Tullex

Package leaflet: Information for the user

Tullex, 5 mg, solution for injection in prefilled syringe
Tullex, 7.5 mg, solution for injection in prefilled syringe
Tullex, 10 mg, solution for injection in prefilled syringe
Tullex, 12.5 mg, solution for injection in prefilled syringe
Tullex, 15 mg, solution for injection in prefilled syringe
Tullex, 17.5 mg, solution for injection in prefilled syringe
Tullex, 20 mg, solution for injection in prefilled syringe
Tullex, 22.5 mg, solution for injection in prefilled syringe
Tullex, 25 mg, solution for injection in prefilled syringe
Tullex, 27.5 mg, solution for injection in prefilled syringe
Tullex, 30 mg, solution for injection in prefilled syringe
Methotrexatum
Read carefully all the information in this leaflet before using this medicine, as it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any adverse reactions, including any not listed in this leaflet, they should inform their 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 down 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 properties.

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 medicinal products 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 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 joints in 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 can 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 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, or gastric or intestinal ulcers;
• if the patient is pregnant or breastfeeding (see section "Pregnancy, breastfeeding and fertility");
• if the patient is receiving a vaccine containing live microorganisms at the same time.

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 health;
• 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 rheumatologic disease during methotrexate treatment. If the patient experiences haemoptysis (coughing up blood-stained sputum), seek immediate medical advice.

Recommended tests and safety measures
Severe adverse effects may occur even after administration of small doses of Tullex, solution for injection. 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 starting treatment to check whether the patient has an adequate number of blood cells. Blood will also be tested to assess liver function and to detect whether the patient has hepatitis (liver inflammation). In addition, serum albumin (a blood protein), presence/occurrence of hepatitis (liver infection) and kidney function will be evaluated.
The doctor may also decide to perform other liver tests; some of these 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 whether the patient has 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 serum methotrexate 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
• monitoring of the respiratory tract and, if necessary, lung function tests

It is very important that the patient attends these scheduled tests.
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 effects 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 in elderly patients.

Methotrexate may affect the immune system, vaccination outcomes and immunological test results. It may reactivate latent chronic diseases (e.g. shingles, tuberculosis, hepatitis B or C virus). Vaccines containing live microorganisms should not be used 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 intense sunlight, wear appropriate clothing or use a high-protection sunscreen.

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

Lymphadenopathy (swollen lymph nodes, lymphoma) 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.

Encephalopathy (brain disease) and leukoencephalopathy (a specific brain disease affecting white matter) have been reported in patients with malignancies 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, solution for injection
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 female patient should avoid becoming pregnant during methotrexate treatment and for at least 6 months after completion of treatment. The male 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
Tullex, solution for injection should not be used in children under 3 years of age due to insufficient experience with methotrexate in this age group.

Tullex, solution for injection and other medicines
Inform your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to use.

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

• drugs 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 (sulphur-containing medicines used to prevent and treat certain infections), ciprofloxacin and cephalothin;
• non-steroidal anti-inflammatory drugs or salicylates (painkillers and/or anti-inflammatory medicines);
• probenecid (used in the treatment of gout);
• weak organic acids such as loop diuretics (diuretics), or certain painkillers and anti-inflammatory drugs (e.g. acetylsalicylic acid, diclofenac and ibuprofen), and pyrazoles (used to treat pain);
• metamizole (synonyms: novaminsulfone and dipyrone) (a strong painkiller and/or antipyretic);
• 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.

Vaccines containing live microorganisms should not be administered 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 drinks 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 a 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 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 ruled out before starting treatment by 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 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 defects or miscarriages following paternal methotrexate exposure at doses below 30 mg per week. However, the risk cannot be completely excluded. Methotrexate may be genotoxic, meaning that the drug 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.
If the patient feels drowsy or fatigued, driving vehicles or operating machinery must be avoided.

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, injection solution

Important warning regarding the 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.
Taking more than the prescribed amount of Tullex (methotrexate) may result in death.
Please read section 3 of this leaflet very 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.
Please follow carefully 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 the drug 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 in this regard.
Never attempt to self-administer the injection without having received 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 rinse 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.

Taking more than the recommended dose 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 the appropriate treatment depending on the severity of poisoning.

Missed dose of Tullex, injection solution
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 according to schedule.

Stopping treatment with Tullex, injection solution
Do not stop or discontinue treatment with Tullex, injection solution, 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 effects

Like all medicines, this medicine can cause adverse effects, 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 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
frequency not known: cannot be estimated from the available data

The frequency and severity of adverse effects depend on the dose and frequency of administration of the medicine. Since severe adverse effects 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, platelet count, and lymphoma) 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 effects 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 blood-stained sputum;
• 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 the hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty 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 the 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 may occur, such as a specific type of pneumonia (Pneumocystis carinii pneumonia) and blood poisoning (septicaemia) [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 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 pain or urinary disturbances; 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 or vomit, or appearance of petechiae (small red or purple spots on the skin caused by bleeding); these may be symptoms of significant reduction 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 possible adverse effects:
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, 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
• 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 urinary bladder or vagina, impaired kidney function, urinary disturbances
• 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
• pericarditis, fluid in the pericardial sac
• low blood pressure
• pulmonary fibrosis, shortness of breath, bronchial asthma, fluid accumulation in the pleural sac around the lung
• electrolyte disturbances.

Very rare:

• profuse bleeding, toxic dilation of the large intestine (toxic megacolon)
• increased nail pigmentation, 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 numbness and tingling sensations, reduced response to stimuli, taste changes (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
• enlarged lymph nodes (lymphadenopathy)
• lymphoproliferative disorders (overproduction of white blood cells).

Frequency not known:

• leukoencephalopathy (a disease of the white matter of the brain)
• pulmonary haemorrhage
• redness and peeling of the skin
• oedema
• jaw bone 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 decrease during the course of treatment.

Reporting of adverse effects
If any adverse effects occur, including any adverse effects not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring 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 effects can also be reported to the marketing authorisation holder.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Tullex, solution for injection

Keep this 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 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 injection solution 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 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 syringe-pen with an injection needle and a safety mechanism, available in packs containing 1 syringe-pen or 4, 12 syringe-pens. 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 directed by your doctor or pharmacist.
Tullex injection solution is for single use only. Any unused solution remaining in the syringe-pen must be discarded.
The solution should be clear and must not contain 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 syringe-pen of Tullex injection solution
• One alcohol swab (included in the pack)

Wash your hands thoroughly.
Inspect the syringe-pen: check whether the syringe or the 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 consider the syringe-pen unsuitable for use, dispose of it in a container for biologically contaminated (sharp) instruments.

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 change the injection site with each dose to reduce the risk of irritation at the injection site.
Never inject into skin areas that are painful, have petechiae (small bleeding spots), are red, hard, or contain scars or stretch marks. If you have psoriasis, avoid injecting directly into raised, thickened, red, or scaly psoriatic lesions.

Injecting the solution

1. Unpack the syringe-pen and carefully read the leaflet included in the package. Remove the syringe-pen from its packaging at room temperature.
2. Disinfection

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

3. Remove the needle cap. Carefully pull the needle cap straight off along the line of the needle. Warning: Do NOT touch the needle of the syringe-pen! After removing the needle cap, dispose of it in a container for biologically contaminated (sharp) instruments.

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 pressing the plunger.

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

6. Dispose of the device 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 household waste bins.

Avoid contact of methotrexate with 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 syringe-pen.

Disposal and preparation of the medicinal product for use
Handling and disposal of the product must comply with the guidelines for cytotoxic medicines and applicable regulations. Pregnant healthcare personnel should not handle or (and) administer methotrexate.