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 carefully all the information in this leaflet before using this medicine, as 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. The medicine may harm someone else, 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).

Table of contents

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 defence 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 been ineffective.
• Severe psoriatic arthritis in adults (psoriatic arthritis particularly affects fingers and toes, and is associated with psoriatic skin and nail changes).
• Severe, treatment-resistant psoriasis in adults (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, diarrhoea, 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 microorganisms;
• 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 liver function disorders;
• if the patient has dehydration (lack of water in the body);
• if the patient has diabetes and is treated with insulin.

Cases of acute pulmonary haemorrhage have been reported in patients with underlying rheumatologic disease during methotrexate treatment. If the patient experiences haemoptysis (coughing up blood), seek immediate medical advice.

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 methotrexate treatment and for at least 6 months after the end of treatment. Male patients should avoid impregnating their partner during methotrexate 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 reactions may occur. To detect them early, your doctor must perform regular check-ups and laboratory tests.

Before starting treatment
Prior to initiating treatment, a blood test 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. Additionally, 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 include imaging tests, while others may require a small liver tissue sample to be taken for more detailed examination. The doctor may also check for 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;
• liver biopsy (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 appointments.
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 their doctor to detect any adverse reactions as early as possible. Age-related impairments in liver and kidney function, as well as reduced folate reserves in older age, require relatively low doses of methotrexate.

Methotrexate may affect the immune system and the response to vaccinations. It may also influence the results of immunological tests. During methotrexate treatment, latent chronic diseases (e.g. shingles, tuberculosis, hepatitis B or C virus) may reactivate.

Do not receive live vaccines during treatment with Methofill SD.

Methotrexate may increase skin sensitivity to sunlight. Avoid intense sun exposure and do not use solariums or tanning lamps without consulting your doctor. To protect the skin from intense sunlight, wear appropriate clothing or use a high-protection sunscreen.

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 treatment.

Enlargement of lymph nodes (lymphadenopathy) may occur. In such a case, treatment should be discontinued.

Diarrhoea may be a sign of toxicity from Methofill SD and requires treatment interruption. 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 reactions 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, contact the doctor immediately, 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 administration 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 and 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 (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 agents (medicines that reduce blood sugar levels).

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

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

Vitamin supplements containing folic acid should be used only 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 as well as 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 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 pregnancy do not take methotrexate. If the patient is of childbearing age, pregnancy must be definitively ruled out before starting treatment by appropriate means, e.g. 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 possible 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 abnormalities or miscarriages after paternal exposure to methotrexate at doses below 30 mg/week. However, the risk cannot be completely excluded. 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 reactions affecting 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. Do not drive or operate machinery if feeling sleepy or fatigued.

Methofill SD contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, meaning it is considered "sodium-free".

3. How to use Methofill SD

This medicine should always be used as directed 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 physician or trained medical
personnel, or under their supervision, only once a week. 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 only once a week. Administration of an excessive dose of Methofill SD (methotrexate) can 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-course 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.
Methofill SD should only be prescribed 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 physician may determine that the patient is capable of self-injecting Methofill SD independently. The patient will be properly trained accordingly.
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 should not use or administer Methofill SD.
Avoid contact of methotrexate with skin surfaces or mucous membranes. In case of contamination, immediately flush the affected area thoroughly with water.
Administration instructions:
Carefully read the instructions for using Methofill SD in the pre-filled syringe.
Self-administration of the pre-filled syringe requires proper training by a physician.
If in doubt, contact your doctor, pharmacist, or nurse.
Before starting administration:

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

Preparing for administration:

• Wash hands with warm water and soap

• Select the injection site (abdomen or thigh if the patient self-injects, or optionally the upper outer area of the 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: to remove, twist and pull downward. 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.
• The injection should be administered within 5 minutes of 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. Administer 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 waste:

• Dispose of the used Methofill SD pre-filled syringe in a sharps container. Disposal guidelines may vary depending on country/region. For up-to-date information, 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, immediately flush the affected area thoroughly with water.
If the patient or someone in their household is accidentally injured with the syringe needle, inform the doctor immediately and do not use this syringe.
Overdose of Methofill SD
If more than the recommended 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 treatment with Methofill SD
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 severe adverse effects may occur even after administration of small doses, regular medical examinations are necessary.
Your doctor should arrange for 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 must inform your doctor immediately if any of the following symptoms occur in the patient, as they may indicate severe, potentially life-threatening adverse effects requiring urgent treatment:

• persistent, non-productive dry cough, shortness of breath, and fever; these may be symptoms of pneumonitis [common]
• haemoptysis, i.e. coughing up sputum containing blood; these may be symptoms of bleeding from the lungs [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), formation of scar tissue (liver fibrosis), fatty degeneration of the liver (fatty liver) [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 the 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 the hands, ankles, or feet or changes in the 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 (Pneumocystis jirovecii pneumonia) or blood poisoning (septicaemia) [rare]
• symptoms such as: weakness on one side of the body (stroke) or pain, swelling, redness and warmth in one of the legs (deep vein thrombosis). This may occur when a blood clot blocks a blood vessel (thromboembolic event) [rare]
• fever and severe deterioration in general health or sudden fever accompanied by sore throat or mouth 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 sensitivity to light; 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, movement disorders (ataxia), visual disturbances, or memory impairment [frequency not known]
• 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]

Other adverse effects that may occur are listed below:
Very common: may affect more than 1 in 10 people

• inflammation of the mucous membrane of the mouth, indigestion, 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, itching
• headache, fatigue, drowsiness
• 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

• sore throat
• enteritis, vomiting, pancreatitis, black or tarry stools, ulcers and bleeding from the gastrointestinal tract
• reactions resembling sunburn due to increased skin sensitivity to sunlight, hair loss, increase in number of rheumatoid nodules, shingles, 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 bladder or vagina, kidney dysfunction, urinary disturbances
• 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, impaired heart chamber filling due to fluid accumulation in the pericardium
• low blood pressure
• formation of scar tissue in the lungs (pulmonary fibrosis), shortness of breath 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 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 or tingling sensation, reduced response to stimuli, taste disturbances (metallic taste), seizures, paralysis, acute aseptic meningitis
• non-inflammatory eye disease (retinopathy), impaired vision
• decreased libido, impotence, gynaecomastia in men
• disturbances in sperm production (oligospermia), menstrual disorders, vaginal discharge
• enlarged lymph nodes (lymphadenopathy)
• lymphoproliferative disorders (overproduction of white blood cells)

Frequency not known: 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 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, discoloration, itching, intense pruritus, pain) decreasing during treatment have been observed.
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 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 effects can also be reported to the marketing authorisation holder.
Reporting adverse effects helps to provide more information on the safety of this medicine.

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 solid particles.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These 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 of solution contains 7.5 mg of methotrexate.
1 pre-filled syringe with 0.20 ml of solution contains 10 mg of methotrexate.
1 pre-filled syringe with 0.25 ml of solution contains 12.5 mg of methotrexate.
1 pre-filled syringe with 0.30 ml of solution contains 15 mg of methotrexate.
1 pre-filled syringe with 0.35 ml of solution contains 17.5 mg of methotrexate.
1 pre-filled syringe with 0.40 ml of solution contains 20 mg of methotrexate.
1 pre-filled syringe with 0.45 ml of solution contains 22.5 mg of methotrexate.
1 pre-filled syringe with 0.50 ml of solution contains 25 mg of methotrexate.
1 pre-filled syringe with 0.55 ml of solution contains 27.5 mg of methotrexate.
1 pre-filled syringe with 0.60 ml of 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 brownish 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 of 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.
Taśmowa Street 7
02-677 Warsaw
Tel: +48 22 577 28 00

Manufacturer/Importer
Accord Healthcare Polska Sp. z o.o.
Lutomierska Street 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: