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, 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 doubts.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm another person, even if their symptoms are the same.
• If you experience any adverse effects, including any possible adverse effects 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 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 these membranes and joint swelling.
• Polyarticular course of severe, active juvenile idiopathic arthritis when treatment with non-steroidal anti-inflammatory drugs (NSAIDs) has been ineffective. (Juvenile arthritis occurs in children and adolescents under 16 years of age.)
• 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. 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 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 rheumatologic disease during methotrexate treatment. If the patient develops haemoptysis (coughing up blood), seek immediate medical advice.

Special precautions for the use of Methofill SD
Methotrexate temporarily impairs the production of sperm and oocytes; this effect usually resolves. Methotrexate may cause miscarriage and severe congenital malformations. Female patients 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 and precautions:
Even when methotrexate is used at low doses, serious 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, 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 rule out hepatitis. Additionally, serum albumin (a blood protein), presence of liver inflammation (liver infection), and kidney function will be assessed. The doctor may also decide to perform other liver tests. Some of these may include imaging studies, while others may require a small liver tissue sample 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 detailed examination);
• blood tests to monitor kidney function;
• monitoring of 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 the doctor to detect any adverse reactions as early as possible. Age-related impairments in liver and kidney function, as well as lower folate reserves in older age, require relatively low doses of methotrexate.

Methotrexate may affect the immune system and vaccine responses. It may also influence the results of immunological tests. During methotrexate treatment, reactivation of latent chronic diseases (e.g. shingles, tuberculosis, hepatitis B or C virus) 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 solariums 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, 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 (lymphadenopathy) may occur. In such cases, 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, 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 currently or recently taken, as well as any medicines planned for future use. This includes all medicines, even those to be used in the future.

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

Vitamin supplements 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, alcohol consumption as well as 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 extremely 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, e.g. a pregnancy test. The patient should avoid becoming pregnant during methotrexate treatment and for at least 6 months after its completion, using reliable contraception 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 pre-conception counselling.

Male fertility
Available evidence does not indicate an increased risk of developmental abnormalities or miscarriages following paternal methotrexate exposure at doses below 30 mg/week. However, risk cannot be completely excluded. Methotrexate may be genotoxic, meaning it may cause genetic mutations. Methotrexate may affect sperm and lead to congenital malformations. Therefore, male patients should avoid impregnating their partner and must not act as sperm donors 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. If feeling drowsy or fatigued, do not drive or operate machinery.

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 seen 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, only once a week. 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 only once a week. Administering too high a 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 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 injected once a week!
The duration of treatment is determined by the treating physician. Treatment of rheumatoid
arthritis, juvenile idiopathic arthritis, psoriasis vulgaris, psoriatic arthritis, and Crohn’s disease with
Methofill SD is long-term therapy.
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 injection by medical
personnel. However, the doctor may determine that the patient is capable of self-injecting Methofill
SD. 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 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 flushed 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 you have any doubts, 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.

Preparation for administration:

• Wash hands with warm water and soap.

• Select injection site (abdomen or thigh if the patient is self-injecting, or optionally the upper back 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.
• Administer the injection within 5 minutes after removing the cap.

Injection:

• Place the injection device at the selected injection site at a right angle (90°).
• Press the plunger steadily until the full dose is delivered. Inject at a comfortable speed for the patient. Do not move the position of the syringe during administration.

• Maximum plunger depression is signaled by a distinct click; the orange part of the dose indicator becomes invisible.
• After completing the injection, a yellow ring becomes visible, indicating needle shield lockout.

Disposal of used device:

• 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 flushed thoroughly with water.
If the patient or someone in their household is accidentally injured by the injection needle, inform the doctor immediately and do not use this syringe.
Accidental overdose of Methofill SD
If more medicine is taken than recommended, 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 order tests to rule out abnormalities in blood parameters (e.g. low white blood cell count, low platelet count, lymphoma) and changes in the liver and kidneys.
You should immediately inform your doctor 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, 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]
• symptoms 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], hepatitis (acute hepatitis) [rare], and liver failure [very rare]
• hypersensitivity symptoms 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]
• symptoms 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]
• symptoms of infection, e.g. fever, chills, soreness, 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 of the legs (deep vein thrombosis). This may occur when a blood clot blocks the blood vessel lumen (thromboembolic event) [rare]
• fever and severe deterioration in general health or sudden fever accompanied by sore throat or oral cavity pain or urinary disturbances; 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 associated with 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]

Below 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
• sunburn-like reactions 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 function disorders, 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 haemorrhages 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
• formation of scar tissue 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 nail cuticle (acute paronychia), deep infection of hair follicles (folliculitis), 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

Not known: cannot be estimated from available data

• increased number of certain white blood cells
• nosebleeds
• proteinuria
• asthenia (weakness)
• 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 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, 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 authorization holder.
Reporting adverse effects helps to gather more information on the safety of the 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 should 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 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 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 syringes, each in a cardboard box.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Accord Healthcare Polska Sp. z o.o.
Taśmowa Street 7
02-677 Warsaw, Poland
Tel: +48 22 577 28 00

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

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