METOTREXATE Orion Pharma 10 mg TABLETS (weekly)

Introduction

Package Leaflet:information for the user

Methotrexate Weekly Orion Pharma 10 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 pack

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

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

The active substance in this medicine, methotrexate, is a substance with the following properties:

• suppresses the growth of certain cells in the body that reproduce quickly
• 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 and disabling 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 from 3 years of age.

Your doctor will tell you how this medicine can help you in your particular situation.

2. What you need to know before you take Methotrexate Weekly Orion Pharma

Do not take Methotrexate Weekly Orion Pharma:

• if you are allergic (hypersensitive) to methotrexate or any of the other ingredients of this medicine (listed in section 6)
• if you are breastfeeding, and also, 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 problems (your doctor will decide the severity of your disease)
• if you have had bone marrow or blood disorders
• if you have acute or chronic severe infections or immunodeficiency syndrome
• if you have mouth ulcers or inflammation of the mouth mucosa
• 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 liver or kidney disease
• if you have any long-standing inactive infection (e.g., tuberculosis, hepatitis B or C, shingles), as they may recur
• if you have poor general health
• if you have lung function problems
• if you are overweight
• if you have excess fluid in the abdomen (ascites) or around the lungs (pleural effusions)
• if you have diabetes mellitus and are being treated with insulin
• if you are dehydrated or suffer from any disease that causes dehydration (vomiting, diarrhea, constipation, inflammation of the mouth mucosa).

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.

Diarrhea can be a possible side effect of this medicine and requires interruption of treatment. If you suffer from diarrhea, please talk to your doctor.

Methotrexate temporarily affects the production of sperm and eggs. Methotrexate can cause spontaneous 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 stopping treatment. If you are a man, you should avoid fathering a child during treatment with methotrexate and for at least 3 months after stopping treatment. See section "Pregnancy, breastfeeding, and fertility".

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

Methotrexate can make your skin more sensitive to sunlight. Avoid intense sunlight and do not use sunlamps or sunbeds unless your doctor tells you to. Wear protective clothing or use sunscreen with a high protection factor to protect your skin from intense sunlight.

Enlarged lymph nodes (lymphoma) can occur in patients receiving methotrexate at low doses, and if this is the case, treatment should be discontinued.

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

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

Recommended precautions and follow-up examinations

Even when methotrexate is used at low doses, serious side effects can occur. Your doctor will perform blood and urine tests to ensure that any side effects are identified quickly.

Before starting treatment

Before starting treatment, you will have a blood test to confirm that you have enough blood cells. Your blood will also be tested to check your liver function and to see if you have hepatitis. Additionally, your serum albumin levels (a blood protein) will be checked, as well as your hepatitis status 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 taking a small tissue sample from your liver for closer examination. Your doctor may also check if you have tuberculosis and perform a chest X-ray or lung function test.

During treatment:

Your doctor may perform the following tests:

• examination of the oral cavity and pharynx to detect changes in the mucosa such as inflammation or ulceration
• blood tests/blood count with the number of blood cells and measurement of methotrexate levels in the blood
• blood tests to monitor liver function
• imaging tests to monitor liver status
• taking a small tissue sample from the liver for closer examination
• blood tests to monitor kidney function
• monitoring of the respiratory tract 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 remarkable, your doctor will adjust your treatment accordingly.

Children, adolescents, and elderly people

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

The age-related deterioration of liver and kidney function, as well as the low body reserves of folic acid in old age, require a relatively low dose of methotrexate.

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

Other medicines and Methotrexate Weekly Orion Pharma

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

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

• metamizole (synonyms: novaminsulfon and dipyrone) (medicine for severe pain and/or fever)
• antibiotics (medicines to prevent/combating certain infections) such as penicillins, sulfonamides, ciprofloxacin, cephalothin, trimethoprim/sulfamethoxazole, tetracycline, and chloramphenicol. E.g., penicillins such as amoxicillin can reduce the excretion of methotrexate, potentially causing an increase in adverse effects

• other medicines used to treat rheumatoid arthritis such as leflunomide, sulfasalazine, and azathioprine
• certain pain 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)
• anticancer agents (e.g., mercaptopurine, 5-fluorouracil, doxorubicin, and procarbazine)
• antiepileptic medicines (prevention of convulsions)
• omeprazole or pantoprazole (medicines used to stop stomach acid production)
• diuretics (water tablets)
• medicines to reduce blood sugar levels, such as metformin
• cholestyramine (a medicine that binds to bile acids and can be used, for example, to reduce cholesterol levels)
• cyclosporin (a medicine that can inhibit or prevent the immune response)
• retinoids (for the treatment of psoriasis and other skin diseases)
• oral contraceptives
• barbiturates (sleeping medicines)
• sedatives
• nitrous oxide (used for general anesthesia)
• probenecid (a medicine used to treat gout)
• theophylline (a medicine used to treat respiratory diseases)
• vitamin preparations or other products containing folic acid, folinic acid, or other derivatives

• live vaccines.

Taking Methotrexate Weekly Orion Pharma with food, drinks, and alcohol

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

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

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

Methotrexate can cause birth defects, harm the fetus, or cause miscarriages. It is associated with malformations of the skull, face, heart, and blood vessels, brain, and limbs. Therefore, it is very important that methotrexate is not administered to pregnant women or women who plan to become pregnant, unless it is used as cancer treatment.

For non-oncological indications, in women of childbearing age, any possibility of pregnancy should be excluded before starting treatment, for example, by a pregnancy test.

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 stopping treatment. To do this, you must ensure that you are using reliable contraceptive methods during this entire time (see also section "Warnings and precautions").

If you become pregnant during treatment or think 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 wish to become pregnant, consult your doctor, who may refer you to a specialist for information before the planned start of 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 should stop breastfeeding.

Male fertility

Available data do not indicate an increased risk of malformations or miscarriages 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 on higher doses of methotrexate. Methotrexate can be genotoxic. This means that the medicine can cause genetic mutations. Methotrexate can affect sperm production, which is associated with the possibility of birth defects.

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

Consult your doctor or pharmacist before taking any medicine.

Driving and using machines

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

Methotrexate Weekly Orion Pharma contains lactose

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

3. How to Take Metotrexato Semanal Orion Pharma

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

• Patient with rheumatoid arthritis, psoriasis, or psoriatic arthritis should take their tablets orally once a weekon the same day each 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 tablets once a weekon the same day each week. The usual dose is between 7.5 and 15 mg once a week.

Dose in Maintenance Therapy for Acute Lymphoblastic Leukemia

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

Special Populations

Generally, a reduced dose is used for elderly patients and for patients with renal or hepatic insufficiency, as prescribed by a doctor. See also section 2, "Do not take Metotrexato Semanal Orion Pharma".

Use in Children and Adolescents

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

Safe Handling of Metotrexato Semanal Orion Pharma Tablets

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

Skin or mucous membrane contact should be avoided. If metotrexato 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 metotrexato out of the reach of children, preferably in a locked cabinet.

Accidental ingestion can be fatal for children.

If You Take More Metotrexato Semanal Orion Pharma Than You Should

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

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

An overdose of metotrexato can cause severe toxic reactions, including death. The symptoms of overdose may include rapid bruising or bleeding, unusual weakness, mouth sores, nausea, vomiting, black or bloody stools, coughing up blood or vomit with a coffee-ground appearance, and decreased urination. See also section 4, "Possible Side Effects".

Take the medication with you if you go to the doctor or hospital. If you have taken too much metotrexato, you will receive calcium folinate to reduce the adverse effects of metotrexato.

If You Forget to Take Metotrexato Semanal Orion Pharma

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

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

If You Stop Taking Metotrexato Semanal Orion Pharma

Do not stop treatment with 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 further questions about the use of this medication, ask your doctor, pharmacist, or nurse.

4. Possible Side Effects

Like all medications, this medication can cause side effects, although not everyone will experience them. In general, the incidence and severity of metotrexato side effects are related to the dose and frequency of administration. Most side effects are reversible if detected early.

Tell Your Doctor Immediatelyif you experience any of the following symptoms, as they may indicate a serious, potentially life-threatening side effect that requires specific treatment:

• dry cough and/or pain or difficulty breathing or shortness of breath, chest pain or fever
• blood when coughing or spitting
• unusual bleeding (including vomiting blood), bruising, or nosebleeds
• nausea, vomiting, abdominal discomfort, or severe diarrhea
• mouth ulcers
• black or tarry stools
• severe allergic reaction causing fever, rash, swelling, and, in some cases, a drop in blood pressure
• a very severe allergic reaction with skin blisters or ulcers, commonly in the form of blisters or ulcers in the mouth and eyes, and other mucous membranes such as the genitals (Stevens-Johnson syndrome, toxic epidermal necrolysis)
• any symptoms of infection, such as fever or a marked worsening of your general health, or fever with local signs of infection such as sore throat/inflammation of the throat or mouth or problems urinating; consult your doctor immediately. Metotrexato can reduce the number of white blood cells and thus 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 metotrexato for cancer treatment. They are not as common and not as severe in the doses used for treating psoriasis or rheumatoid arthritis.

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

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

Common(may affect up to 1 in 10 people)

• infections
• reduced formation of blood cells with decreased white blood cells and/or red blood cells and/or platelets (leukopenia, anemia, thrombocytopenia)
• headache, dizziness, unusual fatigue, drowsiness
• lung infection (pneumonia), dry cough
• diarrhea
• skin rash, skin redness, and itching
• hair loss.

Uncommon(may affect up to 1 in 100 people)

• cancer of the lymph nodes (or tissues)
• diabetes mellitus
• depression, confusion
• seizures, dizziness
• ulcers and bleeding in the digestive tract
• nasal bleeding
• formation of excess fibrous connective tissue in an organ (fibrosis)
• decrease in serum albumin levels
• inflammation of blood vessels, often with skin rash (vasculitis), increased skin pigmentation, slow wound healing, increased rheumatoid nodules
• reactions similar to sunburn due to increased skin sensitivity to sunlight
• ulcers and inflammation of the bladder, urination problems
• liver damage
• kidney dysfunction
• joint or muscle pain, decreased bone mineral density, a type of bone disease (osteoporosis)
• vaginal inflammation and ulceration
• chills.

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

• life-threatening inflammation of the whole body (sepsis), herpes zoster
• a blood disorder characterized by the appearance of very large red blood cells (megaloblastic anemia)
• mood changes
• weakness in movements (also limited to the left or right side of the body)
• significant visual disturbances
• 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
• liver inflammation (acute hepatitis)
• skin lesions (acne, skin depigmentation, hives, erythema multiforme, skin burning, psoriatic lesions, skin ulcers, red or purple spots due to vascular bleeding), nail detachment, darkened areas on the nails.
• stress fractures
• decreased or absent urine production, abnormal electrolyte levels
• menstrual disorders, impotence.

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

• immune deficiency (hypogammaglobulinemia), increased susceptibility to infections
• lymphoproliferative disorders (excessive growth of white blood cells)
• insomnia
• brain inflammation, difficulty speaking (dysarthria), irritation, drowsiness, fatigue (lethargy), temporary mild problems with intellectual functions ("mental fog"), abnormal sensations in the head, muscle weakness, feeling of numbness or tingling/sensitivity less than normal, changes in taste (metallic taste)
• redness and irritation of the thin membrane covering the eye (conjunctivitis), visual impairment, damage to the retina of the eye
• inflammation of blood vessels (vasculitis), vomiting blood
• reactivation of chronic liver inflammation, liver failure
• enlargement of the colon associated with inflammation/infection
• infection around the nail, deep infection of the hair follicles (furunculosis), bruising, acne
• presence of protein or blood in the urine, pain when urinating, bladder inflammation
• low sperm count, breast enlargement in men, vaginal bleeding, decreased libido
• fever.

Also Reported are the Following Side Effects, but the Frequency is Unknown:

Sepsis resulting in death, abnormally low number of blood cells, lung bleeding, jawbone damage (secondary to excessive white blood cell growth), brain disease, pathological change in the white matter of the brain (leukoencephalopathy), alveolitis, physical weakness, increased risk of toxic reactions during radiation therapy, skin redness and peeling, swelling. The red, scaly skin patches associated with psoriasis may worsen when exposed to ultraviolet light sources, such as the sun, and when taking metotrexato. Skin problems after radiation therapy (radiation-induced dermatitis) or sunburn may recur when taking metotrexato.

*(reported with metotrexato when used in patients with underlying rheumatologic disease)

Reporting of Side Effects

If you experience any side effects, consult your doctor, pharmacist, or nurse, even if they are possible side effects not listed in this leaflet. You can also report them directly through the Spanish Medicines and Healthcare Products Agency's website (https://www.notificaram.es). By reporting side effects, you can help provide more information on the safety of this medication.

5. Storage of Metotrexato Semanal Orion Pharma

Keep this medication out of 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 stated on the blister or carton. The expiration date is the last day of the month indicated.

This medication does not require any special storage temperature. Store the blisters in the outer packaging to protect them from light.

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

Any unused medication or waste material should be disposed of according to local requirements for cytotoxic agents.

Medications should not be thrown away in drains or trash. Deposit the packaging and any unused medication in the pharmacy's SIGRE point. Ask your pharmacist how to dispose of the packaging and any unused medication. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Metotrexato Semanal Orion Pharma

• The active ingredient is metotrexato. Each tablet contains 10 mg of metotrexato (as metotrexato disodium).
• The other ingredients are lactose monohydrate, microcrystalline cellulose, and magnesium stearate.

Appearance of Metotrexato Semanal Orion Pharma and Package Contents

Metotrexato Semanal Orion Pharma 10 mg tablets: Yellow, capsule-shaped, convex, uncoated, engraved with ORN 59 on one side and scored on the other side, 14 mm long and 6 mm wide. The tablet can be divided into equal doses.

Package sizes:

Blister Packs:

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

Not all package sizes may be marketed.

Marketing Authorization Holder

Orion Corporation

Orionintie 1

FI-02200 Espoo

Finland

Manufacturer

Orion Corporation Orion Pharma

Joensuunkatu 7

FI-24100 Salo

Finland

or

Orion Corporation Orion Pharma

Tengströminkatu 8

FI-20360 Turku

Finland

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

Orion Pharma, S.L.

Avda. Alberto Alcocer 46B

28016 – Madrid

Spain

Phone: +34 91 59 9 86 01

This medication is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Date of Last Revision of this Leaflet: May 2025

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