Methotrexate Ever Pharma

Leaflet attached to the packaging: information for the user

Methotrexate EVER Pharma, 7.5 mg, solution for injection in a pre-filled syringe

Methotrexate EVER Pharma, 10 mg, solution for injection in a pre-filled syringe

Methotrexate EVER Pharma, 12.5 mg, solution for injection in a pre-filled syringe

Methotrexate EVER Pharma, 15 mg, solution for injection in a pre-filled syringe

Methotrexate EVER Pharma, 17.5 mg, solution for injection in a pre-filled syringe

Methotrexate EVER Pharma, 20 mg, solution for injection in a pre-filled syringe

Methotrexate EVER Pharma, 22.5 mg, solution for injection in a pre-filled syringe

Methotrexate EVER Pharma, 25 mg, solution for injection in a pre-filled syringe

Methotrexate

You should carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• You should keep this leaflet so that you can read it again if you need to.
• If you have any doubts, you should consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet

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

1. What is Methotrexate EVER Pharma and what is it used for

Methotrexate EVER Pharma contains the active substance methotrexate, which works by:

• reducing inflammation or swelling, and
• reducing the activity of the immune system (the body's defense mechanism). Excessive activity of the immune system is associated with inflammatory diseases.

Methotrexate EVER Pharma is used to treat:

• severe active rheumatoid arthritis in adults. Active rheumatoid arthritis is an inflammatory disease that affects the joints;
• severe active juvenile idiopathic arthritis (a disease also known as polyarticular arthritis) in patients who have not responded adequately to non-steroidal anti-inflammatory drugs (NSAIDs);
• severe psoriasis and psoriatic arthritis in adults;

2. Important information before using Methotrexate EVER Pharma

When not to use Methotrexate EVER Pharma

• if the patient is allergic to methotrexate or any of the other ingredients of this medicine (listed in section 6)
• if the patient has a severe or active infection
• if the patient has inflammation of the mucous membrane of the mouth or ulcers of the digestive tract
• if the patient has severe kidney disease (the doctor will assess whether the kidney disease is severe)
• if the patient has severe liver disease (the doctor will assess whether the liver disease is severe)
• if the patient has a blood disease
• if the patient has immune system disorders
• if the patient consumes excessive amounts of alcohol, has alcoholic liver disease, or other chronic liver disease
• if the patient is pregnant or breastfeeding (see "Pregnancy, breastfeeding, and fertility")
• if the patient is receiving live vaccines at the same time.

Warnings and precautions

Important warning regarding the dosage of Methotrexate EVER Pharma:

Methotrexate EVER Pharma, used to treat rheumatic diseases or skin diseases, should only be administered once a week. Dosage errors during methotrexate treatment can cause severe side effects, including death. You should read section 3 of this leaflet very carefully. If you have any questions, you should consult a doctor or pharmacist before taking this medicine. Before starting treatment with Methotrexate EVER Pharma, you should discuss it with your doctor if:

• the patient has diabetes and is being treated with insulin
• the patient has a non-active, chronic infection (e.g., tuberculosis, hepatitis B or C, shingles)
• the patient has or has had kidney or liver disease in the past
• the patient has lung function disorders
• if the patient is severely overweight
• if the patient has fluid accumulation in the abdominal cavity or in the space between the lungs and the chest wall (ascites, pleural effusion)
• the patient is dehydrated or has disorders leading to dehydration (e.g., vomiting, diarrhea, inflammation of the mucous membrane of the mouth).

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, they should contact their doctor immediately, as these may be symptoms of a very rare, serious brain infection called progressive multifocal leukoencephalopathy (PML). Methotrexate temporarily affects sperm production and ovulation. Methotrexate may cause miscarriage and severe birth defects in the fetus. Women should avoid becoming pregnant while taking methotrexate and for at least six months after treatment. Men should avoid fatherhood while being treated with methotrexate and for at least three months after treatment. See also "Pregnancy, breastfeeding, and fertility". During treatment with Methotrexate EVER Pharma, there may be a recurrence of radiation-induced skin inflammation or sunburn. Exposure to ultraviolet radiation during treatment with Methotrexate EVER Pharma may exacerbate psoriatic skin lesions. During methotrexate treatment, cases of acute pulmonary bleeding have been reported in patients with underlying rheumatologic disease. If the patient experiences hemoptysis, they should consult their doctor immediately. Diarrhea is a side effect of Methotrexate EVER Pharma that may require discontinuation of treatment. If diarrhea occurs, the patient should consult their doctor. In patients receiving low doses of methotrexate, lymph node enlargement (lymphoma) may occur. In such cases, treatment should be discontinued. Recommended tests and precautions Even with low doses of methotrexate, severe side effects may occur. To detect these effects early, the doctor must perform tests and laboratory tests. Before starting treatment:

• the doctor will prescribe blood tests to check if the patient has a sufficient number of blood cells to receive the medicine. The doctor will also prescribe blood tests to check liver function and to determine if the patient has hepatitis. Additionally, blood tests will be performed to check the albumin level in the blood serum (a protein in the blood), the degree of liver inflammation (liver infection), and kidney function. The doctor may also decide to perform other liver tests, some of which may be imaging tests of the liver, and others may require taking a small tissue sample from the liver for further examination. The doctor may also check if the patient has tuberculosis and prescribe a chest X-ray or lung function tests.

During treatment: The doctor may prescribe the following tests:

• examination of the mouth and throat to check for changes in the mucous membrane, such as inflammation or ulcers
• blood tests/morphology with determination of the number of blood cells and measurement of methotrexate levels in the blood serum
• blood tests to monitor liver function
• imaging tests to assess liver condition
• taking a small tissue sample from the liver for further examination
• blood tests to monitor kidney function
• monitoring of the respiratory tract and, if necessary, performing lung function tests

It is very important for the patient to attend all scheduled blood tests. If the result of any of these tests is abnormal, the doctor will adjust the treatment accordingly.

Children, adolescents, and the elderly

Methotrexate EVER Pharma is not recommended for use in children under 3 years of age due to insufficient experience in this age group. During treatment with Methotrexate EVER Pharma, children, adolescents, and the elderly should be under close medical supervision to detect any potential side effects as early as possible. In the elderly, a relatively low dose of methotrexate should be used due to decreased liver and kidney function and lower folate reserves that occur with age.

Methotrexate EVER Pharma and other medicines

The patient should tell their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take, including those that are available without a prescription, herbal medicines, and dietary supplements, such as vitamins. It is especially important to inform the doctor about the use of:

• non-steroidal anti-inflammatory drugs or salicylates (medicines used to treat pain and/or inflammation, such as acetylsalicylic acid, diclofenac, and ibuprofen)
• azathioprine (a medicine used to prevent rejection of a transplanted organ)
• retinoids (medicines used to treat psoriasis and other skin diseases)
• metamizole (a medicine used to reduce pain and fever)
• other medicines used to treat rheumatoid arthritis or psoriasis, such as leflunomide, sulfasalazine (also used to treat ulcerative colitis), penicillamine, or cyclosporine
• antiepileptic drugs (medicines used to prevent seizures), such as phenytoin, valproate, or carbamazepine
• anticancer drugs, such as mercaptopurines or fluorouracil
• barbiturates (sleeping pills given by injection)
• sedatives
• para-aminobenzoic acid (a medicine used to treat skin diseases)
• hydroxychloroquine (a medicine used to prevent and treat malaria)
• oral contraceptives
• probenecid (a medicine used to treat gout)
• antibiotics and medicines used to treat infections, such as tetracyclines, chloramphenicol, non-absorbable broad-spectrum antibiotics, trimethoprim with sulfamethoxazole, penicillin, glycopeptides, sulfonamides, ciprofloxacin, and cephalothin. Penicillins may decrease methotrexate excretion, which may increase the frequency of side effects
• pyrimethamine (a medicine used to prevent and treat malaria)
• medicines containing folic acid and vitamin preparations
• proton pump inhibitors (medicines that reduce stomach acid production, used to treat severe heartburn or ulcers), such as omeprazole or pantoprazole
• theophylline (a medicine used to treat asthma)
• nitrous oxide (a gas used for general anesthesia)
• any live vaccines (should be avoided), such as measles, mumps, or yellow fever vaccines
• cholestyramine (used to reduce cholesterol levels in the blood)

Methotrexate EVER Pharma with food and alcohol

During treatment with Methotrexate EVER Pharma, the patient should not drink alcohol and should also avoid consuming excessive amounts of coffee, caffeinated beverages, and black tea, as they may increase the risk of side effects or affect the efficacy of Methotrexate EVER Pharma. During treatment with Methotrexate EVER Pharma, the patient should drink plenty of fluids, as dehydration (reduced water content in the body) may increase the toxic effects of Methotrexate EVER Pharma.

Pregnancy, breastfeeding, and fertility

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor or pharmacist before using this medicine. Pregnancy Do not use Methotrexate EVER Pharma if the patient is pregnant or plans to become pregnant. Methotrexate may cause birth defects, harm the unborn child, or cause miscarriage. It may cause skull, face, heart, blood vessels, brain, and limb defects. Therefore, it is very important not to use methotrexate in pregnant women or women planning to become pregnant. In women of childbearing age, pregnancy should be ruled out before starting treatment, e.g., by performing a pregnancy test. The patient should avoid becoming pregnant during methotrexate treatment and for at least six months after treatment. During this time, effective methods of preventing pregnancy should be used (see also "Warnings and precautions"). If the woman becomes pregnant during treatment or thinks she may be pregnant, she should consult her doctor as soon as possible. The doctor will advise the patient on the risk associated with treatment. If the patient plans to become pregnant, the treating doctor may refer her to a specialist for consultation before planned treatment. Breastfeeding Do not breastfeed during treatment, as methotrexate passes into breast milk. If the treating doctor considers methotrexate treatment absolutely necessary at this time, breastfeeding should be discontinued. Male fertility Available data do not indicate an increased risk of birth defects or miscarriage when the father is treated with methotrexate at doses less than 30 mg per week. However, the risk cannot be completely ruled out. Methotrexate may have genotoxic effects, meaning it may cause genetic changes. Methotrexate may affect sperm production, potentially causing birth defects. Therefore, patients treated with methotrexate should avoid fatherhood or donating sperm during treatment and for at least three months after treatment.

Driving and using machines

During treatment with Methotrexate EVER Pharma, side effects from the central nervous system, such as fatigue and dizziness, may occur, which may affect the ability to drive vehicles and/or operate machines. If the patient feels tired or dizzy, they should not drive vehicles or operate machines.

Methotrexate EVER Pharma contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per pre-filled syringe, which means the medicine is considered "sodium-free".

3. How to use Methotrexate EVER Pharma

Important warning regarding the dosage of Methotrexate EVER Pharma (methotrexate)

In the treatment of rheumatoid arthritis, active juvenile idiopathic arthritis, and psoriasis, Methotrexate EVER Pharma should be used only once a week. Using more Methotrexate EVER Pharma may result in death. You should read section 3 of this leaflet very carefully. If you have any questions, you should consult a doctor or pharmacist before taking this medicine. This medicine should always be used as directed by the doctor. If you are unsure, you should consult a doctor or pharmacist. Methotrexate EVER Pharma is administered only once a week. Together with the doctor, you should choose a suitable day of the week for the injection. Incorrect use of Methotrexate EVER Pharma may lead to severe side effects, which may result in death. The recommended dose is: Dosing in patients with rheumatoid arthritis The recommended initial dose is 7.5 mg of methotrexate once a week. If the dose used is not effective and the patient tolerates the medicine well, the doctor may increase the dose by 2.5 mg per week. The average weekly dose of methotrexate is 15-20 mg. In general, the weekly dose should not exceed 25 mg. After achieving the desired therapeutic effect, the doctor may gradually reduce the dose of Methotrexate EVER Pharma to the smallest effective maintenance dose. The expected response to treatment usually occurs after 4-8 weeks of treatment. After discontinuing Methotrexate EVER Pharma, symptoms may return. Use in children and adolescents (aged 3 and older) with polyarticular forms of juvenile idiopathic arthritis The doctor will calculate the required dose based on the child's body surface area (m2). Methotrexate EVER Pharma is not recommended for use in children under 3 years of age due to insufficient experience in this age group. Adults with severe psoriasis or psoriatic arthritis The doctor will administer a single test dose of 2.5-5 mg to assess potential toxic effects. If the test dose is well tolerated, treatment will be continued after one week with a dose of approximately 7.5 mg (for an adult with an average body weight of 70 kg). In general, the weekly dose should not exceed 25 mg. After achieving the desired therapeutic effect, the doctor may gradually reduce the dose of Methotrexate EVER Pharma to the smallest effective maintenance dose. The expected response to treatment usually occurs after 2-6 weeks. Depending on the severity of symptoms and the results of blood and urine tests, treatment should be continued or discontinued. In the elderly, the dose should be reduced due to decreased liver and kidney function and lower folate reserves that occur with age. Method of administration and duration of treatment Methotrexate EVER Pharma is administered by subcutaneous injection (under the skin). The medicine should be used by injection once a week. It is recommended to perform injections of Methotrexate EVER Pharma on the same day of the week. Initially, the doctor or medical staff may administer the injection. However, the doctor may decide that the patient is able to learn how to self-administer the injection. The patient will be properly trained in this regard. Never attempt to self-administer the injection without prior training.

How to self-administer Methotrexate EVER Pharma

If the patient has difficulty handling the syringe, they should consult their doctor or pharmacist. Do not attempt to self-administer the injection if the patient has not been properly trained on how to do it. If the patient is unsure, they should immediately contact their doctor or nurse.

Before self-administering Methotrexate EVER Pharma

• Check the expiration date of the medicine. Do not use the medicine after the expiration date.
• Check if the syringe is damaged and if the medicine contained in it is a clear yellow solution. If not, use another syringe.
• Check if there is redness, discoloration, swelling, effusion, or persistent pain at the site of the last injection. If such symptoms occur, consult a doctor or nurse.
• Choose the injection site. The injection site should be changed each time.

Instructions for self-administering Methotrexate EVER Pharma

• 1. Open the packaging. Make sure the packaging is intact.
• 2. Place the syringe and needle with the protective cap on a clean surface.

• 3. Wash your hands thoroughly with soap and water.
• 4. Sit or lie down in a relaxed, comfortable position. Make sure you can see the area of skin where the medicine will be injected. The best injection sites are the skin of the abdominal wall or the front of the thigh.

• 5. The syringe is pre-filled and ready for use. Check the syringe for visible defects (or cracks). Check the solution. It should be a clear yellow liquid. A small air bubble may be visible in the solution, which will not affect the injection or pose a risk to the patient. Do not attempt to remove the air bubble before injecting – it may cause loss of some of the medicine.

The Methotrexate EVER Pharma pre-filled syringe has a needle protection system that prevents needlestick injury after use. The following instructions apply to pre-filled syringes with this system and may differ from the instructions for other injection systems.

• 6. Holding the syringe body with one hand, remove the protective cap by pulling it straight off to avoid bending the needle. Be careful not to touch the needle with your fingers to maintain its sterility.

• 7. Using two fingers, create a skin fold. Creating a skin fold will allow the active substance to reach the subcutaneous fatty tissue. With a quick motion, insert the needle into the skin at the appropriate angle (45° to 90°) and push the plunger all the way down. Visually check if there is any residual solution in the syringe. If there is, it means that not all of the medicine was injected properly, and the patient should consult their doctor.

• 8. When the plunger is fully depressed, the needle will be safely hidden. Only then can the skin fold be released.

• 9. Press the injection site with a cotton ball. Do not rub the injection site, as it may cause irritation.
• 10. Immediately dispose of the syringe in a sharps container. Close the container tightly and keep it out of the reach of children. If methotrexate accidentally comes into contact with the skin or soft tissues, the area should be rinsed with a large amount of water.

Women who are pregnant or plan to become pregnant should not come into contact with Methotrexate EVER Pharma. The duration of treatment is determined by the treating doctor. Treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis, and psoriatic arthritis requires long-term use of Methotrexate EVER Pharma. If the patient feels that the effect of Methotrexate EVER Pharma is too strong or too weak, they should consult their doctor or pharmacist.

Using a higher dose of Methotrexate EVER Pharma than recommended

The patient should use the dose prescribed by their doctor. The dose should not be changed without the doctor's advice. If the patient suspects that they have used a higher dose of Methotrexate EVER Pharma than they should have, they should immediately contact their doctor or the emergency department of the nearest hospital. Patients who visit their doctor or hospital should bring the medicine packaging and leaflet with them. Overdose of methotrexate can cause severe toxic reactions. Symptoms of overdose may include easy bruising or bleeding, unexplained weakness, mouth sores, nausea, vomiting, black or bloody stools, coughing up blood or vomiting coffee-ground-like material, and decreased urine output. See also section 4.

Missing a dose of Methotrexate EVER Pharma

The patient should not take a double dose to make up for a missed dose. They should consult their doctor for advice.

Stopping treatment with Methotrexate EVER Pharma

The patient should not stop or discontinue treatment with Methotrexate EVER Pharma without consulting their doctor. If they suspect severe side effects, they should immediately consult their doctor. If the patient has any further doubts about using this medicine, they should consult their doctor or pharmacist.

4. Possible side effects

Like all medicines, Methotrexate EVER Pharma can cause side effects, although not everybody gets them. The frequency and severity of side effects depend on the dose and frequency of administration of the medicine. Since severe side effects may occur even with low doses, regular medical check-ups are necessary. The treating doctor should prescribe tests and laboratory tests to rule out abnormalities in blood parameters (e.g., low white blood cell count, low platelet count, and lymphoma) and changes in the liver and kidneys. The patient should immediately inform their doctorif they experience any of the following symptoms, as they may indicate severe, potentially life-threatening side effects that require immediate treatment:

• sudden wheezing, difficulty breathing, swelling of the eyelids, face, or lips, rash, or itching (especially if it affects the whole body)
• pneumonitis (inflammation of the lungs, which may be characterized by a general feeling of being unwell, a dry, irritating cough, shortness of breath, difficulty breathing while at rest, chest pain, or fever)
• hemoptysis or coughing up blood
• severe skin peeling or blistering
• unexplained bleeding or bruising
• severe diarrhea
• mouth ulcers
• black or bloody stools
• blood in the urine or stool
• small red spots on the skin
• fever
• jaundice (yellowing of the skin)
• pain or difficulty urinating
• feeling thirsty and/or frequent urination
• seizures
• loss of consciousness
• blurred vision or changes in vision

The following side effects have also been reported: Very common(may affect more than 1 in 10 people):

• loss of appetite
• nausea (vomiting)
• abdominal pain
• inflammation of the mucous membrane of the mouth
• digestive disorders
• increased liver enzyme activity.

Common(may affect up to 1 in 10 people):

• decreased production of blood cells with decreased white blood cell count and/or red blood cell count or platelet count (leukopenia, anemia, thrombocytopenia)
• headache
• fatigue
• drowsiness
• pneumonitis with a dry, irritating cough without expectoration, shortness of breath, and fever
• diarrhea
• rash
• skin redness
• itching.

Uncommon(may affect up to 1 in 100 people):

• decreased blood cell count and platelet count
• dizziness
• disorientation
• depression
• mouth ulcers
• vasculitis (inflammation of blood vessels)
• ulcers and bleeding in the digestive tract
• liver function disorders
• diabetes
• decreased protein levels in the blood
• hives
• photosensitivity
• blisters on the skin
• hair loss
• enlargement of rheumatoid nodules
• skin ulcers
• shingles
• joint or muscle pain
• osteoporosis (decreased bone mass)
• inflammation and ulcers of the urinary bladder (may be accompanied by hematuria)
• kidney function disorders
• painful urination
• inflammation and ulcers of the vagina.

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

• infection (including reactivation of non-active chronic infection)
• sepsis
• eye redness
• allergic reactions
• anaphylactic shock
• decreased antibody levels in the blood
• restrictive cardiomyopathy due to fluid accumulation in the pericardium
• Pneumocystis jiroveci pneumonia
• vision disturbances
• pericarditis (inflammation of the pericardium)
• fluid accumulation in the pericardium
• low blood pressure
• blood clots
• lung damage
• shortness of breath
• asthma
• fluid accumulation in the pleural cavity
• gingivitis (inflammation of the gums)
• acute hepatitis
• skin discoloration
• acne
• presence of red or purple spots on the skin due to bleeding
• allergic vasculitis
• fever
• bone fractures
• kidney failure
• decreased or absent urine production
• electrolyte disturbances
• slow wound healing.

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

• significant decrease in the number of certain white blood cells (agranulocytosis)
• severe bone marrow failure
• liver failure
• lymph node enlargement
• pain
• muscle weakness
• tingling or numbness (reduced sensitivity to stimuli)
• taste disturbances (metallic taste in the mouth)
• cramps
• meningitis (inflammation of the membranes covering the brain, which may cause paralysis or vomiting)
• visual impairment
• Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome)
• nail discoloration
• retinal damage
• hematemesis (vomiting blood)
• fever, sore throat, fatigue with subsequent skin damage
• decreased libido
• erectile dysfunction
• paronychia (infection of the nail bed) of the hands
• severe gastrointestinal complications
• furuncles (boils)
• visible dilation of small blood vessels
• leukorrhea (vaginal discharge)
• gynecomastia (breast enlargement in men)
• lymphoproliferative disorders (excessive growth of white blood cells)
• disorders of sperm production
• menstrual disorders.

Unknown(frequency cannot be estimated from the available data):

• redness and peeling of the skin
• swelling
• destruction of tissue at the injection site
• increased white blood cell count (eosinophilia)
• certain brain disorders (encephalopathy/leukoencephalopathy)
• epistaxis (nosebleed)
• hemoptysis (coughing up blood)
• proteinuria (presence of protein in the urine)
• fatigue
• jawbone damage (secondary to lymphoma).

Subcutaneous administration of methotrexate is locally well tolerated. Only mild skin reactions (such as burning, redness, swelling, discoloration, severe itching, pain) have been observed after administration of Methotrexate EVER Pharma, which decrease during continued treatment.

Reporting side effects

If side effects occur, including any side effects not listed in this leaflet, the patient should tell their doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181 C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl. Side effects can also be reported to the marketing authorization holder. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Methotrexate EVER Pharma

The medicine should be stored out of the sight and reach of children. Do not store above 25°C. Do not store in the refrigerator or freeze. Store the pre-filled syringe in the outer packaging to protect it from light. Do not use this medicine after the expiration date stated on the label of the pre-filled syringe and the carton after: Expiration date. The expiration date refers to the last day of the month stated. Do not use this medicine if you notice that the syringe is damaged or if the solution is not clear and contains precipitated particles. Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Methotrexate EVER Pharma contains

• The active substance of the medicine is methotrexate. One mL of the solution for injection contains 25 mg of methotrexate.

Methotrexate EVER Pharma, 7.5 mg Each pre-filled syringe with 0.3 mL of the solution for injection contains 7.5 mg of methotrexate. Methotrexate EVER Pharma, 10 mg Each pre-filled syringe with 0.4 mL of the solution for injection contains 10 mg of methotrexate. Methotrexate EVER Pharma, 12.5 mg Each pre-filled syringe with 0.5 mL of the solution for injection contains 12.5 mg of methotrexate. Methotrexate EVER Pharma, 15 mg Each pre-filled syringe with 0.6 mL of the solution for injection contains 15 mg of methotrexate. Methotrexate EVER Pharma, 17.5 mg Each pre-filled syringe with 0.7 mL of the solution for injection contains 17.5 mg of methotrexate. Methotrexate EVER Pharma, 20 mg Each pre-filled syringe with 0.8 mL of the solution for injection contains 20 mg of methotrexate. Methotrexate EVER Pharma, 22.5 mg Each pre-filled syringe with 0.9 mL of the solution for injection contains 22.5 mg of methotrexate. Methotrexate EVER Pharma, 25 mg Each pre-filled syringe with 1 mL of the solution for injection contains 25 mg of methotrexate.

• The other ingredients are sodium chloride, sodium hydroxide (to adjust pH), hydrochloric acid (to adjust pH), and water for injections.

What Methotrexate EVER Pharma looks like and contents of the pack

Methotrexate EVER Pharma is available in 1 mL pre-filled syringes made of colorless glass (type I), with a fixed stainless steel needle, closed with a bromobutyl rubber stopper, and a needle protection system. The pre-filled syringes are equipped with a protection system that prevents needlestick injury after use. The packaging is a blister pack made of PET foil. The following pack sizes are available, with syringes in a single carton: 1 pre-filled syringe in a blister pack 4 pre-filled syringes in two double blister packs 12 pre-filled syringes in six double blister packs Not all pack sizes may be marketed.

Marketing authorization holder

EVER Valinject GmbH Oberburgau 3 4866 Unterach am Attersee Austria

Manufacturer

EVER Pharma Jena GmbH Otto-Schott-Strasse 15 07745 Jena Germany