Patient Information Leaflet

Jiax Weekly 2 mg/ml Oral Solution

Metotrexate

Read this leaflet carefully before starting to take this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only, and you should 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.

1.What is Jiax Weekly and what it is used for

2.What you need to know before starting to take Jiax Weekly

3.How to take Jiax Weekly

4.Possible side effects

5.Storage of Jiax Weekly

6.Contents of the pack and additional information

Methotrexate is the active ingredient of Jiax Semanal. It acts by reducing inflammation or swelling and the activity of the immune system (the body's defense mechanism). Hyperactivity of the immune system has been associated with the presence of inflammatory diseases.

Low doses of Jiax Semanal are indicated for:

• Treating active and severe juvenile idiopathic polyarticular arthritis (when five or more joints are affected) after failure of nonsteroidal anti-inflammatory drugs (NSAIDs).

Consult your doctor about the risks and benefits of metotrexate treatment before starting this medication. Follow exactly the administration instructions for metotrexate indicated by your doctor.You may experience adverse effects and even death if you take metotrexate more frequently or in higher doses than prescribed by your doctor.

Do not take Jiax Semanal:

• If you are allergic to metotrexate or any of the other components of this medication (including those listed in section 6).
• If you are pregnant, or breastfeeding (see section "Pregnancy, breastfeeding and fertility").
• If you have liver disease (liver insufficiency) or severe kidney disease (severe kidney insufficiency).
• If you have liver damage due to excessive alcohol consumption (alcoholic liver disease), if you have chronic liver damage (chronic liver disease) or if you drink excessively.
• If you have an immune system disorder (immunodeficiency syndromes).
• If you have abnormal levels of red blood cells, white blood cells or platelets in your blood.
• If you have mouth, stomach or intestinal ulcers.
• If you have a severe infection.
• If you need to be vaccinated.

Warnings and precautions

Consult your doctor, pharmacist or nurse before starting to take Jiax Semanal:

• If you have diabetes mellitus treated with insulin.
• If you have chronic infections (e.g. tuberculosis, hepatitis B or C, zoster [herpes zoster]) because they may cause new episodes.
• If you have had kidney or liver disease.
• If you have respiratory problems.
• If you have significant overweight.
• If you have abnormal accumulation of fluid in the abdomen (ascites) or around the lungs (pleural effusions).
• If you have dehydration or have conditions that cause it (vomiting, diarrhea, constipation, inflammation of the mucous membrane of the mouth).

Pulmonary hemorrhage has been reported in patients with underlying rheumatic disease treated with metotrexate. If you observe blood when coughing or spitting, you should contact your doctor immediately.

If you have had skin problems after radiation therapy (radiation dermatitis) or sunburn, as these reactions may recur after treatment with metotrexate (memory reaction).

Patients receiving metotrexate at low doses may experience lymph node enlargement (lymphoma) and, in such cases, treatment should be discontinued.

Diarrea may be a possible adverse effect of Jiax Semanal and requires discontinuation of treatment. If you experience diarrhea, consult your doctor.

Certain brain disorders (encephalopathy/leucoencephalopathy) have been reported in patients with cancer receiving metotrexate. These adverse effects cannot be ruled out when using metotrexate to treat other diseases.

If you, your partner or caregiver notice the appearance or worsening of neurological symptoms, such as general muscle weakness, visual disturbances, 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).

Skin changes in psoriasis cases may worsen during treatment with metotrexate in cases of exposure to UV light.

Metotrexate may make the skin more sensitive to sunlight. Avoid intense sunlight and do not use tanning beds or UV lamps without medical advice. To protect your skin from intense sunlight, wear suitable clothing or use a high-protection sunscreen.

Special precautions for Jiax Semanal treatment:

Metotrexate temporarily affects the production of sperm and eggs, which is reversible in most cases. Metotrexate can cause miscarriage and severe birth defects. If you are a woman, avoid becoming pregnant while using metotrexate and for at least 6 months after stopping treatment. If you are a man, avoid fathering a child while receiving metotrexate and for at least 3 months after stopping treatment. See also section "Pregnancy, breastfeeding and fertility".

Recommended explorations and follow-up precautions:

Even if metotrexate is used at low doses, severe adverse reactions can occur. To detect them in time, your doctor will perform tests and blood tests for control.

Before starting treatment:

Before starting treatment, you will have blood tests to check that you have enough blood cells. You will also have blood tests to check liver function and to see if you have hepatitis. In addition, your albumin serum (a blood protein) will be checked, as well as your liver status (liver infection) and kidney function. Your doctor may also decide to perform other liver tests; some of these may be images of the liver, and others may require a small sample of liver tissue to examine in more detail. Your doctor may also check if you have tuberculosis, and may perform a chest X-ray or a lung function test.

During treatment:

Your doctor may perform the following tests:

• oral cavity and pharynx examination to identify changes in the mucous membrane, such as inflammation or ulceration.
• blood tests/blood counts with blood cell count and measurement of serum metotrexate levels.
• blood tests to control liver function.
• imaging tests to control liver function.
• extraction of a small sample of liver tissue to examine in more detail.
• blood tests to control kidney function.
• control of the respiratory tract and, if necessary, a lung function test.

It is very important that you attend these scheduled tests.

If the results of any of these tests are abnormal, your doctor will adjust your treatment accordingly.

Older patients:

Older patients on metotrexate treatment should be closely monitored by a doctor to detect possible adverse effects as soon as possible.

The deterioration of liver and kidney function related to age and low vitamin B12 reserves in the elderly requires a relatively low dose of metotrexate.

Children and adolescents:

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

Other medications and Jiax Semanal:

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

Some medications may interact with metotrexate. It is essential to inform your doctor if you are taking the following medications:

• Medications to treat certain types of cancer, such as cisplatin, mercaptopurine, cytarabine and L-asparaginase.
• Non-steroidal anti-inflammatory drugs or salicylates (pain and/or inflammation medications such as aspirin and other salicylates, diclofenac, ibuprofen and ketoprofen).
• Inhibitors of the proton pump, such as omeprazole (medications that reduce stomach acid production and used to treat stomach acid or gastrointestinal ulcers).
• Leflunomide (used to treat arthritis).
• Medications with high protein binding capacity (including salicylates, phenylbutazone, phenytoin, sulfonamides, sulfonylureas, amino benzoic acid, some antibiotics and medications to treat abnormal cholesterol and lipid levels, such as cholestyramine).
• Probenecid (a 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.

Penicillins may reduce metotrexate excretion and cause a potential increase in adverse effects.

• Medications that cause liver toxicity (including leflunomide, azathioprine, sulfasalazine and retinoids).
• Theophylline (used to treat respiratory problems such as asthma).
• Vitamins or vitamin supplements containing folic acid or its derivatives.
• Nitrous oxide (anesthetic).
• Amiodarone (used to treat heart diseases).
• Diuretics (such as triamterene).
• Metamizole (synonyms novaminsulfon and dipirona) (pain medication).

It is not recommended to administer certain vaccines during metotrexate treatment, for example, attenuated vaccines such as measles, mumps, flu or yellow fever.

Additionally, some treatments may interact with metotrexate, such as PUVA (methoxalen and UV light) in patients with psoriasis or a condition known as mycosis fungoides, as well as radiation therapy.

Caution should be exercised when receiving a blood transfusion during metotrexate treatment.

Use of Jiax Semanal with food, drinks and alcohol:

Do not consume alcohol while taking metotrexate, as it may increase the likelihood of adverse effects, especially liver-related ones. Your doctor may recommend that you drink more liquids than usual. This will help eliminate the medication from your body and prevent kidney problems.

Pregnancy, breastfeeding and fertility:

If you arepregnant or breastfeeding, think you may be pregnant or intend to become pregnant, consult your doctor or pharmacistbefore using this medication.

Consult your doctor or pharmacist before using any medication.

Pregnancy:

Do not use Jiax Semanal during pregnancy or if you are planning to become pregnant. Metotrexate can cause birth defects, harm the fetus or cause miscarriage. It is associated with skull, face, heart and blood vessel malformations, brain and limb malformations. Therefore, it is essential that metotrexate is not administered to pregnant patients or those planning to become pregnant. In fertile women, any possibility of pregnancy should be excluded with appropriate measures, for example, a pregnancy test before starting treatment. You should avoid becoming pregnant while taking metotrexate and for at least 6 months after stopping treatment, using reliable contraceptive methods during this 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. You will be offered 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 the planned start of treatment.

Breastfeeding:

Metotrexate has been shown to be excreted in breast milk, so it is contraindicated during breastfeeding.

Male fertility:

The available data do not indicate a higher risk of malformations or miscarriage if the father takes a metotrexate dose of less than 30 mg/week. However, this risk cannot be completely ruled out. Metotrexate may be genotoxic, meaning it can cause genetic mutations. Metotrexate may affect sperm production and cause birth defects. Therefore, you should avoid fathering a child or donating sperm while taking metotrexate and for at least 3 months after stopping treatment.

As metotrexate treatment may cause infertility, it may be advisable for male patients to conserve their sperm before starting treatment (see also section "Warnings and precautions").

Driving and operating machinery:

Do not drive or operate machinery after taking Jiax Semanal, as some of the possible adverse effects, such as dizziness and fatigue, may affect your ability to drive and operate machinery.

Jiax Semanal contains parahydroxybenzoate of methyl (sodium salt), parahydroxybenzoate of ethyl (sodium salt) and sulfites (flavorings).

This medication may cause allergic reactions (possibly delayed), as it contains parahydroxybenzoate of methyl, sodium salt (E219) and parahydroxybenzoate of ethyl, sodium salt (E215).

Rarely, this medication may cause hypersensitivity reactions and bronchospasm (sudden feeling of lack of breath) due to the presence of sulfites.

Follow exactly the administration instructions of this medication as indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist. You may experience adverse effects and even death if you take methotrexate more frequently or in higher doses than prescribed by your doctor.

Follow exactly the administration instructions of this medication as indicated by your doctor. It is very important that you check if the dose has been prescribed in ml or mg.

Recommended dose:

TAKE JIAX WEEKLY ONLY ONCE A WEEK.

The initial recommended dose for juvenile idiopathic polyarticular arthritis in children and adolescents is 10-15mg/m2of body surface areaonce a weekby oral route. Your doctor may adjust the dose according to the response to treatment and any adverse effect you may experience.

How to take this medication correctly

Jiax Weekly is supplied in a container of 35 or 65ml for oral administration.

Wash your hands before and after administering a dose. If you are a parent or caregiver who administers the medication, you must wear disposable gloves when handling methotrexate.

If methotrexate comes into contact with the skin, eyes, or nose, you must wash the affected area with water and soap.

Clean up any spills immediately.

Women who are pregnant, intend to become pregnant, or are breastfeeding should not handle methotrexate.

Keep this medication out of the sight and reach of children, preferably in a locked cabinet. Accidental ingestion can be fatal for children.

Keep the container tightly closed to avoid medication loss and reduce the risk of accidental spillage.

Remember that Jiax Weekly SHOULD ONLY BE ADMINISTERED ONCE A WEEK. Note the day of the week on which you have decided to take the medication using the space provided on the container.

IT IS VERY IMPORTANT THAT YOU TAKE THIS MEDICATION EXACTLY AS INDICATED BY YOUR DOCTOR AND THAT YOU ONLY TAKE THE AMOUNT PRESCRIBED FOR YOUR CONDITION.

You may not appreciate all the benefits of the medication until many months have passed. Do not increase the dose or take this medication more frequently or for a longer period than prescribed. Your condition will not improve faster. In fact, it may increase the risk of adverse effects, which could be potentially fatal.

How to take the oral solution: illustrated instructions

Instructions for use

• Shake the container.

• Open the container by pressing the cap down and turning it counterclockwise (Figure 1).

• Insert the adapter into the neck of the container (Figure 2).

• Take the syringe and insert it into the opening of the adapter (Figure 3).

• Place the container upside down (Figure 4).

• Fill the syringe with a small amount of solution by pulling the plunger down (Figure 4A). Then, press the plunger up to remove any air bubbles (Figure 4B). Finally, pull the plunger down to the graduation mark corresponding to the dose in milliliters (ml) prescribed by your doctor. The top of the plunger should be aligned with the corresponding graduation mark (Figure 4C).

• Place the container in an upright position (Figure 5A).

• Remove the syringe from the adapter (Figure 5B).

• Insert the tip of the syringe into the mouth and press the plunger slowly to administer the medication.
• Next, fill the syringe with water and take it to ensure that all the medication has been ingested.
• Then, drink a glass of water to eliminate any remaining methotrexate from the mouth and lips.
• Leave the adapter on the syringe in the container and close the container with the plastic cap.
• Wash the syringe with soap and warm water and rinse it thoroughly. To clean the inside of the syringe, submerge it in water and move the plunger up and down several times. Let it dry before reusing it. Store the syringe in a clean place with the medication (Figure 6).

• WASH YOUR HANDS THOROUGHLY with soap and warm water IMMEDIATELY after use.

Use in patients with renal and hepatic disorders

Consult your doctor, as the dose may need to be adjusted. In some cases, the medication may be contraindicated.

If you take more Jiax Weekly than you should

If you have taken more Jiax Weekly than you should, consult your doctor or pharmacist immediately or go to the nearest hospital emergency department immediately.

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 methotrexate overdose can cause severe reactions. Symptoms of overdose may include bleeding, unusual feeling of weakness, mouth ulcers, nausea, vomiting, black or bloody stools, coughing or vomiting blood with a coffee ground appearance, and reduced urine output.

If you forget to take Jiax Weekly

Do not take a double dose to compensate for the missed dose. Take the next dose as prescribed.

If you interrupt treatment with Jiax Weekly

Do not interrupt 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.

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

Inform your doctor immediately if you experience wheezing, difficulty breathing, swelling of the eyelids, face, or lips, skin rash, or itching (especially if it affects your entire body) suddenly.

Severe side effects

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

• Pneumonia (symptoms may include general discomfort, dry and irritating cough, difficulty breathing, shortness of breath at rest, chest pain, or fever)
• Bleeding when coughing or sneezing
• Severe skin peeling or blistering
• Bleeding (including vomiting blood) or unusual bruising
• Intense diarrhea
• Mouth ulcers
• Black or tar-like stools
• Blood in urine or stools
• Small red spots on the skin
• Fever
• Yellow discoloration of the skin (jaundice)
• Pain or difficulty urinating
• Excessive thirst and/or frequent urination
• Seizures
• Loss of consciousness
• Blurred or decreased vision

The following side effects have also been reported:

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

Loss of appetite, nausea (desire to vomit), vomiting, stomach pain, inflammation, and ulcers in the mouth and throat, and elevated liver enzymes.

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

Reduction in the formation of blood cells with decreased white blood cells and/or red blood cells and/or platelets (leukopenia, anemia, thrombocytopenia), headache, fatigue, drowsiness, pneumonia (inflammation of the lungs) with dry and non-productive cough, difficulty breathing, and fever, diarrhea, skin rash, skin redness, itching.

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

Reduction in the number of blood cells and platelets, dizziness, confusion, depression, seizures, inflammation of blood vessels, lung damage, ulcers, and bleeding in the digestive tract, liver disorders, diabetes, reduced blood proteins, urticaria, sunburn-like reactions due to increased skin sensitivity to sunlight, brown skin, alopecia, increased rheumatoid nodules, shingles, painful psoriasis, muscle or joint pain, osteoporosis (bone loss), inflammation, and ulcers of the bladder (possibly with blood in the urine), painful urination, severe allergic reactions, inflammation, and ulcers in the vagina, slow wound healing.

Rare(may affect up to 1 in 1000patients):

Inflammation of the sac surrounding the heart, fluid in the sac surrounding the heart, severe visual disorder, changes in mood, low blood pressure, blood clots, sore throat, respiratory arrest, asthma, inflammation of the digestive tract, bloody stools, inflammation of the gums, digestive problems, acute hepatitis (inflammation of the liver), nail color change, acne, red or purple spots due to vascular hemorrhage, bone fracture, renal insufficiency, reduced or absent urination, electrolyte disorders, defective sperm production, menstrual disorders.

Very rare(may affect up to 1 in 10000people):

Infections, severe bone marrow insufficiency, severe liver insufficiency, inflammation of glands, insomnia, pain, muscle weakness, numbness or tingling/sensitivity to minor stimuli, changes in taste (metallic taste), inflammation of the membrane covering the brain and causing paralysis or vomiting, red eyes, retinal eye damage, fluid in the lungs, vomiting blood, fever, protein in urine, loss of sexual desire, erectile dysfunction, infection around a nail, severe complications of the digestive tract, furuncles, small blood vessels in the skin, fungal infections, skin damage to blood vessels, vaginal discharge, infertility, breast enlargement in males (gynecomastia), inflammation of the brain, lymphoproliferative disorders (excessive increase in white blood cells)

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

Pulmonary hemorrhage, jawbone fractures (secondary to excessive increase in white blood cells), skin redness and peeling, swelling.

Jiax Semanal may cause a decrease in the number of white blood cells, which may reduce resistance to infections. If you experience an infection with symptoms such as fever and severe deterioration of your general condition, or fever with local infection symptoms such as sore throat/pharynx/mouth or urinary problems, you must immediately consult your doctor. They will perform a blood test to determine if there has been a decrease in the number of white blood cells (agranulocytosis). It is essential to inform your doctor if you are taking Jiax Semanal.

It is known that methotrexate causes bone disorders, such as joint and muscle pain and osteoporosis. The frequency of these risks in children is unknown.

Jiax Semanal may cause severe side effects (sometimes potentially fatal). Your doctor will perform tests to detect abnormalities in the blood (e.g., low white blood cell and platelet counts, lymphoma) and changes in the kidneys and liver.

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is not listed in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: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.

Do not store at a temperature above 25°C.

Do not refrigerate.

Store the bottle in the outer packaging to protect it from light.

Do not use this medication after the expiration date that appears on the bottle after «CAD». The expiration date is the last day of the month indicated. This product has a 6month shelf life after opening.

Medicines should not be disposed of through drains or in the trash. Deposit empty containers and unused medications at the SIGREpoint of the pharmacy. Ask your pharmacist how to dispose of empty containers and unused medications. By doing so, you will help protect the environment.

Composition of Jiax Semanal

• The active principle is methotrexate disodium. Each ml of solution contains 2.19mg of methotrexate disodium, equivalent to 2mg of methotrexate.

• The other components are: methyl parahydroxybenzoate (sodium salt) (E219), ethyl parahydroxybenzoate (sodium salt) (E215), dihydrate disodium hydrogen phosphate, citric acid monohydrate, raspberry flavoring, sucralose, and purified water.

Appearance of the product and contents of the packaging

Jiax Semanal is a yellow transparent solution.

It is presented in an amber glass bottle containing 35 or 65ml of oral solution for administration with a child-resistant closure. Each package contains a bottle, a bottle adapter, and a dosing syringe.

Only some package sizes may be marketed.

Marketing Authorization Holder

Gebro Pharma, S.A.

Av. Tibidabo, 29

08022 Barcelona

Spain

Responsible for Manufacturing

Jenson R+ (Ireland) Ltd,

Unit 15, Daingean Hall,

N4 Axis Centre,

Longford,

N39 W6K0

Ireland

This medicine is authorized in the member states of the European Economic Area with the following names:

SpainJiax Semanal 2 mg/ml oral solution

Last review date of this leaflet:October2024

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