Tullex

Package leaflet: Information for the user

Tullex, 5 mg, solution for injection in ampoule-syringe
Tullex, 7.5 mg, solution for injection in ampoule-syringe
Tullex, 10 mg, solution for injection in ampoule-syringe
Tullex, 12.5 mg, solution for injection in ampoule-syringe
Tullex, 15 mg, solution for injection in ampoule-syringe
Tullex, 17.5 mg, solution for injection in ampoule-syringe
Tullex, 20 mg, solution for injection in ampoule-syringe
Tullex, 22.5 mg, solution for injection in ampoule-syringe
Tullex, 25 mg, solution for injection in ampoule-syringe
Tullex, 27.5 mg, solution for injection in ampoule-syringe
Tullex, 30 mg, solution for injection in ampoule-syringe
Methotrexatum
Please read this leaflet carefully before using this medicine, as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

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

1. What Tullex solution for injection is and what it is used for

Methotrexate is a substance with the following properties:

• Slows down the growth of certain cells in the body that divide rapidly;
• Reduces the activity of the immune system (the body's defence mechanism);
• Has anti-inflammatory effects.

Indications for Tullex solution for injection:

• Active rheumatoid arthritis in adult patients;
• Polyarticular forms of severe, active juvenile idiopathic arthritis when response to non-steroidal anti-inflammatory drugs is inadequate;
• Severe, treatment-resistant, disabling psoriasis that has not responded satisfactorily to phototherapy, PUVA therapy, and retinoids, and severe psoriatic arthritis in adult patients;
• Mild to moderate Crohn's disease in adult patients when appropriate treatment with other drugs is not possible.

Rheumatoid arthritis (RA) is a chronic disease classified among the collagenoses, characterized by inflammation of the synovial membranes lining the joints. These membranes produce fluid that acts as a lubricant for many joints. The inflammatory process causes thickening of the membranes and joint swelling.
Juvenile arthritis occurs in children and adolescents under 16 years of age. The polyarticular form is defined by involvement of 5 or more joints within the first 6 months of the disease.
Psoriatic arthritis is a type of joint inflammation associated with psoriatic skin and nail changes, 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, tightly adherent scales.
Tullex solution for injection modifies and slows the progression of the disease.
Crohn's disease is a type of inflammatory bowel disease that may affect any segment of the gastrointestinal tract, causing symptoms such as abdominal pain, diarrhoea, vomiting, or weight loss.

2. Important information before using Tullex, solution for injection

If the patient, their partner or caregiver notices new onset or worsening of neurological symptoms, including generalised muscle weakness, vision disturbances, changes in thinking, memory and orientation leading to confusion and personality changes, contact a doctor immediately, as these may be symptoms of a very rare, serious brain infection called progressive multifocal leukoencephalopathy (PML).

When not to use Tullex, solution for injection

• if the patient is allergic to methotrexate or any of the other ingredients of this medicine (listed in section 6);
• if the patient has severe liver, kidney or blood disease;
• if the patient regularly drinks large amounts of alcohol;
• if the patient has a severe infection, e.g. tuberculosis, HIV infection or other immunodeficiency syndromes;
• if the patient has oral ulcers, gastric or intestinal ulcers;
• if the patient is pregnant or breastfeeding (see section "Pregnancy, breastfeeding and fertility");
• if the patient is simultaneously receiving a vaccine containing live microorganisms.

Warnings and precautions
Before starting treatment with Tullex, solution for injection, discuss with your doctor or pharmacist:

• if the patient is elderly, weakened or in poor general condition;
• if the patient has impaired liver function;
• if the patient has been diagnosed with dehydration (lack of water in the body).

Cases of acute pulmonary haemorrhage have been reported in patients with underlying rheumatological disease during methotrexate therapy. If the patient develops haemoptysis (coughing up blood-stained sputum), seek immediate medical advice.

Recommended tests and safety measures
Severe adverse effects may occur even after administration of low doses of Tullex, solution for injection. To detect them in time, the doctor must perform regular check-ups and laboratory tests.

Before starting therapy
Before starting treatment, the patient's blood will be tested to check whether they have an adequate number of blood cells. Blood will also be tested to assess liver function and to detect possible hepatitis (liver infection). In addition, serum albumin (a blood protein), presence/occurrence of hepatitis and kidney function will be monitored.
The doctor may also decide to perform other liver tests, some of which may involve imaging studies of the liver, while others may require a small tissue sample taken from the liver for more detailed examination. The doctor may also check for tuberculosis and may perform a chest X-ray or lung function tests.

During treatment
The doctor may perform the following tests:

• examination of the mouth and throat for mucosal changes such as inflammation or ulcers
• blood tests including complete blood count and measurement of methotrexate serum concentration
• blood tests to monitor liver function
• imaging studies to monitor liver status
• liver biopsy (taking a small tissue sample from the liver for detailed examination)
• blood tests to monitor kidney function
• monitoring of the respiratory tract and, if necessary, lung function tests

It is very important that the patient attends these scheduled examinations.
If any of these test results raise concern, the doctor will adjust the treatment accordingly.

Elderly patients
Elderly patients receiving methotrexate should be closely monitored by the doctor to allow early detection of possible adverse effects.
Age-related impairments in liver and kidney function, as well as reduced body stores of a vitamin called folic acid, require relatively low doses of methotrexate.

Methotrexate may affect the immune system, vaccination responses and immunological test results. It may lead to reactivation of latent chronic diseases (e.g. shingles, tuberculosis, hepatitis B or C virus). Do not use vaccines containing live microorganisms during treatment with Tullex, solution for injection.

Methotrexate may increase skin sensitivity to sunlight. Avoid intense sun exposure and do not use sunbeds or tanning lamps without consulting your doctor. To protect the skin from strong sunlight, wear appropriate clothing or use a high-protection sunscreen.

Radiation-induced dermatitis and sunburn ("recall reaction") may be triggered during methotrexate therapy. Exposure to UV radiation during methotrexate treatment may worsen psoriatic skin lesions.

Lymph node enlargement (lymphadenopathy) may occur. In such cases, treatment should be discontinued.

Diarrhoea may be a sign of toxic effects of Tullex, solution for injection and requires interruption of treatment. If the patient develops diarrhoea, inform the doctor.

Encephalopathy (brain disease) and leukoencephalopathy (a specific brain disease affecting white matter) have been reported in patients with malignancies receiving methotrexate therapy. Such adverse effects cannot be ruled out when methotrexate is used to treat other diseases.

Special precautions for the use of Tullex, solution for injection
Methotrexate temporarily impairs sperm and egg cell production; in most cases, this effect is reversible. Methotrexate may cause miscarriage and severe congenital malformations. The patient should avoid becoming pregnant during methotrexate treatment and for at least 6 months after completion of treatment. The patient should avoid impregnating his partner and must not be a sperm donor during methotrexate treatment and for at least 3 months after its completion. See also section "Pregnancy, breastfeeding and fertility".

Children
Do not use Tullex, solution for injection in children under 3 years of age due to insufficient experience with methotrexate in this age group.

Tullex, solution for injection and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines they plan to take.

Concomitant administration of certain medicines may affect the action of Tullex, solution for injection:

• medicines that damage the liver or reduce blood cell counts, e.g. leflunomide;
• antibiotics (medicines used to prevent and treat certain infections), e.g.: tetracyclines, chloramphenicol, non-absorbable broad-spectrum antibiotics, penicillins, glycopeptides, sulfonamides (medicines used to prevent and treat certain infections containing sulphur), ciprofloxacin and cephalothin;
• non-steroidal anti-inflammatory drugs or salicylates (pain-relieving and/or anti-inflammatory medicines);
• probenecid (used in the treatment of gout);
• weak organic acids such as loop diuretics (diuretics), or certain pain-relieving and anti-inflammatory medicines (e.g. acetylsalicylic acid, diclofenac and ibuprofen), and pyrazoles (used to treat pain);
• metamizole (synonyms: novaminsulfone and dipyrone) (a strong analgesic and/or antipyretic medicine);
• medicinal products that may adversely affect bone marrow function, e.g. trimethoprim-sulfamethoxazole (an antibiotic) or pyrimethamine;
• other medicines used to treat rheumatoid arthritis, e.g. penicillamine, hydroxychloroquine, sulfasalazine, azathioprine and cyclosporine;
• mercaptopurine (a cytostatic medicine);
• retinoids (medicines for psoriasis and other skin diseases);
• theophylline (a medicine for bronchial asthma and other lung diseases);
• proton pump inhibitors (medicines used for stomach disorders);
• hypoglycaemic agents (medicines that reduce blood glucose concentration).

Vitamin preparations containing folic acid or folinic acid should be used only if prescribed by a doctor, as they may reduce the effectiveness of methotrexate.

Do not receive vaccines containing live microorganisms during treatment with Tullex, solution for injection.

Tullex, solution for injection with food, drink and alcohol
During treatment with Tullex, solution for injection, avoid alcohol consumption and large amounts of coffee, caffeine-containing beverages and black tea.

Pregnancy, breastfeeding and fertility

If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to have a child, she should consult her doctor or pharmacist before using this medicine.

Pregnancy
Do not use Tullex, solution for injection if the patient is pregnant or trying to become pregnant. Methotrexate may cause congenital malformations, harm the unborn child or cause miscarriage. This is associated with developmental abnormalities of the skull, face, heart and blood vessels, brain and limbs. Therefore, it is extremely important that women who are pregnant or planning pregnancy do not take methotrexate. If the patient is of childbearing age, pregnancy must be definitively ruled out before starting treatment by appropriate means, e.g. performing a pregnancy test. The patient should avoid becoming pregnant during methotrexate treatment and for at least 6 months after its completion, using reliable contraception methods throughout this period (see also section "Warnings and precautions").

If the patient becomes pregnant during treatment or suspects she may be pregnant, she should consult her doctor as soon as possible. The patient should seek advice regarding the potential harmful effects of the treatment on the child.

If the patient plans to become pregnant, she should consult her treating doctor, who may refer her to a specialist for advice before planned initiation of treatment.

Breastfeeding
Breastfeeding must be discontinued before starting and during treatment with Tullex, solution for injection.

Male fertility
Available evidence does not indicate an increased risk of developmental abnormalities or miscarriages following paternal exposure to methotrexate at doses below 30 mg per week. However, the risk cannot be completely ruled out. Methotrexate may be genotoxic, meaning that it may cause genetic mutations. Methotrexate may affect sperm and cause congenital malformations. Therefore, the patient should avoid impregnating his partner and must not be a sperm donor during methotrexate treatment and for at least 3 months after its completion.

Driving and using machines
During treatment with Tullex, solution for injection, adverse effects on the central nervous system may occur, such as fatigue and dizziness. Therefore, the ability to drive motor vehicles and/or operate machinery may be impaired in some cases.
Do not drive or operate machinery if feeling drowsy or fatigued.

Tullex, solution for injection contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per dose, i.e. the medicine is considered "sodium-free".

3. How to use Tullex, solution for injection

Important warning regarding dosing of Tullex (methotrexate)
In the treatment of rheumatoid arthritis, juvenile idiopathic arthritis,
psoriasis, psoriatic arthritis, and Crohn's disease, Tullex must be used only once a week.
Administration of more frequent doses of Tullex (methotrexate) may result in death.
Please read section 3 of this leaflet carefully. If you have any questions, consult your doctor or pharmacist before taking this medicine.
This medicine should always be used according to the instructions given by your doctor or pharmacist.
Carefully follow the instructions provided at the end of this leaflet. If in doubt, consult your doctor or pharmacist.
Tullex, solution for injection, should be administered by a doctor or healthcare professional, or under their supervision, only once a week.
The day for injection should be agreed upon by the patient and the doctor.
Tullex, solution for injection, may be administered subcutaneously (under the skin).

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

Use in children
Tullex, solution for injection, should not be used in children under 3 years of age due to insufficient experience with the use of this medicine in this age group.

Method and timing of administration
Tullex, solution for injection, is administered once a week!
The duration of treatment will be determined by the treating physician. Treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis, psoriatic arthritis, and Crohn's disease with Tullex, solution for injection, is long-term therapy.

At the beginning of treatment, Tullex, solution for injection, may be administered by medical personnel. However, the doctor may decide that the patient is capable of self-injecting the medicine. The patient will be properly trained in this regard.
Never attempt self-injection of the medicine without prior training.

Handling and disposal of the medicine must comply with the guidelines for cytotoxic medicinal products and applicable local regulations. Pregnant healthcare personnel should not handle or administer Tullex, solution for injection.

Avoid contact of methotrexate with skin surfaces or mucous membranes. In case of contamination, immediately flush the affected area thoroughly with water.

If you feel that the effect of Tullex, solution for injection, is too strong or too weak, consult your doctor or pharmacist.

Overdose of Tullex, solution for injection
Use only the dose prescribed by your doctor. Do not change the dose on your own.
If you suspect that an overdose of Tullex, solution for injection, has been administered, contact your doctor immediately. The doctor will decide on the appropriate treatment depending on the severity of poisoning.

Missed dose of Tullex, solution for injection
Do not take a double dose to make up for a missed dose.
Take the dose prescribed by your doctor as soon as possible and continue treatment in the following weeks.

Stopping treatment with Tullex, solution for injection
Do not interrupt or discontinue treatment with Tullex, solution for injection, without consulting your doctor.
If you suspect serious adverse reactions, seek immediate medical advice from your doctor.

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
The following are the frequencies of occurrence of symptoms. These frequencies are defined as follows:
very common: may occur in more than 1 in 10 patients
common: may occur in up to 1 in 10 patients
uncommon: may occur in up to 1 in 100 patients
rare: may occur in up to 1 in 1,000 patients
very rare: may occur in up to 1 in 10,000 patients
unknown frequency: cannot be estimated from the available data

The frequency and severity of adverse reactions depend on the dose and frequency of administration of the medicine. Since severe adverse reactions may occur even after administration of small doses, regular medical examinations are necessary. The treating physician should order tests to rule out abnormalities in blood parameters (e.g. low white blood cell count, platelets and lymphoma) and changes in the liver and kidneys.

You should tell your doctor immediately if any of the following symptoms occur in the patient, as they may indicate severe, potentially life-threatening adverse reactions requiring urgent treatment:

• persistent dry cough without sputum, shortness of breath, and fever; these may be symptoms of lung inflammation [common]
• haemoptysis, i.e. coughing up sputum containing blood
• symptoms of liver damage, e.g. yellowing of the skin and whites of the eyes; methotrexate may cause chronic liver damage (liver cirrhosis), scarring of liver tissue (liver fibrosis), fatty degeneration of the liver [all uncommon], inflammation of the liver (acute hepatitis) [rare], and liver failure [very rare]
• symptoms of hypersensitivity such as skin rash, including red, itchy skin, swelling of hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty in swallowing or breathing), and a feeling of fainting; these may be symptoms of severe allergic reactions or anaphylactic shock [rare]
• symptoms of kidney damage such as swelling of hands, ankles or feet, or changes in frequency of urination, reduced urine volume (oliguria), or absence of urine (anuria); these may be symptoms of kidney failure [rare]
• symptoms of infection, e.g. fever, chills, soreness, sore throat; methotrexate may increase susceptibility to infections. Severe infections such as a specific type of pneumonia (Pneumocystis carinii pneumonia) and blood poisoning (septicaemia) may occur [rare]
• severe diarrhoea, bloody vomiting, black or tarry stools; these symptoms may indicate rare, severe gastrointestinal complications caused by methotrexate treatment, e.g. stomach and intestinal ulcers
• symptoms such as weakness on one side of the body (stroke) or pain, swelling, redness and unusual warmth in one of the legs (deep vein thrombosis); this may occur if a dislodged blood clot blocks a blood vessel (thromboembolic event) [rare]
• fever and severe worsening of general health or sudden fever accompanied by sore throat or mouth sores or disturbances in urination; methotrexate may cause a sudden 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 urine, blood in vomit, or appearance of small red or purple spots on the skin (petechiae); these may be symptoms of a significant decrease in the number of platelets due to severe bone marrow suppression [very rare]
• severe skin rash or blisters on the skin (which may also occur in the mouth, eyes, and genital organs); these may be symptoms of Stevens-Johnson syndrome or toxic epidermal necrolysis (toxic epidermal necrolysis).

Other adverse reactions that may occur:
Very common:

• inflammation of the mucous membrane of the mouth, indigestion, nausea, decreased appetite
• increased activity of liver enzymes.

Common:

• mouth ulcers, diarrhoea
• rash, redness of the skin, itching
• headache, feeling of fatigue, drowsiness
• decreased production of blood cells with reduced number of white and/or red blood cells or platelets (leukopenia, anaemia, thrombocytopenia).

Uncommon:

• sore throat, enteritis, vomiting
• reactions resembling sunburn due to increased sensitivity of the skin to sunlight
• hair loss, increased number of rheumatoid nodules, shingles, vasculitis, herpes-like rash, urticaria
• onset of diabetes
• dizziness, confusion, depression
• decreased serum albumin concentration
• decreased number of all blood cells and platelets
• inflammation and ulceration of the bladder or vagina, impaired kidney function, disturbances in urination
• joint pain, muscle pain, osteoporosis (decreased bone mass).

Rare:

• intense skin pigmentation, acne, blue spots on the skin due to bleeding from blood vessels, allergic vasculitis, fever, redness of the eyes, infection, slow wound healing, decreased concentration of antibodies in the blood
• visual disturbances
• inflammation of the sac surrounding the heart (pericarditis), fluid in the sac surrounding the heart
• low blood pressure
• pulmonary fibrosis, shortness of breath and bronchial asthma, accumulation of fluid in the sac around the lung (pleural effusion)
• electrolyte disturbances.

Very rare:

• severe bleeding, toxic dilatation of the colon (toxic megacolon)
• increased pigmentation of the nails, inflammation of the epidermis, deep infection of hair follicles (furunculosis), visible enlargement of small blood vessels
• local tissue damage (formation of sterile abscesses, changes in fatty tissue) at the site of intramuscular or subcutaneous injection
• blurred vision, pain, loss of muscle strength, or tingling or numbness, reduced sensitivity to stimuli, changes in taste (metallic taste), seizures, paralysis, severe headache with fever
• retinopathy (non-inflammatory eye disease)
• decreased libido, impotence, breast enlargement in men (gynaecomastia), disturbances in semen production, menstrual disorders, vaginal discharge
• enlargement of lymph nodes (lymphadenopathy)
• lymphoproliferative disorders (overproduction of white blood cells).

Unknown frequency:

• leukoencephalopathy (a disease of the white matter of the brain)
• pulmonary haemorrhage
• redness and peeling of the skin
• oedema
• jaw bone damage (as a result of overproduction of white blood cells).

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

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, you should inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, Poland
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Tullex, solution for injection

Keep the medicine out of the sight and reach of children.
Store below 25°C. Do not store in the refrigerator and do not freeze.
Keep the pre-filled syringe in the outer packaging to protect from light.
Do not use this medicine after the expiry date stated on the label and carton after "EXP".
The expiry date refers to the last day of the stated month.
Tullex, solution for injection is intended for single use only. Any unused pre-filled syringe must be discarded.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack and other information

What Tullex, solution for injection contains

• The active substance is methotrexate.
• The other components are sodium chloride, sodium hydroxide, hydrochloric acid and water for injections.

This medicine contains less than 1 mmol (23 mg) of sodium per 1 ml, meaning the medicine is considered "sodium-free".

What Tullex, solution for injection looks like and contents of the pack

Tullex, solution for injection is a syringe containing a clear, yellowish solution, without visible solid particles.

Tullex, solution for injection is a prefilled syringe with a needle for injection and a safety mechanism, available in packs containing 1 prefilled syringe or 4, 12 prefilled syringes. The pack contains alcohol swabs.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder
Egis Pharmaceuticals PLC
Keresztúri út 30-38
1106 Budapest
Hungary

Manufacturer
Basic Pharma Manufacturing B.V.
Burgemeester Lemmensstraat 352
6163 JT Geleen
The Netherlands

This medicinal product is authorised in the European Economic Area countries under the following names:

Netherlands (RMS) Methotrexaat Basic Pharma 5 mg, oplossing voor injectie in een voorgevulde spuit 37.5 mg/ml
Methotrexaat Basic Pharma 7.5 mg, oplossing voor injectie in een voorgevulde spuit 37.5 mg/ml
Methotrexaat Basic Pharma 10 mg, oplossing voor injectie in een voorgevulde spuit 37.5 mg/ml
Methotrexaat Basic Pharma 12.5 mg, oplossing voor injectie in een voorgevulde spuit 37.5 mg/ml
Methotrexaat Basic Pharma 15 mg, oplossing voor injectie in een voorgevulde spuit 37.5 mg/ml
Methotrexaat Basic Pharma 17.5 mg, oplossing voor injectie in een voorgevulde spuit 37.5 mg/ml
Methotrexaat Basic Pharma 20 mg, oplossing voor injectie in een voorgevulde spuit 37.5 mg/ml
Methotrexaat Basic Pharma 22.5 mg, oplossing voor injectie in een voorgevulde spuit 37.5 mg/ml
Methotrexaat Basic Pharma 25 mg, oplossing voor injectie in een voorgevulde spuit 37.5 mg/ml
Methotrexaat Basic Pharma 27.5 mg, oplossing voor injectie in een voorgevulde spuit 37.5 mg/ml
Methotrexaat Basic Pharma 30 mg, oplossing voor injectie in een voorgevulde spuit 37.5 mg/ml
Poland Tullex

Instructions for use

Before starting the injection, read the instructions carefully. Always administer the injection as recommended by your doctor or pharmacist.

Tullex, solution for injection is intended for single use only. Any unused solution remaining in the prefilled syringe must be discarded.

The solution should be clear and free from any solid particles.

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

Preparation

Prepare a clean, well-lit, flat working surface.

Before you begin, gather all necessary items:

• one prefilled syringe of Tullex, solution for injection
• one alcohol swab (included in the pack)

Wash your hands thoroughly.

Inspect the prefilled syringe: check whether the syringe or the safety mechanism is damaged or if any parts are detached. Ensure that the safety device is in the safe position before use. Do not use the prefilled syringe if it does not match the illustration below:

Figure 1.: Safety device

If you consider the prefilled syringe unsuitable for use, dispose of it in a container for biologically contaminated (sharp) waste.

Injection site

The best injection sites are:

• the upper thigh,
• the abdomen, except the area around the navel.

If another person is assisting you with the injection, they may also administer it into the back of the upper arm, just below the shoulder.

Always rotate injection sites with each dose. This helps reduce the risk of irritation at the injection site.

Never inject into areas of skin that are painful, have petechiae (small bleeding spots), are red, hard, or contain scars or stretch marks. If you have psoriasis, try to avoid injecting directly into raised, thickened, red or flaky psoriatic lesions.

Administering the solution

1. Unpack the prefilled syringe and carefully read the package leaflet included in the pack. Remove the prefilled syringe from its packaging at room temperature.

2. Disinfection

Select the injection site and disinfect it using the included alcohol swab. Allow the disinfected injection site to dry for at least 60 seconds.

3. Remove the needle cap. Carefully remove the needle cap by pulling it straight off along the needle axis. Warning: Do not touch the needle of the prefilled syringe! After removing the needle cap, dispose of it in a container for biologically contaminated (sharp) waste.

4. Inserting the needle. With one hand, gently pinch the skin at the injection site using two fingers. With the other hand, insert the needle at a 45 to 90 degree angle into the injection site, without pressing the plunger.

5. Injecting and needle safety activation. Press the plunger fully down until it is completely depressed. When the plunger is fully depressed, the needle will be safely retracted.

6. Dispose of the device. Immediately after using the prefilled syringe, dispose of it in a container for biologically contaminated waste (sharps). Do not dispose of the used prefilled syringe in a household waste bin.

Avoid contact of methotrexate with the skin surface or mucous membranes. In case of contamination, immediately rinse the affected area thoroughly with large amounts of water.

If the patient or any other person is accidentally injured by the needle, seek immediate medical advice and do not use that particular prefilled syringe.

Disposal and preparation of the medicinal product for use

Handling and disposal of the product must comply with the guidelines for cytotoxic medicinal products and applicable regulations. Pregnant healthcare personnel should not handle or administer methotrexate.