Methofill Pen 22.5 mg/0.45 ml solution for injection in pre-filled pen EFG: detailed information

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Methofill Pen 22.5 mg/0.45 ml solution for injection in a pre-filled pen EFG

methotrexate

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

Keep this leaflet as you may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you. It may harm them.
If you experience any side effects, talk to your doctor or pharmacist, even if they are possible side effects not listed in this leaflet. See section 4.

Contents of the leaflet

What Methofill Pen is and what it is used for
What you need to know before using Methofill Pen
How to use Methofill Pen
Possible side effects
How to store Methofill Pen
Contents of the pack and other information

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

This medicine is indicated for the treatment of:

active rheumatoid arthritis in adult patients,
severe active polyarticular forms of juvenile idiopathic arthritis in children and adolescents under 16 years of age, when the response to non-steroidal anti-inflammatory drugs (NSAIDs) has been inadequate,
moderate to severe psoriasis in adult patients, and severe psoriatic arthritis in adults,
mild to moderate Crohn's disease in adult patients when adequate treatment with other medications is not possible.

Rheumatoid arthritis (RA) is a chronic collagen disease characterized by inflammation of the synovial membranes (joint membranes). These membranes produce a fluid that acts as a lubricant in many joints. Inflammation causes thickening of the membrane and joint swelling.

Juvenile arthritis affects children and adolescents under 16 years of age. Polyarticular forms are defined by involvement of five or more joints within the first six months of the disease.

Psoriasis is a common chronic skin disease characterized by red patches covered with thick, dry, silvery, adherent scales.

Psoriatic arthritis is a type of arthritis associated with psoriatic skin and nail lesions, particularly affecting the joints of the fingers and toes.

This medicine modifies and slows the progression of the disease.

Crohn's disease is a type of inflammatory bowel disease that can affect any part of the gastrointestinal tract, causing symptoms such as abdominal pain, diarrhea, vomiting, or weight loss.

2. What you need to know before using Methofill Pen

Do not use Methofill Pen

if you are allergic to methotrexate or to any of the other ingredients of this medicine (listed in section 6),
if you have severe liver or kidney disease or blood disorders,
if you regularly consume large amounts of alcohol,
if you have a serious infection, such as tuberculosis, HIV or other immunodeficiency syndromes,
if you have mouth ulcers, gastric or intestinal ulcers,
if you are pregnant or breastfeeding (see section "Pregnancy, breastfeeding and fertility"),
if you are receiving vaccines made with attenuated microorganisms at the same time.

Warnings and precautions

Methotrexate may make your skin more sensitive to sunlight. Avoid strong sunlight and do not use sunbeds or ultraviolet lamps without medical advice. To protect your skin from intense sunlight, wear suitable clothing or use a high-protection sunscreen.

Consult your doctor or pharmacist before starting to use this medicine if:

you are elderly or generally feel unwell and weak,
you have problems with liver function,
you are dehydrated (loss of fluids).

Acute pulmonary hemorrhage has been reported with methotrexate in patients with underlying rheumatological disease. If you notice blood when coughing or spitting, contact your doctor immediately.

Special precautionary measures for Methofill Pen treatment

Methotrexate temporarily affects sperm and egg production, which is reversible in most cases. Methotrexate may cause miscarriage and severe birth defects. If you are a woman, you must avoid becoming pregnant while receiving methotrexate and for at least 6 months after stopping treatment with methotrexate. If you are a man, you must avoid fathering a child while receiving methotrexate and for at least 3 months after stopping treatment. See also section "Pregnancy, breastfeeding and fertility".

Follow-up tests and recommended safety measures:

Even when administered at low doses, serious adverse reactions may occur. To detect them early, your doctor must perform blood tests and check-ups.

Before starting treatment with Methofill Pen:

Before starting treatment, blood tests will be performed to ensure you have sufficient blood cells, and tests to check liver function and determine whether you have hepatitis. Additionally, serum albumin levels (a blood protein), hepatitis status (liver infection), and kidney function will be assessed. Your doctor may also decide to perform additional liver tests, some of which may include imaging of your liver and others may require taking a small tissue sample from the liver for closer examination. Your doctor will also check for tuberculosis (an infectious disease associated with small nodules in affected tissue) and perform a chest X-ray or lung function test.

During treatment:

Your doctor will perform the following tests:

examination of the oral cavity and pharynx to detect changes in the mucous membrane, such as inflammation or ulceration
blood analysis / complete blood count including blood cell count and measurement of serum methotrexate levels
blood tests to monitor liver function
imaging tests to monitor liver status
liver biopsy (a small tissue sample taken from the liver for closer examination)
blood tests to monitor kidney function
respiratory system examination and, if necessary, lung function test

It is very important that you attend these scheduled tests.

If any of these test results are abnormal, your doctor will adjust your treatment accordingly.

Methotrexate may affect the immune system and vaccination outcomes. It may also affect the results of immunological tests. It may reactivate inactive chronic infections (such as herpes zoster ["shingles"], tuberculosis, hepatitis B or C). During treatment with this medicine, you must not receive vaccines made with attenuated microorganisms.

During treatment with methotrexate, radiation-induced dermatitis and sunburns may reappear (memory reactions). Psoriatic lesions may worsen during UV radiation and simultaneous administration of methotrexate.

An increase in the size of lymph nodes (lymphoma) may occur, and in such cases, treatment must be discontinued.

Diarrhea may be an adverse effect of this medicine requiring discontinuation of treatment. If you have diarrhea, speak with your doctor.

Certain brain disorders (encephalopathy/leukoencephalopathy) have been reported in cancer patients treated with methotrexate. These adverse effects cannot be ruled out when methotrexate is used to treat other diseases.

If you, your partner or caregiver notice the onset or worsening of neurological symptoms such as general muscle weakness, vision disturbances, changes in thinking, memory and orientation leading to confusion, or personality changes, contact your doctor immediately, as these may be symptoms of a very rare serious brain infection called progressive multifocal leukoencephalopathy (PML).

Elderly patients

Elderly patients receiving methotrexate must be closely monitored by a physician to detect possible side effects as early as possible.

Age-related decline in liver and kidney function, as well as low body reserves of folic acid in older age, require a relatively low dose of methotrexate.

Using Methofill Pen with other medicines

Inform your doctor or pharmacist if you are taking, have recently taken or might need to take any other medicines. Keep this in mind also for medicines you may take in the future.

The effect of treatment may be affected if this medicine is taken at the same time as certain medicines:

Antibiotics such as: tetracyclines, chloramphenicol, non-absorbable broad-spectrum antibiotics, penicillins, glycopeptides, sulfonamides, ciprofloxacin and cephalothin (medicines to prevent or treat certain infections).
Amoxicillin (penicillins may reduce methotrexate excretion, potentially increasing side effects).
Non-steroidal anti-inflammatory drugs (NSAIDs) or salicylates (medicines for pain or inflammation such as acetylsalicylic acid, diclofenac and ibuprofen or pyrazolones).
Probenecid (a medicine for gout).
Weak organic acids such as loop diuretics.
Medicines that may cause adverse effects on the bone marrow, such as trimethoprim-sulfamethoxazole (an antibiotic) and pyrimethamine.
Other medicines used to treat rheumatoid arthritis such as leflunomide, sulfasalazine and azathioprine.
Mercaptopurine (a cytostatic medicine).
Retinoids (medicines for psoriasis and other skin diseases).
Theophylline (a medicine for bronchial asthma and other lung diseases).
Some medicines for stomach discomfort such as omeprazole and pantoprazole.
Hypoglycemics (medicines used to lower blood sugar levels).

Metamizole (synonyms: novaminsulfone and dipyrone) (a medicine for severe pain and/or fever);

Vitamins containing folic acid may alter the effect of your treatment and should only be taken if advised by your doctor.

Vaccination with vaccines made from attenuated microorganisms must be avoided.

Using Methofill Pen with food, drinks and alcohol

During treatment with this medicine, consumption of alcohol, large amounts of coffee, caffeinated soft drinks and black tea should be avoided.

Pregnancy, breastfeeding and fertility

Pregnancy

Do not use this medicine during pregnancy or if you are trying to become pregnant. Methotrexate may cause birth defects, harm the fetus or cause miscarriage. It is associated with malformations of the skull, face, heart and blood vessels, brain and limbs. Therefore, it is very important that methotrexate not be given to pregnant patients or those planning to become pregnant. In women of childbearing potential, pregnancy must be excluded using appropriate measures, for example, a pregnancy test before starting treatment. You must avoid becoming pregnant while taking methotrexate and for at least 6 months after stopping treatment, using reliable contraceptive methods throughout this period (see also section "Warnings and precautions").

If you become pregnant during treatment or suspect you may be pregnant, consult your doctor as soon as possible. You should be provided with information about the risk of harmful effects on the child during treatment.

If you wish to become pregnant, consult your doctor, who may refer you to a specialist for counseling before the planned start of treatment.

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Breastfeeding

Discontinue breastfeeding before and during treatment with this medicine.

Male fertility

Available data do not indicate an increased risk of birth defects or miscarriage if the father takes a methotrexate dose below 30 mg/week. However, this risk cannot be completely ruled out. Methotrexate may be genotoxic, meaning it may cause genetic mutations. Methotrexate may affect sperm production and cause birth defects. Therefore, you must avoid fathering a child or donating semen while taking methotrexate and for at least 3 months after stopping treatment.

Driving and using machines

Treatment with this medicine may cause adverse reactions affecting the central nervous system, such as fatigue and dizziness. Therefore, your ability to drive or use machines may, in some cases, be impaired. If you feel tired or drowsy, you should not drive or operate machinery.

Methofill Pen contains sodium

This medicine contains less than 23 mg of sodium (1 mmol) per dose; this is essentially "sodium-free".

3. How to use Methofill Pen

Follow exactly the instructions for administering this medicine as given by your doctor. If in doubt, consult your doctor or pharmacist again.

Your doctor will determine the dose, which will be individually adjusted. Usually, treatment takes between 4 and 8 weeks to take effect.

The injection of this medicine is administered subcutaneously (under the skin) by or under the supervision of a doctor or healthcare professional only once a week. Together with your doctor, you will choose a day of the week suitable for you to receive the injection.

At the beginning of treatment, this medicine may be injected by medical staff. However, your doctor may decide that you can learn to self-inject this medicine. You will receive appropriate training for this. Under no circumstances should you attempt to inject yourself unless you have been taught how to do so.

Important safety information about the dose of Methofill Pen (methotrexate):

Use Methofill Pen only once a week for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis, psoriatic arthritis, and Crohn's disease. Taking too much Methofill Pen (methotrexate) can be fatal. Read section 3 of this leaflet very carefully. If you have any questions, consult your doctor or pharmacist before using this medicine.

Use in children and adolescents

The doctor determines the appropriate dose for children and adolescents with polyarticular forms of juvenile idiopathic arthritis.

This medicine is not recommended for use in children under 3 years of age due to limited experience in this age group.

Duration and method of administration

This medicine is injected once weekly.

The treating physician will decide the duration of treatment. Treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis vulgaris, psoriatic arthritis, and Crohn's disease with this medicine is intended as long-term therapy.

At the beginning of treatment, this medicine may be administered by healthcare professionals. However, your doctor may decide that you can learn to self-inject Methofill Pen. You will receive appropriate training for this purpose.

Under no circumstances should you attempt to self-inject unless you have been properly trained to do so.

You may also find guidance on how to use this medicine in the section “Instructions for use”.

Please note that the entire content must be used.

Handling and disposal of the medicine and the pre-filled pen must comply with local regulations. Pregnant healthcare personnel must not handle or administer this medicine.

Methotrexate must not come into contact with the skin surface or mucous membranes. If contact occurs, the affected area must be immediately rinsed with copious amounts of water.

Instructions for use

Recommendations

Read the instructions carefully before starting to administer the injection.
Always use the administration technique advised by your doctor, nurse, or pharmacist.

Additional information

Handling and disposal of the medicine and the pre-filled pen must comply with local regulations. Pregnant healthcare personnel must not handle or administer this medicine.

Methotrexate must not come into contact with the skin surface or mucous membranes. If contact occurs, the affected area must be immediately rinsed with copious amounts of water.

What you should do before administering your injection

Select a clean, flat, and well-lit work surface.
Check the expiry date. Do not use if the expiry date has passed.
Take an alcohol-impregnated wipe and a sharps container for disposal of sharp objects.
Open the box containing the methotrexate pre-filled pen and place the pre-filled pen of this medicine on a clean, flat surface (such as a table). Read the package leaflet carefully.

How to prepare the injection

	Wash your hands thoroughly. Before use, inspect the methotrexate syringe for any visible defects (or cracks).
	Choose the injection site. The most suitable areas for your injection are: the upper thigh, the abdomen, except the area around the navel. If someone around you administers the injection, that person may also use the upper part of the back of the arm, just below the shoulder. Change the injection site with each injection. This will minimize any local reaction at the injection site. Never inject into skin that is painful, bruised, red, hardened, or has scars or stretch marks. If you have psoriasis, do not attempt to inject directly into lesions or raised, thickened, red, or scaly patches of skin.
	Clean your skin at the chosen injection site with the alcohol wipe.
	Check the integrity of the system. Do not use the prefilled pen if it appears damaged. Use another pen and contact your doctor, pharmacist, or nurse. If there is a small air bubble visible through the transparent viewing window, this will not affect your dose or cause you any harm. If you are unable to see or properly examine the system before injection, ask someone nearby to assist you. Do not use the device: If you notice any damage (breakage of the syringe or device) or loss of components; If the device is in the safety position before use, as this indicates the system has already been activated. In general, the device cannot be used if it does not match the figure on the left. If so, dispose of the device in a biological hazard container (sharps container).
	Remove the protective cap: twist and pull off the lower cap to remove it. Keep hands away from the needle shield after removing the cap. Immediately discard the cap into a biological hazard container (sharps container). Do not inject yourself if the prefilled pen has been dropped after removing the cap. If you cannot remove the cap, ask someone nearby to help you. Note: Once you have removed the cap, administer your injection within the next 5 minutes.

How to inject yourself

	Place the injector directly onto the skin (approximately at a 90-degree angle).
	Push the push-button downward: the medication is injected as you push. Do this at a comfortable pace. Do not remove the pre-filled pen from the skin before the injection is complete to avoid incomplete dosing.
	Once the push-button is fully depressed, a click is heard and the orange body disappears, indicating the injection is complete. Remove the pre-filled pen by lifting it upward: the yellow band indicates that the needle shield is locked.
	Dispose of the used pre-filled pen by placing it in an approved sharps container. Consult your doctor or pharmacist for information on proper disposal. Note: Do not discard the pen in household waste.

Methotrexate must not come into contact with the skin surface or mucous membranes. In case of contamination, the affected area should be immediately rinsed with abundant water.

Who to contact if needed

If you have any questions or problems, contact your doctor, pharmacist, or nurse.

If you or someone close to you is injured by the needle, consult your doctor immediately and do not use this pre-filled syringe.

Disposal and other handling

Handling and disposal of the medicine and the pre-filled syringe must be carried out in accordance with local regulations. Pregnant healthcare personnel must not handle or administer methotrexate.

If you use more Methofill Pen than you should

If you use more medication than you should, consult your doctor immediately.

If you forget to use Methofill Pen

Do not use a double dose to make up for missed doses.

If you stop treatment with Methofill Pen

If you interrupt treatment with this medicine, consult your doctor immediately.

If you feel that the effect of this medicine is too strong or too weak, consult your doctor or pharmacist.

If you suspect that you (or someone else) has administered too much Methofill Pen, contact your doctor or go immediately to the nearest hospital, or call the Toxicology Information Service at 91 562 04 20. They will determine which measures to take depending on the severity of the poisoning. Take the medicine with you if you go to the doctor or to a hospital.

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 and frequency of administration. It is important that your doctor performs regular check-ups, as serious adverse effects may occur even with the lowest doses. Your doctor will carry out tests to detect abnormalities in the blood (such as low white blood cell count, low platelet count, or lymphoma) and changes in the kidneys and liver.

If you experience any of the following symptoms, contact your doctor immediately, as they may indicate a serious, potentially life-threatening adverse effect requiring urgent specific treatment:

Persistent dry cough without phlegm, difficulty breathing, and fever; these may be signs of lung inflammation [frequent]
Coughing up blood or blood in sputum; these may be signs of pulmonary hemorrhage [frequency not known]
signs of liver damage, such as yellowing of the skin or whites of the eyes; methotrexate may cause chronic liver injury (hepatic cirrhosis), scarring of the liver (hepatic fibrosis), fatty degeneration of the liver [all uncommon], inflammation of the liver (acute hepatitis) [rare], and liver failure [very rare]
allergic symptoms, such as skin rash including itching, swelling of the hands, feet, ankles, face, lips, mouth, or throat (which may cause difficulty swallowing or breathing), and feeling faint; these may be signs 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, reduced (oliguria) or absent (anuria) urine output; these may be signs of kidney failure [rare]
signs of infection, e.g., fever, chills, aches, sore throat; methotrexate may make you more susceptible to infections. Serious infections such as a specific type of pneumonia (Pneumocystis jirovecii pneumonia) or blood poisoning (sepsis) may occur [rare]
symptoms such as weakness on one side of the body (stroke) or pain, swelling, redness, and unusual warmth in one leg (deep vein thrombosis); this may occur when a dislodged blood clot causes blockage of a blood vessel (thromboembolic event) [rare]
fever and severe worsening of your general condition, or sudden fever accompanied by sore throat or mouth pain, or urinary problems; methotrexate may cause a sudden drop in certain white blood cells (agranulocytosis) and severe myelosuppression [very rare]
unexpected bleeding, e.g., bleeding gums, blood in urine, vomiting blood, or bruising; these may be signs of a severe decrease in platelets caused by serious episodes of bone marrow suppression [very rare]
symptoms such as severe headache often combined with fever, neck stiffness, nausea, vomiting, disorientation, and sensitivity to light; these may indicate inflammation of the membranes surrounding the brain (acute aseptic meningitis) [very rare]
certain brain disorders (encephalopathy/leukoencephalopathy) have been reported in cancer patients treated with methotrexate; these adverse effects cannot be ruled out when methotrexate treatment is used for other diseases; signs of such brain disorders may include mental status changes, movement disorders (ataxia), visual disturbances, or memory problems [frequency not known]
severe skin rash or blistering of the skin (this may also affect the mouth, eyes, and genitals); these may be signs of a condition 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 lining of the mouth, indigestion, nausea, loss of appetite, abdominal pain.
Abnormal results in liver function tests (ASAT, ALAT, bilirubin, alkaline phosphatase).

Common: may affect up to 1 in 10 people

Mouth ulcers, diarrhea.
Rash, redness of the skin, itching.
Headache, fatigue, drowsiness.
Decreased production of blood cells with reduced numbers of white blood cells, red blood cells, or platelets.

Uncommon: may affect up to 1 in 100 people

Sore throat.
Inflammation of the intestine, vomiting, inflammation of the pancreas, black or tarry stools, gastrointestinal ulcers and bleeding.
Sunburn-like reactions due to increased sensitivity of the skin to sunlight, hair loss, increase in the number of rheumatoid nodules, skin ulcer, shingles (herpes zoster), inflammation of blood vessels, herpes-like rash, urticaria.
Development of diabetes mellitus.
Dizziness, confusion, depression.
Decreased serum albumin.
Decreased number of all blood cells and platelets.
Inflammation and ulceration of the urinary bladder or vagina, decreased kidney function, urinary disorders.
Joint pain, muscle pain, reduced bone mass.

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

Inflammation of the gum tissue.
Increased skin pigmentation, acne, skin bruising due to bleeding from blood vessels (ecchymoses, petechiae), allergic inflammation of blood vessels.
Decreased number of antibodies in the blood.
Infection (including reactivation of inactive chronic infections), red eyes (conjunctivitis).
Mood changes (mood disturbances).
Visual disturbances.
Inflammation of the sac surrounding the heart, fluid accumulation in the sac around the heart, obstruction of heart filling due to fluid in the sac surrounding the heart.
Low blood pressure.
Scarring of lung tissue (pulmonary fibrosis), breathing difficulty and bronchial asthma, fluid accumulation in the sac surrounding the lung.
Stress fracture.
Electrolyte imbalances.
Fever, impaired wound healing.

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

Acute toxic dilation of the intestine (toxic megacolon).
Increased pigmentation of the nails, inflammation of the cuticles (acute paronychia), deep infection of hair follicles (furunculosis), visible enlargement of small blood vessels.
Pain, loss of strength, or numbness or tingling sensations/reduced sensitivity to stimuli, taste disturbances (metallic taste), seizures, paralysis, meningism.
Visual impairment, non-inflammatory eye disorder (retinopathy).
Loss of sexual appetite, impotence, male breast enlargement, altered sperm formation (oligospermia), menstrual disorders, vaginal discharge.
Enlargement of lymph nodes (lymphoma).
Lymphoproliferative disorders (excessive increase in white blood cells).

Frequency not known: cannot be estimated from available data

Increase in certain white blood cells.
Nosebleeds.
Protein in the urine.
Feeling of weakness.
Jaw bone damage (secondary to excessive increase in white blood cells).
Tissue destruction at the injection site.
Redness and peeling of the skin.
Swelling.

Subcutaneous administration of methotrexate is well tolerated locally. Only mild local skin reactions (such as burning sensation, erythema, swelling, discoloration, severe itching, pain) were observed, which decreased during treatment.

Reporting of adverse effects

If you experience any adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: at www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Methofill Pen

Keep this medicine out of the sight and reach of children.

Store below 30 °C.

Keep the pre-filled pens in the outer packaging to protect them from light.

Do not use this medicine after the expiry date stated on the carton and on the pre-filled pen after CAD. The expiry date refers to the last day of the month indicated.

Medicines must not be disposed of via wastewater or household waste. Dispose of empty containers and unused medicines at the SIGRE collection point at your pharmacy. Ask your pharmacist how to dispose of containers and medicines you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Methofill Pen

The active substance is methotrexate. 1 ml of solution contains methotrexate disodium equivalent to 50 mg of methotrexate.

1 pre-filled pen containing 0.45 ml of solution contains 22.5 mg of methotrexate.

The other components are sodium chloride, sodium hydroxide to adjust pH, water for injections.

Appearance of the medicinal product and contents of the pack

The pre-filled pens of Methofill Pen contain a yellow-brown transparent 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 injectable solution, available in packs of 1 or multipacks of 4 (4 packs of 1) pre-filled pens.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Accord Healthcare S.L.U.

World Trade Center

Moll de Barcelona, s/n

Edifici Est 6ª planta,

08039 Barcelona,

Spain

Manufacturer:

Accord Healthcare Polska Sp.z.o.o.

ul.Lutomierska 50

Pabianice, 95-200

Poland

Laboratori Fundació DAU

C/ C, 12-14 Pol. Ind. Zona Franca, Barcelona

Spain

Date of the most recent revision of this leaflet: August 2024

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) http://www.aemps.es