Trexan Neo

Package Leaflet: Information for the User

Trexan Neo, 2.5 mg, tablets

Trexan Neo, 10 mg, tablets

Methotrexate

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

• You should keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information

• 1. What is Trexan Neo and what is it used for
• 2. Before you take Trexan Neo
• 3. How to take Trexan Neo
• 4. Possible side effects
• 5. How to store Trexan Neo
• 6. Contents of the pack and other information

1. What is Trexan Neo and what is it used for

The active substance in Trexan Neo tablets, methotrexate, has the following properties:

• inhibits the growth of certain cells in the body that multiply quickly
• reduces the activity of the immune system (the body's defense mechanism).

Methotrexate is used:

• to treat active rheumatoid arthritis in adults
• to treat severe, treatment-resistant psoriasis that does not respond to other treatments, such as phototherapy, PUVA, and retinoids in adults
• to treat severe psoriatic arthritis in adults
• as maintenance therapy for acute lymphoblastic leukemia (ALL) in adults, adolescents, and children over 3 years of age.

Your doctor will explain how Trexan Neo tablets can help you with your condition.

2. Before you take Trexan Neo

When not to take Trexan Neo:

• if you are allergic (hypersensitive) to methotrexate or any of the other ingredients of this medicine (listed in section 6);
• if you are breastfeeding, and also during pregnancy, if you are taking the medicine for non-oncological indications (for the treatment of non-cancerous diseases) (see section "Pregnancy, breastfeeding, and fertility");
• if you have severe liver or kidney disease (the severity of the disease will be determined by your doctor);
• if you have diseases of the bone marrow or severe blood diseases;
• if you have severe acute or chronic infections or immune deficiency syndrome;
• if you have oral mucositis or oral ulcers;
• if you have stomach or intestinal ulcers;
• if you have alcoholic disease;
• if you have recently received a live vaccine or plan to receive one.

Warnings and precautions

Important warning about dosing with Trexan Neo (methotrexate):

In the treatment of rheumatoid arthritis, psoriasis, or psoriatic arthritis, Trexan Neo should be taken only once a week. Taking too high a dose of Trexan Neo (methotrexate) can lead to death. You should read the contents of section 3 of this leaflet very carefully. If you have any questions, you should consult your doctor or pharmacist before taking this medicine.
Before starting treatment with Trexan Neo, you should discuss the following with your doctor, pharmacist, or nurse:

• if you have ever had liver or kidney disease;
• if you have a hidden, chronic infection (e.g., tuberculosis, viral hepatitis B or C, shingles), due to the possibility of reactivation of these diseases;
• if you are in poor general condition;
• if you have lung function disorders;
• if you are severely overweight;
• if you have fluid accumulation in the abdominal cavity (ascites) or in the space between the lungs and the chest wall (pleural effusion);
• if you have diabetes treated with insulin;
• if you are dehydrated or have disorders leading to dehydration (e.g., vomiting, diarrhea, constipation, oral mucositis).

During methotrexate treatment, cases of acute bleeding from the lungs have been reported in patients with underlying rheumatologic disease. If you experience coughing up blood or bloody sputum, you should immediately consult your doctor.
A side effect of Trexan Neo may be diarrhea, which requires discontinuation of treatment.
If you experience diarrhea, you should consult your doctor.
Methotrexate has a temporary effect on the production of sperm and egg cells.
Methotrexate may cause miscarriage and severe birth defects. Women should avoid becoming pregnant while taking methotrexate and for at least 6 months after treatment ends. Men taking methotrexate should avoid fatherhood or donating sperm during treatment and for at least 3 months after treatment ends. See also the section "Pregnancy, breastfeeding, and fertility".
Radiation therapy during Trexan Neo treatment may increase the risk of soft tissue or bone necrosis. During methotrexate treatment, previously radiation-induced skin changes may recur (radiation dermatitis) or sunburn-like reactions (recall reactions). While taking methotrexate, psoriatic skin lesions may worsen if you are exposed to UV radiation.
Methotrexate may increase the sensitivity of your skin to sunlight. You should avoid intense sun exposure and not use a sunbed or sunlamp without consulting your doctor.
To protect your skin from intense sunlight, you should wear appropriate clothing or use a sunscreen with a high protection factor.
In patients receiving low-dose methotrexate, lymphoma (lymph node cancer) may occur. In such cases, treatment should be discontinued.
If you, your partner, or caregiver notice new or worsening neurological symptoms, including general muscle weakness, vision disturbances, changes in thinking, memory, and orientation leading to disorientation and personality changes, you should immediately contact your doctor, as these may be symptoms of a very rare, serious brain infection called progressive multifocal leukoencephalopathy (PML).
In patients with cancer receiving methotrexate, certain other brain disorders (encephalopathy/leukoencephalopathy) have been reported. Such side effects cannot be ruled out when methotrexate is used to treat other diseases.
Recommended tests and precautions
Even with low doses of methotrexate, severe side effects may occur. To detect these side effects early, your doctor will need to perform tests and laboratory tests.
Before starting treatment:

• Your doctor will recommend blood tests to check if you have enough blood cells to take the medicine. Your doctor will also recommend blood tests to check your liver function and to determine if you have hepatitis. Additionally, blood tests will be performed to check the albumin level in your blood (a protein in the blood), the degree of liver inflammation (liver infection), and kidney function. Your doctor may also decide to perform other liver tests, some of which may be imaging tests of the liver, and others may require taking a small tissue sample from the liver for further examination. Your doctor may also check if you have tuberculosis and recommend a chest X-ray or lung function tests.

During treatment:

• Your doctor may recommend the following tests:
• examination of the mouth and throat to check for changes in the mucous membranes, such as inflammation or ulcers
• blood tests/morphology with determination of blood cell count and measurement of methotrexate levels in the blood
• blood tests to monitor liver function
• imaging tests to assess liver condition
• taking a small tissue sample from the liver for further examination
• blood tests to monitor kidney function
• monitoring of the respiratory tract and, if necessary, performing lung function tests.

It is very important that you attend all scheduled blood tests. If any of these tests are abnormal, your doctor will adjust your treatment accordingly.

Children, adolescents, and elderly patients

During Trexan Neo therapy, children, adolescents, and elderly patients treated with methotrexate should be closely monitored by their doctor to detect any potential side effects as early as possible.
In elderly patients, it is necessary to use a relatively low dose of methotrexate due to impaired liver and kidney function and lower folate reserves in the elderly.
Methotrexate is not recommended for use in children under 3 years of age due to insufficient experience in this age group.

Trexan Neo and other medicines

Other medicines taken at the same time may affect the efficacy and safety of Trexan Neo. Trexan Neo may also affect the efficacy and safety of other medicines.
You should tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take. You should remember to inform your doctor about taking Trexan Neo if you are prescribed another medicine. It is especially important to inform your doctor if you are taking:

• metamizole (synonyms: novaminsulfone and dipyrone) [a strong pain reliever and/or antipyretic];
• certain antibiotics (medicines used to prevent or treat certain infections), such as penicillins, sulfonamides, ciprofloxacin, cephalothin, trimethoprim/sulfamethoxazole, tetracycline, and chloramphenicol; For example, penicillins, such as amoxicillin, may reduce the excretion of methotrexate, which may increase the risk of side effects;
• other medicines used to treat rheumatoid arthritis or psoriasis, such as leflunomide, sulfasalazine, and azathioprine;
• certain pain relievers and/or anti-inflammatory medicines, known as non-steroidal anti-inflammatory drugs (e.g., ibuprofen, diclofenac, salicylates, such as acetylsalicylic acid);
• pyrimethamine (a medicine used to prevent and treat malaria);
• anticancer medicines (e.g., mercaptopurine, 5-fluorouracil, doxorubicin, and procarbazine);
• antiepileptic medicines (medicines that prevent seizures);
• omeprazole or pantoprazole (medicines that reduce stomach acid production);
• diuretics (medicines that increase urine production);
• medicines that lower blood sugar levels, such as metformin;
• cholestyramine (a medicine that binds bile acids, which may be used to lower cholesterol levels in the blood);
• cyclosporine (a medicine that suppresses or prevents immune responses);
• retinoids (medicines used to treat psoriasis and other skin diseases);
• oral contraceptives;
• barbiturates (sleeping medicines);
• sedatives;
• nitrous oxide (used for general anesthesia);
• probenecid (a medicine used to treat gout);
• theophylline (a medicine used to treat respiratory diseases);
• vitamin preparations and other products containing folic acid, folinic acid, and their derivatives;
• vaccines containing live microorganisms.

Trexan Neo with food, drink, and alcohol

During Trexan Neo therapy, you should avoid alcohol, as well as large amounts of coffee, caffeine-containing beverages, and black tea. While taking Trexan Neo, you should drink plenty of fluids, as dehydration (reduced water content in the body) may increase the risk of methotrexate side effects.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, you should consult your doctor or pharmacist before taking this medicine.
Pregnancy
Trexan Neo should notbe taken during pregnancy, unless your doctor has recommended it for cancer treatment.
Methotrexate may cause birth defects, harm the unborn child, or lead to miscarriage. This is associated with developmental abnormalities of the skull, face, heart, and blood vessels, brain, and limbs. Therefore, it is very important not to give methotrexate to pregnant women or women planning to become pregnant, unless the medicine is used for cancer treatment.
In non-oncological indications, in women of childbearing age, before starting treatment, you should rule out the possibility of pregnancy, e.g., by performing a pregnancy test.
You should not take Trexan Neo if you are trying to become pregnant. You should avoid becoming pregnant while taking methotrexate and for at least 6 months after treatment ends. During this time, you should use effective contraception (see also the section "Warnings and precautions").
If you become pregnant during treatment or think you may be pregnant, you should consult your doctor as soon as possible. If you become pregnant during treatment, you should receive advice on the risk of methotrexate harming your child.
If you plan to become pregnant, you should consult your doctor, who may refer you to a specialist for advice before planned treatment begins.
Breastfeeding
Since methotrexate passes into breast milk, you should not breastfeed while taking this medicine. If your doctor considers it necessary to take methotrexate during breastfeeding, you should stop breastfeeding.
Male fertility
Available data do not indicate an increased risk of birth defects or miscarriages after the father has taken methotrexate at a dose below 30 mg/week. However, this risk cannot be completely ruled out; there is also no information on higher doses of methotrexate. Methotrexate may have genotoxic effects. This means that the medicine may cause genetic mutations. Methotrexate may affect sperm production, which is associated with the possibility of birth defects.
You should avoid fertilizing your partner or donating sperm while taking methotrexate and for at least 3 months after treatment ends. Due to the potential risk of infertility and genetic mutations when taking higher doses of methotrexate, typically used in cancer treatment, it may be recommended to store sperm obtained before starting treatment (see also the section "Warnings and precautions").
Before taking any medicine, you should consult your doctor or pharmacist.

Driving and using machines

During Trexan Neo therapy, you may experience fatigue and dizziness. If these symptoms occur, you should not drive or operate machinery.

Trexan Neo contains lactose

These tablets contain lactose. If you have been diagnosed with intolerance to some sugars, you should consult your doctor before taking this medicine.

3. How to take Trexan Neo

This medicine should always be taken exactly as directed by your doctor or pharmacist. If you are unsure, you should consult your doctor or pharmacist.

• Patient with rheumatoid arthritis, psoriasis, or psoriatic arthritis must take the tablets orally only once a week, always on the same day of the week.
• You should not take more tablets than your doctor has recommended.
• Daily intake may lead to severe toxic reactions, including death.
• Tablets should be taken while sitting or standing, with a glass of water.

Dosing in rheumatoid arthritis, psoriasis, and severe psoriatic arthritis
Tablets should be taken once a week, always on the same day of the week. The dose is usually between 7.5 and 15 mg once a week.
Dosing for maintenance therapy in acute lymphoblastic leukemia
Your doctor will calculate the required dose based on your body surface area. Your doctor will decide on the appropriate dose. Further information can be obtained from your doctor.
Special patient populations
In elderly patients and patients with impaired liver or kidney function, a reduced dose is usually used, depending on the doctor's decision. See also section 2: "When not to take Trexan Neo".

Use in children and adolescents

In children and adolescents receiving maintenance therapy for acute lymphoblastic leukemia, the doctor will calculate the dose individually based on body surface area.

Safe handling of Trexan Neo tablets

You should follow the appropriate procedures for handling cytotoxic agents. Anyone coming into contact with methotrexate should wash their hands before and after administering the dose. When handling methotrexate tablets, you should use disposable gloves. Women who are pregnant, planning to become pregnant, or breastfeeding should avoid contact with methotrexate.
You should avoid skin and mucous membrane contact. If methotrexate comes into contact with your skin or mucous membranes, you should immediately wash the affected area with soap and water.
You should advise parents, caregivers, and patients to store methotrexate in a place that is inaccessible to children, preferably in a locked cabinet.
Accidental ingestion by a child may lead to death.

Overdose of Trexan Neo

If you (or someone else) have taken more than the recommended dose of Trexan Neo, you should immediately contact your doctor or the nearest hospital emergency department.
Overdose of methotrexate can lead to severe toxic reactions, including death.
Symptoms of overdose may include: bleeding tendency or bruising, unusual weakness, oral ulcers, nausea, vomiting, black or bloody stools, coughing up blood or coffee-ground-like vomit, and decreased urine output. See also section 4: "Possible side effects".
When going to your doctor or hospital, you should take the medicine package with you. If you have taken too much methotrexate, you will be given calcium folinate to alleviate the side effects of methotrexate.

Missed dose of Trexan Neo

If you miss a dose, you should take it as soon as possible, provided that you remember within 2 days. However, if more than 2 days have passed since the scheduled dose, you should consult your doctor. You should not take a double dose to make up for the missed dose.
Before going on vacation or a trip, you should ensure that you have a sufficient supply of medicine.

Stopping Trexan Neo treatment

Unless your doctor advises you to do so, you should not stop taking Trexan Neo. If you need to stop taking Trexan Neo, your doctor will decide on the best method of withdrawal.
If you have any further questions about taking this medicine, you should consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, Trexan Neo can cause side effects, although not everybody gets them.
Generally, the frequency and severity of methotrexate side effects are related to the dose and frequency of administration. Most side effects are reversible if detected early.
You should tell your doctor immediatelyif you experience any of the following symptoms, as they may indicate a severe, potentially life-threatening side effect that requires special treatment:

• dry cough and/or chest pain or difficulty breathing, shortness of breath, chest pain, or fever;
• coughing up blood or bloody sputum*;
• unusual bleeding (including bloody vomiting), bruising, or nosebleeds;
• nausea, vomiting, abdominal discomfort, or severe diarrhea;
• oral ulcers;
• black or tarry stools;
• severe allergic reaction, causing fever, rash, swelling, and sometimes a drop in blood pressure;
• exceptionally severe allergic reaction involving rash, often in the form of blisters on the skin or ulcers in the mouth, eyes, and genitals (Stevens-Johnson syndrome or toxic epidermal necrolysis);
• if you experience any symptoms of infection, such as fever and significant deterioration of your general condition or fever with local signs of infection, such as throat pain or mouth ulcers, or problems with urination, you should immediately consult your doctor. Methotrexate may reduce the number of white blood cells and thus reduce the immune response. Your doctor will recommend a blood test to check if your white blood cell count has decreased (agranulocytosis);
• jaundice (yellowing of the skin);
• pain or difficulty urinating;
• thirst and/or frequent urination;
• blurred or impaired vision.

Most of the following side effects occur only in patients receiving high doses of methotrexate for cancer treatment. In the treatment of psoriasis or rheumatoid arthritis, they are less common and less severe.
Very common(may affect more than 1 in 10 people):

• loss of appetite, nausea, vomiting, indigestion, abdominal pain, oral ulcers;
• increased liver enzyme activity.

Common(may affect up to 1 in 10 people):

• infections;
• suppression of blood cell production with a decrease in white blood cells and/or red blood cells and/or platelets (leukopenia, anemia, thrombocytopenia);
• headache, dizziness, unusual fatigue, drowsiness;
• pneumonitis, dry cough;
• diarrhea;
• rash, redness, itching;
• hair loss.

Uncommon(may affect up to 1 in 100 people):

• lymphoma (lymph node cancer);
• diabetes;
• depression, confusion;
• seizures, dizziness of inner ear origin;
• ulcers and bleeding from the gastrointestinal tract;
• nosebleeds;
• excessive formation of fibrous connective tissue in organs (fibrosis);
• decreased albumin levels in the blood;
• inflammation of blood vessels, often with a rash (allergic vasculitis), excessive skin pigmentation, slow wound healing, increased number of rheumatoid nodules;
• reactions similar to sunburn, due to increased skin sensitivity to sunlight;
• ulcers and inflammation of the bladder, urinary disorders;
• liver damage;
• kidney function disorders;
• joint or muscle pain, a type of bone disease that leads to a decrease in bone mineral content (osteoporosis);
• inflammation and ulcers of the vagina;
• chills.

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

• generalized inflammatory state leading to death (sepsis), shingles;
• blood disorders characterized by the presence of very large red blood cells (megaloblastic anemia);
• mood swings;
• limited mobility (including limited mobility on one side of the body);
• severe vision disturbances;
• fluid accumulation in the sac surrounding the heart. This can lead to cardiac tamponade, a life-threatening condition in which the heart cannot pump blood properly due to external pressure. Medical intervention may be necessary to remove the fluid and pressure;
• low blood pressure, presence of blood clots;
• respiratory failure or severe weakness of respiratory muscles, shortness of breath, inflammation of the back of the throat;
• pancreatitis, gum inflammation;
• hepatitis (acute liver inflammation);
• skin reactions (acne, skin discoloration, hives, erythema multiforme, burning sensation in psoriatic lesions, skin ulcers, red or purple spots due to bleeding from blood vessels), separation of the nail plate, dark spots on the nails;
• stress fractures;
• decreased or absent urine production, abnormal electrolyte levels in the blood;
• menstrual disorders, impotence.

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

• immunodeficiency (hypogammaglobulinemia), increased susceptibility to infection;
• lymphoproliferative disorders (overproduction of white blood cells);
• insomnia;
• brain swelling, speech disorders (dysarthria), irritation, drowsiness and fatigue (lethargy), transient cognitive impairment ("brain fog"), unusual sensations in the head, muscle weakness, tingling or numbness, reduced sensitivity to stimuli, changes in taste (metallic taste);
• redness and irritation of the thin membrane covering the eye (conjunctivitis), vision disturbances, eye damage;
• inflammation of blood vessels, bloody vomiting;
• reactivation of chronic hepatitis, liver failure;
• enlargement of the colon, accompanied by inflammation/infection;
• infection around the nail, deep infection of hair follicles (furuncles), bruising, acne;
• presence of protein or blood in the urine, painful urination, urinary tract infection;
• low sperm count, breast enlargement in men, vaginal bleeding, loss of libido;
• fever.

Other side effects have also been reported, but their frequency is unknown:

Septicemia leading to death, abnormally low blood cell count, bleeding from the lungs*, bone jaw damage (due to overproduction of white blood cells), brain disease, pathological changes in the white matter of the brain (leukoencephalopathy), inflammation of the air sacs in the lungs, weakness, increased risk of toxic reactions during radiation therapy, redness and peeling of the skin, swelling. Psoriatic skin lesions may worsen during concurrent exposure to ultraviolet light, such as sunlight, and methotrexate. During methotrexate treatment, previously radiation-induced skin changes may recur (radiation dermatitis) or sunburn-like reactions (recall reactions).
*(reported during methotrexate treatment in patients with underlying rheumatologic disease)

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, you should tell your doctor, pharmacist, or nurse. You can also report side effects directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products:
Jerozolimskie Avenue 181C,
02-222 Warsaw,
phone: 22 49 21 301,
fax: 22 49 21 309,
website: https://smz.ezdrowie.gov.pl
You can also report side effects to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Trexan Neo

The medicine should be stored out of sight and reach of children, preferably in a locked cabinet. Accidental ingestion by a child may lead to death.
Do not use this medicine after the expiry date stated on the blister or outer carton. The expiry date refers to the last day of the month.
There are no special storage instructions for this medicine. Blisters should be stored in the outer carton to protect from light.
You should follow the appropriate procedures for handling cytotoxic agents. Anyone coming into contact with methotrexate should wash their hands before and after administering the dose. When handling methotrexate tablets, you should use disposable gloves. Women who are pregnant, planning to become pregnant, or breastfeeding should avoid contact with methotrexate.
Any unused medicine or waste material should be disposed of in accordance with local regulations for cytotoxic agents.
Medicines should not be disposed of via wastewater or household waste. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Trexan Neo contains

• The active substance is methotrexate. Each tablet contains 2.5 mg or 10 mg of methotrexate (as methotrexate disodium).
• The other ingredients are lactose monohydrate, microcrystalline cellulose, and magnesium stearate.

What Trexan Neo looks like and contents of the pack

Trexan Neo, 2.5 mg, tablets: yellow, round, uncoated, flat tablets with a dividing line and the marking "ORN 57" embossed on one side, with a diameter of 6 mm. The dividing line on the tablet is only to facilitate breaking the tablet and not to divide it into equal doses.
Trexan Neo, 10 mg, tablets: yellow, capsule-shaped, uncoated, convex tablets with the marking "ORN 59" embossed on one side and a dividing line on the other side, with a length of 14.0 mm and a width of 6.0 mm. The tablet can be divided into equal doses.
Pack sizes:
PVC/Aluminum blisters
2.5 mg: 4, 8, 10, 12, 16, 20, 24, 30, 36, 40, 48, 50, 60, 100, and 120 tablets.
10 mg: 4, 8, 10, 12, 16, 20, 24, 30, 36, 40, 48, 50, 60, 100, and 120 tablets.
Not all pack sizes may be marketed.

Marketing authorization holder

Orion Corporation
Orionintie 1
FI-02200 Espoo
Finland

Manufacturer

Orion Corporation Orion Pharma
Tengströminkatu 8
FI-20360 Turku
Finland
Orion Corporation Orion Pharma
Joensuunkatu 7
FI-24100 Salo
Finland

This medicine is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Denmark, Estonia, Finland, Lithuania:
Trexan
France:
Imenor
Spain:
Methotrexate Semanal Orion Pharma
Ireland, Norway, Hungary, United Kingdom:
Methotrexate Orion
Iceland, Sweden:
Methotrexate Orion Pharma
Czech Republic, Poland, Slovakia:
Trexan Neo
To obtain more detailed information on this medicine, you should contact the local representative of the marketing authorization holder:
Orion Pharma Poland Sp. z o.o.
kontakt@orionpharma.info.pl
Date of last revision of the leaflet:05/2025