Package leaflet: Information for the user

TREXOTHER 2.5 mg tablets

Equivalent medicine
“Take TREXOTHER once a week”
Please read all of this leaflet carefully before you start taking this medicine, as it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor, pharmacist or nurse.
This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it could be harmful.
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What TREXOTHER is and what it is used for

TREXOTHER contains the active substance methotrexate. Methot游戏副本

2. What you need to know before taking TREXOTHER

Do not take TREXOTHER if:

you are allergic to methotrexate or to any of the other ingredients of this medicine (listed in section 6);
you have severe kidney disease (or if your doctor considers your kidney disease to be severe);
you have severe liver disease;
you have disorders of the blood-forming system, such as bone marrow hypoplasia, leucopenia, thrombocytopenia, or significant anaemia;
you consume large amounts of alcohol;
your immune system is compromised;
you have a severe or pre-existing infection, for example tuberculosis or HIV;
you have gastrointestinal ulcers;
you have inflammation of the mucous membrane in the mouth or mouth ulcers;
you are breastfeeding, and additionally, for non-oncological indications (not for cancer treatment), if you are pregnant (see section “Pregnancy, breastfeeding and fertility”);
you have recently received or are about to receive vaccination with live vaccines.

Follow-up examinations and recommended safety measures
Even when methotrexate is administered at low doses, serious adverse effects may occur.
To detect them early, your doctor must carry out regular check-ups and laboratory tests.
Before treatment
Before starting treatment, a blood sample should be taken to check that you have an adequate number of blood cells. Liver function tests will also be performed to detect possible hepatitis. Additionally, serum albumin levels (a blood protein), hepatitis status (a liver infection), and kidney function will be evaluated. Your doctor may also decide to perform further liver tests, some of which may include imaging of the liver, while others may require a small tissue sample taken from the liver for closer examination. Your doctor will also ensure you do not have tuberculosis (an infectious disease associated with small nodules in affected tissue) by performing a chest X-ray or pulmonary function test.
During treatment
Your doctor may perform the following tests:

Examination of the mouth and throat to check for mucosal changes such as inflammation or ulceration;
Blood tests / complete blood count with measurement of blood cell counts and serum methotrexate levels;
Blood test to monitor liver function;
Imaging tests to monitor liver condition;
Liver biopsy (small tissue sample taken from the liver for closer examination);
Blood test to monitor kidney function;
Respiratory system examination and, if necessary, pulmonary function tests.
It is very important that you attend these scheduled examinations. If any of these test results are abnormal, your doctor will adjust your treatment accordingly.

Elderly patients
Elderly patients receiving methotrexate must be closely monitored by a doctor so that possible side effects can be detected as early as possible.
Age-related impairment of liver and kidney function, as well as low body reserves of vitamin folic acid in older age, require a relatively low dose of methotrexate.

Warnings and precautions
Important warnings regarding the dosage of TREXOTHER (methotrexate):
Take TREXOTHER only once a week for the treatment of rheumatic diseases or skin conditions (RA, AIG, psoriasis or psoriatic arthritis).
An overdose of TREXOTHER (methotrexate) can be fatal.
Please read section 3 of this leaflet carefully.
If you have any doubts or questions, consult your doctor or pharmacist before using this medicine.
Talk to your doctor or pharmacist before taking TREXOTHER if:

you have diabetes mellitus and are being treated with insulin;
you have inactive, long-standing infections (e.g., tuberculosis, hepatitis B or C, shingles [herpes zoster]), as they may reactivate;
you have/have had liver or kidney disease;
you have problems with lung function;
you are severely overweight;
you have abnormal accumulation of fluid in the abdomen (ascites) or in the cavity between the lungs and the chest wall (pleural effusion);
you are dehydrated or in conditions that cause dehydration (vomiting, diarrhoea, constipation, mouth mucositis).
If you have had skin problems after radiation therapy (radiation dermatitis) or sunburn, these conditions may reappear during treatment with methotrexate (recall reaction).

Enlarged lymph nodes (lymphomas) may occur in patients receiving low doses of methotrexate, and in such cases, treatment should be discontinued.
Cases of acute pulmonary haemorrhage have been reported in patients with rheumatological disease treated with methotrexate. If you notice blood in your saliva or after coughing, contact your doctor immediately.
Diarrhoea may be a possible adverse effect of TREXOTHER and requires interruption of therapy. If you experience diarrhoea, consult your doctor.
Cases of brain disorders (encephalopathy/leukoencephalopathy) have been reported in oncology patients treated with methotrexate, and their occurrence cannot be ruled out in non-oncological methotrexate therapy.
Skin changes caused by psoriasis may worsen during methotrexate treatment if exposed to ultraviolet light.
Methotrexate temporarily affects sperm and egg production. Methotrexate may cause miscarriage and severe birth defects. During treatment with methotrexate and for at least six months after treatment ends, you must avoid pregnancy or fathering a child. See also section “Pregnancy, breastfeeding and fertility”.
Recommended monitoring and precautions
Even when methotrexate is used at low doses, serious adverse effects may occur. Your doctor will arrange investigations and laboratory tests to ensure that all possible adverse effects are identified quickly.
If you, your partner, or caregiver notice new onset or worsening of neurological symptoms, including general muscle weakness, vision disturbances, changes in thinking, memory, and orientation leading to confusion, or personality changes, contact your doctor immediately, as these may be symptoms of a very rare and serious brain infection called progressive multifocal leukoencephalopathy (PML).

Children and adolescents:
Children and adolescents receiving methotrexate must be under particularly careful medical supervision to rapidly detect significant adverse effects.
This medicine is not recommended for children under 3 years of age, as sufficient data on use in this age group are not available.

Other medicines and TREXOTHER
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including over-the-counter medicines, herbal remedies, and non-prescription drugs.
Remember to inform your doctor about your treatment with TREXOTHER if another medicine is prescribed during your therapy.
It is particularly important that you inform your doctor if you are taking:

other treatments for rheumatoid arthritis or psoriasis such as leflunomide, azathioprine (a medicine also used to prevent organ transplant rejection), sulfasalazine (a medicine also used for ulcerative colitis);
cyclosporine (to suppress the immune system);
non-steroidal anti-inflammatory drugs or salicylates (pain-relieving or anti-inflammatory medicines such as acetylsalicylic acid, diclofenac, ibuprofen, or pyrazoles);
live vaccines;
diuretics (medicines that reduce fluid retention);
medicines to lower blood sugar levels such as metformin;
retinoids (for the treatment of psoriasis and other skin diseases);
anticonvulsant medicines (to prevent seizures);
barbiturates (sleeping medicines);
sedatives;
oral contraceptives;
probenecid (for gout);
antibiotics;
pyrimethamine (for prevention and treatment of malaria);
vitamin preparations containing folic acid;
proton pump inhibitors (for treatment of heartburn, ulcers, and other stomach disorders);
theophylline (for respiratory problems);
mercaptopurine (for treatment of certain types of leukaemia);
cancer treatments (such as doxorubicin and procarbazine during high-dose methotrexate therapy).

TREXOTHER with food, drinks and alcohol
This medicine may be taken with or without food. After taking your dose, drink water and swallow thoroughly to ensure the full dose has been taken and that no methotrexate remains in the mouth.
During treatment with TREXOTHER, you must not drink alcohol and should avoid excessive consumption of coffee, caffeinated beverages, and black tea. Ensure you drink plenty of fluids during treatment with TREXOTHER to prevent dehydration (reduction of body fluids), which may increase methotrexate’s adverse effects.

Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor before taking this medicine.
Pregnancy
Do not use TREXOTHER during pregnancy unless prescribed by your doctor as oncological treatment. Methotrexate may cause birth defects, harm the foetus, or cause miscarriage. It is associated with malformations of the skull, face, heart and blood vessels, brain, and limbs. For these reasons, it is very important that women who are pregnant or planning a pregnancy are not treated with methotrexate, except in oncological treatment.
For non-oncological indications, pregnancy must be ruled out in women of childbearing potential, for example by performing pregnancy tests before starting treatment.
Do not use TREXOTHER if you are trying to become pregnant. During treatment with methotrexate and for at least 6 months after treatment ends, you must avoid pregnancy by using a reliable contraceptive method throughout this period (see also section “Warnings and precautions”).
If you become pregnant during treatment or suspect pregnancy, consult your doctor as soon as possible. If pregnancy occurs during treatment, you should be offered counselling regarding the risk of harmful effects on the child due to treatment.
If you plan a pregnancy, you should consult your doctor, who may refer you for specialist counselling before the planned start of treatment.
Breastfeeding
Do not breastfeed during treatment, as methotrexate passes into breast milk. If your doctor considers methotrexate treatment absolutely necessary during breastfeeding, breastfeeding must be discontinued.
Fertility
Male fertility
Available evidence does not indicate an increased risk of birth defects or miscarriage if the father takes methotrexate at a dose below 30 mg (15 ml)/week. However, a risk cannot be completely excluded, and there is no information regarding higher doses of methotrexate. Methotrexate may have genotoxic effects; that is, this medicine may cause genetic mutations. Methotrexate may affect sperm production and potentially lead to birth defects.
While taking methotrexate and for at least 6 months after treatment ends, you must avoid fathering a child or donating sperm. As treatment with higher doses of methotrexate commonly used in cancer treatment may cause infertility and genetic mutations, it is advisable to seek advice on the possibility of sperm preservation before starting methotrexate treatment at doses exceeding 30 mg (15 ml)/week (see also section “Warnings and precautions”).
Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines
! Caution: This medicine may affect your reaction ability and capacity to drive.
During treatment with TREXOTHER, adverse effects on the central nervous system may occur, such as fatigue and dizziness. In some cases, the ability to drive vehicles and/or operate machinery may be impaired. If you feel tired or dizzy, do not drive or operate machinery.

TREXOTHER contains lactose
TREXOTHER contains lactose. If your doctor has informed you that you have an intolerance to certain sugars, contact them before taking this medicine.

3. How to use TREXOTHER

TREXOTHER must be prescribed only by physicians who are well familiar with the various properties and
mechanism of action of the medicine.
Always take this medicine exactly as instructed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
Incorrect administration of TREXOTHER may cause serious adverse effects, which may
become fatal.
The total duration of treatment must be determined by your doctor. Treatment of rheumatoid arthritis,
severe juvenile idiopathic arthritis, severe psoriasis, and severe psoriatic arthritis with
TREXOTHER is a long-term treatment.

Recommended dose
Your doctor will decide the dose of TREXOTHER to prescribe based on the type and severity of the condition being treated and your overall health status. Strictly adhere to the prescribed dose and follow exactly your doctor's instructions regarding when to take the medicine.

Dose in rheumatic and skin diseases (RA, JIA, psoriasis or psoriatic arthritis)
Take TREXOTHER only once a week.
Decide together with your doctor which day of the week is most suitable for taking the medicine.

Dose in adults with Rheumatoid Arthritis:
The usual starting dose is 7.5 mg - 15 mg orally, once a week.

Dose for psoriasis and psoriatic arthritis:
The usual starting dose is 7.5 mg - 15 mg orally, once a week.
Your doctor may increase the dose if the current dose is not effective but well tolerated.
Your doctor may adjust the dose according to your individual needs based on your response to treatment
and
on any adverse effects.

Doses in acute lymphoblastic leukemia
Your doctor will inform you about the dose required for your condition and when to take it. Follow this dose exactly. To be taken orally, once a week.

Use in children and adolescents
Your doctor will calculate the required dose based on the child's body surface area (m²), and the dose is
expressed in mg/m².

Elderly patients
Due to reduced hepatic and renal function and lower folate reserves in elderly patients, it is advisable to choose a relatively low dosage.

Safe handling of TREXOTHER
Appropriate procedures for the safe handling of cytotoxic agents must be followed. Disposable gloves should be worn when handling methotrexate tablets. Pregnant women should avoid handling methotrexate tablets, if possible.

If you take more TREXOTHER than you should
Follow the dosing recommendations provided by your doctor. Do not change the dose without first consulting your doctor. If you think you or someone else has taken too much TREXOTHER, inform your doctor immediately or contact the emergency department of the nearest hospital. Your doctor will decide whether treatment is necessary.
An overdose of methotrexate may cause severe toxic reactions. Symptoms of overdose may include bleeding, unusual weakness, oral 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".
Bring the medicine packaging with you and show it to the doctor or hospital staff.
The specific antidote in case of overdose is calcium folinate.

If you forget to take TREXOTHER
Do not take a double dose to make up for the missed dose; continue with your prescribed dose. Ask your doctor for advice.

If you stop using TREXOTHER
Do not interrupt or discontinue treatment with TREXOTHER without first discussing it with your doctor. If you think you are experiencing a serious adverse effect, contact your doctor immediately.

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
Contact your doctor immediately if you notice shortness of breath, difficulty breathing, swelling of the eyelids, face or lips, a skin rash or itching (especially if widespread throughout the body).
Contact your doctor immediately if you notice one or more of the following side effects:

breathing problems (symptoms include general malaise, dry and irritating cough, shortness of breath, breathlessness at rest, chest pain or fever)
blood in saliva or when coughing*
severe peeling or blistering of the skin
bleeding (including vomiting blood), unusual bruising or nosebleeds
nausea, vomiting, abdominal pain or discomfort, or severe diarrhoea
mouth ulcers
black or tarry stools
blood in the urine or stools
small red spots on the skin
fever, sore throat, flu-like symptoms
yellowing of the skin (jaundice) or dark urine
pain or difficulty urinating
excessive thirst and/or frequent urination
seizures
loss of consciousness
blurred or reduced vision
severe fatigue. *Side effect reported in patients with rheumatological disease treated with methotrexate.

The following side effects have also been reported:
Very common (may affect more than 1 in 10 people):

loss of appetite, feeling unwell (nausea), vomiting, stomach ache, indigestion, inflammation and ulcers of the mouth and throat
blood tests showing increased liver enzyme levels.

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

infections
reduced production of blood cells, leading to decreased numbers of white blood cells and/or red blood cells and/or platelets (leucopenia, anaemia, thrombocytopenia)
headache, fatigue, mental confusion
lung inflammation (pneumonitis) with dry cough, shortness of breath and fever
diarrhoea
skin rashes, skin redness, itching.

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

lymphoma (lump in neck, groin or under the arms, with resulting back pain, weight loss or night sweats)
severe allergic reactions
diabetes
depression
dizziness, confusion, seizures
lung damage
ulcers and bleeding in the digestive tract
liver disorders, decreased blood protein levels
urticaria, skin sensitivity to strong light, brown skin discoloration, hair loss, increase in the number of rheumatoid nodules, shingles, painful psoriasis, delayed wound healing
joint or muscle pain, osteoporosis (reduced bone mass)
kidney disease, inflammation and ulcers of the bladder (possibly with blood in the urine), painful urination
inflammation and ulcers of the vagina.

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

a blood disorder characterised by the appearance of very large red blood cells (megaloblastic anaemia)
mood changes
weakness in movement, even limited to the left or right side of the body
severe vision disorders
inflammation of the membrane surrounding the heart (pericarditis), fluid accumulation in the membrane surrounding the heart
low blood pressure, blood clot formation
tonsillitis, breathing interruption, asthma
pancreatitis, inflammation of the digestive tract, blood in stools, inflamed gums, digestive disturbances
acute hepatitis (liver inflammation)
change in nail colour, acne, red or purple spots due to bleeding from blood vessels
worsening of psoriasis during treatment with ultraviolet light therapy
skin lesions resembling sunburn or radiation dermatitis
bone fractures
kidney failure, reduced urine output or absence of urine, abnormal blood electrolyte levels
problems related to sperm formation, menstrual disorders.

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

systemic viral, fungal or bacterial infections
severe bone marrow suppression (anaemia), swollen glands
lymphoproliferative disorders (excessive growth of white blood cells)
insomnia
pain, muscle weakness, taste changes (metallic taste), inflammation of the lining of the brain with paralysis or vomiting, numbness or tingling sensations/reduced sensitivity to stimulation compared to normal
impaired movement of muscles used for speech articulation, speech difficulties, language disorders, drowsiness, fatigue, confusion, dizziness, fluid accumulation in the brain (cerebral oedema), ringing in the ears
red eyes, damage to the retina of the eye
fluid accumulation in the lungs, lung infections
vomiting blood, severe complications in the digestive tract
liver failure
infections around the nails, nail detachment from the nail bed, boils, dilation of small blood vessels, damage to small blood vessels in the skin, allergic inflammation of blood vessels
protein in the urine
loss of sexual desire, erectile dysfunction, vaginal discharge, infertility, breast enlargement in men (gynaecomastia)
fever.

Not known (frequency cannot be estimated from the available data)

pathological changes in the brain's white matter (leukoencephalopathy)
haemorrhages
pulmonary haemorrhage*
redness and peeling of the skin
damage to the jawbone (secondary to excessive growth of white blood cells)
swelling. *Side effect reported in patients with rheumatological disease treated with methotrexate.

Methotrexate can cause a reduction in the number of white blood cells, which may decrease resistance to infections. If you develop an infection with symptoms such as fever and a significant worsening of your general health condition, or fever with symptoms of local infection such as inflamed throat/pharynx/mouth or urinary problems, contact your doctor immediately. A blood test will be performed to check for a possible reduction in white blood cells (agranulocytosis). It is important that you inform your doctor about all medicines you are taking.
Methotrexate can cause serious side effects (which may sometimes be fatal). Your doctor will carry out tests to monitor for possible changes in the blood (e.g. reduced white blood cell count, reduced platelets, lymphoma) and changes affecting the kidneys and liver.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the Italian Medicines Agency (Agenzia Italiana del Farmaco) website: www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store TREXOTHER

Keep this medicine out of the sight and reach of children.
Expiry

Do not use this medicine after the expiry date stated on the blister and carton after EXP. The expiry date refers to the last day of that month.

Storage
This medicine does not require any special storage temperature conditions.
Blister: store in the original packaging to protect the medicine from light.
Disposal
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

The active substance is methotrexate.
Each tablet contains 2.5 milligrams (mg) of methotrexate.
The other components are anhydrous calcium hydrogen phosphate, monohydrate lactose, sodium starch glycolate (type A),
microcrystalline cellulose, talc and magnesium stearate (E470b).
Description of the appearance of TREXOTHER and the contents of the pack
Metotrexate 2.5 mg tablets are biconvex, uncoated, circular, yellow tablets with a diameter of 4.50±0.20 mm, smooth on both sides.
The tablets are packaged in blisters (consisting of an amber-coloured PVC film and an aluminium foil).
Pack sizes:
PVC/AL blisters: 10, 12, 15, 20, 24, 25, 28, 30, 50 and 100 tablets.
Perforated single-dose PVC/AL blisters: 10x1, 12x1, 15x1, 20x1, 24x1, 25x1, 28x1, 30x1, 50x1
and 100x1 tablets.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Accord Healthcare S.L.U.
World Trade Center,
Moll de Barcelona,
s/n, Edifici Est 6ª planta,
08039 Barcelona,
Spain
Manufacturer
Accord Healthcare B.V.,
Winthontlaan 200,
3526 KV Utrecht,
The Netherlands
Accord Healthcare Polska Sp.z o.o.,
ul. Lutomierska 50, 95-200 Pabianice,
Poland

Trexother