Methofill

Leaflet accompanying the packaging: information for the user

Methofill, 50 mg/ml, solution for injection in a pre-filled syringe

Methotrexate

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

• Keep this leaflet, so you can read it again if you need to.
• Consult a doctor, pharmacist, or nurse if you have any doubts.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same as yours.
• If you experience any side effects, including any possible side effects not listed in this leaflet, tell your doctor, pharmacist, or nurse (see section 4).

Table of contents of the leaflet

• 1. What is Methofill and what is it used for
• 2. Important information before using Methofill
• 3. How to use 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

The active substance of Methofill is methotrexate.
Methotrexate is a substance characterized by the following properties:

• It inhibits the growth of certain rapidly dividing cells
• It reduces the activity of the immune system (defense mechanisms of the body)
• It has anti-inflammatory effects

Indications for the use of Methofill:

• active rheumatoid arthritis in adult patients,
• polyarticular forms of severe, active juvenile idiopathic arthritis, if the response to non-steroidal anti-inflammatory drugs is insufficient,
• severe, refractory psoriasis, in which a satisfactory response has not been achieved after phototherapy, PUVA therapy, and retinoids, and severe psoriatic arthritis in adult patients,
• Crohn's disease with a mild to moderate course in adult patients, when treatment with other drugs is not possible.

Rheumatoid arthritis (RA) is a chronic disease classified as collagenosis, characterized by inflammation of the synovial membranes lining the joints. The synovial membranes produce fluid that acts as a lubricant for many joints. The inflammatory state causes thickening of the membranes and swelling of the joints.
Juvenile arthritis occurs in children and adolescents under the age of 16. The polyarticular form is indicated by the fact that 5 or more joints are affected within the first 6 months of the disease.
Psoriatic arthritis means inflammation of the joints, especially the fingers of the hands and feet, with psoriatic changes on the skin and nails.
Psoriasis, a common chronic skin disease, is characterized by red patches covered with thick, dry, silvery, tightly adhering scales.
Methofill modifies and slows down the progression of the disease.
Crohn's disease is a type of inflammatory bowel disease that can affect any part of the digestive tract, causing symptoms such as abdominal pain, diarrhea, vomiting, or weight loss.

2. Important information before using Methofill

When not to use 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 liver or kidney disease or blood disorders;
• if the patient regularly consumes large amounts of alcohol;
• if the patient has a severe infection, such as tuberculosis, HIV infection, or other immunodeficiency syndromes;
• if the patient has ulcers in the mouth, stomach, or intestines;
• if the patient is receiving a vaccine containing live microorganisms at the same time;
• if the patient is pregnant or breastfeeding (see "Pregnancy, breastfeeding, and fertility").

Warnings and precautions

Before starting Methofill, discuss with your doctor or pharmacist:

• if you are an elderly person, are weakened, or are in poor general condition;
• if you have liver function disorders;
• if you have dehydration (lack of water in the body);
• if you have diabetes and are being treated with insulin.

During methotrexate treatment, cases of acute bleeding from the lungs have been reported in patients with underlying rheumatologic disease. If you experience coughing up blood, you should immediately consult a doctor.

Special precautions for the use of Methofill

Methotrexate temporarily disrupts the production of sperm and egg cells; in most cases, this effect disappears. Methotrexate can cause miscarriage and severe birth defects. Female patients should avoid becoming pregnant while taking methotrexate and for at least 6 months after stopping treatment. Male patients should avoid fathering a child while taking methotrexate and for at least 3 months after stopping treatment. See also "Pregnancy, breastfeeding, and fertility".

Recommended tests and precautions:

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

Before starting treatment:

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

During treatment:

The doctor may perform the following tests:

• examination of the mouth and throat for mucosal changes, such as inflammation or ulcers;
• blood tests/morphology with an assessment of the number of blood cells and measurement of methotrexate levels in the serum;
• blood tests to monitor liver function;
• imaging tests to monitor liver condition;
• removal of 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 adults, require relatively low doses of methotrexate.
Methotrexate can affect the immune system, vaccination results, and immunological test results. There may be a reactivation of latent chronic diseases (e.g., shingles, tuberculosis, hepatitis B or C). During Methofill treatment, do not use live vaccines.
Methotrexate can increase skin sensitivity to sunlight. Avoid intense sun exposure and do not use a sunbed or sunlamp without consulting a doctor.
To protect your skin from intense sunlight, wear appropriate clothing or use a sunscreen with a high protection factor.
During methotrexate treatment, a recurrence of radiation-induced skin inflammation and sunburn (so-called "recall reaction") may occur. Psoriatic skin lesions may worsen during UV light exposure and concurrent methotrexate administration.
Lymph node enlargement (lymphoma) may occur. In such cases, treatment should be discontinued.
Diarrhea may be a sign of toxic effects of Methofill and requires discontinuation of treatment.
If you experience diarrhea, tell your doctor.
There have been reports of encephalopathy (brain disorder)/leukoencephalopathy (disorder of the white matter of the brain) in oncology patients receiving methotrexate; this cannot be ruled out in patients taking methotrexate for other indications.
If you, your partner, or caregiver notice new or worsening neurological symptoms, including general muscle weakness, vision disturbances, changes in thinking, memory, and orientation leading to disorientation and personality changes, consult a doctor immediately, as these may be symptoms of a very rare, severe brain infection called progressive multifocal leukoencephalopathy (PML).

Methofill and other medicines

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.
Concomitant use of certain medicines may affect the action of Methofill:

• antibiotics (used to prevent and treat certain infections), such as tetracyclines, chloramphenicol, non-absorbable broad-spectrum antibiotics, penicillins, glycopeptides, sulfonamides, ciprofloxacin, and cephalothin (sulfur-containing medicines used to prevent and treat certain infections);
• non-steroidal anti-inflammatory drugs or salicylates (pain-relieving and/or anti-inflammatory medicines);
• probenecid (used to treat gout);
• weak organic acids such as loop diuretics (diuretics) or certain pain-relieving or anti-inflammatory medicines (e.g., acetylsalicylic acid, diclofenac, and ibuprofen) and pyrazoles;
• medicines that can harm bone marrow function, such as trimethoprim-sulfamethoxazole (bactericidal substance) or pyrimethamine;
• other medicines used to treat rheumatoid arthritis, such as leflunomide, sulfasalazine, and azathioprine;
• cyclosporine (a medicine that suppresses the immune system);
• mercaptopurine (a cytostatic medicine);
• retinoids (medicines used to treat psoriasis and other skin diseases);
• theophylline (a medicine used to treat asthma and other lung diseases);
• proton pump inhibitors (used to treat stomach diseases, such as omeprazole and pantoprazole);
• blood glucose-lowering medicines (medicines that lower blood sugar levels).

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

• metamizole (synonyms: novaminsulfon and dipyrone) (a strong pain-relieving and/or antipyretic medicine).

Vitamin products containing folic acid should only be used if prescribed by a doctor, as they may reduce the effect of methotrexate.
Do not receive live vaccines.

Methofill with food, drink, and alcohol

While taking Methofill, avoid consuming alcohol and large amounts of coffee, caffeinated beverages, and black tea.

Pregnancy, breastfeeding, and fertility

Pregnancy
Do not use Methofill if you are pregnant or trying to become pregnant. Methotrexate can cause birth defects, harm the unborn baby, or cause miscarriage.
This is related to developmental abnormalities of the skull, face, heart, and blood vessels, brain, and limbs. Therefore, it is very important that female patients who are pregnant or planning to become pregnant do not take methotrexate. If you are of childbearing age, it is essential to confirm that you are not pregnant before starting treatment, by taking a pregnancy test, for example. You should avoid becoming pregnant while taking methotrexate and for at least 6 months after stopping treatment, using reliable contraception methods throughout this time (see also "Warnings and precautions").
If you become pregnant while taking methotrexate or suspect you may be pregnant, consult a doctor as soon as possible. You should receive advice on the potential harmful effects of treatment on the baby.
If you plan to become pregnant, consult your doctor, who may refer you to a specialist for advice before starting treatment.
Male fertility
Available evidence does not indicate an increased risk of birth defects or miscarriages after the father has taken methotrexate at a dose below 30 mg/week. However, this risk cannot be entirely ruled out. Methotrexate can be genotoxic, meaning it can cause genetic mutations. Methotrexate can affect sperm and cause birth defects. Therefore, male patients should avoid fathering a child while taking methotrexate and for at least 3 months after stopping treatment.
Breastfeeding
Stop breastfeeding before starting and during Methofill treatment.

Driving and using machines

While taking Methofill, side effects such as fatigue and dizziness may occur. Therefore, the ability to drive vehicles or operate machines may be impaired in some cases.
If you feel drowsy or tired, do not drive or operate machines.

Methofill contains sodium

The medicine contains less than 1 mmol (23 mg) of sodium per dose, which means it is considered "sodium-free".

3. How to use Methofill

Always use Methofill as directed by your doctor. If you are unsure, consult your doctor or pharmacist.
The doctor will decide on the dosage, which is individualized for each patient.
The effects of treatment are usually visible only after 4-8 weeks.
Methofill is administered subcutaneously (under the skin) by a doctor or healthcare professional, or under their supervision, only once a week. The day of injection should be determined by the patient in consultation with the doctor.

Important warning regarding Methofill dosing (methotrexate):

In the treatment of rheumatoid arthritis, juvenile arthritis, psoriatic arthritis, psoriasis, and Crohn's disease, Methofill should be used only once a week. Using too high a dose of Methofill (methotrexate) can be fatal. Read section 3 of this leaflet carefully. If you have any questions before using this medicine, consult your doctor or pharmacist.
Use in children and adolescents
The doctor will decide on the appropriate dose for children and adolescents with polyarticular juvenile idiopathic arthritis.
Methofill is not recommended for use in children under 3 years of age due to insufficient experience in this age group.
Method and duration of administration
Methofill is injected once a week.
The duration of treatment is determined by the doctor. Treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis, and Crohn's disease with Methofill is long-term.
Initially, Methofill may be administered by medical personnel. However, the doctor may decide that the patient is able to learn self-injection of Methofill. The patient will be properly trained in this regard. Never attempt to self-inject without prior training.
Read the instructions at the end of the leaflet.
Remember to use the entire contents of the pre-filled syringe.
The method of handling and disposal must be the same as for other cytostatic medicines and in accordance with local regulations. Pregnant women should not handle or administer Methofill.
Avoid contact between methotrexate and skin or mucous membranes. In case of contamination, rinse the affected area thoroughly with water.

Overdose of Methofill

In case of overdose, tell your doctor immediately.

Missed dose of Methofill

Do not take a double dose to make up for a missed dose.

Stopping Methofill treatment

If you stop taking Methofill, tell your doctor immediately.
If you feel that the effect of Methofill is too strong or too weak, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, Methofill can cause side effects, although not everybody gets them.
The frequency and severity of side effects depend on the dose and frequency of administration of the medicine. Since severe side effects can occur even at low doses, regular medical check-ups are necessary. The doctor should perform tests to rule out abnormalities in blood parameters (e.g., low white blood cell count, low platelet count, and lymphoma) and changes in liver and kidney function.
Tell your doctor immediatelyif you experience any of the following symptoms, as they may indicate severe, potentially life-threatening side effects that require urgent treatment:

• Persistent, non-productive dry cough, shortness of breath, and fever; these may be symptoms of pneumonia [common]
• Coughing up blood; these may be symptoms of pulmonary bleeding [frequency unknown]
• Signs of liver damage, such as yellowing of the skin and whites of the eyes; methotrexate can cause chronic liver damage (liver cirrhosis), scarring (liver fibrosis), fatty liver degeneration [all uncommon], acute liver inflammation (acute hepatitis) [rare], and liver failure [very rare]
• Allergy symptoms, such as skin rash, including red, itchy skin, swelling of hands, feet, ankles, face, lips, mouth, or throat, which may cause difficulty swallowing or breathing and a feeling of impending faint; these may be symptoms of severe allergic reactions or anaphylactic shock [rare]

Other side effects that may occur:

• Signs of kidney damage, such as swelling of hands, feet, or ankles, or changes in urine frequency or volume (oliguria or anuria); these may be symptoms of kidney failure [rare]
• Infection symptoms, such as fever, chills, pain, or sore throat; methotrexate can increase the risk of infections. Severe infections, such as a specific type of pneumonia (Pneumocystis jirovecii pneumonia) or blood poisoning (sepsis), may occur [rare]
• Symptoms such as weakness on one side of the body (stroke) or pain, swelling, redness, and warmth in one leg (deep vein thrombosis); the cause may be a blood clot that blocks the blood vessel (thromboembolic event) [rare]
• Fever and severe deterioration of general health or sudden fever, accompanied by sore throat or mouth ulcers; methotrexate can cause a severe decrease in the number of certain white blood cells (agranulocytosis) and severe bone marrow suppression [very rare]
• Unexpected bleeding, such as bleeding from the gums, blood in the urine, vomit, or appearance of blood blisters; these may be symptoms of a significant decrease in platelet count due to severe bone marrow suppression [very rare]
• Symptoms such as severe headache, often accompanied by fever, stiff neck, nausea, vomiting, disorientation, and sensitivity to lightmay indicate meningitis (inflammation of the membranes surrounding the brain) [very rare]
• in patients with cancer treated with methotrexate, certain brain disorders (encephalopathy/leukoencephalopathy) have been reported; this cannot be ruled out in patients taking methotrexate for other indications. Symptoms of these brain disorders may include: altered mental state, movement disorders (ataxia), vision disturbances, or memory disturbances[frequency unknown]
• Severe skin rash or blisters on the skin (which may also occur in the mouth, eyes, and genital area); these may be symptoms of conditions called Stevens-Johnson syndrome or toxic epidermal necrolysis (Lyell's syndrome) [very rare]

Other side effects that may occur:

• Very common:may occur in more than 1 in 10 people
• mouth ulcers, nausea, loss of appetite, abdominal pain
• abnormal liver function test results (increased AST, ALT, alkaline phosphatase, and bilirubin levels)

Common:may occur in up to 1 in 10 people

• mouth ulcers, diarrhea
• skin rash, redness, itching
• headache, fatigue, drowsiness
• decreased production of blood cells, leading to a decrease in white blood cells, red blood cells, and/or platelets

Uncommon:may occur in up to 1 in 100 people

• pharyngitis
• enteritis, vomiting, pancreatitis, black or tarry stools, gastrointestinal ulcers, and bleeding
• reactions similar to sunburn, increased sensitivity of the skin to sunlight, hair loss, increased number of rheumatoid nodules, skin ulcers, shingles, vasculitis, rash similar to herpes, hives
• diabetes onset
• dizziness, confusion, depression
• decreased serum albumin levels
• decreased platelet count
• inflammation and ulcers of the bladder or vagina, kidney function disorders, urination disorders
• joint pain, muscle pain, decreased bone mass

Rare:may occur in up to 1 in 1,000 people

• gingivitis
• increased pigmentation of the skin, acne, subcutaneous nodules (erythema nodosum)
• allergic vasculitis
• decreased antibody levels in the blood
• infections (including reactivation of latent chronic infections), conjunctivitis
• mood changes
• vision disturbances
• pericarditis, pericardial effusion, impaired cardiac filling due to pericardial effusion
• low blood pressure
• pulmonary fibrosis, dyspnea, asthma, pleural effusion
• stress fractures
• electrolyte disturbances
• fever
• wound healing disorders

Very rare:may occur in up to 1 in 10,000 people

• severe bleeding, acute toxic dilation of the colon (toxic megacolon)
• increased pigmentation of the nails, acute paronychia (infection of the nail bed), deep infection of the hair follicles (furunculosis), visible dilation of small blood vessels
• local damage (sterile abscess, changes in fatty tissue) at the injection site
• pain, muscle weakness, or numbness, tingling, or altered sensation, metallic taste, seizures, paralysis, meningeal reaction
• impaired vision, non-inflammatory eye disease (retinopathy)
• decreased libido, impotence, gynecomastia in men, sperm disorders (oligospermia), menstrual disorders, vaginal discharge
• lymphoma
• lymphoproliferative disorders (overproduction of white blood cells)

Frequency unknown:cannot be estimated from available data

• increased white blood cell count
• nosebleeds
• proteinuria
• weakness
• pulmonary bleeding
• bone damage in the jaw (due to overproduction of white blood cells)
• tissue damage at the injection site
• skin redness and peeling
• edema

Subcutaneously administered methotrexate doses are locally well-tolerated. Only mild, local skin reactions (such as burning, redness, swelling, discoloration, itching, intense itching) that decrease during treatment have been observed.

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 Adverse Reaction Monitoring 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.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Methofill

Keep the medicine out of sight and reach of children.
Store at a temperature below 30°C.
Store the pre-filled syringes in the outer packaging to protect them from light.
Do not use this medicine after the expiry date stated on the label/carton after EXP.
The expiry date refers to the last day of the month.
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 packaging and other information

What Methofill contains

• The active substance is methotrexate. 1 ml of solution contains methotrexate disodium equivalent to 50 mg of methotrexate.
• The other ingredients are sodium chloride, sodium hydroxide (to adjust pH), and water for injections.

What Methofill looks like and contents of the packaging

Methofill is a clear, yellow to brown solution in pre-filled syringes.
The pre-filled syringe has a protective needle shield. The packaging contains pre-filled syringes with a fixed needle and a protective shield. The pre-filled syringe packaging is designed for single use and contains a pre-filled syringe with a fixed needle and a protective shield.
The following packaging sizes are available:
Pre-filled syringes containing 0.15 ml, 0.20 ml, 0.30 ml, and 0.40 ml of solution are available in packaging containing 1, 2, 4, 5, 6, 8, 10, 12, or 24 pre-filled syringes with fixed needles and shields. The pre-filled syringe has a protective needle shield.
Pre-filled syringes containing 0.25 ml, 0.35 ml, 0.45 ml, 0.55 ml, and 0.60 ml of solution are available in packaging containing 1, 4, 5, 6, 8, or 12 pre-filled syringes with fixed needles and shields. The pre-filled syringe has a protective needle shield.
Pre-filled syringes containing 0.50 ml of solution are available in packaging containing 1, 2, 4, 5, 6, 8, 10, or 12 pre-filled syringes with fixed needles and shields. The pre-filled syringe has a protective needle shield.
Not all packaging 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

Accord Healthcare Polska Sp. z o.o.
ul. Lutomierska 50
95-200 Pabianice

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

Date of last revision of the leaflet: December 2024

Instructions for use

Read the instructions below carefully before starting the injection and always follow the injection technique recommended by your doctor, pharmacist, or nurse.
If you have any problems or questions, consult your doctor, pharmacist, or nurse.

Preparation

Choose a well-lit, clean, and flat work surface.
Prepare the necessary items before starting:

• 1 pre-filled syringe of Methofill with a protective needle shield.

Wash your hands thoroughly. Before use, inspect the Methofill pre-filled syringe for visible damage (or cracks).
The best injection sites include:

• the upper thigh,
• the abdomen, except for the navel area.
• If someone else is helping you with the injection, they can also inject into the back of the arm, just below the shoulder.
• Each time, choose a different injection site. This helps to reduce the risk of irritation at the injection site.
• Never inject into an area that is painful, bruised, red, hard, scarred, or has stretch marks. In the case of psoriasis, do not inject into raised, thickened, red, or scaly areas of the skin or lesions.
• 1. Injecting the solution

Remove the pre-filled syringe from the packaging and read the leaflet carefully.
Remove the pre-filled syringe from the packaging at room temperature.

• 2. Disinfection

Choose an injection site and disinfect it with an alcohol swab.
Wait at least 60 seconds for the disinfectant to dry.

• 3. Check if the pre-filled syringe mechanism is damaged

Do not use the product:

• if there is any visible damage (the syringe or needle shield is broken) or if any parts are missing.
• if the needle shield is in the safety position before use, as shown in Figure 7, indicating that it has already been used. The product should not be used if the appearance of the pre-filled syringe does not match the drawing in Figure 3. If so, the product should be discarded into a sharps disposal container
• 4. Remove the plastic protective cap

Hold the pre-filled syringe by the needle shield with the needle facing away from you, without touching the plunger.
With your other hand, remove the needle shield and discard it into a sharps disposal container.

• 5. Insert the needle

Gently grasp the skin at the injection site with one hand, and with your other hand, without touching the plunger, insert the needle into the skin at a 90-degree angle

• 6. Inject the solution

Use your thumb to press the plunger and inject the contents of the syringe with a firm motion.
Hold the skin fold stable until the injection is complete.

• 7. Needle safety system

The safety system is activated when the plunger is fully depressed.
While holding the syringe, release the pressure on the plunger by slowly lifting your thumb.
The plunger will move up with your thumb, and the spring will cause the needle to retract, automatically covering it with the shield.

• 8. Remove the shield

After using the syringe, discard the remaining shield with the needle into a sharps disposal container.

Do not dispose of it in a regular trash can.

Methotrexate should not come into contact with skin or mucous membranes.
In case of contact, rinse the affected area thoroughly with water.

Disposal and handling

The method of handling and disposal of the medicine and pre-filled syringe must be in accordance with local regulations. Pregnant healthcare workers should not prepare or administer Methofill.