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 because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you personally. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet contents

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 rapidly dividing cells in the body;
• Reduces the activity of the immune system (the body's defense 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 psoriasis causing disability, in which satisfactory response has not been achieved with phototherapy, PUVA therapy, and retinoids, and severe psoriatic arthritis in adult patients;
• Crohn's disease of mild to moderate severity in adult patients when appropriate treatment with other medications is not possible.

Rheumatoid arthritis (RA) is a chronic disease classified as a collagenosis, 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 16 years of age. Polyarticular form is defined by involvement of five or more joints within the first six 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 part of the gastrointestinal tract, causing symptoms such as abdominal pain, diarrhea, vomiting, or weight loss.

2. Important information before using Tullex injection solution

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, injection solution

• 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, or stomach 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, injection solution, discuss with the 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 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 experiences haemoptysis (coughing up blood-stained sputum), seek medical advice immediately.

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

Before starting therapy
The patient's blood will be tested before treatment begins to check whether they have an adequate number of blood cells. Blood will also be tested to assess liver function and to detect hepatitis (liver infection). Serum albumin (a blood protein), presence/occurrence of hepatitis and kidney function will also be checked. The doctor may also decide to perform additional liver tests, some of which may be imaging tests 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 / blood count with measurement of blood cell counts and serum methotrexate concentration;
• blood tests to monitor liver function;
• imaging tests to monitor liver status;
• taking a small tissue sample from the liver for more 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 concerns, the doctor will adjust the treatment accordingly.

Elderly patients
Elderly patients treated with methotrexate should be closely monitored by the doctor to detect any adverse reactions as early as possible. 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, vaccination outcomes 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, injection solution.

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

During methotrexate treatment, radiation-induced skin inflammation and sunburn (recall reaction) may be reactivated. Exposure to UV radiation during methotrexate treatment may worsen psoriatic skin lesions.

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

Diarrhoea may be a sign of toxic effects of Tullex, injection solution and requires discontinuation 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 cancer patients receiving methotrexate treatment. Such adverse effects cannot be ruled out when methotrexate is used to treat other diseases.

Special precautions for the use of Tullex, injection solution
Methotrexate temporarily impairs the production of sperm and egg cells; 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 treatment ends. The patient should avoid impregnating their 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, injection solution in children under 3 years of age due to insufficient experience with methotrexate in this age group.

Tullex, injection solution and other medicines
Tell the 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, injection solution:

• 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 and 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 pain-relieving 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 products containing folic acid or folinic acid should only be used if recommended by a doctor, as they may reduce the effectiveness of methotrexate.

During treatment with Tullex, injection solution, do not receive vaccines containing live microorganisms.

Tullex, injection solution with food, drink and alcohol
During treatment with Tullex, injection solution, avoid alcohol consumption as well as large amounts of coffee, caffeine-containing drinks 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 a doctor or pharmacist before using this medicine.

Pregnancy
Do not use Tullex, injection solution 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 defects 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 by taking appropriate measures, 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 a doctor as soon as possible. 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, injection solution.

Male fertility
Available evidence does not indicate an increased risk of developmental defects or miscarriages following paternal exposure to methotrexate at doses below 30 mg per week. However, the risk cannot be completely excluded. Methotrexate may be genotoxic. This means that the medicine 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 operating machinery
During treatment with Tullex, injection solution, adverse reactions affecting the central nervous system may occur, e.g. 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, injection solution contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per dose, meaning 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 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, solution for injection, should be administered by a doctor or healthcare professional, or under their supervision, only once a week.
The day for administration should be agreed between 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, must 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 is 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.

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 accordingly. Never attempt to self-inject 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 must not handle or administer Tullex, solution for injection.

Avoid contact of methotrexate with skin surfaces or mucous membranes. In case of contamination, immediately rinse 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 appropriate treatment depending on the severity of intoxication.

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

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.

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 frequencies of occurrence of symptoms are listed below. These frequencies are defined as follows:
very common may affect more than 1 in 10 people
common may affect up to 1 in 10 people
uncommon may affect up to 1 in 100 people
rare may affect up to 1 in 1,000 people
very rare may affect up to 1 in 10,000 people
unknown frequency cannot be estimated based on available data
The frequency and severity of adverse reactions depend on the dose size 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 lymph nodes) and 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 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 (fatty liver) [all uncommon], liver inflammation (acute hepatitis) [rare], and liver failure [very rare]
• allergic symptoms 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 impending 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 change in frequency of urination or reduced 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 may occur, such as a specific type of pneumonia (pneumonia caused by Pneumocystis carinii) and blood poisoning (sepsis) [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 when a dislodged clot blocks a blood vessel (thromboembolic event) [rare]
• fever and severe worsening of general health or sudden fever accompanied by sore throat or mouth or disturbances in urination; methotrexate may cause acute reduction 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, in vomit or appearance of petechiae; these may be symptoms of significant reduction in the number of

platelets during severe bone marrow suppression [very rare]

• severe skin rash or blisters on the skin (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 liver enzyme activity.

Common:

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

Uncommon:

• sore throat, enteritis, vomiting
• reactions resembling sunburn due to increased skin sensitivity to sunlight
• hair loss, increased number of rheumatoid nodules, shingles, vasculitis, herpes-like rash, urticaria
• onset of diabetes
• dizziness, confusion, depression
• decreased albumin concentration in serum
• decreased number of all blood cells and platelets
• inflammatory condition 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 blood
• visual disturbances
• inflammation of the sac surrounding the heart, 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
• electrolyte disturbances.

Very rare:

• profuse bleeding, toxic dilation of the large intestine (toxic megacolon)
• increased pigmentation of nails, dermatitis, 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 sensation of numbness or tingling, reduced response 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 (lymphoma)
• lymphoproliferative disorders (overproduction of white blood cells).

Unknown:

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

Subcutaneous administration of methotrexate is well tolerated locally. 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 adverse reactions not listed
in the leaflet, inform your doctor or pharmacist. Adverse reactions can be reported
directly to the Department of Monitoring of Adverse Drug Reactions of 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, more information can be gathered regarding the
safety of using the medicine.

5. How to store Tullex, injection solution

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, injection solution 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 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, yellowish solution without visible solid particles.

Tullex injection solution is a syringe-pen with an injection needle and a safety mechanism, available in packs containing 1, 4, or 12 syringe-pens. 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 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 directed by your doctor or pharmacist.

Tullex injection solution is intended for single use only. Any unused solution remaining in the syringe-pen 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 surface for the procedure.

Before you begin, gather all necessary items:

• One syringe-pen of Tullex injection solution
• One alcohol-impregnated swab (included in the pack)

Wash your hands thoroughly.

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

Figure 1.: Safety device

If you determine that the syringe-pen 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, 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 administration to reduce the risk of irritation at the injection site.

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 syringe-pen and carefully read the package leaflet. Remove the syringe-pen 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 off along the needle axis. Caution: Do NOT touch the needle of the syringe-pen! 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, without pressing the plunger.

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

6. Disposal
   Immediately after use, dispose of the syringe-pen in a container for biologically contaminated waste (sharps). Do NOT dispose of the used syringe-pen 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 large amounts of water.

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

Disposal and preparation of the medicinal product for use

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