Patient Information Leaflet: Information for the Patient

Methotrexate Wyeth 2.5 mg Tablets

Read this leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as 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, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

Metotrexato Wyeth belongs to a group of medications known as folate acid analog antimetabolites.

Metotrexate at high doses is indicated for the treatment of certain types of cancer, such as gestational trophoblastic neoplasia (choriocarcinoma), which is the development of a tumor directly associated with pregnancy.

Before starting to use this medication, you must consult your doctor about the risks and benefits of treatment with methotrexate. It is very important that you use methotrexate exactly as your doctor has instructed you.If you use methotrexate more frequently or in higher doses than indicated by your doctor, you may suffer from severe adverse reactions, including death.

Do not take Metotrexato Wyeth

• If you are allergic to methotrexate or to any of the other components of this medication (including those listed in section 6).
• If you have liver dysfunction (hepatic insufficiency).
• If you have severe kidney dysfunction (severe renal insufficiency).
• If you have liver damage due to excessive alcohol consumption (alcoholic hepatitis), if you have chronic liver damage (chronic hepatitis) or if you are an alcoholic.
• If you have altered blood levels of red blood cells, white blood cells, and platelets.
• If you have any immune system disease (immunodeficiency syndromes).
• Severe, acute, or chronic infections such as tuberculosis and HIV.
• If you have ulcers in the mouth, stomach, or intestines.
• If you are to be vaccinated.
• If you are breastfeeding (see section "Pregnancy, breastfeeding, and fertility").

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to take this medication.

Your doctor will inform you of the benefits and risks of treatment with methotrexate, as well as the symptoms that may indicate possible toxicity due to the medication.

Before starting treatment and while on treatment with methotrexate, your doctor may perform tests such as blood tests, kidney function tests, and liver function tests, hepatitis infection tests, or chest X-rays.

If you are in any of the following situations, consult your doctor before using Metotrexato Wyeth.

• If you develop signs or symptoms due to possible medication toxicity at the gastrointestinal and/or neuronal level, in the liver, kidneys, lungs, blood, or skin, go to your doctor.
• Follow the dose exactly as instructed by your doctor.
• If you are at risk of pregnancy and have a neoplastic disease, the benefit of treatment must be weighed against the risk to the fetus in each case.
• If you have folate deficiency, as this may increase the toxicity of methotrexate.
• If you experience vomiting, diarrhea, or inflammation of the mouth (stomatitis), inform your doctor, as you may become dehydrated. If this occurs, your doctor may interrupt your treatment until you have fully recovered. Also inform your doctor if you have a peptic ulcer or any type of colitis.
• If you have altered blood levels of white blood cells, red blood cells, and platelets. Methotrexate may decrease white blood cells in the blood. If this occurs, you must take a series of precautions, including avoiding contact with people with infections; consulting your doctor if you think you may have an infection due to fever or chills, cough, back pain, or difficulty urinating; consult your doctor before undergoing dental procedures. Additionally, methotrexate may decrease the number of platelets in the blood necessary for coagulation. Therefore, it is essential to consult your doctor if you have noticeable petechiae or bleeding from the gums or nose, red spots on the skin, blood in the urine or black stools, and to inform your dentist that you are on treatment with methotrexate.
• If you are taking nonsteroidal anti-inflammatory drugs (NSAIDs).
• If you have liver problems, as methotrexate may cause acute hepatitis and chronic liver disorders. Moderate liver alterations may require closer monitoring by your doctor but do not require suspension of treatment. Alcohol, obesity, advanced age, or the use of products containing arsenic may increase the risk of liver problems.
• If you have kidney problems, as methotrexate may cause renal damage.
• If you have any type of infection.
• If you are to be vaccinated, as this may cause a severe infection or reduce the response to the vaccine.
• If during or after treatment you experience symptoms of toxicity at the nervous system level, such as headache, back pain, neck stiffness, fever, confusion, irritability, drowsiness, coordination disorders, dementia, convulsions, transient blindness, abnormal reflexes, behavioral abnormalities, and localized movement and perception disorders.
• If during treatment you experience dry cough, fever, chest pain, and/or difficulty breathing, inform your doctor.
• If during treatment or days after you develop skin alterations, consult your doctor. Skin lesions in patients with psoriasis may worsen with exposure to sunlight. Previous skin lesions and sunburns may reappear with the use of methotrexate.Methotrexate may make the skin more sensitive to sunlight. Avoid intense sunlight and do not use tanning beds or ultraviolet lamps without medical advice. To protect your skin from intense sunlight, wear suitable clothing or use a high-protection sunscreen.
• A severe pulmonary hemorrhage has been reported in patients with underlying rheumatological disease. If you observe blood when coughing or expectorating, you must immediately contact your doctor.
• Methotrexate temporarily affects the production of sperm and eggs. Methotrexate may cause miscarriages and severe birth defects. If you are a woman, you must avoid pregnancy during treatment with methotrexate and for at least 6 months after the end of treatment. If you are a man, you must avoid fathering a child if you are being administered methotrexate at the time and for at least 3 months after completing your treatment. See also section "Pregnancy, breastfeeding, and fertility".
• If you, your partner, or caregiver notice the appearance or worsening of neurological symptoms, such as general muscle weakness, vision changes, changes in thought, memory, and orientation that cause confusion, and changes in personality, contact your doctor immediately, as these may be symptoms of a rare and severe brain infection called progressive multifocal leukoencephalopathy (PML).

Your doctor will regularly monitor your condition to check if the medication is having the expected effect.

Other medications and Metotrexato Wyeth

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.

It is especially important to inform your doctor if you are taking any of the following medications:

• Medications used to treat certain types of cancer, such as cisplatin, mercaptopurine, cytarabine, and L-asparaginase.
• Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin and other salicylates, and especially ketoprofen.
• Inhibitors of the proton pump (used to treat digestive tract ulcers).
• Leflunomide (medication for the treatment of arthritis).
• Metamizol (synonyms novaminsulfon and dipirona) (medication for intense pain and/or fever).
• Medications with high plasma protein binding (such as salicylates, phenylbutazone, phenytoin, sulfonamides, sulfonylureas, aminobenzoic acid, some antibiotics, and medications for abnormal cholesterol and lipid levels such as cholestyramine).
• Probenecid (medication used to reduce uric acid levels).
• Antibiotics (ciprofloxacin, penicillins, sulfonamides, tetracyclines, chloramphenicol, pyrimethamine, trimethoprim/sulfamethoxazole) and broad-spectrum antibiotics that are not absorbed in the digestive tract.
• Medications that cause liver toxicity (such as leflunomide, azathioprine, sulfasalazine, and retinoids).
• Theophylline (medication for the treatment of asthma).
• Vitamins or vitamin preparations containing folic acid or its derivatives.
• Nitrous oxide (anesthetic).
• Amiodarone (medication for the treatment of cardiac arrhythmias).
• Diuretics (such as triamterene).

Additionally, certain therapies may interact with methotrexate. This is the case of PUVA therapy (methoxalen and ultraviolet light) in patients with psoriasis or a disease called mycosis fungoides, as well as radiation therapy.

During treatment with methotrexate, you should exercise caution when receiving a blood transfusion.

Use of Metotrexato Wyeth with food, drinks, and alcohol

While taking methotrexate, you should avoid consuming alcohol, as this may increase the likelihood of adverse effects, especially in the liver.

You should avoid excessive consumption of coffee, caffeinated soft drinks, and black tea.Your doctor may instruct you to drink more fluids than usual. This will help you eliminate the medication and prevent kidney problems.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, if you think you may be pregnant, or if you plan to become pregnant, consult your doctor or pharmacist before using this medication.

Consult your doctor or pharmacist before using any medication.

• Pregnancy:

Do not use this medication during pregnancy except if your doctor has prescribed it as an oncological treatment (cancer treatment). Methotrexate may cause birth defects, damage the fetus, or cause miscarriages. It is associated with skull, face, heart, and blood vessel malformations, brain, and limb malformations. Therefore, it is very important that it is not administered to pregnant women or those planning to become pregnant, except if it is used as an oncological treatment.

In non-oncological indications (not related to cancer) in fertile women, any possibility of pregnancy should be excluded, for example, by a pregnancy test, before starting treatment.

Do not use this medication if you are trying to become pregnant. You must avoid becoming pregnant while taking methotrexate and for at least 6 months after completing treatment. To do this, you must ensure that you are using reliable contraceptive methods during that time (see also section "Warnings and precautions").

If you become pregnant during treatment or suspect you may be pregnant, consult your doctor as soon as possible. If you become pregnant during treatment, you must receive information about the risk of adverse effects on the child during treatment.

If you want to become pregnant, consult your doctor, who may refer you to a specialist to inform you before starting treatment.

• Breastfeeding:

Do not breastfeed your child during treatment, as methotrexate passes into breast milk. If your doctor considers it absolutely necessary to continue treatment with methotrexate during the breastfeeding period, you must stop breastfeeding.

• Male fertility:

The available data do not indicate a higher risk of malformations or miscarriages if the father takes a methotrexate dose of less than 30 mg/week. However, this risk cannot be completely ruled out, and there is no information on higher doses of methotrexate. Methotrexate may be genotoxic, meaning it may cause genetic mutations. Methotrexate may affect sperm production, which is associated with the possibility of birth defects.

Therefore, you must avoid fathering a child or donating semen during treatment with methotrexate and for at least 3 months after completing treatment. Since treatment with methotrexate at higher doses commonly used in cancer treatment may cause infertility and genetic mutations, it is recommended that men treated with methotrexate doses above 30 mg/week consider semen conservation before starting treatment (see also section "Warnings and precautions").

Driving and operating machinery

It is not recommended to drive vehicles or operate machinery after taking Metotrexato Wyeth, as some possible adverse effects, such as dizziness and fatigue, may affect your ability to drive vehicles and operate machinery.

Metotrexato Wyeth contains lactose

This medication contains lactose. If your doctor has told you that you have intolerance to certain sugars, consult with them before taking this medication.

Follow the exact administration instructions for this medication as indicated by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

IT IS VERY IMPORTANT THAT YOU USE METHOTREXATE EXACTLY AS DIRECTED BY YOUR DOCTOR. IF YOU USE METHOTREXATE MORE FREQUENTLY OR IN HIGHER DOSES THAN THOSE INDICATED BY YOUR DOCTOR, YOU MAY EXPERIENCE SEVERE ADVERSE REACTIONS, INCLUDING DEATH.

Recommended dose:

The usual dose is 15-30 mg (6-12 tablets) per day administered orally for 5 days and repeated every 12-14 days as needed.

Methotrexate Wyeth is presented in a package containing 2 blisters, each with 12 tablets. Each tablet contains a dose of 2.5 mg of methotrexate.

Use in patients with kidney and liver problems

Consult your doctor as it may be necessary to adjust the dose and in some cases the medication may be contraindicated.

Children and adolescents

Children and adolescents treated with methotrexate should be under close medical supervision to identify any possible adverse effects as soon as possible.

The use of methotrexate is not recommended in children under 3 years of age, as there are not enough efficacy and safety data available for this patient group.

If you take more Methotrexate Wyeth than you should

If you have taken more Methotrexate Wyeth than you should, consult your doctor or pharmacist immediately.

For accidental ingestion or overdose, consult the Toxicological Information Service, phone 91 562 04 20, indicating the medication and the amount ingested.

A methotrexate overdose can cause severe toxic reactions. Symptoms of overdose may include rapid formation of hematomas or hemorrhages, unusual weakness, mouth sores, nausea, vomiting, black or bloody stools, coughing up blood or vomiting with coffee ground appearance, and decreased urination (urine retention). See also section 4.

If you receive more methotrexate than you should, it is recommended to administer folinic acid as soon as possible, as well as hydrate and alkalize the urine.

If you forget to takeMethotrexate Wyeth

Do not take a double dose to make up for the missed dose. Take the next dose when it is due.

If you interrupt treatment withMethotrexate Wyeth

Do not stop treatment unless your doctor tells you to. If you have any other questions about the use of this medication, ask your doctor, pharmacist, or nurse.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

If you consider that any of the side effects you are experiencing are severe or if you notice any side effect not mentioned in this leaflet, inform your doctor or pharmacist.

Inform your doctor immediatelyif you experience ringing in the ears, difficulty breathing, swelling of the eyelids, face, or lips, skin rash, or itching (especially if it affects your entire body).

Inform your doctor immediately if you notice any of the following side effects:

• breathing problems (symptoms may include general feeling of discomfort, dry, irritating cough, shortness of breath, difficulty breathing, chest pain, or fever)
• blood when coughing or spitting*
• severe peeling or blisters on the skin
• bleeding (including blood in vomit) or unusual bruising or nasal bleeding
• nausea, vomiting, abdominal discomfort, or intense diarrhea
• mouth sores
• black or tar-like stools
• blood in urine or stools
• red spots on the skin
• fever, sore throat, flu-like symptoms
• yellow discoloration of the skin (jaundice) or dark-colored urine
• pain or difficulty urinating
• excessive thirst and/or frequent urination
• seizures
• loss of consciousness
• restricted or blurred vision
• intense fatigue

*reported with methotrexate when used in patients with underlying rheumatological disease.

The following side effects have also been reported:

Very common (may affect more than 1 in 10 people):

• loss of appetite, nausea (desire to vomit), vomiting, abdominal pain, digestive problems, inflammation, and ulcers in the mouth and throat
• blood tests indicating an increase in liver enzymes.

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

• infections
• reduced formation of red blood cells, white blood cells, or platelets (leucopenia, anemia, thrombocytopenia)
• headache, fatigue, dizziness
• inflammation of the lungs (pneumonia) with dry cough, difficulty breathing, and fever
• diarrhea
• skin rash, redness of the skin, and itching.

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

• lymphoma (swelling in the neck, groin, or armpits, accompanied by 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 disease, decreased blood proteins
• hives, reactions similar to sunburn due to increased skin sensitivity to sunlight
• brown discoloration of the skin, hair loss, increased number of rheumatoid nodules, herpes zoster, painful psoriasis, slow wound healing
• joint or muscle pain, osteoporosis (bone softening)
• kidney disease, inflammation, or ulcers of the bladder (possibly with blood in the urine), painful urination
• inflammation and ulcers in the vagina.

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

• blood disorder characterized by the presence of very large red blood cells (megaloblastic anemia)
• mood changes
• weakness in movement, sometimes limited to the right or left side of the body
• significant visual disturbances
• inflammation of the sac surrounding the heart, accumulation of fluid in the sac surrounding the heart
• low blood pressure, blood clots
• tonsillitis, respiratory arrest, asthma
• inflammation of the pancreas, inflammation of the digestive tract, blood in stools, inflammation of the gums, digestive problems
• acute hepatitis (inflammation of the liver)
• change in nail color, acne, red or purple spots due to bleeding in blood vessels
• psoriasis worsening during radiation therapy
• skin lesions similar to sunburn or radiation-induced dermatitis
• bone fractures
• renal insufficiency, decreased or absent urine production, abnormal levels of electrolytes in the blood
• defective sperm formation, menstrual disorders.

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

• systemic viral, fungal, or bacterial infections
• severe bone marrow disorder (anemia), inflammation of the glands
• lymphoproliferative disorders (excessive growth of white blood cells)
• insomnia
• headache, muscle weakness, changes in taste (metallic taste), inflammation of the membrane covering the brain with paralysis or vomiting, numbness or tingling/sensitivity to minor stimuli
• speech movement disorder, difficulty speaking, language impairment, feeling of sleep or fatigue, feeling of confusion, abnormal sensations in the head, inflammation of the brain, ringing in the ears
• redness of the eyes, damage to the retina of the eye
• fluid accumulation in the lungs, pulmonary infections
• vomiting with blood, severe complications in the digestive tract
• liver insufficiency
• finger or toenail infections, nail separation from the nail bed, furuncles, dilation of small blood vessels, damage to blood vessels in the skin, allergic inflammation of blood vessels
• protein in the urine
• decreased libido, erectile dysfunction, vaginal discharge, infertility, breast enlargement in men (gynecomastia)
• fever.

Frequency unknown (cannot be estimated from available data):

• pathological changes in the white matter of the brain (leucoencephalopathy)
• hemorrhages
• lung hemorrhage*
• redness and peeling of the skin
• jawbone fractures (secondary to excessive growth of white blood cells)
• swelling

*reported with methotrexate when used in patients with underlying rheumatological disease.

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect not listed in this leaflet. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not store at a temperature above 25°C.

Do not use this medication after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Medications should not be disposed of through drains or in the trash.Deposit the packaging and medications you no longer need atthe SIGREpoint at the pharmacy. In case of doubtask your pharmacist how to dispose of the packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition of Metotrexato Wyeth

• The active ingredient is methotrexate.
• The other components are: cornstarch, lactose monohydrate, magnesium stearate, and sodium hydroxide.

Appearance of the product and content of the container

Methotrexate Wyeth 2.5 mg tablets are presented in PVC/aluminum blisters containing 24 tablets for oral administration.

Holder of the marketing authorization

WYETH FARMA, S.A.

Ctra. Burgos, Km. 23

San Sebastián de los Reyes

28700 – Madrid

Spain

Responsible for manufacturing

Excella GmbH & Co. KG

Nürnberger Strasse 12,

90537 Feucht,

Germany

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Pfizer, S.L.

Avda. de Europa, 20-B

Parque Empresarial La Moraleja

28108 Alcobendas (Madrid)

Spain

Last review date of this leaflet:March 2025.

The detailed and updated information about this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/