Tullex

Package leaflet: Information for the user

Tullex, 5 mg, solution for injection in pre-filled syringe
Tullex, 7.5 mg, solution for injection in pre-filled syringe
Tullex, 10 mg, solution for injection in pre-filled syringe
Tullex, 12.5 mg, solution for injection in pre-filled syringe
Tullex, 15 mg, solution for injection in pre-filled syringe
Tullex, 17.5 mg, solution for injection in pre-filled syringe
Tullex, 20 mg, solution for injection in pre-filled syringe
Tullex, 22.5 mg, solution for injection in pre-filled syringe
Tullex, 25 mg, solution for injection in pre-filled syringe
Tullex, 27.5 mg, solution for injection in pre-filled syringe
Tullex, 30 mg, solution for injection in pre-filled syringe
Methotrexatum
Please read all of this leaflet carefully before using this medicine, because 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 person only. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any adverse 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. Important information 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:

• It slows the growth of certain rapidly dividing cells in the body;
• It reduces the activity of the immune system (the body's defence mechanism);
• It 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 the response to non-steroidal anti-inflammatory drugs is inadequate;
• Severe, treatment-resistant psoriasis leading to disability, in which an adequate response has not been achieved with 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 medicines 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. Inflammation causes thickening of the membranes and joint swelling.
Juvenile arthritis occurs in children and adolescents under the age of 16. 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 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 part 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 general 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 the following with your doctor or pharmacist:

• if the patient is elderly, frail 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 treatment. If the patient develops haemoptysis (coughing up blood-stained sputum), seek immediate medical advice.

Recommended tests and safety measures

Severe adverse reactions 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 initiating 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). Additionally, serum albumin (a blood protein), presence/occurrence of hepatitis, and kidney function will be evaluated. The doctor may also decide to perform further liver tests, some of which may include imaging studies of the liver, while others may require a small tissue sample taken from the liver for closer 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 oral cavity and throat for mucosal changes such as inflammation or ulceration
• blood tests including complete blood count and measurement of methotrexate serum concentration
• blood tests to monitor liver function
• imaging tests to monitor liver status
• liver biopsy (taking a small tissue sample from the liver for detailed examination)
• blood tests to monitor kidney function
• respiratory monitoring 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

Patients treated with methotrexate in older age groups should be closely monitored by the doctor to allow early detection of possible adverse reactions. Age-related impairments in liver and kidney function, as well as low body reserves of a vitamin called folic acid, require relatively low doses of methotrexate.

Methotrexate may affect the immune system, vaccine 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 solariums or tanning lamps without consulting a doctor. To protect the skin from strong sunlight, wear appropriate clothing or use a high-protection sunscreen.

Radiation-induced dermatitis and sunburns ("recall reaction") may be triggered during methotrexate treatment. UV radiation exposure during methotrexate therapy may exacerbate 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 discontinuation of treatment. If the patient develops diarrhoea, inform the doctor immediately.

Encephalopathy (brain disease) and leukoencephalopathy (a specific brain disease affecting white matter) have been reported in cancer patients receiving methotrexate treatment. The occurrence of such adverse reactions cannot be excluded 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; this effect usually resolves. Methotrexate may cause miscarriage and severe congenital malformations. The patient should avoid becoming pregnant during methotrexate treatment and for at least 6 months after treatment ends. The patient should avoid impregnating their partner and must not donate sperm 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 use in this age group.

Tullex, solution for injection and other medicines

Inform your doctor or pharmacist about all medicines currently or recently taken, as well as any medicines planned for use.

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 (sulphur-containing medicines used to prevent and treat certain infections), 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 potent 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 as well as 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 is planning 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 very important that women who are pregnant or planning pregnancy do not take methotrexate. If the patient is of childbearing age, pregnancy must be definitively excluded before starting treatment, e.g. by performing a pregnancy test. The patient should avoid becoming pregnant during methotrexate treatment and for at least 6 months after its completion by using reliable contraception methods (see also section "Warnings and precautions").

If the patient becomes pregnant during treatment or suspects she may be pregnant, she should consult her doctor immediately. The patient should seek advice regarding the possible harmful effects of 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 treatment initiation.

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 methotrexate use at doses below 30 mg per week. However, the risk cannot be completely excluded. Methotrexate may be genotoxic, meaning it may cause genetic mutations. Methotrexate may affect sperm and cause congenital malformations. Therefore, the patient should avoid impregnating his partner and must not donate sperm during methotrexate treatment and for at least 3 months after its completion.

Driving and operating machinery

During treatment with Tullex, solution for injection, adverse reactions affecting 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 the medicine Tullex, injection solution

Important warning regarding dosing of the medicine Tullex (methotrexate)
In the treatment of rheumatoid arthritis, juvenile idiopathic arthritis,
psoriasis, psoriatic arthritis and Crohn's disease, the medicine Tullex must be used only once a week.
Administration of a higher frequency 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 exactly as prescribed 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, injection solution should be administered by a doctor or healthcare professional, or under their supervision, only once a week.
The day for administration should be agreed upon by the patient and the doctor.
Tullex, injection solution 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, injection solution 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, injection solution 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, injection solution is long-term therapy.

At the beginning of treatment, Tullex, injection solution 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 accordingly. Never attempt self-injection without prior training.

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

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, injection solution is too strong or too weak, consult your doctor or pharmacist.

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

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

Stopping treatment with Tullex, injection solution
Do not stop or discontinue treatment with Tullex, injection solution without consulting your doctor.
If you suspect severe adverse effects, seek immediate medical advice.

If you have any further doubts regarding 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 will experience 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 no more than 1 in 10 patients
uncommon – may occur in no more than 1 in 100 patients
rare – may occur in no more than 1 in 1,000 patients
very rare – may occur in no more than 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, low platelet count, and lymphadenopathy) as well as changes in the liver and kidneys.

You should immediately inform the doctor if the patient experiences any of the following symptoms, as they may indicate serious, 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
• Signs 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 liver degeneration [all uncommon], inflammation of the liver (acute hepatitis) [rare], and liver failure [very rare]
• Allergic symptoms such as skin rash, including red, itchy skin, swelling of the hands, feet, ankles, face, lips, mouth, or throat (which may cause difficulty swallowing or breathing), and a feeling of faintness; these may be symptoms of severe allergic reactions or anaphylactic shock [rare]
• Signs of kidney damage such as swelling of the hands, ankles, or feet, or changes in the frequency of urination, reduced urine volume (oliguria), or absence of urine (anuria); these may be symptoms of kidney failure [rare]
• Signs 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 (sepsis) 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 leg (deep vein thrombosis); this may occur if a dislodged clot blocks a blood vessel (thromboembolic event) [rare]
• Fever and severe deterioration in general health or sudden fever accompanied by sore throat or mouth pain 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 or vomit, or appearance of petechiae (small red or purple spots caused by bleeding); these may be symptoms of a significant decrease in platelet count 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, loss of appetite
• Increased activity of liver enzymes.

Common:

• Mouth ulcers, diarrhoea
• Rash, skin redness, itching
• Headache, fatigue, drowsiness
• Decreased production of blood cells with reduced numbers of white and/or red blood cells or platelets (leukopenia, anaemia, thrombocytopenia).

Uncommon:

• Sore throat, intestinal inflammation, vomiting
• Sunburn-like reactions 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 (reduced bone mass).

Rare:

• Intense skin pigmentation, acne, blue spots on the skin due to bleeding from blood vessels, allergic vasculitis, fever, eye redness, infection, slow wound healing, decreased concentration of antibodies in the blood
• Visual disturbances
• Inflammation of the sac surrounding the heart (pericarditis), fluid in the pericardial sac
• Low blood pressure
• Pulmonary fibrosis, shortness of breath, bronchial asthma, accumulation of fluid in the pleural sac around the lung
• Electrolyte disturbances.

Very rare:

• Profuse bleeding, toxic dilation of the large intestine (toxic megacolon)
• Increased pigmentation of the nails, epidermitis, 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 numbness and tingling, reduced sensitivity to stimuli, taste disturbances (metallic taste), seizures, paralysis, severe headache with fever
• Retinopathy (non-inflammatory eye disease)
• Decreased libido, impotence, breast enlargement in men (gynaecomastia), disturbances in sperm production, menstrual disorders, vaginal discharge
• Enlargement of lymph nodes (lymphadenopathy)
• Lymphoproliferative disorders (overproduction of white blood cells).

Unknown frequency:

• Leukoencephalopathy (a disease of the brain's white matter)
• Pulmonary haemorrhage
• Redness and peeling of the skin
• Oedema
• Jawbone damage (due to overproduction of white blood cells).

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

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C, 02-222 Warsaw
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 authorization holder.
By reporting adverse reactions, additional information on the safety of the medicine can be collected.

5. How to store Tullex, solution for injection

Keep the medicine out of 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 the 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 in use. This will help protect the environment.

6. Contents of the pack and other information

What Tullex injection solution contains

• The active substance is methotrexate.
• The other ingredients 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 it is considered "sodium-free".

What Tullex injection solution looks like and contents of the pack

Tullex injection solution is a pre-filled syringe containing a clear, slightly yellow solution without visible solid particles.

Tullex injection solution is a safety syringe with a needle and a safety mechanism, available in packaging containing 1, 4, or 12 safety syringes. Alcohol-impregnated swabs are included in the pack.

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 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 injection solution is intended for single use only. Any unused solution remaining in the pre-filled 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 pre-filled syringe of Tullex injection solution
• One alcohol-impregnated swab (included in the pack)

Wash your hands thoroughly.

Inspect the pre-filled syringe: check that the syringe or the safety mechanism is not damaged and that no parts are detached. Ensure that the safety device is in the safe position before use. Do not use the pre-filled syringe if it does not match the image below:

Figure 1: Safety device

If you determine that the pre-filled syringe is 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, avoiding 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 to reduce the risk of local irritation.

Never inject into areas of skin that are painful, bruised, red, hard, or contain scars or stretch marks. If you have psoriasis, avoid injecting directly into raised, thickened, red, or scaly psoriatic lesions.

Administering the solution

1. Unpack the pre-filled syringe and carefully read the leaflet provided in the pack. Remove the pre-filled syringe from its packaging at room temperature.
2. Disinfection

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

3. Remove the needle cap. Carefully remove the needle cap by pulling it straight along the needle axis. Warning: Do NOT touch the needle of the pre-filled 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 an angle of 45 to 90 degrees into the injection site, without touching the plunger.

5. Injecting and needle safety. Press the plunger fully downward until it is completely depressed. Once the plunger is fully pressed, the needle will be safely retracted.

6. Disposal. Immediately after use, dispose of the pre-filled syringe in a container for biologically contaminated waste (sharps). Do NOT dispose of the used pre-filled syringe in a household waste bin.

Avoid contact between methotrexate and skin or mucous membranes. In case of contamination, immediately rinse the affected area thoroughly with plenty of water.

If the patient or anyone else is accidentally injured by the needle, seek immediate medical advice and do not use that particular pre-filled 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.