TREXOTHER 2.5 mg Tablet

Зміст інструкції

1. TREXOTHER 2,5 mg tablets
   1. What is TREXOTHER and what is it used for
   2. What you need to know before taking TREXOTHER
   3. How to use TREXOTHER
   4. Possible side effects
   5. How to store TREXOTHER
   6. Contents of the pack and other information

TREXOTHER 2,5 mg tablets

Equivalent medicine

“Take TREXOTHER once a week”
Read this leaflet carefully before you start to use 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 pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What is TREXOTHER and what is it used for

TREXOTHER contains the active substance methotrexate. Methotrexate is an antimetabolite and
immunosuppressant (a medicine that influences the reproduction of body cells and reduces the activity of the
immune system).
TREXOTHER is used for the treatment of:

• active rheumatoid arthritis in adults,
• severe psoriasis, particularly the plaque type, in patients who have tried other therapies but their condition has not improved,
• active psoriatic arthritis in adult patients,
• acute lymphoblastic leukemia (ALL) in adults, adolescents and children 3 years of age and older. Your doctor will be able to explain how TREXOTHER might help in your particular situation.

2. What you need to know before taking TREXOTHER

Do not take TREXOTHER if:

• you are allergic to methotrexate or any of the other ingredients of this medicine (listed in section 6);
• you have a severe kidney disease (or if your doctor considers your kidney disease to be severe)
• you have a severe liver disease
• you have disorders of the system with which the body produces blood cells, such as bone marrow hypoplasia, leukopenia, thrombocytopenia or significant anemia
• you consume a lot of alcohol
• your immune system is compromised
• you have a severe or pre-existing infection, such as tuberculosis or HIV
• you have gastrointestinal ulcers
• you have inflammation of the mouth mucosa or mouth ulcers
• you are breastfeeding and, also, 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

Further tests and recommended safety measures
Even if methotrexate is administered at a low dose, serious side effects can occur.
To identify them promptly, the doctor must perform checks and laboratory tests.

Before therapy
Before starting treatment, a blood sample must be taken to check that there is a
sufficient number of blood cells and tests must be performed to check liver function and to
discover if you have hepatitis. The amount of serum albumin (a blood protein), the status of hepatitis (a liver infection) and kidney function will also be checked. The doctor may also decide
to perform other liver tests, some of these may be liver images and others may
require a small tissue sample taken from the liver to examine it more closely. The doctor
will also make sure that you do not suffer from tuberculosis (infectious disease associated with small nodules in the affected tissue) by performing a chest X-ray or a pulmonary function test.

During therapy
The doctor may perform the following tests:

• Examination of the mouth and throat to check for changes in the mucosa such as inflammation or ulceration
• Blood tests/complete blood count with blood cell count and measurement of serum methotrexate levels
• Blood test to monitor liver function
• Imaging tests to monitor liver conditions
• Small tissue sample taken from the liver to examine it more closely
• Blood test to monitor kidney function
• Check of the respiratory system and, if necessary, pulmonary function tests. It is very important that you attend these scheduled tests. If the results of any of these tests are evident, the doctor will adjust the treatment accordingly.

Elderly patients
Elderly patients treated with methotrexate should be carefully monitored by a doctor in
order for possible side effects to be detected as soon as possible.
Age-related impairment of liver and kidney function, as well as low levels of vitamin folic acid in old age, require a relatively low dose of methotrexate.

Warnings and precautions
Important warnings about the dosage of TREXOTHER (methotrexate):
Take TREXOTHER only once a weekfor the treatment of rheumatic diseases or skin (RA, AIA and psoriasis or psoriatic arthritis).
An overdose of TREXOTHER (methotrexate) can be fatal.
If you have doubts or questions, consult your doctor or pharmacist before using this medicine.
Contact your doctor or pharmacist before taking TREXOTHER if:

• you have diabetes mellitus and are being treated with insulin
• you have inactive, prolonged infections (e.g., tuberculosis, hepatitis B or C, shingles [herpes zoster]) as they may reactivate
• you have/have had a liver or kidney disease
• you have problems with lung function
• you are severely overweight
• you have an 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 are in conditions that cause dehydration (vomiting, diarrhea, constipation, inflammation of the mouth mucosa) If you have had skin problems after radiation therapy (radiation dermatitis) or a sunburn, these conditions may recur during treatment with methotrexate (recall reaction).

In patients receiving low doses of methotrexate, enlarged lymph nodes (lymphomas) may occur, and,
in such cases, therapy should be discontinued.
Cases of acute pulmonary bleeding have been reported in patients with rheumatic disease and
treated with methotrexate. If you observe blood in your saliva or after coughing, contact
your doctor immediately.
Diarrhea may be a possible side effect of TREXOTHER and requires discontinuation of
therapy. If you suffer from diarrhea, consult your doctor.
In oncological patients treated with methotrexate, cases of brain diseases
(encephalopathy/leukoencephalopathy) have been reported and the possibility of their occurrence in methotrexate therapy for
non-oncological indications cannot be excluded.
Skin changes caused by psoriasis may worsen during treatment with methotrexate in
case of exposure to ultraviolet rays.
Methotrexate temporarily affects the production of sperm and eggs. Methotrexate can
cause miscarriages and serious birth defects. During the use of methotrexate and for at least six months
after the end of treatment, you must avoid pregnancy or having children. See also the
section “Pregnancy, breastfeeding and fertility”.
Control tests and recommended precautions
Even if methotrexate is used at low doses, serious side effects can occur. Your doctor will make
you undergo investigations and laboratory tests to ensure that all possible side effects are identified
quickly.
If you, your partner or anyone assisting you notices a new onset or worsening of neurological symptoms
including general muscle weakness, visual disturbances, changes in thinking, memory and
orientation leading to confusion and personality changes, contact your doctor immediately
because these may be symptoms of a very rare and serious brain infection called
progressive multifocal leukoencephalopathy (PML).

Children and adolescents:
Children and adolescents undergoing treatment with methotrexate should be subjected to particularly careful medical monitoring to be able to quickly detect important adverse effects.
This medicine is not recommended for children under 3 years of age because there is not enough data available
on use in this age group.

Other medicines and TREXOTHER
Tell your doctor or pharmacist if you are taking, have recently taken or may take any
other medicines, including over-the-counter medicines, including those that do not require
prescription and herbal medicines.
Remember to inform your doctor about the treatment with TREXOTHER if you are prescribed another
medicine during treatment.
It is particularly important that you tell your doctor if you are taking:

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

TREXOTHER with food, drinks and alcohol
This medicine can be taken with or without food. When you have taken your dose, drink water and
swallow to make sure you have taken the entire dose and that no methotrexate has remained in your mouth.
During treatment with TREXOTHER, you should not drink alcohol and should avoid drinking too much coffee, caffeinated beverages
and black tea. Make sure you drink plenty of fluids during treatment with TREXOTHER to prevent
dehydration (reduction of fluids in the body), which can increase the side effects of
methotrexate.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect or are planning a pregnancy, or if you are breastfeeding with
milk, ask your doctor for advice before taking this medicine.
Pregnancy

Do notuse TREXOTHER during pregnancy unless your doctor has prescribed it as
oncological treatment. Methotrexate can cause birth defects, be harmful to the fetus or
cause abortion. It is associated with malformations of the skull, face, heart and blood vessels, brain and limbs. For
these reasons, it is very important that patients who are expecting a child or who desire a pregnancy
are not treated with methotrexate, except in the case of oncological treatment.
For non-oncological indications, in women of childbearing age, the possibility of a
pregnancy must be excluded, for example, with pregnancy tests before the start of treatment.
Do not use TREXOTHER if you are trying to become pregnant. During treatment with methotrexate and
for at least 6 months after the end of treatment, you must avoid pregnancy, therefore, making sure to use
a reliable contraceptive method throughout the entire period (see also the section “Warnings and
precautions”).
If you become pregnant during treatment, or suspect a pregnancy, consult your doctor as soon as
possible. If you become pregnant during treatment, you should be offered advice on the risk
of harmful effects to the baby due to treatment.
If you wish to become pregnant, you should consult your doctor, who may refer you for advice from a
specialist before the scheduled start of treatment.
Breastfeeding

Male fertility
Available evidence does not indicate an increased risk of malformations or miscarriages if the father
takes methotrexate at a dose of less than 30 mg (15 ml)/week. However, a risk cannot be
completely excluded and there is no information regarding higher doses of methotrexate. Methotrexate
can have a genotoxic effect. That is, this medicine can cause genetic mutations. Methotrexate
can affect the production of sperm and eggs with the possibility of causing birth defects.
While using methotrexate and for at least 6 months after the end of treatment, you must avoid having a child or donating sperm.
Because treatment with methotrexate at the higher doses commonly used for
cancer treatment can cause infertility and genetic mutations, it is useful to get advice on
sperm preservation before starting treatment with methotrexate at doses greater than
30 mg (15 ml)/week (see also the section “Warnings and precautions”).
Ask your doctor or pharmacist before taking any medicine.

Driving and using machines

Warning: This medicine may affect your ability to react and your ability to
drive.
During treatment with TREXOTHER, side effects on the central nervous system may occur,
such as fatigue and dizziness. In some cases, the ability to drive vehicles and/or use machinery
may be impaired. If you feel tired or dizzy, do not drive or use machinery.

TREXOTHER contains lactose
TREXOTHER contains lactose. If your doctor has told you that you have an intolerance to some sugars, contact
him before taking this medicine.

!

3. How to use TREXOTHER

TREXOTHER must be prescribed exclusively by doctors who are well acquainted with the different properties and the
mechanism of action of the medicine.
Take this medicine following exactly the instructions of your doctor or pharmacist. If you have
doubts, consult your doctor or pharmacist.
Incorrect administration of TREXOTHER can cause serious side effects, which can
become fatal.
The overall duration of treatment must be decided by the doctor. Treatment of rheumatoid arthritis,
severe juvenile idiopathic arthritis, severe psoriasis and severe psoriatic arthritis with
TREXOTHER is a long-term treatment.
Recommended dose
The doctor will decide the dose of TREXOTHER to prescribe you based on the type and severity of the condition for
which you are being treated and your overall health conditions. Strictly adhere to the dose and follow
exactly the doctor's instructions on when to take the medicine.

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

Dose in adults withRheumatoid 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.
The doctor may increase the dose if the dose used is not effective but is well tolerated.
The doctor may adjust the dose to adapt it to the patient's needs based on their response to treatment
and
adverse effects.

Doses in acute lymphoblastic leukemia
The doctor will tell you which dose you should take for your condition and when you should take the dose. Strictly adhere
to this dose. To be taken orally, once a week.

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

Elderly
Due to reduced liver and kidney 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. When
handling methotrexate tablets, disposable gloves must be used. Pregnant women
should avoid handling methotrexate tablets, if possible.

If you take more TREXOTHER than you should
Follow the dose recommendations provided by your doctor. Do not change the dose without consulting
your doctor. If you think you have used too much TREXOTHER or that someone else has, notify
your doctor immediately or contact the emergency room of the nearest hospital. The doctor will decide if
treatment is necessary.
An overdose of methotrexate can cause serious toxic reactions. Symptoms of an overdose
may include bleeding, unusual weakness, oral ulcers, nausea, vomiting, black or bloody stools,
coughing up blood or vomiting coffee-ground-like material, and decreased urine output.
See also section 4 "Possible side effects".
Bring the package of the medicine with you and show it to the doctor or in the hospital.
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 a missed dose but continue with the prescribed dose.
Ask your doctor for advice.

If you stop taking TREXOTHER
Do not stop or discontinue treatment with TREXOTHER before talking to your doctor. If you think
you have a serious side effect, contact your doctor immediately.
If you have any doubts about the use of this medicine, ask 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 immediatelyif you notice shortness of breath, difficulty breathing, swelling of the eyelids, face or lips, a skin rash or itching (especially all over the body).
Contact your doctor immediately if you notice one or more of the following side effects:

• breathing problems (symptoms include a general feeling of unwellness, dry, irritating cough, shortness of breath, breathlessness at rest, chest pain or fever)
• blood in saliva or after coughing*
• severe skin peeling or blistering
• bleeding (including vomiting blood), unusual bruising or nosebleeds
• nausea, vomiting, abdominal pain or discomfort, or severe diarrhea
• mouth ulcers
• black or tarry stools
• blood in urine or stools
• red spots on the skin
• fever, sore throat, flu-like symptoms
• yellowing of the skin (jaundice) or dark urine
• pain or difficulty urinating
• thirst and/or frequent urination
• seizures
• loss of consciousness
• blurred or decreased 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 pain, 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
• decreased formation of blood cells with a reduction in the number of white blood cells and/or red blood cells and/or platelets (leukopenia, anemia, thrombocytopenia)
• headache, fatigue, dizziness
• lung inflammation (pneumonia) with dry cough, shortness of breath and fever
• diarrhea
• skin rashes, skin redness, itching.

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

• lymphoma (lump in the neck, groin or underarms with resulting back pain, weight loss or night sweats)
• severe allergic reactions
• diabetes
• depression
• dizziness, confusion, seizures
• lung damage
• ulcers and bleeding of the digestive tract
• liver disorders, decreased blood proteins
• hives, skin sensitivity to bright light, browning of the skin, hair loss, increased number of rheumatic nodules, shingles, painful psoriasis, delayed wound healing
• joint or muscle pain, osteoporosis (decreased bone mass)
• kidney disease, inflammation and ulcers of the bladder (with possible blood in the urine), painful urination
• inflammation and ulcers of the vagina.

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

• a blood disease characterized by the appearance of very large red blood cells (megaloblastic anemia)
• mood changes
• weakness in movements, even limited to the left or right side of the body
• severe vision disorders
• inflammation of the membrane surrounding the heart, fluid formation in the membrane surrounding the heart
• low blood pressure, formation of blood clots
• tonsillitis, cessation of breathing, asthma
• inflammation of the pancreas, inflammation of the digestive tract, blood in the stool, inflamed gums, digestive disorders
• acute hepatitis (liver inflammation)
• change in the color of the nails, acne, red or purplish spots due to bleeding of blood vessels
• worsening of psoriasis during treatment with ultraviolet radiation therapy
• skin lesions similar to sunburns or radiotherapy dermatitis
• bone fractures
• kidney failure, reduced amount or absence of urine, abnormal electrolyte levels in the blood
• problems related to sperm formation, menstrual disorders.

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

• general (systemic) viral, fungal or bacterial infections
• severe suppression of the bone marrow (anemia), swelling of the glands
• lymphoproliferative disorders (excessive growth of white blood cells)
• insomnia
• pain, muscle weakness, changes in taste (metallic taste), inflammation of the lining of the brain with paralysis or vomiting, sensation of numbness or tingling/decreased sensitivity to stimulation compared to normal
• impairment of the movement of the muscles used for speech articulation, difficulty speaking, speech disorders, drowsiness, fatigue, confusion, feelings of dizziness, accumulation of fluid (cerebral edema), 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, detachment of the nail from the nail bed, boils, dilation of small blood vessels, damage to small blood vessels in the skin, allergic inflammation of blood vessels
• proteins in the urine
• loss of sexual desire, problems with erection, vaginal discharge, infertility, increased breast size in men (gynecomastia)
• fever.

Not known(frequency cannot be estimated based on available data)

• pathological mutation of the white matter of the brain (leukoencephalopathy)
• hemorrhages
• pulmonary bleeding*
• redness and peeling of the skin
• damage to the bone of the mandible/jaw (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 and the resistance to infections may
decrease. If you should have an infection with symptoms such as fever and a severe worsening of your general
health or fever with symptoms of local infection such as an inflamed throat/pharynx/mouth or urinary problems,
consult your doctor immediately. A blood test will be performed to check for a possible reduction in the number of
white blood cells (agranulocytosis). It is important that you tell your doctor all the medicines you are using.
Methotrexate can cause serious side effects (which can sometimes be fatal). The doctor will perform
tests to check for any changes in the blood (e.g. reduction in the number of white blood cells, platelets, lymphoma) and
changes affecting the kidneys and liver.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please inform your
doctor or pharmacist. You can also report side effects directly through the Italian Medicines Agency Website: www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side
effects you can contribute to providing 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 date

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

Storage
This medicine does not require any particular temperature storage conditions.
Blister: store in the original package to protect the medicine from light.

Disposal
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to eliminate the
medicines that you no longer use. This will help protect the environment.

6. Contents of the pack and other information

The active ingredient is methotrexate.
Each tablet contains 2.5 milligrams (mg) of methotrexate.
The other ingredients are anhydrous calcium hydrogen phosphate, lactose monohydrate, sodium starch glycolate (type A),
microcrystalline cellulose, talc and magnesium stearate (E470b).

Description of the appearance of TREXOTHER and contents of the pack
Methotrexate 2.5 mg tablets are uncoated, circular, biconvex tablets, yellow in colour, with
a diameter of 4.50± 0.20 mm, smooth on both sides.
The tablets are packaged in blisters (containing a coloured amber PVC film and aluminium foil).
Packs:
PVC/AL blisters: 10, 12, 15, 20, 24, 25, 28, 30, 50 and 100 tablets.
Perforated PVC/AL blisters divisible for unit dose: 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,
Netherlands
Accord Healthcare Polska Sp.z o.o.,
ul. Lutomierska 50,95-200 Pabianice,
Poland