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 all of 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 pass it on to others. It may harm other people, even if their symptoms are the same.
• If you experience any adverse effects, including any possible adverse effects not listed in this leaflet, tell 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 is a substance with 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. The synovial membranes produce fluid that acts as a lubricant for many joints. Inflammation causes thickening of these 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 proven ineffective.
• Severe psoriatic arthritis in adults (psoriatic arthritis particularly affects fingers and toes, with psoriatic skin and nail changes).
• Severe, treatment-resistant psoriasis (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. Important 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 simultaneously receiving a vaccine containing live organisms;
• 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 health;
• 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 hemorrhage have been reported in patients with underlying rheumatological disease during methotrexate treatment. If the patient develops hemoptysis (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; in most cases, this effect is reversible. 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 ends. Male patients should avoid impregnating their partner during treatment and for at least 3 months after treatment ends. See also section "Pregnancy, breastfeeding and fertility".
Recommended monitoring tests and precautions:
Even when methotrexate is used in low doses, severe adverse effects may occur. To detect them early, the doctor must perform regular check-ups and laboratory tests.
Before starting treatment
Before treatment begins, blood tests will be performed to check whether the patient has an adequate number of blood cells. Blood will also be tested to assess liver function and to determine whether the patient has hepatitis. In addition, serum albumin (a blood protein), presence of hepatitis (liver infection), and kidney function will be evaluated. 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 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/hematology to assess blood cell counts and measure serum methotrexate concentration;
• blood tests to monitor liver function;
• imaging tests to monitor liver status;
• taking a small tissue sample from the liver for 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 receiving methotrexate should be closely monitored by the doctor to detect any adverse effects 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 the results of vaccinations. It may also affect the results of immunological tests. During methotrexate treatment, latent chronic diseases (e.g., shingles, tuberculosis, hepatitis B or C) may reactivate.
During treatment with Methofill SD, live vaccines must not be administered.
Methotrexate may increase skin sensitivity to sunlight. Exposure to intense sunlight should be avoided, and the use of solariums or tanning lamps is not recommended without consulting a doctor. To protect the skin from intense sunlight, appropriate clothing should be worn or a high-protection sunscreen filter should be applied.
During methotrexate treatment, a recurrence of skin inflammation caused by radiotherapy or sunburn (so-called "recall reaction") may occur. Psoriatic skin lesions may worsen during UV light exposure combined with methotrexate administration.
Lymph node enlargement (lymphadenopathy) may occur. In such a case, treatment should be discontinued.
Diarrhea may be a sign of toxicity from Methofill SD and requires treatment interruption. If the patient develops diarrhea, this should be reported to the doctor.
Cases of certain brain disorders (encephalopathy/leukoencephalopathy) have been reported in oncology patients receiving methotrexate. The occurrence of these adverse effects cannot be ruled out in patients receiving methotrexate for other indications.
If the patient, their partner, or caregiver notices 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, immediate medical advice should be sought, as these may be symptoms of a very rare but serious brain infection called progressive multifocal leukoencephalopathy (PML).
Methofill SD with other medicines
Inform your doctor or pharmacist about all medicines currently used, recently used, or planned for use. This includes any medicines the patient intends to 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 [pain-relieving 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 (diuretic medicines);
• medicines that may adversely affect bone marrow function, e.g., trimethoprim-sulfamethoxazole (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;
• hypoglycemic agents (medicines that reduce blood sugar levels).

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

• metamizole (synonyms: novaminsulfone and dipyrone) (a strong analgesic and (or) antipyretic medicine).

Vitamin products containing folic acid should only be used if recommended by a doctor, as they may reduce the effectiveness of methotrexate.
Methofill SD with food, drink, and alcohol
During treatment with Methofill SD, consumption of alcohol, large amounts of coffee, caffeine-containing beverages, and black tea should be avoided.
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, pregnancy must be definitively ruled out before starting treatment by appropriate measures, such as 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 initiation of treatment.
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, the risk cannot be completely excluded. Methotrexate may be genotoxic. This means that the medicine 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 must be avoided.
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 the doctor. If in doubt, consult
your doctor or pharmacist.
The doctor decides on 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 between the patient and the doctor.
Important warning regarding dosing of Methofill SD (methotrexate):
In the treatment of rheumatoid arthritis, juvenile idiopathic 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. Please 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 determines the appropriate dose for children and adolescents with polyarticular juvenile
idiopathic arthritis.
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 of rheumatoid
arthritis, juvenile idiopathic arthritis, psoriasis, psoriatic arthritis, and Crohn's disease with Methofill
SD is long-term therapy.
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 the
medicine 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 independently.
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 follow procedures equivalent to those for other cytotoxic medicines and in
accordance with local regulations. Pregnant women must not use or administer Methofill SD.
Avoid contact of methotrexate with skin 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 doctor.
If in doubt, contact your doctor, pharmacist, or nurse.

Before 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 thoroughly with soap and warm water.

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

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

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 plunger has been depressed after removing the cap.
• Administer the injection within 5 minutes after removing the cap.

Injection:

• Place the pre-filled syringe perpendicularly (at a 90° angle) against the selected injection site.
• 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 injection, a yellow ring becomes visible, indicating needle shield lockout.

Disposal of waste:

• Dispose of the used Methofill SD pre-filled syringe in a sharps container. Disposal guidelines may vary depending on country/region. For current guidelines, consult 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 a person in their household is accidentally injured by the syringe needle, inform
the doctor immediately and do not use that syringe.

Accidental overdose of Methofill SD
If an overdose is taken, 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 effects

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

• persistent, non-productive dry cough, dyspnoea, 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 not known]
• signs of liver damage such as yellowing of the skin and whites of the eyes; methotrexate may cause chronic liver damage (liver cirrhosis), scar tissue formation (liver fibrosis), fatty degeneration of the liver (fatty liver) [all uncommon], hepatitis (acute hepatitis) [rare], and liver failure [very rare]
• signs of hypersensitivity such as skin rash, including red, itchy skin, swelling of the hands, feet, ankles, face, lips, oral cavity 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 the 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 feeling of warmth in one leg (deep vein thrombosis). This may occur when a blood clot blocks the lumen of a blood vessel (thromboembolic event) [rare]
• fever and severe deterioration in general health or sudden fever accompanied by sore throat or oral cavity pain or disturbances in urination; methotrexate may cause acute decrease 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 decrease in platelet count during 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 effects 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 not known]
• severe skin rash or blisters on the skin (may also occur in the oral cavity, 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]

The following are other adverse effects that may occur:
Very common: may affect more than 1 in 10 people

• inflammation of the mucous membrane of the mouth, 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

• ulceration of the oral mucosa, diarrhoea
• rash, skin redness, itching
• headache, fatigue, somnolence
• reduced blood cell production leading to decreased number of white and/or red blood cells and/or platelets

Uncommon: may affect up to 1 in 100 people

• sore throat
• enteritis, vomiting, pancreatitis, black or tarry stools, ulcers and bleeding from the gastrointestinal tract
• reactions resembling sunburn due to increased sensitivity of the skin to sunlight, hair loss, increase in number of rheumatoid nodules, herpes zoster, vasculitis, herpes-like rash, urticaria
• onset of diabetes
• dizziness, confusion, depression
• decreased serum albumin concentration
• decreased number of all blood cells, including platelets
• inflammatory condition and ulceration of the bladder or vagina, kidney function disorders, disturbances in urination
• 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, ecchymoses)
• 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, disturbances in ventricular filling due to fluid accumulation in the pericardium
• low blood pressure
• scar tissue formation in the lungs (pulmonary fibrosis), dyspnoea 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 dilation of the large intestine (toxic megacolon)
• increased nail pigmentation, inflammation of the skin around the nail (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 or tingling sensation, or reduced response to stimuli, taste disturbances (metallic taste), seizures, paralysis, acute aseptic meningitis
• non-inflammatory eye disease (retinopathy), visual impairment
• decreased libido, impotence, gynaecomastia in men
• disturbances in sperm production (oligospermia), menstrual disorders, vaginal discharge
• lymphadenopathy (lymphoma)
• lymphoproliferative disorders (overproduction of white blood cells)

Frequency not known: cannot be estimated from the 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 the injection site
• redness and peeling of the skin
• oedema

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

5. How to store Methofill SD

Keep this 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 change in the colour of the solution or the presence of particulate matter.
Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures 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 syringe is a clear, yellow to brown solution.
The following pack sizes are available:
Pre-filled syringes of 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 containing 1, 4 or 8 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 Member States of the European Economic Area and the United Kingdom (Northern Ireland) under the following names: