Methofill

Leaflet accompanying the packaging: Information for the user

Methofill, 2.5 mg, tablets

Methofill, 10 mg, tablets

Methotrexate

The Methofill tablet should be taken once a week

It is necessary to carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• The leaflet should be kept in case it needs to be read again.
• In case of any doubts, the doctor or pharmacist should be consulted.
• This medicine has been prescribed specifically for this person. It should not be given to others. The medicine may harm another person, even if the symptoms of their illness are the same.
• If any side effects occur, including any possible side effects not listed in the leaflet, the doctor or pharmacist should be informed (see section 4).

Table of contents of the leaflet

• 1. What is Methofill and what is it used for
• 2. Important information before taking Methofill
• 3. How to take Methofill
• 4. Possible side effects
• 5. How to store Methofill
• 6. Contents of the packaging and other information

1. What is Methofill and what is it used for

Methofill contains the active substance methotrexate. Methotrexate is an antimetabolite and an immunosuppressive drug (a drug that affects cell proliferation and reduces the activity of the immune system).

Methotrexate is used to treat:

• active rheumatoid arthritis in adults,
• severe psoriasis, especially plaque psoriasis, in patients who have taken other medicines without improvement in their condition,
• active psoriatic arthritis in adult patients,
• acute lymphoblastic leukemia in adults, adolescents, and children over 3 years of age.

The doctor will explain how Methofill can help the patient with their condition.

2. Important information before taking Methofill

When not to take Methofill

• if the patient is allergic to methotrexate or any of the other ingredients of this medicine (listed in section 6);
• if the patient has severe kidney failure (or the doctor classifies the disorder as severe)
• if the patient has liver function disorders
• if the patient has blood disorders, such as bone marrow hypoplasia, leukopenia, thrombocytopenia, or significant anemia
• if the patient abuses alcohol
• if the patient has a weakened immune system
• if the patient suffers from a serious infection, such as tuberculosis or HIV
• if the patient has stomach or intestinal ulcers
• if the patient has inflammation of the mucous membrane of the mouth or mouth ulcers
• if the patient is breastfeeding and also has non-oncological indications (in non-cancer treatment)
• if the patient is pregnant (see "Pregnancy, breastfeeding, and fertility")
• if the patient has recently been vaccinated with a live vaccine or is about to receive one

Recommended tests and precautions

Even if methotrexate is used in small doses, serious side effects may occur. To detect them as early as possible, the doctor must perform tests and laboratory tests.

Before starting treatment:

Before starting treatment, blood will be tested to check if the patient has a sufficient number of blood cells. Blood will also be tested for liver function to determine if the patient has hepatitis. Additionally, serum albumin (protein in the blood), the presence of hepatitis (liver infection), and kidney function will be checked. The doctor may also decide to perform other liver tests. Some of these may be imaging tests, while others may require taking a small tissue sample from the liver for further examination. The doctor may also check for tuberculosis, order a chest X-ray, or test lung function.

During treatment:

The doctor may perform the following tests:

• examination of the mouth and throat for mucous membrane changes, such as inflammation or ulcers
• blood tests/morphology with assessment of blood cell count and measurement of methotrexate concentration in serum
• blood tests to monitor liver function
• imaging tests to monitor liver condition
• taking a small tissue sample from the liver for further examination
• blood tests to monitor kidney function
• monitoring of the respiratory tract and, if necessary, lung function tests It is very important for the patient to attend scheduled tests. If the results of any of these tests are abnormal, the doctor will adjust the treatment accordingly.

Elderly patients

Elderly patients treated with methotrexate should be closely monitored by the doctor to detect any potential side effects as early as possible. Age-related liver and kidney function disorders, as well as low folate reserves in older age, require relatively low doses of methotrexate.

Warnings and precautions

Important warning about Methofill dosage (methotrexate):

Methotrexate tablets should only be taken once a week for the treatment of rheumatic or skin diseases (RAS and psoriasis or psoriatic arthritis)

Taking too much Methofill (methotrexate) can be fatal.

Please read section 3 of this leaflet carefully.

If you have any questions, you should discuss them with your doctor or pharmacist before taking this medicine.

Before starting Methofill, you should inform your doctor or nurse:

• if you have diabetes treated with insulin
• if you have inactive, chronic infections (e.g., tuberculosis, hepatitis B or C, shingles), as they may worsen
• if you have ever had liver or kidney disease
• if you have respiratory function disorders
• if you are significantly overweight
• if you have abnormal fluid accumulation in the abdominal cavity (ascites) or around the lungs (pleural effusion)
• if you are dehydrated or have conditions that cause dehydration (vomiting, diarrhea, constipation, mouth ulcers)

Methotrexate may increase skin sensitivity to sunlight. You should avoid intense sun exposure and not use a sunbed or sunlamp without consulting your doctor. To protect your skin from intense sunlight, you should wear appropriate clothing or use a sunscreen with a high protection factor.

If you have had skin problems after radiation therapy (radiation dermatitis) or sunburn, these reactions may recur after methotrexate treatment (a reaction similar to a recall reaction).

Psoriatic skin changes may worsen during methotrexate treatment if you are exposed to UV light.

In patients receiving low doses of methotrexate, lymph node enlargement (lymphoma) may occur, and treatment should be discontinued in such cases.

During methotrexate treatment, cases of acute pulmonary hemorrhage have been reported in patients with underlying rheumatologic disease. If you experience hemoptysis (coughing up blood), you should immediately consult your doctor.

Diarrhea is a possible side effect of Methofill and requires treatment discontinuation.

If you experience diarrhea, you should discuss it with your doctor.

In patients with cancer receiving methotrexate, certain brain disorders (encephalopathy/leukoencephalopathy) have been reported. Such side effects cannot be ruled out when methotrexate is used to treat other diseases.

Methotrexate temporarily affects sperm and egg production. Methotrexate may cause miscarriage and severe birth defects in the fetus. Female patients should avoid becoming pregnant during methotrexate treatment and for at least 6 months after treatment ends. Male patients should avoid fertilizing their partner during methotrexate treatment and for at least 3 months after treatment ends. See also "Pregnancy, breastfeeding, and fertility".

Recommended tests and precautions

Severe side effects may occur even when methotrexate is used in small doses. The doctor must perform tests and laboratory tests to detect them as early as possible.

If the patient, their partner, or caregiver notices new or worsening neurological symptoms, including general muscle weakness, vision disturbances, changes in thinking, memory, and orientation leading to disorientation and personality changes, they should immediately contact their doctor, as these may be symptoms of a very rare, serious brain infection called progressive multifocal leukoencephalopathy (PML).

Children and adolescents

Children and adolescents treated with methotrexate should be subject to particularly close medical observation to quickly detect significant side effects.

This medicine is not recommended for use in children under 3 years of age, as experience in this age group is insufficient.

Methofill and other medicines

You should tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take, including those available without a prescription and herbal or natural products. You should remember to inform your doctor about methotrexate treatment if another medicine is prescribed during treatment.

It is especially important to inform your doctor about the use of the following medicines:

• other medicines used for rheumatoid arthritis or psoriasis, such as leflunomide, azathioprine (also used to prevent organ transplant rejection), sulfasalazine (also used to treat ulcerative colitis)
• cyclosporine (used to suppress the immune system)
• non-steroidal anti-inflammatory drugs or salicylates (painkillers and/or anti-inflammatory drugs, such as acetylsalicylic acid, diclofenac, and ibuprofen or pyrazole)
• live vaccines
• diuretics that reduce fluid retention
• drugs that lower blood sugar, such as metformin
• retinoids (used to treat psoriasis and other skin diseases)
• antiepileptic drugs (seizure prevention)
• barbiturates (sleeping pills)
• sedatives
• oral contraceptives
• probenecid (used to treat gout)
• antibiotics
• pyrimethamine (used to prevent and treat malaria)
• vitamin preparations containing folic acid
• proton pump inhibitors (used to treat heartburn, ulcers, and other stomach problems)
• theophylline (used to treat breathing problems) and mercaptopurine (used to treat certain types of leukemia)
• anticancer drugs (such as doxorubicin and procarbazine during high-dose methotrexate treatment)
• metamizole (synonyms: novaminsulfone and dipyrone) (strong painkiller and/or antipyretic)

Methotrexate Accord with food, drink, and alcohol

This medicine can be taken with or without food. After taking a dose, you should drink some water to ensure that the entire dose is taken and that no methotrexate residue remains in the mouth. During methotrexate treatment, you should not drink alcohol and should avoid drinking excessive amounts of coffee, caffeine-containing beverages, and black leaf tea. You should make sure to drink plenty of fluids during methotrexate treatment, as dehydration (reduced water in the body) may exacerbate methotrexate side effects.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, you should consult your doctor or pharmacist before taking this medicine.

Pregnancy

Methofill should not be used during pregnancy, unless the doctor has prescribed it for cancer treatment.

Methotrexate may cause birth defects, harm the unborn child, or cause miscarriage. This is associated with skull, face, heart, and blood vessel deformities, brain, and limb abnormalities. Therefore, it is very important that methotrexate is not given to pregnant women or women planning to become pregnant, unless it is used for cancer treatment.

In cases of non-oncological indications, in women of childbearing age, pregnancy should be ruled out before starting treatment, e.g., using pregnancy tests.

Methofill tablets should not be taken if you plan to become pregnant. You should avoid becoming pregnant during methotrexate treatment and for at least 6 months after treatment ends. Therefore, you should use effective contraception throughout this period (see also "Warnings and precautions").

If you become pregnant during treatment or suspect you may be pregnant, you should consult your doctor as soon as possible. If you become pregnant during treatment, you should receive advice on the risk of harmful treatment effects on the child. If you wish to become pregnant, you should discuss it with your doctor, who may refer you to a specialist before planned treatment begins.

Breastfeeding

You should not breastfeed during treatment, as methotrexate passes into breast milk.

You must stop breastfeeding if your doctor considers methotrexate treatment absolutely necessary during this period.

Fertility

Male fertility

Available data do not indicate an increased risk of birth defects or miscarriage if the father takes methotrexate at a 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 have genotoxic effects. This means that the drug may cause genetic mutations. Methotrexate may affect sperm production, which is associated with the possibility of birth defects.

You should avoid conceiving a child or donating sperm during methotrexate treatment and for at least 3 months after treatment ends. Since methotrexate treatment at higher doses, commonly used in cancer therapy, may cause infertility and genetic mutations, in the case of male patients treated with methotrexate at doses higher than 30 mg/week, it may be advisable to consider sperm preservation before starting treatment (see also "Warnings and precautions").

Before taking any medicine, you should consult your doctor or pharmacist.

Driving and using machines

Note: this medicine may affect your ability to react and drive vehicles.

During Methofill treatment, side effects may occur that affect the central nervous system, such as fatigue or dizziness. In some cases, this may affect your ability to drive vehicles and operate machines. If you feel tired or dizzy, you should not drive vehicles or operate machines.

Methofill contains lactose

Methofill contains lactose. If your doctor has determined that you have an intolerance to certain sugars, you should consult your doctor before taking this medicine.

3. How to take Methofill

Methofill should only be prescribed by doctors who are familiar with the properties of the medicine and its mode of action.

This medicine should always be taken as directed by your doctor or pharmacist. If you have any doubts, you should consult your doctor or pharmacist.

Incorrect use of Methofill may cause serious side effects, even death.

The duration of treatment is determined by the doctor. Treatment of rheumatoid arthritis, severe psoriasis, and severe psoriatic arthritis with Methofill is long-term.

Recommended dose

The doctor will decide what dose of Methofill to take, depending on the disease being treated, its severity, and overall health. You should strictly follow the dose and your doctor's instructions on when to take the medicine.

Dosing in rheumatic and skin diseases (RAS, MIZS, and psoriasis or psoriatic arthritis)

Methofill should be taken only once a week.

You should agree with your doctor on the most suitable day of the week to take the medicine.

Dosing in rheumatoid arthritis in adults:The usual initial dose is 7.5-15 mg orally, once a week.

Dosing in psoriasis and psoriatic arthritis:The usual initial dose is 7.5-15 mg orally, once a week.

The doctor may increase the dose if the applied dose is not effective but is well tolerated.

The doctor may adjust the dose based on the response to treatment and side effects.

Dosing in acute lymphoblastic leukemia (ALL)

The doctor will inform you what dose to take and when to take it.

You should strictly follow the recommended dose. The dose should be taken orally, once a week.

Use in children and adolescents

The doctor will calculate the required dose based on the child's body surface area (m^2), and the dose is expressed in mg/m^2.

Elderly patients

Due to decreased liver and kidney function, as well as lower folate reserves in this patient group, a lower dose should be used.

Methofill 10 mg tablets: The dividing line is only intended to facilitate breaking the tablet in case of difficulty swallowing it whole.

Safe handling of Methofill

Appropriate procedures for handling cytotoxic agents should be followed. When handling methotrexate tablets, single-use gloves should be worn. Whenever possible, pregnant women should avoid contact with methotrexate tablets.

Overdose of Methofill

You should follow your doctor's instructions regarding dosing. Never change the dose yourself. If you suspect that you (or someone else) have taken too much Methofill, you should immediately inform your doctor or go to the emergency department of the nearest hospital. The doctor will decide if any treatment is needed.

Methotrexate overdose can cause serious reactions. Overdose symptoms may include bleeding, unusual feeling of weakness, mouth ulcers, nausea, vomiting, black or bloody stools, coughing up blood or bloody vomit resembling coffee grounds, and decreased urine output. See also section 4 "Possible side effects".

When visiting your doctor or hospital, you should bring the medicine packaging with you. The antidote in case of overdose is calcium folinate.

Missed dose of Methofill

You should never take a double dose to make up for a missed dose but continue taking the prescribed dose. You should ask your doctor for advice.

Stopping Methofill treatment

You should not stop taking Methofill without first discussing it with your doctor. If you suspect you have a serious side effect, you should immediately contact your doctor.

If you have any further doubts about using this medicine, you should consult your doctor or pharmacist

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

You should immediately inform your doctorif you suddenly experience wheezing, difficulty breathing, swelling of the eyelids, face, or lips, rash, or itching (especially if it affects the whole body).

You should immediately contact your doctor if you experience any of the following side effects:

• breathing problems (including general feeling of illness, dry, irritating cough, shortness of breath, difficulty breathing, chest pain, or fever)
• coughing up blood or bloody sputum*
• severe skin peeling or blistering
• abnormal bleeding (including bloody vomit), bruising, or nosebleeds
• nausea, vomiting, discomfort in the abdominal cavity, or severe diarrhea
• mouth ulcers
• black or tarry stools
• blood in urine or stool
• small red spots on the skin
• fever, sore throat, flu-like symptoms
• yellowing of the skin (jaundice) or dark urine
• pain or difficulty urinating
• thirst and/or frequent urination
• seizures (convulsions)
• loss of consciousness
• blurred or limited vision
• severe fatigue *Reported in patients with underlying rheumatologic disease treated with methotrexate.

The following side effects have also been reported:

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

• loss of appetite, nausea, vomiting, abdominal pain, indigestion, inflammation, and ulcers of the mouth and throat
• blood tests showing elevated liver enzyme activity

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

• infections
• reduced blood cell production with decreased white and/or red blood cell and/or platelet count (leukopenia, anemia, thrombocytopenia)
• headache, fatigue, dizziness
• pneumonia with dry cough, shortness of breath, and fever
• diarrhea
• skin rash, redness, and itching

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

• lymphoma (a lump in the neck, armpit, or groin with accompanying back pain, weight loss, or night sweats)
• severe allergic reactions
• diabetes
• depression
• dizziness, confusion, seizures
• lung damage
• ulcers and bleeding from the digestive tract
• liver disease, decreased blood protein levels
• hives, reactions similar to sunburn, brown skin discoloration, hair loss, increased number of rheumatoid nodules, shingles, painful psoriasis, slow wound healing
• joint or muscle pain, osteoporosis (bone weakening)
• kidney disease, inflammation, or ulcers of the bladder (possibly with blood in the urine), painful urination
• vaginal inflammation and ulcers

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

• blood disorder characterized by the appearance of very large red blood cells (megaloblastic anemia)
• mood swings
• weakness of movement, also limited to the left or right side of the body
• severe vision disturbances
• inflammation of the sac surrounding the heart, fluid accumulation in the pericardial sac
• low blood pressure, blood clots
• tonsillitis, respiratory arrest, asthma
• pancreatitis, gastrointestinal inflammation, bloody stools, gum inflammation, indigestion
• acute hepatitis
• nail discoloration, acne, red or purple spots due to bleeding from blood vessels

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

• systemic viral, fungal, or bacterial infections
• severe bone marrow disorder (anemia), lymph node swelling
• lymphoproliferative disorders (excessive growth of white blood cells)
• insomnia
• pain, muscle weakness, changes in taste (metallic taste), inflammation of the membrane surrounding the brain causing paralysis or vomiting, numbness or tingling/ reduced sensitivity to stimuli
• disorders of muscle movement used for speech production, difficulty speaking, speech disorders, feeling of drowsiness or fatigue, feeling of disorientation, strange sensations in the head, brain swelling, ringing in the ears
• redness of the eyes, eye retina damage
• fluid accumulation in the lungs, lung infections
• bloody vomit, severe gastrointestinal complications
• liver failure
• nail infections, nail separation from the nail bed, boils, widened small blood vessels, skin blood vessel damage, allergic blood vessel inflammation
• protein in the urine
• loss of sexual desire, erection problems, discharge, infertility, breast enlargement in men (gynecomastia)
• fever

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

• pathological change in the white matter of the brain (leukoencephalopathy)
• bleeding
• pulmonary hemorrhage*
• skin redness and peeling
• jawbone damage (secondary to excessive white blood cell growth)
• fluid accumulation *Reported in patients with underlying rheumatologic disease treated with methotrexate.

Methotrexate may decrease the number of white blood cells, thereby weakening the immune system. If you notice any signs of infection, such as fever or a significant worsening of your general condition, or fever with local signs of infection, such as sore throat/pharyngitis or mouth ulcers, you should immediately contact your doctor. A blood test will be performed to check if you have a decreased white blood cell count (agranulocytosis). It is essential to inform your doctor about all medicines you are taking.

Methotrexate may cause serious (sometimes life-threatening) side effects. Therefore, the doctor will perform tests to check for any changes in blood (e.g., low white blood cell count, low platelet count, lymphoma), kidney, or liver function.

Reporting side effects

If you experience any side effects, including any side effects not listed in the leaflet, you should inform your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products

Al. Jerozolimskie 181C

02-222 Warsaw

tel.: +48 22 49 21 301

fax: +48 22 49 21 309

website: https://smz.ezdrowie.gov.pl

Side effects can also be reported to the marketing authorization holder.

5. How to store Methofill

The medicine should be stored out of sight and reach of children.

Do not use this medicine after the expiry date stated on the blister/packaging after EXP.

The expiry date refers to the last day of the month stated.

There are no special storage temperature recommendations for this medicine.

Blister: the blister should be stored in the outer packaging to protect it from light.

Medicines should not be disposed of via wastewater or household waste. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Methofill contains

The active substance is methotrexate.

One tablet contains 2.5 milligrams of methotrexate.

One tablet contains 10 milligrams of methotrexate.

The other ingredients are calcium hydrogen phosphate anhydrous, lactose monohydrate, sodium carboxymethylcellulose (type A), microcrystalline cellulose, talc, magnesium stearate (E470b).

What Methofill looks like and contents of the pack

Methofill 2.5 mg is a yellow, round, biconvex uncoated tablet with a diameter of 4.5 ± 0.2 mm, smooth on both sides.

Methofill 10 mg is a yellow, uncoated, biconvex capsule-shaped tablet with a length of 10.0 ± 0.2 mm and a width of 5.0 ± 0.2 mm, with a dividing line on one side and smooth on the other.

The tablets are packaged in blisters with orange PVC coating and aluminum foil.

Blister PCV/Aluminum

Package sizes: 10, 12, 15, 20, 24, 25, 28, 30, 50, or 100 tablets.

Single-dose blister PVC/Aluminum

Package sizes: 10 x 1, 12 x 1, 15 x 1, 20 x 1, 24 x 1, 25 x 1, 28 x 1, 30 x 1, 50 x 1, or 100 x 1 tablets.

Not all package sizes may be marketed.

Marketing authorization holder

Accord Healthcare Polska Sp. z o.o.

ul. Taśmowa 7

02-677 Warsaw

Tel: +48 22 577 28 00

Manufacturer/Importer

Accord Healthcare B.V.

Winthontlaan 200

3526 KV Utrecht

Netherlands

Accord Healthcare Polska Sp.z o.o.

ul. Lutomierska 50

95-200 Pabianice

The medicine has been authorized in European Economic Area (EEA) member states under the following names:

Date of last revision of the leaflet: December 2024