Methofill

Package Leaflet: Information for the User

Methofill, 2.5 mg, tablets

Methofill, 10 mg, tablets

Methotrexate

The Methofill tablet should be taken once a week

Read the package leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• Ask your doctor or pharmacist if you have any further questions.
• This medicine has been prescribed for a specific person. Do not give it to others. The medicine may harm another person, even if their symptoms are the same.
• If you experience any side effects, including any possible side effects not listed in this leaflet, tell your doctor or pharmacist (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 pack and other information

1. What is Methofill and what is it used for

Methofill contains the active substance methotrexate. Methotrexate is an antimetabolite and immunosuppressive medicine (a medicine that affects cell growth 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,
• active psoriatic arthritis in adult patients,
• acute lymphoblastic leukemia in adults, adolescents, and children over 3 years of age.

Your doctor will explain how Methofill can help you with your condition.

2. Important information before taking Methofill

When not to take Methofill

• if you are allergic to methotrexate or any of the other ingredients of this medicine (listed in section 6);
• if you have severe kidney failure (or your doctor considers it severe)
• if you have liver function disorders
• if you have blood disorders, such as bone marrow hypoplasia, leukopenia, thrombocytopenia, or significant anemia
• if you abuse alcohol
• if you have a weakened immune system
• if you have a serious infection, such as tuberculosis or HIV
• if you have stomach or intestinal ulcers
• if you have oral mucositis or oral ulcers
• if you are breastfeeding, and also with non-oncological indications (in non-cancer treatment)
• if you are pregnant (see "Pregnancy, breastfeeding, and fertility")
• if you have recently been vaccinated with a live vaccine or are about to receive one

Recommended tests and precautions

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

Before starting treatment:

Before starting treatment, your blood will be tested to check if you have a sufficient number of blood cells. Your blood will also be tested for liver function to see if you have liver inflammation. Additionally, serum albumin (protein in the blood), the presence of liver inflammation (liver infection), and kidney function will be checked. Your 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. Your doctor may also check if you have tuberculosis, order a chest X-ray, or test lung function.

During treatment:

Your doctor may perform the following tests:

• examination of the mouth and throat for mucosal 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 that the patient attends 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 their doctor to detect any adverse reactions as early as possible. Age-related disorders of liver and kidney function, as well as low folate reserves in the elderly, require relatively low doses of methotrexate.

Warnings and precautions

Important warning about Methofill dose (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, talk to your doctor or pharmacist before taking this medicine.
Before starting Methofill, tell your doctor or nurse:

• if you have diabetes treated with insulin
• if you have inactive, chronic infections (e.g., tuberculosis, viral hepatitis B or C, shingles), as they may worsen
• if you have ever had liver or kidney disease
• if you have lung 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, oral mucositis)

Methotrexate may increase skin sensitivity to sunlight. Avoid intense sun exposure and do not use a sunbed or tanning lamp without consulting your doctor. To protect your skin from intense sunlight, 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 radiation recall).
Psoriatic skin lesions may worsen during methotrexate treatment if you are exposed to UV light.
Patients taking low doses of methotrexate may experience lymph node enlargement (lymphoma) and should discontinue treatment in such cases.
Methotrexate has been associated with acute pulmonary hemorrhage in patients with underlying rheumatologic disease. If you experience hemoptysis (coughing up blood), contact your doctor immediately.
Diarrhea is a possible side effect of Methofill and requires discontinuation of treatment.
If you experience diarrhea, talk to your doctor.
In patients with cancer treated with methotrexate, certain brain disorders (encephalopathy/leukoencephalopathy) have been reported. Such adverse reactions 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 fathering a child 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. Your doctor must perform tests and laboratory tests to detect them as early as possible.
If you, your partner, or caregiver notice new onset or worsening of neurological symptoms, including general muscle weakness, vision disturbances, changes in thinking, memory, and orientation leading to disorientation and personality changes, contact your doctor immediately, 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 closely monitored by their doctor to detect any significant adverse reactions early.
This medicine is not recommended for use in children under 3 years of age, as experience in this age group is limited.

Methofill and other medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take, including those available without a prescription and herbal or natural products.
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 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 medicines, such as acetylsalicylic acid, diclofenac, and ibuprofen or pyrazole)
• live vaccines
• diuretics that reduce fluid retention
• medicines that lower blood sugar, such as metformin
• retinoids (used to treat psoriasis and other skin diseases)
• antiepileptic medicines (to prevent seizures)
• barbiturates (sleeping pills)
• sedatives
• oral contraceptives
• probenecid (for gout treatment)
• antibiotics
• pyrimethamine (for malaria prevention and treatment)
• vitamin preparations containing folic acid
• proton pump inhibitors (for heartburn, ulcers, and other stomach problems)
• theophylline (for breathing problems) and mercaptopurine (for certain types of leukemia)
• anticancer medicines (such as doxorubicin and procarbazine during high-dose methotrexate treatment)
• metamizole (synonyms: novaminsulfone and dipyrone) (a strong painkiller and/or antipyretic)

Methofill with food, drink, and alcohol

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

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy
Do not take Methofill during pregnancy unless your 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 non-oncological indications, in women of childbearing age, pregnancy should be excluded before starting treatment, e.g., using pregnancy tests.
Do not take Methofill tablets if you plan to become pregnant. Avoid becoming pregnant during methotrexate treatment and for at least 6 months after treatment ends. Therefore, use effective contraception (see also "Warnings and precautions") during this entire period.
If you become pregnant during treatment or think you may be pregnant, talk to your doctor as soon as possible. If you become pregnant during treatment, you should receive advice on the risk of harmful effects on the child. If you wish to become pregnant, talk to your doctor, who may refer you to a specialist before planned treatment begins.
Breastfeeding
Do not breastfeed during methotrexate 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 less than 30 mg/week. However, this risk cannot be entirely ruled out, and there is no information on higher doses of methotrexate.
Methotrexate may have genotoxic effects. This means that the medicine may cause genetic mutations. Methotrexate may affect sperm production, which is associated with the possibility of birth defects.
Avoid becoming pregnant 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 male patients treated with methotrexate at doses higher than 30 mg/week, it may be advisable to consider preserving sperm before starting treatment (see also "Warnings and precautions").
Before taking any medicine, consult your doctor or pharmacist.

Driving and using machines

Caution: 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, do not drive vehicles or operate machines.

Methofill contains lactose

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

3. How to take Methofill

Methofill should only be prescribed by doctors who are familiar with the medicine and its effects.
Always take this medicine exactly as your doctor or pharmacist has told you. If you are not sure, ask your doctor or pharmacist.
Incorrect use of Methofill may cause serious side effects, even death.
The duration of treatment is determined by your doctor. Treatment of rheumatoid arthritis, severe psoriasis, and severe psoriatic arthritis with Methofill is long-term.
Recommended dose
Your doctor will decide what dose of Methofill you should take, depending on the disease being treated, its severity, and your overall health. Follow your doctor's instructions exactly, and take the medicine as directed.

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

Take Methofill only once a week.
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.
Your doctor may increase the dose if the initial dose is not effective but is well tolerated.
Your doctor may adjust the dose based on the response to treatment and side effects.
Dosing in acute lymphoblastic leukemia (ALL)
Your doctor will inform you about the dose to take and when to take it.
Follow the recommended dose exactly. Take the dose orally, once a week.

Use in children and adolescents

Your doctor will calculate the required dose based on the child's body surface area (m²), and the dose is expressed in mg/m².

Elderly patients

Due to decreased liver and kidney function, as well as lower folate reserves in this patient group, a relatively lower dose should be used.
Methofill 10 mg tablets: The dividing line is only to facilitate breaking the tablet if you have difficulty swallowing it whole.

Safe handling of Methofill

Follow the appropriate procedures for handling cytotoxic agents. When handling methotrexate tablets, wear disposable gloves. If possible, pregnant women should avoid contact with methotrexate tablets.

Taking a higher dose of Methofill than recommended

Follow your doctor's dosing instructions. Never change the dose yourself. If you suspect that you (or someone else) have taken too much Methofill, contact your doctor or go to the emergency department of your nearest hospital immediately. Your doctor will decide if any treatment is needed.
Methotrexate overdose can cause serious reactions. Overdose symptoms may include bleeding, unusual weakness, oral ulcers, nausea, vomiting, black or bloody stools, coughing up blood or coffee-ground-like vomit, and decreased urine output. See also section 4 "Possible side effects".
When visiting your doctor or hospital, bring the medicine package with you. The antidote in case of overdose is calcium folinate.

Missing a dose of Methofill

Never take a double dose to make up for a missed dose, but continue with the prescribed dose. Ask your doctor for advice.

Stopping Methofill treatment

Do not stop taking Methofill without discussing it with your doctor first. If you suspect a serious side effect, contact your doctor immediately.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist

4. Possible side effects

Like all medicines, Methofill can cause side effects, although not everybody gets them.
Tell your doctor immediatelyif you suddenly experience wheezing, difficulty breathing, swelling of the eyelids, face, or lips, rash, or itching (especially if it affects the whole body).
Contact your doctor immediately 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
• unusual bleeding (including bloody vomiting), bruising, or nosebleeds
• nausea, vomiting, abdominal discomfort, or severe diarrhea
• oral 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 impaired 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
• decreased 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 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 (weakened bones)
• 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 1,000 people):

• a blood disorder characterized by the presence of very large red blood cells (megaloblastic anemia)
• mood changes
• weakness of movement, also limited to one side of the body
• severe vision disturbances
• pericarditis, 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

skin rash

• worsening of psoriasis during UV light treatment
• skin changes similar to sunburn or radiation dermatitis
• bone fractures
• kidney failure, decreased or absent urine production, abnormal electrolyte levels in the blood
• impaired sperm production, menstrual disorders

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), meningitis (inflammation of the membrane surrounding the brain), seizures, numbness or tingling, reduced sensitivity to stimuli
• disorders of movement, speech difficulties, memory and orientation changes leading to disorientation and personality changes, feeling of drowsiness or fatigue, feeling of confusion, strange sensations in the head, brain swelling, tinnitus
• eye redness, retinal damage
• fluid accumulation in the lungs, lung infections
• bloody vomiting, severe gastrointestinal complications
• liver failure
• nail infections, nail separation from the nail bed, boils, purple spots due to bleeding from blood vessels, allergic blood vessel inflammation
• protein in the urine
• loss of sex drive, erection problems, vaginal discharge, infertility, breast enlargement in men (gynecomastia)
• fever

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

• abnormal change in brain tissue (leukoencephalopathy)
• bleeding
• hemoptysis* (coughing up blood)
• skin peeling and shedding
• jawbone damage (secondary to excessive white blood cell growth)
• edema *Reported in patients with underlying rheumatologic disease treated with methotrexate.

Methotrexate may decrease the number of white blood cells, 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 oral ulcers, contact your doctor immediately. 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, your doctor will perform tests to check for any changes in your 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 possible side effects not listed in this leaflet, tell your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring, 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

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister/pack after EXP.
The expiry date refers to the last day of the month.
There are no special storage instructions for this medicine.
Blister: Store the blister in the outer packaging to protect from light.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack 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 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.
Tablets are packaged in blisters with orange PVC and aluminum foil.
Blister size: 10, 12, 15, 20, 24, 25, 28, 30, 50, or 100 tablets.
Single-dose blister PVC/Aluminum.
Blister size: 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.
Not all pack sizes may be marketed.

Marketing authorization holder

Accord Healthcare Polska Sp. z o.o.
ul. Taśmowa 7
02-677 Warsaw
Phone: +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

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

Date of last revision of the leaflet: December 2024