Methofill sd

Package leaflet: Information for the patient

Methofill SD, 7.5 mg, solution for injection in pre-filled syringe
Methofill SD, 10 mg, solution for injection in pre-filled syringe
Methofill SD, 12.5 mg, solution for injection in pre-filled syringe
Methofill SD, 15 mg, solution for injection in pre-filled syringe
Methofill SD, 17.5 mg, solution for injection in pre-filled syringe
Methofill SD, 20 mg, solution for injection in pre-filled syringe
Methofill SD, 22.5 mg, solution for injection in pre-filled syringe
Methofill SD, 25 mg, solution for injection in pre-filled syringe
Methofill SD, 27.5 mg, solution for injection in pre-filled syringe
Methofill SD, 30 mg, solution for injection in pre-filled syringe
Methotrexatum
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet so that you can read it again if necessary.
• Consult your doctor, pharmacist, or nurse if you have any questions.
• This medicine has been prescribed for a specific individual. Do not share it with others. This medicine may harm another person, even if their symptoms are the same.
• If you experience any adverse reactions, including any possible adverse reactions not listed in this leaflet, inform your doctor, pharmacist, or nurse (see section 4).

Contents of the leaflet

1. What Methofill SD is and what it is used for
2. Important information before using Methofill SD
3. How to use Methofill SD
4. Possible side effects
5. How to store Methofill SD
6. Contents of the pack and other information

1. What Methofill SD is and what it is used for

The active substance in Methofill SD is methotrexate.
Methotrexate has the following properties:

• Inhibits the growth of certain rapidly dividing cells
• Reduces the activity of the immune system (the body's defense mechanisms)
• Has anti-inflammatory effects

Indications for Methofill SD:

• Rheumatoid arthritis in adults (RA) – a chronic disease characterized by inflammation of the membranes lining the joints. Synovial membranes produce fluid that acts as a lubricant for many joints. Inflammation causes thickening of the membranes and joint swelling.
• Polyarticular juvenile idiopathic arthritis in children and adolescents under 16 years of age, when treatment with non-steroidal anti-inflammatory drugs (NSAIDs) has been ineffective.
• Severe psoriatic arthritis in adults (psoriatic arthritis particularly affects fingers and toes, with psoriatic skin and nail changes).
• Severe psoriasis resistant to other treatments (psoriasis is a common chronic skin disease characterized by red patches covered with thick, dry, silvery, tightly adherent scales).
• Crohn's disease in adults (an inflammatory bowel disease causing symptoms such as abdominal pain, diarrhea, vomiting, or weight loss).

Methofill SD modifies and slows the progression of the disease.

2. Information before using Methofill SD

When not to use Methofill SD

• 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, kidney, or blood disease;
• 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 section "Pregnancy, breastfeeding and fertility").

Warnings and precautions
Before starting treatment with Methofill SD, discuss with your doctor or pharmacist:

• if the patient is elderly, weakened, or in poor general condition;
• if the patient has impaired liver function;
• if the patient has dehydration (lack of water in the body);
• if the patient has diabetes and is being treated with insulin.

Cases of acute pulmonary haemorrhage have been reported in patients with underlying rheumatological disease treated with methotrexate. If the patient experiences haemoptysis (coughing up blood-stained sputum), medical advice should be sought immediately.
Special precautions for the use of Methofill SD
Methotrexate temporarily impairs the production of sperm and egg cells; this effect usually resolves in most cases. Methotrexate may cause miscarriage and severe congenital malformations. The female patient should avoid becoming pregnant during treatment with methotrexate and for at least 6 months after treatment has ended. Male patients should avoid impregnating their partner during treatment with methotrexate and for at least 3 months after treatment has ended. See also section "Pregnancy, breastfeeding and fertility".
Recommended monitoring tests and precautions:
Even when methotrexate is used in low doses, serious adverse reactions may occur. To detect them early, your doctor must perform regular check-ups and laboratory tests.
Before starting treatment
Before starting treatment, blood tests will be performed to check whether the patient has an adequate number of blood cells. Blood will also be tested for liver function to determine whether the patient has hepatitis. Additionally, serum albumin (a blood protein), presence of hepatitis (liver infection), and kidney function will be assessed. The doctor may also decide to perform other liver tests. Some of these may include imaging tests, while others may require taking a small tissue sample from the liver for more detailed examination. The doctor may also check whether the patient has tuberculosis, order a chest X-ray, or perform lung function tests.
During treatment
The doctor may perform the following tests:

• examination of the mouth and throat for mucosal changes, such as inflammation or ulceration;
• blood tests including complete blood count to assess blood cell counts and measurement of methotrexate serum concentration;
• blood tests to monitor liver function;
• imaging tests to monitor liver status;
• taking a small tissue sample from the liver for more detailed 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 all scheduled check-ups.
If any of these test results 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 adverse reactions as early as possible. Age-related impairments in liver and kidney function, as well as low folate reserves in older age, require relatively low doses of methotrexate.
Methotrexate may affect the immune system and vaccination outcomes. It may also affect the results of immunological tests. During treatment with methotrexate, reactivation of latent chronic diseases (e.g. shingles, tuberculosis, hepatitis B or C) may occur.
During treatment with Methofill SD, live vaccines must not be administered.
Methotrexate may increase skin sensitivity to sunlight. Avoid intense sun exposure and do not use sunbeds or tanning lamps without consulting your doctor. To protect the skin from strong sunlight, wear appropriate clothing or use a high-protection sunscreen.
During methotrexate treatment, recurrence of skin inflammation caused by radiotherapy or sunburn (so-called "recall reaction") may occur. Psoriatic skin lesions may worsen during UV light exposure and concurrent methotrexate administration.
Lymph node enlargement (lymphadenopathy) may occur. In such a case, treatment should be discontinued.
Diarrhoea may be a sign of toxic effects of Methofill SD and requires discontinuation of treatment. If the patient develops diarrhoea, inform the doctor immediately.
Cases of certain brain disorders (encephalopathy/leukoencephalopathy) have been reported in oncology patients receiving methotrexate. These adverse effects cannot be ruled out in patients receiving methotrexate for other indications.
If the patient, their partner, or caregiver notice new onset or worsening of neurological symptoms, including general muscle weakness, visual disturbances, changes in thinking, memory, and orientation leading to disorientation, and personality changes, seek immediate medical advice, as these may be symptoms of a very rare but serious brain infection called progressive multifocal leukoencephalopathy (PML).
Methofill SD and other medicines
Inform your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take. This includes medicines the patient may take in the future.
Concurrent use of certain medicines may affect the action of Methofill SD:

• antibiotics such as tetracyclines, chloramphenicol, non-absorbable broad-spectrum antibiotics, penicillins, glycopeptides, sulfonamides, ciprofloxacin, and cephalothin (medicines used to prevent and treat certain infections);
• non-steroidal anti-inflammatory drugs or salicylates [painkillers and (or) anti-inflammatory medicines such as acetylsalicylic acid, diclofenac, ibuprofen, or pyrazoles];
• probenecid (used in the treatment of gout);
• weak organic acids such as loop diuretics (diuretics);
• medicines that may adversely affect bone marrow function, e.g. trimethoprim-sulfamethoxazole (a bactericidal agent) or pyrimethamine;
• other medicines used in the treatment of rheumatoid arthritis, such as leflunomide, sulfasalazine, and azathioprine;
• cyclosporine (an immunosuppressive medicine);
• mercaptopurine (a cytostatic medicine);
• retinoids (medicines for psoriasis and other skin diseases);
• theophylline (a medicine for bronchial asthma and other lung diseases);
• certain medicines used for stomach disorders, such as omeprazole and pantoprazole;
• hypoglycaemic medicines (medicines that reduce blood sugar levels).

It is particularly important to inform the doctor about the use of the following substance:

• metamizole (synonyms: novaminsulfone and dipyrone) (a strong painkiller and/or antipyretic).

Vitamin products containing folic acid should only be used if prescribed by a doctor, as they may reduce the effectiveness of methotrexate.
Methofill SD with food, drink, and alcohol
During treatment with Methofill SD, avoid consuming alcohol and large amounts of coffee, caffeine-containing beverages, and black tea.
Pregnancy, breastfeeding and fertility
Pregnancy
Do not use Methofill SD if the patient is pregnant or trying to become pregnant. Methotrexate may cause congenital malformations, harm the unborn child, or cause miscarriage. This is associated with developmental defects of the skull, face, heart and blood vessels, brain, and limbs. Therefore, it is very important that women who are pregnant or planning pregnancy do not take methotrexate. If the patient is of childbearing age, it is essential to definitively confirm before starting treatment that she is not pregnant, by taking appropriate measures, such as performing a pregnancy test. The patient should avoid becoming pregnant during methotrexate treatment and for at least 6 months after its completion, using reliable contraception methods throughout this period (see also section "Warnings and precautions").
If the patient becomes pregnant during treatment or suspects she may be pregnant, she should consult her doctor as soon as possible. The patient should seek advice regarding the potential harmful effects of treatment on the child.
If the patient plans to become pregnant, she should consult her treating doctor, who may refer her to a specialist for advice before planned treatment initiation.
Male fertility
Available evidence does not indicate an increased risk of developmental defects or miscarriages following paternal exposure to methotrexate at doses below 30 mg/week. However, a risk cannot be completely ruled out. Methotrexate may be genotoxic, meaning it may cause genetic mutations. Methotrexate may affect sperm and cause congenital malformations. Therefore, the patient should avoid impregnating his partner and must not be a sperm donor during methotrexate treatment and for at least 3 months after its completion.
Breastfeeding
Breastfeeding must be discontinued before starting and during treatment with Methofill SD.
Driving and operating machinery
During treatment with Methofill SD, adverse effects on the central nervous system may occur, such as fatigue and dizziness. Therefore, the ability to drive motor vehicles and/or operate machinery may be impaired in some cases. If the patient feels drowsy or fatigued, driving or operating machinery should not be undertaken.
Methofill SD contains sodium
The medicine contains less than 1 mmol (23 mg) of sodium per dose, meaning the medicine is considered "sodium-free".

3. How to use Methofill SD

This medicine should always be used exactly as prescribed by your doctor. If in doubt, consult
your doctor or pharmacist.
Your doctor will determine the dosage, which is individually adjusted to the patient.
Therapeutic effects are usually observed only after 4–8 weeks of treatment.
Methofill SD is administered subcutaneously (under the skin) by a doctor or trained medical
personnel, or under their supervision, once weekly only. The day of injection should be agreed
upon by the patient and the doctor.
Important warning regarding dosing of Methofill SD (methotrexate):
In the treatment of rheumatoid arthritis, juvenile arthritis, psoriatic arthritis, psoriasis, and
Crohn’s disease, Methofill SD must be used once weekly only. Administration of an excessive
dose of Methofill SD (methotrexate) may be fatal. Carefully read section 3 of this leaflet. If you
have any questions before using this medicine, consult your doctor or pharmacist.

Use in children and adolescents
The appropriate dose for children and adolescents with polyarticular juvenile idiopathic
arthritis is determined by the doctor.
Methofill SD is not recommended for use in children under 3 years of age due to insufficient
experience in this age group.

Method and timing of administration
Methofill SD is administered once a week!
The duration of treatment is determined by the treating physician. Treatment with Methofill SD
for rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis, psoriatic arthritis, and Crohn’s
disease is long-term.
Methofill SD should be prescribed only by physicians familiar with the properties and mode of
action of the medicine. The treating physician may decide that the patient can self-administer
Methofill SD subcutaneously.
At the beginning of treatment, Methofill SD may be administered by medical personnel.
However, the doctor may determine that the patient is capable of self-injecting Methofill SD.
The patient will receive appropriate training for this purpose.
Never attempt self-injection without prior training.
For single use only. The entire contents of the pre-filled syringe must be used.
Disposal must be handled in the same manner as for other cytostatic drugs and in accordance
with local regulations. Pregnant women should not use or administer Methofill SD.
Avoid contact of methotrexate with skin surfaces or mucous membranes. In case of contamination,
the affected area should be immediately and thoroughly rinsed with water.

Administration instructions:
Read the full instructions for use of Methofill SD in the pre-filled syringe.
Self-administration of the pre-filled syringe requires proper training by a physician.
If you have any doubts, contact your doctor, pharmacist, or nurse.

Before starting administration:

• Choose a clean, well-lit area,
• Check the expiry date; do not use if expired,
• Prepare an alcohol swab and a waste container.

Preparation for administration:

• Wash hands with warm water and soap

• Select injection site (abdomen or thigh if the patient self-injects, or optionally the upper outer arm if the injection is administered by a doctor or caregiver)

• Clean the area around the selected injection site with an alcohol swab. Allow to dry.

Before injection:

• Visually inspect the solution for discoloration, cloudiness, or presence of particles.
• Remove the protective plastic cap: twist and pull downward to remove. After removing the cap, do not touch the needle shield. Discard the cap and do not replace it. Do not administer the injection if the syringe has been pressed after removing the cap.
• Administer the injection within 5 minutes after removing the cap.

Injection:

• Place the pre-filled syringe against the selected injection site at a 90° angle.
• Press the plunger steadily until the full dose is administered. Inject at a comfortable speed for the patient. Do not move the syringe during administration.

• Full depression of the plunger is indicated by a distinct click; the orange part of the dose indicator becomes invisible.
• After completion of the injection, a yellow ring becomes visible, indicating activation of the needle safety shield.

Disposal of used syringe:

• Dispose of the used Methofill SD pre-filled syringe by placing it in a sharps container. Disposal guidelines may vary depending on country/region. For current guidelines, contact your doctor or pharmacist. Do not dispose of the used syringe in regular household waste.

Avoid contact of methotrexate with skin and mucous membranes. In case of contamination,
the affected area should be immediately and thoroughly rinsed with water.
If the patient or someone in their household is injured with the syringe needle, inform the
doctor immediately and do not use this syringe.

Accidental overdose of Methofill SD
If more than the prescribed dose has been administered, inform your doctor immediately.

Missed dose of Methofill SD
Do not administer a double dose to make up for a missed dose.

Stopping Methofill SD treatment
If treatment with Methofill SD is interrupted, inform your doctor immediately.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
The frequency and severity of adverse reactions depend on the dose size and frequency of administration.
Since severe adverse reactions may occur even after administration of small doses, regular medical examinations are necessary.
Your doctor should order tests to rule out abnormalities in blood parameters (e.g. low white blood cell count, low platelet count, lymphadenopathy) and changes in liver and kidneys.
You should inform your doctor immediately if any of the following symptoms occur in the patient, as they may indicate severe, potentially life-threatening adverse reactions requiring urgent treatment:

• persistent, non-productive dry cough, dyspnea, and fever; these may be symptoms of pneumonitis [common]
• haemoptysis, i.e. coughing up sputum containing blood; these may be symptoms of pulmonary haemorrhage [frequency unknown]
• signs of liver damage such as yellowing of the skin and whites of the eyes (jaundice); methotrexate may cause chronic liver damage (liver cirrhosis), scar tissue formation (liver fibrosis), fatty degeneration of the liver (hepatic steatosis) [all uncommon], inflammation of the liver (acute hepatitis) [rare], and liver failure [very rare]
• signs of hypersensitivity such as skin rash, including red, itchy skin, swelling of hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty in swallowing or breathing and a feeling of impending fainting); these may be symptoms of severe allergic reactions or anaphylactic shock [rare]
• signs of kidney damage such as swelling of hands, ankles, or feet or changes in frequency of urination (oliguria) or reduced volume or absence of urine (anuria); these may be symptoms of kidney failure [rare]
• signs of infection, e.g. fever, chills, malaise, sore throat; methotrexate may increase susceptibility to infections. Severe infections such as a specific type of pneumonia (pneumonia caused by Pneumocystis jirovecii) or blood poisoning (sepsis) [rare]
• symptoms such as: weakness on one side of the body (stroke) or pain, swelling, redness and warmth sensation in one leg (deep vein thrombosis). This may occur when a blood clot blocks a blood vessel (thromboembolic event) [rare]
• fever and severe worsening of general health or sudden fever accompanied by sore throat or mouth ulcers or urinary disturbances; methotrexate may cause acute reduction in white blood cell count (agranulocytosis) and severe bone marrow suppression [very rare]
• unexpected bleeding, e.g. bleeding gums, blood in urine, in vomit, or appearance of petechiae (small red or purple spots on the skin due to bleeding); these may be symptoms of significant reduction in platelet count due to severe bone marrow suppression [very rare]
• symptoms such as: severe headache often accompanied by fever, neck stiffness, nausea, vomiting, disorientation, and photophobia; these may indicate meningitis (acute aseptic meningitis) [very rare]
• in cancer patients receiving methotrexate, certain brain disorders (encephalopathy/leukoencephalopathy) have been reported. Such adverse reactions cannot be excluded when methotrexate treatment is used for other diseases. Symptoms of such brain disorders may include: altered mental status, motor disturbances (ataxia), visual disturbances or memory impairment [frequency unknown]
• severe skin rash or blisters on the skin (may also occur in the mouth, eyes and genital organs); these may be symptoms of very rare conditions called Stevens-Johnson syndrome or toxic epidermal necrolysis (Lyell's syndrome) [very rare]

Below are other adverse reactions that may occur:
Very common: may affect more than 1 in 10 people

• stomatitis, dyspepsia, nausea, loss of appetite, abdominal pain
• abnormal liver function test results (AspAT, AlAT, bilirubin, alkaline phosphatase)

Common: may affect up to 1 in 10 people

• oral mucosal ulcers, diarrhoea
• rash, skin redness, pruritus
• headache, fatigue, somnolence
• reduced blood cell production leading to decreased white blood cells and/or red blood cells and/or platelets

Uncommon: may affect up to 1 in 100 people

• pharyngitis
• enteritis, vomiting, pancreatitis, black or tarry stools, gastrointestinal ulcers and bleeding
• sunburn-like reactions due to increased skin sensitivity to sunlight, hair loss, increase in number of rheumatoid nodules, herpes zoster, vasculitis, herpes-like rash, urticaria
• onset of diabetes
• dizziness, confusion, depression
• decreased albumin concentration in plasma
• decreased number of all blood cells, including platelets
• inflammation and ulceration of the urinary bladder or vagina, kidney function disorders, urinary disorders
• joint pain, muscle pain, decreased bone mass

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

• gingivitis
• increased skin pigmentation, acne, blue spots on the skin due to bleeding from blood vessels (petechiae, purpura)
• hypersensitivity vasculitis
• decreased concentration of antibodies in blood
• infection (including reactivation of inactive, chronic infection), eye redness (conjunctivitis)
• mood changes
• visual disturbances
• pericarditis, fluid accumulation in the pericardium, impaired heart chamber filling due to fluid accumulation in the pericardium
• low blood pressure
• scar tissue formation in the lungs (pulmonary fibrosis), dyspnea and bronchial asthma, fluid accumulation in the pleura
• stress fractures of bones
• electrolyte disturbances
• fever, impaired wound healing

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

• acute toxic megacolon (toxic dilation of the colon)
• increased nail pigmentation, inflammation of the nail fold (acute paronychia), deep infection of hair follicles (furunculosis), visible enlargement of small blood vessels
• local tissue damage (formation of sterile abscess, changes in fatty tissue) at the injection site
• pain, loss of muscle strength, or numbness, tingling, reduced sensitivity to stimuli, taste disturbances (metallic taste), seizures, paralysis, acute aseptic meningitis
• non-inflammatory eye disease (retinopathy), visual impairment
• decreased libido, impotence, gynaecomastia in males
• disturbances in sperm production (oligospermia), menstrual disorders, vaginal discharge
• enlarged lymph nodes (lymphadenopathy)
• lymphoproliferative disorders (overproduction of white blood cells)

Frequency unknown: cannot be estimated from available data

• increased number of certain white blood cells
• nosebleeds
• proteinuria
• weakness (asthenia)
• pulmonary haemorrhage
• jaw bone damage (due to overproduction of white blood cells)
• tissue necrosis at injection site
• skin redness and peeling
• oedema

Subcutaneously administered doses of methotrexate are generally well tolerated locally. Only mild, local skin reactions (such as burning sensation, erythema, swelling, discoloration, pruritus, intense itching, pain) have been observed, which tend to diminish during treatment.
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, you should inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions 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
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Methofill SD

Keep the medicine out of sight and reach of children.
Store below 30°C.
Store in the original packaging to protect from light.
Do not use this medicine after the expiry date stated on the label or carton after EXP. The expiry date refers to the last day of the stated month.
Do not use Methofill SD if the patient notices any changes in the colour of the solution or the presence of solid particles.
Medicines must not be disposed of via wastewater or household waste. Ask a pharmacist how to dispose of medicines no longer required. Such measures will help protect the environment.

6. Contents of the pack and other information

What Methofill SD contains
The active substance is methotrexate.
1 pre-filled syringe with 0.15 ml solution contains 7.5 mg of methotrexate.
1 pre-filled syringe with 0.20 ml solution contains 10 mg of methotrexate.
1 pre-filled syringe with 0.25 ml solution contains 12.5 mg of methotrexate.
1 pre-filled syringe with 0.30 ml solution contains 15 mg of methotrexate.
1 pre-filled syringe with 0.35 ml solution contains 17.5 mg of methotrexate.
1 pre-filled syringe with 0.40 ml solution contains 20 mg of methotrexate.
1 pre-filled syringe with 0.45 ml solution contains 22.5 mg of methotrexate.
1 pre-filled syringe with 0.50 ml solution contains 25 mg of methotrexate.
1 pre-filled syringe with 0.55 ml solution contains 27.5 mg of methotrexate.
1 pre-filled syringe with 0.60 ml solution contains 30 mg of methotrexate.
The other ingredients are: sodium chloride, sodium hydroxide (for pH adjustment) and water for injections.

What Methofill SD looks like and contents of the pack
The medicine in the pre-filled syringe is a clear, yellow to brown solution.
The following pack sizes are available:
Pre-filled syringes containing 0.15 ml, 0.20 ml, 0.25 ml, 0.30 ml, 0.35 ml, 0.40 ml, 0.45 ml, 0.50 ml, 0.55 ml and 0.60 ml solution are available in packs of 1, 4 or 8 pre-filled syringes, each in a cardboard carton.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Accord Healthcare Polska Sp. z o.o.
ul. Taśmowa 7
02-677 Warszawa
Tel: +48 22 577 28 00

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

This medicinal product is authorised in the European Economic Area and the United Kingdom (Northern Ireland) under the following names: