Trexan neo: detailed information

Package leaflet: Information for the user

Trexan Neo, 2.5 mg, tablets
Trexan Neo, 10 mg, tablets
Methotrexatum
Please read all of this leaflet carefully before taking 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, 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 symptoms are the same as yours.
If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet

What Trexan Neo is and what it is used for
What you need to know before you take Trexan Neo
How to take Trexan Neo
Possible side effects
How to store Trexan Neo
Contents of the pack and other information

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

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

inhibits the growth of certain rapidly dividing cells in the body
reduces the activity of the immune system (the body's defence mechanism).

Methotrexate is used:

in the treatment of active rheumatoid arthritis in adults
in the treatment of severe psoriasis resistant to other therapies, which does not respond adequately to other treatments such as phototherapy, PUVA, and retinoids in adults
in the treatment of severe psoriatic arthritis in adults
as maintenance therapy in acute lymphoblastic leukemia (ALL) in adults, adolescents, and children aged 3 years and older.

Your doctor will explain how Trexan Neo tablets can help in the treatment of your condition.

2. Important Information Before Taking Trexan Neo

When not to use Trexan Neo:

if the patient is allergic (hypersensitive) to methotrexate or any of the other ingredients of this medicine (listed in section 6);
if the patient is breastfeeding and, additionally, during pregnancy, if the patient is taking the medicine for non-oncological indications (in the treatment of non-cancerous disease) (see section "Pregnancy, breastfeeding and fertility");
if the patient has severe liver or kidney disease (the severity of which will be determined by the physician);
if the patient has or has had bone marrow disorders or severe blood diseases;
if the patient has severe acute or chronic infections or immunodeficiency syndrome;
if the patient has oral mucositis or oral ulceration;
if the patient has gastric or intestinal ulcers;
if the patient has alcoholic liver disease;
if the patient has recently received a vaccine containing live microorganisms or plans to receive such a vaccine.

Warnings and precautions
Important warning regarding dosing of Trexan Neo (methotrexate):
In the treatment of rheumatoid arthritis, psoriasis or psoriatic arthritis, Trexan Neo should be taken once weekly only. Taking an excessive dose of Trexan Neo (methotrexate) may lead to death. Please read section 3 of this leaflet carefully. If you have any questions, consult your doctor or pharmacist before taking this medicine.
Before starting treatment with Trexan Neo, discuss the following with your doctor, pharmacist or nurse:

if the patient has ever had liver or kidney disease;
if the patient has latent, chronic infection (e.g. tuberculosis, hepatitis B or C virus, shingles), due to the risk of reactivation of these diseases;
if the patient is in poor general health;
if the patient has lung function disorders;
if the patient is significantly overweight;
if fluid has accumulated in the abdominal cavity (ascites) or in the space between the lungs and the chest wall (pleural effusion);
if the patient has diabetes treated with insulin;
if the patient is dehydrated or has conditions leading to dehydration (e.g. vomiting, diarrhoea, constipation, oral mucositis).

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-tinged sputum), immediate medical attention should be sought.
Diarrhoea is a possible adverse effect of Trexan Neo, which may require discontinuation of treatment. If diarrhoea occurs, consult your doctor.
Methotrexate has a temporary effect on sperm and oocyte production.
Methotrexate may cause miscarriage and severe congenital malformations. Women should avoid becoming pregnant during methotrexate treatment and for at least 6 months after treatment ends. Men taking methotrexate should avoid fathering a child or donating sperm during treatment and for at least 3 months after its completion. See also section: "Pregnancy, breastfeeding and fertility".
Radiotherapy during Trexan Neo treatment may increase the risk of soft tissue or bone necrosis. Skin changes caused by previous radiotherapy (radiation dermatitis) or sunburn (radiation-like reactions) may reappear during Trexan Neo treatment. Psoriatic skin lesions may worsen during methotrexate treatment if the patient is exposed to UV radiation.
Methotrexate may increase skin sensitivity to sunlight. Avoid intense sun exposure and do not use solariums or tanning lamps without consulting your doctor. To protect the skin from intense sunlight, wear appropriate clothing or use a high-protection sunscreen.
Lymphadenopathy (swollen lymph nodes, resembling lymphoma) may occur in patients receiving low-dose methotrexate. In such cases, treatment should be discontinued.
If the patient, their partner or caregiver notice new onset or worsening of neurological symptoms, including generalised muscle weakness, visual disturbances, changes in thinking, memory and orientation leading to disorientation, and personality changes, contact a doctor immediately, as these may be symptoms of a very rare but serious brain infection called progressive multifocal leukoencephalopathy (PML).
Certain other brain disorders (encephalopathy/leukoencephalopathy) have been reported in cancer patients receiving methotrexate. Such adverse effects cannot be ruled out when methotrexate is used in the treatment of other diseases.

Recommended monitoring and precautions
Even with low-dose methotrexate, severe adverse effects may occur. To detect these effects early, the doctor must perform regular monitoring and laboratory tests.

Before starting treatment:
Before initiating treatment, the doctor will recommend blood tests to check whether blood cell counts are sufficient for treatment. The doctor will also recommend blood tests to assess liver function and determine whether hepatitis is present. Additionally, blood tests will be performed to check serum albumin levels (a blood protein), degree of liver inflammation (liver infection), and kidney function. The doctor may also decide to perform other liver tests, some of which may involve liver imaging, while others may require a small liver tissue sample for more detailed examination. The doctor may also check for tuberculosis and recommend a chest X-ray or lung function tests.

During treatment:
The doctor may recommend the following tests:

examination of the mouth and throat to check for mucosal changes such as inflammation or ulceration;
blood tests/full blood count to determine blood cell counts and serum methotrexate levels;
blood tests to monitor liver function;
imaging tests to assess liver status;
liver biopsy (a small tissue sample taken 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 all scheduled blood tests.
If any of these test results are abnormal, the doctor will adjust the treatment accordingly.

Children, adolescents and elderly patients
Children, adolescents and elderly patients receiving Trexan Neo (methotrexate) should remain under close medical supervision to detect any adverse effects as early as possible.
In elderly patients, a relatively low dose of methotrexate is necessary due to impaired liver and kidney function and reduced folate reserves associated with aging.
The use of this medicine is not recommended in children under 3 years of age due to insufficient experience in this age group.

Trexan Neo and other medicines
Other medicines taken concurrently may affect the efficacy and safety of this medicine. Trexan Neo may also affect the efficacy and safety of other medicines.
Inform your doctor or pharmacist about all medicines currently or recently taken, as well as any medicines you plan to take. Remember to inform any doctor prescribing a new medicine that you are taking Trexan Neo. It is especially important to inform your doctor if you are taking:

metamizole (synonyms: dipyrone and amidopyrine) [a strong analgesic and/or antipyretic];
certain antibiotics (medicines used to prevent or treat certain infections), e.g. penicillins, sulfonamides, ciprofloxacin, cephalothin, trimethoprim/sulfamethoxazole, tetracycline and chloramphenicol; for example, penicillins such as amoxicillin may reduce methotrexate excretion, potentially increasing adverse effects;
other medicines used in rheumatoid arthritis or psoriasis, such as leflunomide, sulfasalazine and azathioprine;
certain analgesics 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 for malaria prophylaxis and treatment);
antineoplastic medicines (e.g. mercaptopurine, 5-fluorouracil, doxorubicin and procarbazine);
anticonvulsants (medicines preventing seizures);
omeprazole or pantoprazole (medicines reducing gastric acid production);
diuretics (water pills);
blood glucose-lowering medicines such as metformin;
cholestyramine (a bile acid-binding agent that may be used, for example, to reduce blood cholesterol levels);
cyclosporine (an immunosuppressive medicine);
retinoids (medicines used in the treatment of psoriasis and other skin diseases);
oral contraceptives;
barbiturates (sleeping pills);
sedatives;
nitrous oxide (used for general anaesthesia);
probenecid (a medicine used in the treatment of gout);
theophylline (a medicine used in respiratory diseases);
vitamin supplements and other products containing folic acid, folinic acid and its derivatives;
vaccines containing live microorganisms.

Trexan Neo with food, drink and alcohol
During treatment with Trexan Neo, alcohol, large amounts of coffee, caffeine-containing beverages and black tea should be avoided. During Trexan Neo treatment, it is important to drink plenty of fluids, as dehydration (reduced body water) may worsen methotrexate's adverse effects.

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

Pregnancy
Trexan Neo must not be used during pregnancy unless prescribed by a doctor for anticancer treatment.
Methotrexate may cause congenital malformations, 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 administer methotrexate to pregnant women or women planning pregnancy, unless used for anticancer treatment.
For non-oncological indications, pregnancy should be ruled out in women of childbearing potential before starting treatment, e.g. by performing a pregnancy test.
Trexan Neo must not be used if the patient is trying to become pregnant. The patient must strictly avoid pregnancy during methotrexate treatment and for at least 6 months after treatment ends. Effective contraception must be used throughout this period (see also section "Warnings and precautions").
If the patient becomes pregnant during treatment or suspects she may be pregnant, she should consult her doctor immediately. If pregnancy occurs during treatment, advice regarding the risk of harmful effects of methotrexate on the foetus should be provided.
If the patient plans to become pregnant, she should consult her doctor, who may refer her to a specialist for advice before planned treatment initiation.

Breastfeeding
Since methotrexate passes into human milk, breastfeeding must not be performed during treatment with this medicine. If the doctor considers methotrexate treatment absolutely necessary during lactation, breastfeeding must be discontinued.

Fertility in men
Available evidence does not indicate an increased risk of developmental abnormalities or miscarriages following paternal methotrexate use at doses below 30 mg/week. However, the risk cannot be completely excluded; there is also no information regarding higher methotrexate doses. Methotrexate may be genotoxic, meaning it may cause genetic mutations. Methotrexate may affect sperm production, potentially leading to congenital abnormalities.
The patient should avoid impregnating his partner or donating sperm during methotrexate treatment and for at least 3 months after its completion. Given that treatment with higher methotrexate doses, typically used in cancer therapy, may cause infertility and genetic mutations, sperm preservation before treatment initiation may be recommended for men receiving methotrexate doses above 30 mg/week (see also section "Warnings and precautions").

Before taking any medicine, consult your doctor or pharmacist.

Driving and operating machinery
During Trexan Neo treatment, fatigue and dizziness may occur. If these symptoms occur, do not drive or operate machinery.

Trexan Neo contains lactose
These tablets contain lactose. If the patient has previously been diagnosed with intolerance to certain sugars, they should contact their doctor before taking this medicine.

3. How to take Trexan Neo

This medicine should always be taken exactly as directed by the doctor or pharmacist.
If in doubt, consult your doctor or pharmacist.

Patients with rheumatoid arthritis, psoriasis, or psoriatic arthritis must take the tablets orally once weekly, always on the same day of the week.
Do not take more tablets than prescribed by your doctor.
Daily administration may result in severe toxic reactions, including death.
Tablets should be taken while sitting or standing, with a full glass of water.

Dosage for rheumatoid arthritis, psoriasis, and severe forms of psoriatic arthritis
Tablets should be taken once a week, always on the same day of the week. The usual dose ranges from 7.5 to 15 mg once weekly.

Dosage for maintenance treatment in acute lymphoblastic leukaemia
Your doctor will calculate the required dose based on body surface area. The appropriate dose will be determined by your doctor. Further information can be obtained from your doctor.

Special patient populations
Elderly patients and patients with impaired liver or kidney function usually receive a reduced dose, as determined by the doctor. See also section 2: "When not to use Trexan Neo".

Use in children and adolescents
In children and adolescents undergoing maintenance therapy for acute lymphoblastic leukaemia, the doctor will determine the dose individually based on body surface area.

Safe handling of Trexan Neo tablets
Appropriate procedures for safe handling of cytotoxic agents must be observed. Anyone handling methotrexate should wash their hands before and after administering the dose. Disposable gloves should be worn when handling methotrexate tablets. Pregnant women, women planning pregnancy, or breastfeeding women should avoid contact with methotrexate tablets if possible.

Contact with skin and mucous membranes must be strictly avoided. In case of skin or mucous membrane exposure to methotrexate, the affected area should be immediately and thoroughly washed with soap and water.

Parents, caregivers, and patients should be advised to store methotrexate out of reach of children, preferably in a locked cabinet.

Accidental ingestion by a child may result in death.

Taking more Trexan Neo than recommended
If a patient (or another person) has taken more than the recommended dose, contact a doctor or the nearest hospital emergency department immediately.

Methotrexate overdose may lead to severe toxic reactions, including death. Symptoms of overdose may include: tendency to bruise or bleed, unusual weakness, mouth ulcers, nausea, vomiting, black or bloody stools, coughing up blood or vomiting material resembling coffee grounds, and reduced urine output. See also section 4: "Possible side effects".

When going to the doctor or hospital emergency department, bring the medicine packaging with you. If a patient has taken an excessive dose of methotrexate, calcium folinate will be administered to reduce methotrexate-related adverse effects.

Missing a dose of Trexan Neo
If a dose is missed, it should be taken as soon as remembered, provided that it is within two days of the scheduled dose. However, if more than two days have passed since the scheduled dose, contact your doctor. Do not take a double dose to make up for a missed dose.

Before going on holiday or a trip, ensure you have an adequate supply of the medicine.

Stopping Trexan Neo
Unless otherwise instructed by the doctor, do not stop taking Trexan Neo. If discontinuation of Trexan Neo is necessary, the doctor will decide on the best way to stop the treatment.

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

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
The frequency and severity of methotrexate adverse reactions are generally related to the dose and frequency
of administration. Most adverse reactions are reversible if detected early.
You must immediately inform your doctor if any of the following symptoms occur in the patient,
as they may indicate a serious, potentially life-threatening adverse reaction which may require specific treatment:

dry cough and/or chest pain or difficulty breathing, shortness of breath, chest pain or fever;
haemoptysis or coughing up blood-stained sputum*;
unusual bleeding (including vomiting blood), bruising or nosebleeds;
nausea, vomiting, abdominal discomfort or severe diarrhoea;
oral ulceration;
black or tarry stools;
severe allergic reaction causing fever, skin rash, swelling and sometimes a drop in blood pressure;
exceptionally severe allergic reaction involving rash, often with skin blisters or oral, eye or genital ulcers (Stevens-Johnson syndrome or toxic epidermal necrolysis);
if any signs of infection occur, such as fever and significant worsening of general health, or fever with local signs of infection such as sore throat or throat inflammation, oral inflammation, or problems with urination, immediate medical consultation is required. Methotrexate may reduce the number of white blood cells and thereby weaken the immune response. Your doctor will order a blood test to check for a decrease in white blood cells (agranulocytosis);
yellowing of the skin (jaundice);
pain or difficulty passing urine;
thirst and/or frequent urination;
blurred or impaired vision.

Most of the adverse reactions listed below occur only in patients
receiving high-dose methotrexate for cancer treatment. In psoriasis or
rheumatoid arthritis treatment, they are less frequent and less severe.
Very common (may occur in more than 1 in 10 people):

loss of appetite, nausea, vomiting, indigestion, abdominal pain, inflammation of the mouth (oral and lip ulceration);
increased liver enzyme activity.

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

infections;
suppression of blood cell production with reduced numbers of white blood cells and/or red blood cells and/or platelets (leukopenia, anaemia, thrombocytopenia);
headache, dizziness, unusual fatigue, drowsiness;
lung inflammation, dry cough;
diarrhoea;
rash, redness, skin itching;
hair loss.

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

lymph node (or tissue) tumours;
diabetes;
depression, confusion;
seizures, vertigo;
gastrointestinal ulceration and bleeding;
nosebleeds;
excessive formation of fibrous connective tissue in organs (fibrosis);
decreased serum albumin concentration;
vasculitis, often with skin rash (allergic vasculitis), excessive skin pigmentation, slow wound healing, increased number of rheumatoid nodules;
sunburn-like reactions due to increased skin sensitivity to sunlight;
ulceration and inflammation of the urinary bladder, urinary disorders;
liver damage;
kidney function disorders;
joint or muscle pain, a type of bone disease causing reduced mineral content in bones (osteoporosis);
inflammation and ulceration of the vagina;
chills.

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

generalized inflammatory state leading to death (sepsis), shingles;
blood disorders characterized by very large red blood cells (megaloblastic anaemia);
mood swings;
reduced mobility (including paralysis affecting only the left or right side of the body);
severe visual disturbances;
fluid accumulation in the sac surrounding the heart. This may lead to cardiac tamponade, a life-threatening condition in which the heart cannot pump blood properly due to external pressure. Medical intervention may be required to remove the fluid and relieve pressure;
low blood pressure, presence of blood clots;
respiratory arrest or severe weakening of respiratory muscles, shortness of breath, retropharyngeal inflammation, asthma;
pancreatitis, gingivitis;
liver inflammation (acute hepatitis);
skin reactions (acne, skin discoloration, urticaria, erythema multiforme, burning sensation in psoriatic lesions, skin ulceration, nail plate separation, dark spots on nails);
stress fractures;
reduced or absent urine production, abnormal blood electrolyte levels;
menstrual disorders, impotence.

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

immunodeficiency (hypogammaglobulinaemia), increased susceptibility to infection;
lymphoproliferative disorders (overproduction of white blood cells);
insomnia;
brain oedema, speech disorders (dysarthria), irritability, drowsiness and fatigue (lethargy), transient cognitive impairment ("brain fog"), unusual sensations in the head, muscle weakness, tingling and numbness, reduced sensitivity to stimuli, altered taste perception (metallic taste);
redness and irritation of the thin membrane covering the eye (conjunctivitis), visual disturbances, retinal damage;
vasculitis, vomiting blood;
reactivation of chronic hepatitis, liver failure;
colonic dilation associated with inflammation/infection;
infection around the nail, deep hair follicle infections (furuncles), bruising, acne;
presence of protein or blood in urine, painful urination, cystitis;
low sperm count, gynaecomastia in men, vaginal bleeding, loss of libido;
fever.

The following adverse reactions have also been reported, but their frequency is unknown:
Sepsis leading to death, abnormally low blood cell counts, pulmonary haemorrhage*,
jaw bone damage (due to overproduction of white blood cells), brain disease, pathological
changes in brain white matter (leukoencephalopathy), alveolitis, physical weakness, increased
risk of toxic reactions during radiotherapy, redness and peeling of the skin, oedema.
Peeling, red psoriatic lesions may worsen during simultaneous exposure to ultraviolet light, such as sunlight, and methotrexate. Skin disorders caused by radiation (radiation dermatitis) or sunburn may recur during methotrexate treatment.
*(reported during use of methotrexate in patients with underlying rheumatological disease)
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse reactions 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.: 22 49 21 301,
fax: 22 49 21 309,
website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the responsible entity.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Trexan Neo

The medicine should be stored in a place inaccessible and out of sight of children, preferably in a locked cabinet. Accidental ingestion by a child may result in death.
Do not use this medicine after the expiry date stated on the blister pack or outer carton. The expiry date refers to the last day of the specified month.
There are no special requirements regarding storage temperature. The blisters should be stored in the outer packaging to protect from light.
Appropriate procedures for safe handling of cytotoxic agents must be observed. Anyone handling methotrexate should wash their hands before and after administering the dose. Disposable gloves should be worn when handling methotrexate tablets. Pregnant women, women planning to become pregnant, and breastfeeding women should not handle methotrexate.
Any unused medicine or waste material should be disposed of in accordance with local regulations for cytotoxic substances.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures 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 break line and marked with "ORN 57" on one side, 6 mm in diameter. The break line is intended only to facilitate breaking the tablet for easier swallowing and does not ensure equal dose division.
Trexan Neo 10 mg tablets: yellow, capsule-shaped, uncoated, convex tablets marked with "ORN 59" on one side and a break line on the other side, 14.0 mm long and 6.0 mm wide. The tablet can be divided into equal doses.

Pack sizes:
PVC/Aluminium 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 Authorisation 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 medicinal product is authorised in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
Denmark, Estonia, Finland, Lithuania: Trexan
France: Imenor
Spain: Metotrexato Semanal Orion Pharma
Ireland, Norway, Hungary, United Kingdom: Methotrexate Orion
Iceland, Sweden: Methotrexate Orion Pharma
Czech Republic, Poland, Slovakia: Trexan Neo

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
Orion Pharma Poland Sp. z o.o.
[email protected]