METOTREXATE WYETH 2.5 mg TABLETS

Introduction

Package Leaflet: Information for the Patient

Methotrexate Wyeth 2.5 mg Tablets

Read all of this leaflet carefully before you start 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 signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Package Leaflet

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

1. What is Methotrexate Wyeth and what is it used for

Methotrexate Wyeth belongs to a group of medicines called folate analog antimetabolites.

Methotrexate 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.

2. What you need to know before you take Methotrexate Wyeth

Before you start using this medicine, you should 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 indicated. If you use methotrexate more frequently or in higher doses than indicated by your doctor, you may suffer from serious adverse reactions, including death.

Do not take Methotrexate Wyeth

• If you are allergic to methotrexate or any of the other components of this medicine (listed in section 6).
• If you have liver function disorders (liver failure).
• If you have severe kidney function disorders (severe renal failure).
• If you have liver damage due to excessive alcohol consumption (alcoholic hepatopathy), if you have chronic liver damage (chronic hepatopathy), or if you are an alcoholic.
• If you have altered blood levels of red blood cells, white blood cells, and platelets.
• If you suffer from any disease of the immune system (immunodeficiency syndromes).
• Severe, acute, or chronic infections such as tuberculosis and HIV.
• If you have ulcers in the mouth, stomach, or intestine.
• If you are going 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 medicine.

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 medicine.

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

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

• If you develop signs or symptoms due to possible toxicity of the medicine at the gastrointestinal and/or neuronal level, in the liver, kidney, lung, blood, or skin, go to your doctor.
• Follow the dose scrupulously as indicated by your doctor.
• If you are of childbearing age and have a neoplastic disease, the benefit of treatment should be weighed against the risk to the fetus in each case.
• If you have folate deficiency, as it could increase the toxicity to methotrexate.
• If you experience vomiting, diarrhea, or mouth inflammation (stomatitis), inform your doctor, as you may become dehydrated. If this occurs, your doctor may interrupt treatment until you fully recover. Also, inform your doctor if you have peptic ulcer or any type of colitis.
• If you have alterations in blood levels of white blood cells, red blood cells, and platelets. Methotrexate can decrease the white blood cells in the blood. If this occurs, you should take a series of precautions that include: avoiding contact with people with infections; consulting your doctor if you think you may have an infection due to the presence of fever or chills, cough, back pain, or difficulty urinating; consulting your doctor before undergoing dental interventions. Also, methotrexate can decrease the number of platelets in the blood necessary for coagulation. Therefore, it is important that you consult your doctor in the presence of prominent bruising or bleeding from the gums or nose, small red spots on the skin, blood in the urine or stools, or black stools.
• If you are being treated with NSAIDs (non-steroidal anti-inflammatory drugs).
• If you have liver problems, as methotrexate can cause acute hepatitis and chronic liver disorders. Moderate liver alterations may appear that require closer monitoring by the doctor but do not lead to the 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 can cause kidney damage.
• If you suffer from any type of infectious process.
• If you are going to be vaccinated, as a severe infection or a diminished response to the vaccine may occur.
• If during or after treatment, symptoms of toxicity at the level of the nervous system appear, such as headache, back pain, stiffness in the neck, fever, confusion, irritability, drowsiness, discoordination in movements, dementia, convulsions, transient blindness, abnormal reflexes, abnormal behavior, and localized alterations of movement and perception.
• 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 due to sun exposure. Previous skin lesions and sunburns may reappear with the use of methotrexate. Methotrexate can make the skin more sensitive to sunlight. Avoid intense sun and do not use sunbeds or UV lamps without medical advice. To protect your skin from intense sun, wear suitable clothing or use a sunscreen with a high protection factor.
• Acute pulmonary hemorrhage has been reported with methotrexate in patients with underlying rheumatological disease. If you observe blood when coughing or spitting, you should contact your doctor immediately.
• Methotrexate temporarily affects the production of sperm and eggs. Methotrexate can cause abortions and severe birth defects. If you are a woman, you should avoid becoming pregnant during treatment with methotrexate and for at least 6 months after the end of treatment with methotrexate. If you are a man, you should avoid having a child if you are being administered methotrexate at that time and for at least 3 months after the end of your treatment. See also the section "Warnings and Precautions".
• If you, your partner, or your caregiver notice the appearance or worsening of neurological symptoms, such as general muscle weakness, vision alterations, changes in thinking, memory, and orientation that generate 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 check your condition to see if the medicine is having the expected effect.

Other Medicines and Methotrexate Wyeth

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

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

• Medicines used to treat certain types of cancer, such as cisplatin, mercaptopurine, cytarabine, and L-asparaginase.
• Non-steroidal anti-inflammatory drugs, such as aspirin and other salicylates, and especially ketoprofen.
• Proton pump inhibitors (used to treat ulcers of the digestive system).
• Leflunomide (medicine for the treatment of arthritis).
• Metamizole (synonyms novaminsulfon and dipyrone) (medicine for intense pain and/or fever).
• Medicines with high binding to plasma proteins (such as salicylates, phenylbutazone, phenytoin, sulfonamides, sulfonylureas, aminobenzoic acid, some antibiotics, and medicines for the treatment of abnormal cholesterol and lipid levels, such as cholestyramine).
• Probenecid (medicine used to decrease uric acid levels).
• Antibiotics (ciprofloxacin, penicillins, sulfonamides, tetracyclines, chloramphenicol, pyrimethamine, trimethoprim/sulfamethoxazole) and broad-spectrum antibiotics that are not absorbed at the level of the digestive system.
• Medicines that produce liver toxicity (such as leflunomide, azathioprine, sulfasalazine, and retinoids).
• Theophylline (medicine for the treatment of asthma).
• Vitamins or vitamin preparations that contain folic acid or its derivatives.
• Nitrous oxide (anesthetic).
• Amiodarone (medicine for the treatment of cardiac disorders).
• Diuretics (such as triamterene).

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

During treatment with methotrexate, caution should be exercised when receiving a red blood cell transfusion.

Using Methotrexate Wyeth with Food, Drinks, and Alcohol

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

You should avoid excessive consumption of coffee, soft drinks that contain caffeine, and black tea. Your doctor may indicate that you drink more liquids than usual. This will help you eliminate the medicine and prevent kidney problems.

Pregnancy, Breastfeeding, and Fertility

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

Consult your doctor or pharmacist before using any medicine.

• Pregnancy:

Do not use this medicine during pregnancy unless your doctor has prescribed it as oncological treatment (cancer treatment). Methotrexate can cause birth defects, harm the fetus, or cause abortions. It is associated with malformations of the skull, face, heart, and blood vessels, brain, and limbs. Therefore, it is very important that it is not administered to pregnant women or those who plan to become pregnant, unless it is used as oncological treatment.

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

Do not use this medicine if you are trying to become pregnant. You should avoid becoming pregnant while taking methotrexate and for at least 6 months after the end of treatment. To do this, you must ensure that you are using reliable contraceptive methods during this entire time (see also the 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 should receive information about the risk of harmful 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 the planned start of treatment.

• Breastfeeding:

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

• Male Fertility:

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

For this reason, you should avoid fathering a child or donating semen during treatment with methotrexate and for at least 3 months after the end of treatment. Since treatment with methotrexate in higher doses commonly used in cancer treatment can cause infertility and genetic mutations, it is recommended that men treated with doses of methotrexate higher than 30 mg/week consider sperm preservation before starting treatment (see also the section "Warnings and Precautions").

Driving and Using Machines

It is not recommended to drive vehicles or use machines after the administration of Methotrexate Wyeth, as some of the possible side effects, such as dizziness and fatigue, can affect the ability to drive vehicles and use machines.

Methotrexate Wyeth Contains Lactose

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

3. How to Take Methotrexate Wyeth

Follow exactly the administration instructions of this medicine indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

IT IS VERY IMPORTANT THAT YOU USE METHOTREXATE EXACTLY AS YOUR DOCTOR HAS INDICATED. IF YOU USE METHOTREXATE MORE FREQUENTLY OR IN HIGHER DOSES THAN INDICATED BY YOUR DOCTOR, YOU MAY SUFFER FROM SERIOUS ADVERSE REACTIONS, INCLUDING DEATH.

Recommended Dose:

The usual dose is 15-30 mg (6-12 tablets) daily administered orally for 5 days and repeated every 12-14 days according to toxicity.

Methotrexate Wyeth is Presented in a Pack that Contains 2 Blister Packs, 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 medicine may be contraindicated.

Children and Adolescents

Children and adolescents treated with methotrexate should be subject to close medical supervision to identify possible side effects as soon as possible.

The use is not recommended in children under 3 years of age, as there is not enough data on efficacy and safety in this group of patients.

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.

In case of overdose or accidental ingestion, consult the Toxicology Information Service, telephone 91 562 04 20, indicating the medicine and the amount ingested.

An overdose of methotrexate can produce severe toxic reactions. The symptoms of overdose may include rapid formation of hematomas or hemorrhages, unusual weakness, mouth sores, nausea, vomiting, black stools or stools with blood, coughing up blood or vomiting with the appearance of coffee grounds, and decreased urination (evacuation of urine from the bladder). 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 hydration and alkalization of the urine.

If You Forget to Take Methotrexate Wyeth

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

If You Interrupt Treatment with Methotrexate Wyeth

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

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

If you consider that any of the adverse effects you suffer from is serious or if you notice any adverse effect not mentioned in this prospectus, inform your doctor or pharmacist.

Inform your doctor immediatelyif you experience wheezing when breathing, 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 adverse effects:

• breathing problems (symptoms may be a general feeling of discomfort, dry and 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 nosebleeds
• nausea, vomiting, abdominal discomfort, or severe diarrhea
• sores in the mouth
• 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 darkening of urine
• pain or difficulty urinating
• thirst and/or frequent need to urinate
• seizures (convulsions)
• loss of consciousness
• restricted vision or blurred vision
• extreme fatigue

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

The following adverse effects have also been reported:

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

• loss of appetite, nausea (vomiting), 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 (leukopenia, 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.

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

• lymphoma (lump 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, decrease in blood proteins
• hives, reactions similar to sunburn due to increased skin sensitivity to sunlight
• brown skin discoloration, hair loss, increased number of rheumatoid nodules, shingles, painful psoriasis, slow wound healing
• joint or muscle pain, osteoporosis (decrease in bone hardness)
• kidney disease, inflammation, or ulcers of the bladder (possibly with blood in the urine), pain when urinating
• 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 movements, 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 the stool, 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
• worsening of psoriasis during treatment with UV radiation
• skin lesions similar to sunburn or radiation-induced dermatitis
• bone fractures
• kidney failure, decreased or absent urine production, abnormal electrolyte levels 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
• pain, muscle weakness, changes in taste (metallic taste), inflammation of the membrane covering the brain with paralysis or vomiting, feeling of numbness or tingling/sensitivity to stimuli less than normal
• alteration of muscle movement used for speech, difficulty speaking, language impairment, feeling of sleepiness or fatigue, feeling of confusion, abnormal sensations in the head, brain inflammation, ringing in the ears
• redness of the 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
• nail infections, nail detachment from the nail bed, boils, dilation of small blood vessels, damage to blood vessels in the skin, allergic inflammation of blood vessels
• proteins in the urine
• decreased libido, erection problems, vaginal discharge, infertility, breast enlargement in males (gynecomastia)
• fever.

Frequency not known (cannot be estimated from the available data):

• pathological changes in the white matter of the brain (leukoencephalopathy)
• bleeding
• pulmonary bleeding*
• redness and peeling of the skin
• Jawbone injury (secondary to excessive increase in white blood cells)
• swelling

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

Reporting of Adverse Effects

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

5. Storage of Methotrexate Wyeth

Keep this medicine out of sight and reach of children.

Do not store above 25°C.

Do not use this medicine after the expiration date shown on the packaging after CAD. The expiration date is the last day of the month indicated.

Medicines should not be thrown away through wastewater or household waste. Deposit the packaging and medicines you no longer need at the SIGRE point in the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This way, you will help protect the environment.

6. Package Contents and Additional Information

Composition of Methotrexate Wyeth

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

Appearance of the Product and Package Contents

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

Marketing Authorization Holder

WYETH FARMA, S.A.

Ctra. Burgos, Km. 23

San Sebastián de los Reyes

28700 – Madrid

Spain

Manufacturer

Excella GmbH & Co. KG

Nürnberger Strasse 12,

90537 Feucht,

Germany

You can request more information about this medicine 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

Date of the Last Revision of this Prospectus:March 2025.

Detailed and updated information about this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/