Leaflet:information for the user

Methotrexate Weekly Orion Pharma 2.5 mg tablets EFG

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 yourdoctor, pharmacist or nurse.

-This medicine has been prescribed for youonly, and you must not give it to others even if they have the same symptomsas 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.

1.What is Methotrexate Weekly Orion Pharma and what it is used for

2.What you need to knowbeforestarting totake Methotrexate Weekly Orion Pharma

3.How to take Methotrexate Weekly Orion Pharma

4.Possible side effects

5.Storage of Methotrexate Weekly Orion Pharma

6.Contents of the pack and additional information

The active ingredient of this medication, methotrexate, is a substance with the following properties:

-suppresses the growth of certain cells in the body that reproduce rapidly

-reduces the activity of the immune system (the body's own defense mechanism).

Methotrexate is indicated for the treatment of:

-active rheumatoid arthritis in adult patients

-severe, invalidating psoriasis that has not responded adequately to other treatments such as phototherapy, PUVA, and retinoids in adult patients

-severe psoriatic arthritis in adult patients

-maintenance treatment in acute lymphoblastic leukemia (ALL) in adults, adolescents, and children aged 3 years or older.

Your doctor will inform you how this medication can help you in your particular situation.

Do not take Metotrexato Semanal Orion Pharma:

• if you are allergic (hypersensitive) to methotrexate or to any of the other ingredients of this medicine (listed in section 6)
• if you are breastfeeding and, in addition, for non-oncological indications (not related to cancer) if you are pregnant (see section “Pregnancy, breastfeeding and fertility”)
• if you have severe liver or kidney dysfunction (your doctor will decide the severity of your disease)
• if you have or have had bone marrow diseases or severe blood disorders
• if you have acute or chronic severe infections or immunodeficiency syndrome
• if you have inflammation of the mucous membranes of the mouth or mouth ulcers
• if you have stomach or intestinal ulcers
• if you suffer from alcoholism
• if you have recently received a live vaccine or are about to receive one.

Warnings and precautions

Consult your doctor, pharmacist or nurse before taking this medicine:

• if you have ever had any liver or kidney disease
• if you have any prolonged and inactive infection (for example, tuberculosis, hepatitis B or C, shingles [herpes zoster]), as they may recur
• if you have a general poor condition
• if you have respiratory function problems
• if you are overweight
• if you have ascites (excess fluid in the abdomen) or pleural effusions (excess fluid around the lungs)
• if you have diabetes mellitus and are being treated with insulin
• if you are dehydrated or have a disease that makes you dehydrated (vomiting, diarrhea, constipation, inflammation of the mucous membranes of the mouth).

Pulmonary haemorrhage has been reported in patients with underlying rheumatological disease receiving methotrexate. If you observe blood when coughing or spitting, you should contact your doctor immediately.

Diarhea may be a possible side effect of this medicine and requires discontinuation of treatment. If you experience diarrhea, please talk to your doctor.

Methotrexate temporarily affects the production of sperm and eggs. Methotrexate may cause spontaneous abortions and severe birth defects. If you are a woman, you should avoid pregnancy during methotrexate treatment and for at least 6 months after completing treatment. If you are a man, you should avoid fathering a child during methotrexate treatment and for at least 3 months after completing treatment. See section “Pregnancy, breastfeeding and fertility”.

The use of radiation therapy during treatment with this medicine may increase the risk of bone or soft tissue necrosis. If you have skin problems after radiation therapy (radiation dermatitis) or sunburn, as these reactions may recur during methotrexate treatment (recall reactions). Changes in the skin caused by psoriasis may worsen during methotrexate treatment if exposed to ultraviolet light.

Methotrexate may make your skin more sensitive to sunlight. Avoid intense sunlight and do not use lamps or sunbeds unless your doctor tells you to. Wear suitable clothing or use high-factor sunscreen to protect your skin from intense sunlight.

Lymph node enlargement (lymphoma) may occur in patients receiving methotrexate at low doses, and if this is the case, treatment should be discontinued.

If you, your partner or caregiver notice the appearance or worsening of neurological symptoms, such as general muscle weakness, visual disturbances, changes in thinking, memory and orientation that cause confusion and changes in personality, contact your doctor immediately, as these may be symptoms of a rare and serious brain infection called progressive multifocal leukoencephalopathy (PML).

Cerebral disease (encephalopathy/leukoencephalopathy) has been reported as an adverse effect in patients receiving methotrexate for cancer treatment. It cannot be ruled out that this may also occur when taking methotrexate for other diseases.

Recommended precautions and follow-up examinations

Even when used at low doses, methotrexate may cause serious side effects. Your doctor will make blood and urine tests to ensure that any side effects are identified quickly.

Before starting treatment:

Before starting treatment, a blood test will be performed to confirm that you have sufficient blood cells. Your blood will also be tested to check liver function and to see if you have hepatitis. In addition, your albumin (a protein in the blood) levels will be checked, as well as your liver and kidney function. Your doctor may also decide to perform other liver tests, some of which may involve imaging of your liver and others may require a small sample of liver tissue to be taken for closer examination. Your doctor may also check for tuberculosis and perform a chest X-ray or lung function test.

During treatment:

Your doctor may perform the following tests:

• oral cavity and pharynx examination to detect changes in the mucous membranes, such as inflammation or ulceration
• blood test/complete blood count with the number of blood cells and measurement of methotrexate levels in the blood
• blood test to control liver function
• imaging tests to control liver status
• small sample of liver tissue taken for closer examination
• blood test to control kidney function
• control of respiratory pathways and, if necessary, lung function test.

It is very important that you attend these scheduled examinations. If the results of any of these tests are abnormal, your doctor will adjust your treatment accordingly.

Children, adolescents and elderly people

Children, adolescents and elderly people treated with this medicine should be under close medical supervision to identify any possible side effects as soon as possible.

The age-related deterioration of liver and kidney function, as well as the low vitamin B12 reserves in the elderly, require a relatively low dose of methotrexate.

This medicine is not recommended for children under 3 years of age because the experience with the use of this medicine is insufficient in this age group.

Other medicines and Metotrexato Semanal Orion Pharma

The simultaneous use of other medicines may affect the efficacy and safety of this medicine. This medicine may also affect the efficacy and safety of other medicines.

Inform your doctor or pharmacist if you are taking, have taken recently or may need to take any other medicine. Remember to inform your doctor about your treatment with this medicine if you are prescribed another medicine while the treatment is still ongoing. It is especially important to inform your doctor if you are taking:

• metamizol (synonyms: novaminsulfon and dipirona) (painkiller and/or fever reducer)
• antibiotics (medicines to prevent/ combat certain infections) such as penicillins, sulfonamides, ciprofloxacin, cephalothin, trimethoprim/sulfamethoxazole, tetracycline and chloramphenicol. For example, penicillins such as amoxicillin may reduce the excretion of methotrexate, potentially causing an increase in side effects

• other medicines used to treat rheumatoid arthritis such as leflunomide, sulfasalazine and azathioprine
• some painkillers and/or anti-inflammatory medicines known as non-steroidal anti-inflammatory drugs (e.g. ibuprofen, diclofenac, salicylates such as acetylsalicylic acid)
• pyrimethamine (for the prevention and treatment of malaria)
• antineoplastic agents (e.g. mercaptopurine, 5-fluorouracil, doxorubicin and procarbazine)
• antiepileptic medicines (prevention of seizures)
• omeprazole or pantoprazole (medicines used to stop stomach acid production)
• diuretics (tablets to urinate)
• medicines to reduce blood sugar levels, such as metformin
• colestiramine (medicine that binds to bile acids and may be used, for example, to reduce cholesterol levels)
• ciclosporin (medicine that may inhibit or prevent the immune response)
• retinoids (for the treatment of psoriasis and other skin diseases)
• oral contraceptives
• barbiturates (sleeping pills)
• sedatives
• nitrous oxide (used for general anesthesia)
• probencid (medicine used to treat gout)
• theophylline (medicine used to treat respiratory diseases)
• preparations containing vitamin B12 or other derivatives

• live vaccines.

Taking Metotrexato Semanal Orion Pharma with food, drinks and alcohol

During treatment with this medicine, you should avoid consuming alcohol, as well as excessive consumption of coffee, fizzy drinks containing caffeine and black tea. Make sure you drink plenty of fluids during treatment with Metotrexato Orion Pharma tablets, as dehydration (reduction of body water) may increase the side effects of methotrexate.

Pregnancy, breastfeeding and fertility

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

Pregnancy

Nouse this medicine during pregnancy, except if your doctor has prescribed it as cancer treatment.

Methotrexate may cause birth defects, harm the fetus or cause miscarriages. It is associated with cranial, facial, heart and vascular, brain and limb malformations. Therefore, it is very important that methotrexate is not administered to pregnant women or those planning to become pregnant, except if used as cancer treatment.

In non-oncological indications, women of childbearing age should be excluded from any possibility of pregnancy by, for example, 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 completing treatment. To do this, you should 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 should receive information about the risk of harm to 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 breastfeeding, you should 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. This means that the medicine may cause genetic mutations. Methotrexate may affect sperm production, which is associated with the possibility of birth defects.

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

Consult your doctor or pharmacist before taking any medicine.

Driving and operating machinery

You may feel tired and dizzy during treatment with this medicine. Do not drive or operate machinery if you have these symptoms.

Metotrexato Semanal Orion Pharma contains lactose

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

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

• Patients with rheumatoid arthritis, psoriasis, or psoriatic arthritis should take their oral tabletsonce a weekon the same day every week.
• Do not take the tablets more frequently than indicated by your doctor.
• Daily administration may cause severe toxic effects, including death.
• Take the tablets with a glass of water while sitting or standing.

Dose in rheumatoid arthritis, psoriasis, and severe psoriatic arthritis

Take your tabletsonce a weekon the same day every week. The usual dose is between 7.5 and 15 mg once a week.

Dose in maintenance therapy in acute lymphoblastic leukemia

Your doctor will calculate the required dose based on your body surface area. Your doctor will decide the correct dose for you. If you want more information, consult with your doctor.

Special populations

Generally, the reduced dose according to medical prescription is used for elderly patients and patients with renal or hepatic insufficiency. See also section 2. “Do not take Metotrexate Weekly Orion Pharma”.

Use in childrenand adolescents

For children and adolescents with maintenance therapy in acute lymphoblastic leukemia, your doctor will calculate the individual dose based on your body surface area.

Safe handling of Metotrexate Weekly Orion Pharma tablets

Proper procedures for safe handling of cytotoxic agents must be followed. Anyone handling metotrexate must wash their hands before and after administering a dose. Disposable gloves should be used when handling metotrexate tablets. Pregnant women, women planning to become pregnant, or breastfeeding women should avoid handling metotrexate tablets if possible.

Contact with the skin or mucous membranes should be avoided. If metotrexate comes into contact with the skin or mucous membranes, it should be washed immediately and thoroughly with water and soap.

Parents, caregivers, and patients should be warned to keep metotrexate out of the reach of children, preferably in a locked cabinet.

Accidental ingestion can be fatal for children.

If you take more Metotrexate Weekly Orion Pharma than you should

If you take (or someone else has taken) more medication than you should, consult your doctor immediately or the emergency department of the nearest hospital.

In case of overdose or accidental ingestion, contact the Toxicology Information Service, phone 91 562 04 20, indicating the medication and the amount ingested.

A metotrexate overdose can cause severe toxic effects, including death. 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. See also section 4 "Possible side effects".

Carry the medication with you if you visit your doctor or hospital. If you used too much metotrexate, you will receive calcium folinate to reduce the adverse effects of metotrexate.

If you forgot to take Metotrexate Weekly Orion Pharma

Take the missed dose as soon as you remember, as long as it is within the next two days. However, if you forgot to take your dose for more than two days, contact your doctor for advice. Do not take a double dose to compensate for the missed doses.

Before traveling or going on vacation, make sure you have enough medication.

If you interrupt treatment with Metotrexate Weekly Orion Pharma

Do not stop taking this medication unless your doctor tells you to. If you need to stop taking this medication, your doctor will decide the best method for you.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them. Generally, the incidence and severity of metotrexate side effects are related to the dose and frequency of administration. Most side effects are reversible if detected early.

Inform your doctor immediatelyif you experience any of the following symptoms, as they may indicate a severe, potentially life-threatening side effect that requires specific treatment:

• dry cough or difficulty breathing or shortness of breath, chest pain or fever
• blood when coughing or spitting*
• unusual bleeding (including vomiting blood), bruises or nasal bleeding
• nausea, vomiting, abdominal discomfort or intense diarrhea
• mouth ulcers
• black or tar-like stools
• severe allergic reaction that causes fever, skin rash, swelling, and, in some cases, a drop in blood pressure
• an extremely severe allergic reaction with skin rash, commonly in the form of blisters or sores in the mouth and eyes, and other mucous membranes such as the genitals (Stevens-Johnson syndrome, toxic epidermal necrolysis)
• any symptom of an infection such as fever or a marked worsening of your overall health or fever with local signs of an infection such as sore throat/inflammation of the throat or mouth or problems urinating, consult your doctor immediately. Metotrexate can reduce the number of white blood cells and, therefore, weaken your immune defenses. A blood test will be performed to check for a reduction in white blood cells (agranulocytosis).
• yellowing of the skin (jaundice)
• pain or difficulty urinating
• thirst and/or frequent urination
• blurred or decreased vision.

Most of the effects mentioned below would only be observed in patients receiving high doses of metotrexate for cancer treatment. They are not as common and not as severe in the doses used for psoriasis or rheumatoid arthritis treatment.

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

• loss of appetite, nausea (urge to vomit), vomiting, indigestion, stomach pain, stomatitis (mouth and lip pain)
• increased liver enzymes.

Common(may affect up to 1 in 10 people)

• infections
• low cell formation with a decrease in white blood cells and/or red blood cells and/or platelets (leucopenia, anemia, thrombocytopenia)
• headache, dizziness, unusual fatigue, drowsiness
• lung infection (pneumonia), dry cough
• diarrhea
• skin rash, redness of the skin and itching
• hair loss.

Rare(may affect up to 1 in 100 people)

• fatal body inflammation (sepsis), herpes zoster
• a blood disorder characterized by the appearance of very large red blood cells (megaloblastic anemia)
• mood alterations
• weakness in movement (also limited to the left or right side of the body)
• important visual alterations
• fluid in the sac surrounding the heart. It can cause cardiac tamponade, a potentially life-threatening condition in which the heart cannot pump properly due to external pressure. It may require medical intervention to drain the fluid and relieve the pressure.
• low blood pressure, blood clots
• complete or severe weakness of the respiratory muscles, difficulty breathing, inflammation of the back of the throat, asthma
• pancreatitis, gum inflammation
• acute liver inflammation (hepatitis)
• skin lesions (acne, skin depigmentation, urticaria, erythema multiforme, skin burning, psoriatic lesions, skin ulcers, red or purple spots due to vascular hemorrhage), nail detachment, darkened nail areas.
• stress fractures
• low or absent urine production, abnormal electrolyte levels
• menstrual disorders, impotence.

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

• immunodeficiency (hypogammaglobulinemia), increased susceptibility to infections
• lymphoproliferative disorders (excessive growth of white blood cells)
• insomnia
• inflammation of the brain, difficulty speaking (dysarthria), irritation, drowsiness, fatigue (lethargy), mild problems with intellectual functions ("foggy mind"), abnormal sensations in the head, muscle weakness, numbness or tingling/sensitivity to minor stimuli, changes in taste (metallic taste)
• conjunctivitis, visual impairment, eye damage
• inflammation of blood vessels (vasculitis), vomiting blood
• reactivation of chronic liver inflammation, liver insufficiency
• colon enlargement associated with inflammation/infection
• infection around the nail, deep follicular pilosebaceous infection (furunculosis), hematomas, acne
• protein or blood in the urine, painful urination, bladder inflammation
• low sperm count, breast enlargement in men, vaginal bleeding, decreased libido
• fever.

Also, the following side effects have been reported, but the frequency is unknown:

Sepsis leading to death, abnormally low number of blood cells, bleeding from the lungs*, jaw bone damage (secondary to excessive growth of white blood cells), brain disease, pathological change of the white matter of the brain (leucoencephalopathy), alveolitis, physical weakness, increased risk of toxic reactions during radiation therapy, skin redness and peeling, swelling. Red, scaly skin patches associated with psoriasis may worsen when exposed to ultraviolet light sources, such as the sun, and taking metotrexate. Skin problems after radiation therapy (radiation-induced dermatitis) or sunburns may reappear when taking metotrexate.

*(reported with metotrexate 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 that does not appear in this prospectus. You can also report them directly through theSistema Español de Farmacovigilancia de Medicamentos de Uso Humano: 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, preferably in a locked cabinet. Accidental ingestion can be fatal for children.

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

This medication does not require any special temperature for conservation. Store the bottle of tablets or blisters in the outer packaging to protect it from light.

Proper procedures for the safe handling of cytotoxic agents must be followed. Any person handling metotrexate must wash their hands after administering a dose. Disposable gloves should be used when handling metotrexate tablets. Pregnant women, those planning to become pregnant, or breastfeeding women should not handle metotrexate.

Any unused medication or waste must be disposed of in accordance with local requirements for cytotoxic agents.

Medications should not be disposed of through drains or in the trash.Deposit the packaging and medications you no longer need at the SIGRE point of your pharmacy.Ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

Composition of Methotrexate Weekly Orion Pharma

• The active ingredient is methotrexate. Each tablet contains 2.5 mg of methotrexate (as methotrexate disodium).
• The other components are lactose monohydrate, microcrystalline cellulose, and magnesium stearate.

Appearance of Methotrexate Weekly Orion Pharma and packaging contents

Methotrexate Weekly Orion Pharma 2.5 mg tablets EFG:Yellow, round, uncoated, flat, scored, and engraved with ORN 57 on one side, 6 mm in diameter. The scoring line is only for ease of breaking to facilitate swallowing and not for dividing into equal doses.

Packaging sizes:

Child-resistant container with or without a child-resistant closure

10, 12, 24, 28, 30, 50, and 100 tablets.

Blister packaging:

4, 8, 10, 12, 16, 20, 24, 30, 36, 40, 48, 50, 60, 100, and 120 tablets.

Only some packaging sizes may be commercially available.

Marketing Authorization Holder

Orion Corporation

Orionintie 1

FI-02200 Espoo

Finland

Manufacturer

Orion Corporation Orion Pharma

Joensuunkatu7

FI-24100Salo

Finland

or

Orion Corporation Orion Pharma

Tengströminkatu 8

FI-20360 Turku

Finland

For more information about this medication, please contact the local representative of the marketing authorization holder:

Orion Pharma, S.L.

Avda. Alberto Alcocer 46B

28016 Madrid

Spain

Phone: +34 91 599 86 01

This medication is authorized in the member states of the European Economic Area and in the United Kingdom (Northern Ireland) with the following names:

Last review date of thisleaflet:December 2024

For detailed information about this medication, please visit the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/)