea may be a toxic effect of Metoject that requires discontinuation of treatment. If you have diarrhea, speak with your doctor.

Certain brain disorders (encephalopathy/leukoencephalopathy) have been reported in cancer patients treated with methotrexate. The occurrence of these adverse effects cannot be ruled out 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 disturbances, changes in thinking, memory, and orientation leading to confusion, or personality changes, contact your doctor immediately, as these may be symptoms of a very rare but serious brain infection called progressive multifocal leukoencephalopathy (PML).

Other medicines and Metoject

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines. Keep this in mind also for medicines you may take in the future.

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

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

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

Vaccination with vaccines made from attenuated microorganisms must be avoided.

Use of Metoject with food, beverages, and alcohol

During treatment with Metoject, consumption of alcohol, large amounts of coffee, caffeinated soft drinks, and black tea should be avoided.

Pregnancy, breastfeeding, and fertility

Pregnancy

Do not use Metoject during pregnancy or if you are trying to become pregnant. Methotrexate can cause birth defects, harm the unborn baby, or lead to miscarriage. It has been 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 to those planning to become pregnant.

In women of childbearing age, pregnancy must be ruled out by appropriate measures, for example, a pregnancy test before starting treatment.

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

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

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

Breastfeeding

Breastfeeding must be discontinued before and during treatment with Metoject.

Male fertility

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

Driving and use of machines

Treatment with Metoject may cause adverse reactions affecting the central nervous system, such as fatigue and dizziness. Therefore, the ability to drive or operate machinery may, in some cases, be impaired. If you feel tired or drowsy, you should not drive or operate machinery.

Metoject contains sodium

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

3. How to use Metoject

Important warning about the dose of Metoject (methotrexate):

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

Always follow exactly the instructions for using this medicine as given by your doctor. If in doubt, consult your doctor or pharmacist again.

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

Metoject will be administered by or under the supervision of your doctor or healthcare professional as an injection under the skin (subcutaneous injection) only once a week. Together with your doctor, you will choose a day of the week suitable for you to receive the injection.

Use in children and adolescents

The doctor will decide the appropriate dose for children and adolescents with polyarticular forms of juvenile idiopathic arthritis.

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

Duration and method of administration

Metoject is injected subcutaneously once a week.

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

At the beginning of treatment, Metoject may be administered by medical staff. However, your doctor may decide that you can learn to self-inject Metoject under the skin. You will receive appropriate training for this.

Under no circumstances should you attempt to self-inject unless you have been properly taught how to do so.

Refer to the instructions for use at the end of this leaflet.

Handling and disposal of the product must be carried out in accordance with guidelines for other cytotoxic preparations, in line with local regulations. Pregnant healthcare personnel must not handle or administer Metoject.

Methotrexate must not come into contact with the skin surface or mucous membranes. If contact occurs, the affected area must be immediately rinsed with abundant water.

If you use more Metoject than you should

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service at: 91 562 04 20.

If you forget to use Metoject

Do not take a double dose to make up for missed doses.

If you stop using Metoject

If you interrupt treatment with Metoject, consult your doctor immediately.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

The frequency and severity of adverse effects depend on the dose and frequency of administration. It is important that your doctor performs regular check-ups, as serious adverse effects may occur even with the lowest doses. Your doctor will carry out tests to monitor any abnormalities in your blood (such as low white blood cells (leukocytes), low platelets, and lymphoma) and changes in the kidneys and liver.

Contact your doctor immediately if you experience any of the following symptoms, as they may indicate a serious or potentially life-threatening adverse effect requiring urgent specific treatment:

•dry, non-productive cough, difficulty breathing, and fever; these may be signs of lung inflammation [frequent]

•blood in sputum or when coughing; these may be signs of pulmonary hemorrhage [frequency not known]

•symptoms of liver damage, such as yellowing of the skin or eyes; methotrexate may cause chronic liver damage (cirrhosis), scarring of the liver (hepatic fibrosis), fatty degeneration of the liver [all uncommon], inflammation of the liver (acute hepatitis) [rare], and liver failure [very rare]

•symptoms of allergy, such as skin rash including itching and redness of the skin, swelling of the hands, feet, ankles, face, lips, mouth, and throat (which may cause difficulty swallowing or breathing), and feeling faint; 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 frequency of urination, reduced (oliguria) or absent (anuria) urine output; these may be signs of kidney failure [rare]

•symptoms of infection, for example fever, chills, muscle aches, sore throat; methotrexate may make you more susceptible to infections. Serious infections may occur, such as a type of pneumonia (Pneumocystis jirovecii pneumonia) or blood infection (sepsis) [rare]

•symptoms such as weakness on one side of the body (stroke) or pain, swelling, redness, and unusual warmth in one leg (deep vein thrombosis); this may occur when a dislodged blood clot causes blockage of a blood vessel (thromboembolic event) [rare]

•fever and severe deterioration in general condition, or sudden fever accompanied by sore throat or mouth pain, or urinary problems; methotrexate may cause a sudden drop in certain white blood cells (agranulocytosis) and severe myelosuppression [very rare]

•unexpected bleeding, e.g., bleeding gums, blood in urine, vomiting blood, or bruising; these may be signs of a severe decrease in platelets caused by serious episodes of bone marrow suppression [very rare]

•symptoms such as severe headache, often combined with fever, neck stiffness, nausea, vomiting, disorientation, and sensitivity to light; these may indicate inflammation of the membranes surrounding the brain (acute aseptic meningitis) [very rare]

• Certain brain disorders (encephalopathy/leukoencephalopathy) have been reported in cancer patients treated with methotrexate; these adverse effects cannot be ruled out when methotrexate treatment is used for other diseases; signs of such brain disorders may include altered mental status, movement disorders (ataxia), visual disturbances, or memory disorders [frequency not known]

•severe skin rash or blistering of the skin (this may also affect the mouth, eyes, and genitals); these may be signs of a condition called Stevens-Johnson syndrome or toxic epidermal necrolysis (Lyell's syndrome) [very rare]

Below is a list of other adverse effects that may occur:

Very common: may affect more than 1 in 10 people

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

Common: may affect up to 1 in 10 people

• Mouth ulcers, diarrhea.
• Rash, redness of the skin, itching.
• Headache, fatigue, drowsiness.
• Decreased production of blood cells, resulting in reduced numbers of white blood cells, red blood cells, or platelets.

Uncommon: may affect up to 1 in 100 people

• Sore throat.
• Inflammation of the intestine, vomiting, inflammation of the pancreas, black or tarry stools, gastrointestinal ulcers and bleeding.
• Sunburn-like reactions due to increased sensitivity of the skin to sunlight, hair loss, increase in the number of rheumatoid nodules, skin ulcer, shingles (herpes zoster), inflammation of blood vessels, herpes-like rash, hives (urticaria).
• Development of diabetes mellitus.
• Dizziness, confusion, depression.
• Decrease in serum albumin.
• Decrease in all blood cells and platelets.
• Inflammation and ulceration of the urinary bladder or vagina, reduced kidney function, urinary disorders.
• Joint pain, muscle pain, reduced bone mass.

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

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

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

• Acute toxic dilation of the intestine (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.
• Local reaction at the injection site (formation of sterile abscesses, changes in fatty tissue).
• Pain, loss of strength, or numbness and tingling/sensitivity to stimuli less than normal, taste disturbances (metallic taste), seizures, paralysis, meningism.
• Visual disturbances, non-inflammatory eye disorders (retinopathy).
• Loss of sexual desire, impotence, male breast enlargement, altered sperm formation (oligospermia), menstrual disorders, vaginal discharge.
• Enlargement of lymph nodes (lymphoma).
• Lymphoproliferative disorders (excessive increase in white blood cells).

Frequency not known: cannot be estimated from available data

• Increase in certain white blood cells.
• Nosebleeds.
• Protein in urine.
• Feeling of weakness.
• Jaw bone damage (secondary to excessive increase in white blood cells).
• Tissue damage at the injection site.
• Redness and peeling of the skin.
• Swelling.

Subcutaneous administration of methotrexate is well tolerated locally. Only mild local skin reactions have been observed, which decreased during treatment.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Metoject

Keep this medicine out of sight and reach of children.

Store below 25 °C.

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

Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the month indicated.

Medicines should not be disposed of via wastewater or household waste. Dispose of empty containers and unused medicines at the SIGRE collection point at your pharmacy. Ask your pharmacist how to dispose of containers and medicines you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Metoject

• The active substance is methotrexate. 1 ml of solution contains methotrexate disodium equivalent to 50 mg of methotrexate.
• The other components are sodium chloride, sodium hydroxide, water for injections.

Appearance of the product and contents of the pack

The pre-filled syringes of Metoject contain a yellow-brown transparent solution.

The syringe is equipped with a safety system to prevent needle-stick injuries and reuse of the needle.

The following pack sizes are available:

Graduated pre-filled syringes with attached subcutaneous injection needles, packed in blisters, containing 0.15 ml, 0.20 ml, 0.25 ml, 0.30 ml, 0.35 ml, 0.40 ml, 0.45 ml, 0.50 ml, 0.55 ml and 0.60 ml of injectable solution, available in packs of 1, 4, 5, 6, 10, 11, 12 and 24 pre-filled syringes with safety device.

Graduated pre-filled syringes with attached subcutaneous injection needles, packed in blisters, containing 0.15 ml, 0.20 ml, 0.25 ml, 0.30 ml, 0.35 ml, 0.40 ml, 0.45 ml, 0.50 ml, 0.55 ml and 0.60 ml of injectable solution, available in calendar packs of 6 and 12 pre-filled syringes with safety device.

Only some pack sizes may be commercially available.

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

For further information about this medicinal product, please contact 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 medicinal product is authorized in the Member States of the European Economic Area under the following names:

Austria, Belgium, Czech Republic, Finland, Greece, Hungary, Iceland, Netherlands, Slovakia, Slovenia, Spain, Sweden: Metoject

Germany, Denmark, Estonia, Latvia, Lithuania, Norway, Poland and Portugal: Metex

Italy: Reumaflex

Date of latest review of this leaflet: August 2024

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

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

Metoject 7.5 mg/0.15 ml solution for injection in pre-filled syringe:

https://cima.aemps.es/info/71107

Metoject 10 mg/0.20 ml solution for injection in pre-filled syringe:

https://cima.aemps.es/info/71108

Metoject 12.5 mg/0.25 ml solution for injection in pre-filled syringe:

https://cima.aemps.es/info/73716

Metoject 15 mg/0.30 ml solution for injection in pre-filled syringe:

https://cima.aemps.es/info/71109

Metoject 17.5 mg/0.35 ml solution for injection in pre-filled syringe:

https://cima.aemps.es/info/73717

Metoject 20 mg/0.40 ml solution for injection in pre-filled syringe:

https://cima.aemps.es/info/71110

Metoject 22.5 mg/0.45 ml solution for injection in pre-filled syringe:

https://cima.aemps.es/info/73718

Metoject 25 mg/0.50 ml solution for injection in pre-filled syringe:

https://cima.aemps.es/info/71111

Metoject 27.5 mg/0.55 ml solution for injection in pre-filled syringe:

https://cima.aemps.es/info/73719

Metoject 30 mg/0.60 ml solution for injection in pre-filled syringe:

https://cima.aemps.es/info/72384

Instructions for use for subcutaneous administration

Metoject is administered as a subcutaneous injection once weekly only. Read the instructions carefully before starting to administer the injection, and always use the administration technique advised by your doctor, nurse or pharmacist.

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

Preparation

Select a clean, flat and well-lit working surface.

Wash your hands thoroughly.

Open the box containing the methotrexate pre-filled syringe and read the leaflet carefully. Remove the pre-filled syringe from its packaging at room temperature.

Before use, inspect the Metoject syringe for visible defects (or cracks). If a small air bubble is visible in the solution, this will not affect your dose or cause you any harm.

Injection site

The best sites for injection are:

• the upper thigh,

• the abdomen, except the area around the navel.

• If someone is assisting you with the injection, they may also administer the injection into the back of the arm, just below the shoulder.

• Change the injection site each time. This may reduce the risk of developing irritation at the injection site.

• Never administer the injection into painful, bruised, red, hardened skin, or areas with scars or stretch marks. If you have psoriasis, do not attempt to inject directly into lesions or raised, thickened, red or scaly skin patches.

Injecting the solution

1. Select a site for administration and clean the selected injection site and surrounding area with water and soap or disinfectant.

2. Remove the plastic protective cap

Carefully remove the grey plastic cap from the needle by pulling it off the syringe. If you have difficulty removing the cap, gently twist it with an outward motion.

Important: Do not touch the needle of the pre-filled syringe.

Note: Once the cap has been removed, administer the injection without delay.

1. Insertion of the needle

With two fingers, pinch a fold of skin and insert the needle quickly at a 90-degree angle.

1. Injection

Insert the needle completely into the skin fold. Slowly push the plunger and inject the liquid under the skin. Hold the skin firmly until the injection is complete.

Carefully remove the needle straight out.

1. Dispose of the used syringe, including the needle, in a sharps container. Do not throw it into household waste.

Methotrexate must not come into contact with the surface of the skin or mucous membranes. If this occurs, rinse immediately with copious amounts of water.

If you or someone in your household is injured by the needle, consult your doctor immediately and do not use this pre-filled syringe.

Disposal and other handling

Handling and disposal of the medicine and the pre-filled syringe must be carried out in accordance with local regulations. Pregnant healthcare personnel must not handle or administer Metoject.

Instructions for use for subcutaneous administration

Metoject is administered as a subcutaneous injection once weekly only. Read the instructions carefully before starting to administer the injection, and always use the administration technique advised by your doctor, nurse or pharmacist.

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

Preparation

Select a clean, flat and well-lit working surface.

Wash your hands thoroughly.

Open the box containing the methotrexate pre-filled syringe with safety device and read the leaflet carefully. Remove the pre-filled syringe from its packaging at room temperature.

Before use, inspect the Metoject syringe for visible defects (or cracks). If a small air bubble is visible in the solution, this will not affect your dose or cause you any harm.

Injection site

The best sites for injection are:

• the upper thigh,

• the abdomen, except the area around the navel.

• If someone is assisting you with the injection, they may also administer the injection into the back of the arm, just below the shoulder.

• Change the injection site each time. This may reduce the risk of developing irritation at the injection site.

• Never administer the injection into painful, bruised, red, hardened skin, or areas with scars or stretch marks. If you have psoriasis, do not attempt to inject directly into lesions or raised, thickened, red or scaly skin patches.

Injecting the solution

1. Select a site for injection and clean the selected site and surrounding area with water and soap or disinfectant.

2. Remove the plastic protective cap

Carefully remove the grey plastic cap from the needle by pulling it off the syringe. If you have difficulty removing the cap, gently twist it with an outward motion.

Important: Do not touch the needle of the pre-filled syringe.

Note: Once the cap has been removed, administer the injection without delay.

1. Insertion of the needle

With two fingers, pinch a fold of skin and insert the needle quickly at a 90-degree angle.

1. Injection

Insert the needle completely into the skin fold. Slowly push the plunger and inject the liquid under the skin.

1. Needle removal

Hold the skin firmly until the injection is complete.

Carefully remove the needle straight out.

A protective cap will automatically cover the needle.

Note: The safety mechanism activated by releasing the protective cap can only be engaged when the syringe has been completely emptied by pushing the plunger fully down.

1. Dispose of the used syringe, including the needle, in a sharps container. Do not throw it into household waste.

Methotrexate must not come into contact with the surface of the skin or mucous membranes. If this occurs, rinse immediately with copious amounts of water.

If you or someone in your household is injured by the needle, consult your doctor immediately and do not use this pre-filled syringe.

Disposal and other handling

Handling and disposal of the medicine and the pre-filled syringe must be carried out in accordance with local regulations. Pregnant healthcare personnel must not handle or administer Metoject.