REUMAFLEX

PACKAGE LEAFLET: INFORMATION FOR THE USER

Reumaflex 50 mg/ml solution for injection, pre-filled syringe

Methotrexate
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. 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. Do not give it to other people, even if they have the same symptoms as you, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Reumaflex is and what it is used for
2. What you need to know before using Reumaflex
3. How to use Reumaflex
4. Possible side effects
5. How to store Reumaflex
6. Contents of the pack and other information

1. What Reumaflex is and what it is used for

Reumaflex contains methotrexate as the active substance.
Methotrexate is a substance with the following properties:

• interferes with the growth of certain rapidly reproducing cells in the body
• reduces the activity of the immune system (the body's defence mechanism)
• has anti-inflammatory effects

Reumaflex is indicated for the treatment of:

• active rheumatoid arthritis in adult patients;
• severe active polyarticular forms of juvenile idiopathic arthritis with inadequate response to non-steroidal anti-inflammatory drugs (NSAIDs);
• severe, recurrent and disabling psoriasis that does not respond adequately to other therapies such as phototherapy, PUVA, and retinoids, and severe psoriatic arthritis in adult patients;
• mild to moderate Crohn’s disease in adult patients, in cases where adequate treatment with other drugs cannot be administered.

Rheumatoid arthritis (RA) is a chronic connective tissue disease characterized by inflammation of the synovial membranes (joint membranes). These membranes produce a fluid that acts as a lubricant for many joints. Inflammation causes thickening of these membranes and joint swelling.
Juvenile idiopathic arthritis affects children and adolescents under the age of 16. Polyarticular forms are those affecting five or more joints within the first six months after onset of the disease.
Psoriatic arthritis is a type of arthritis associated with psoriatic skin and nail lesions, particularly affecting the joints of the fingers and toes.
Psoriasis is a common chronic skin disease characterized by red patches covered with dry, thick, silvery scales that are difficult to remove.
Reumaflex has been shown to modify and slow the progression of these diseases.
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, diarrhoea, vomiting, or weight loss.

2. What you should know before using Reumaflex

Do not use Reumaflex:

• 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 alcoholic beverages,
• if you have a serious infection, e.g. tuberculosis, HIV or other immunodeficiency syndromes,
• if you have mouth ulcers or gastric or intestinal ulcers,
• if you are pregnant or breastfeeding (see section “Pregnancy, breastfeeding and fertility”),
• if you are simultaneously receiving vaccinations with live vaccines.

Warnings and precautions
Talk to your doctor or pharmacist before using Reumaflex if:

• you are elderly or generally feel unwell and weak,
• you have liver function problems,
• you suffer from dehydration (loss of body water),
• you have diabetes mellitus and are being treated with insulin.

Special precautions for treatment with Reumaflex
Methotrexate temporarily affects sperm and egg cell production, an effect which in most cases is reversible. Methotrexate may cause miscarriage and severe birth defects. If you are a woman, you must avoid pregnancy while taking methotrexate and for at least six months after stopping treatment. If you are a man, you must avoid fathering a child during treatment with methotrexate and for at least 3 months after stopping treatment. See also section “Pregnancy, breastfeeding and fertility”.

Follow-up examinations and precautions
Even when methotrexate is used at low doses, serious adverse effects may occur. To detect them early, your doctor must carry out regular check-ups and laboratory monitoring tests.

Before starting therapy
Before starting treatment, your blood will be tested to ensure you have an adequate number of blood cells. Your blood will also be examined to assess liver function and to check for hepatitis. Furthermore, serum albumin levels (a blood protein), hepatitis status (liver infections), and kidney function will be evaluated.
Your doctor may also decide to perform additional liver tests; some of these may include imaging of the liver, while others may require a small tissue sample taken from the liver for closer examination.
Your doctor may also check for tuberculosis by performing a chest X-ray or lung function tests.

During treatment
Your doctor may perform the following tests:

• Examination of the oral cavity and pharynx for changes in the mucous membrane such as inflammation or ulceration.
• Blood tests / complete blood count including blood cell counts and measurement of serum methotrexate levels.
• Blood tests to monitor liver function.
• Imaging tests to monitor liver condition.
• A small biopsy of liver tissue for closer examination.
• Blood tests to monitor kidney function.
• Monitoring of respiratory tract, and, if necessary, lung function tests.

It is very important that you attend these scheduled examinations.
If any of these test results are significant, your doctor will adjust your treatment accordingly.

Elderly patients
Elderly patients receiving methotrexate must be closely monitored by a physician so that possible side effects can be detected as early as possible.
Age-related impairment of liver and kidney function, as well as reduced body stores of folic acid in older age, require a relatively low dose of methotrexate.

Other precautions
Cases of acute pulmonary hemorrhage have been reported in patients with rheumatological diseases treated with methotrexate. If you notice blood in your saliva or after coughing, contact your doctor immediately.
Methotrexate may affect the immune system and vaccination outcomes. It may also influence the results of immunological tests. Chronic inactive infections such as herpes zoster [shingles], tuberculosis, hepatitis B or C may reactivate. During treatment with Reumaflex, vaccination with live vaccines must not be administered.
Radiation dermatitis and sunburn may reappear during methotrexate therapy (recall reaction). Psoriatic lesions may worsen with concomitant use of ultraviolet radiation and methotrexate.
Enlarged lymph nodes (lymphoma) may appear, and treatment should therefore be discontinued.
Diarrhea may be a toxic effect of Reumaflex and requires interruption of therapy. If you experience diarrhea, discuss it with your doctor.
Certain brain disorders (encephalopathy/leukoencephalopathy) have occurred in patients with tumors treated with methotrexate. These adverse effects cannot be ruled out when methotrexate is used to treat other diseases.
If you, your partner, or your caregiver notice the onset or worsening of neurological symptoms, including general muscle weakness, visual disturbances, changes in thinking, memory, and orientation, leading to confusion and personality changes, contact your doctor immediately, as these may be symptoms of a very rare and serious brain infection called progressive multifocal leukoencephalopathy (PML).

Other medicines and Reumaflex
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Please note that this applies also to medicines you may take in the future.
The effect of treatment may be altered if Reumaflex is taken together with other medicines such as:

• Antibiotics such as: tetracyclines, chloramphenicol and non-absorbable broad-spectrum antibiotics, penicillins, glycopeptides, sulfonamides, ciprofloxacin and cephalothin (medicines used to prevent/fight certain infections)
• Non-steroidal anti-inflammatory drugs or salicylates (analgesics and/or anti-inflammatory agents such as acetylsalicylic acid, diclofenac and ibuprofen or pyrazolone)
• Probenecid (a medicine for gout)
• Weak organic acids such as loop diuretics
• Medicines that may have undesirable effects on the bone marrow, e.g. trimethoprim-sulfamethoxazole (an antibiotic) and pyrimethamine
• Other medicines used to treat rheumatoid arthritis such as leflunomide, sulfasalazine and azathioprine
• Cyclosporine (to suppress the immune system)
• Mercaptopurine (a cytostatic medicine)
• Retinoids (a medicine for psoriasis and other dermatological conditions)
• Theophylline (a medicine for bronchial asthma and other lung diseases)
• Some medicines for stomach disorders such as omeprazole and pantoprazole
• Hypoglycemics (medicines used to lower blood sugar)

Vitamin complexes containing folic acid may interfere with the treatment effect and should be taken only under medical supervision.
Vaccinations with live vaccines must be avoided.

Reumaflex with food, drinks and alcohol
During treatment with Reumaflex, the following should be avoided: alcoholic beverages, large amounts of coffee, caffeine-containing drinks, and black tea.

Pregnancy, breastfeeding and fertility
Pregnancy
Do not use Reumaflex 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 pregnant women or women planning a pregnancy are not treated with methotrexate.
In women of childbearing age, pregnancy must be ruled out by appropriate measures, for example by performing a pregnancy test before starting treatment. During treatment with methotrexate and for at least 6 months after stopping treatment, you must avoid pregnancy by using reliable contraceptive methods throughout the entire period (see also section “Warnings and precautions”).
If you become pregnant during treatment or suspect you are pregnant, contact your doctor as soon as possible. You will receive counseling regarding the risk of harmful effects on the baby due to the treatment.
If you wish to become pregnant, you should consult your doctor, who will refer you to a specialist before the planned start of treatment.

Breastfeeding
Breastfeeding must be discontinued before and during treatment with Reumaflex.

Male fertility
Available evidence does not indicate an increased risk of birth defects or miscarriage if the father takes a weekly dose of methotrexate below 30 mg. However, the risk cannot be completely excluded. Methotrexate may be genotoxic, meaning that the medicine may cause genetic mutations. Methotrexate may affect sperm production, potentially leading to birth defects. Therefore, while taking methotrexate and for at least 3 months after stopping treatment, you must avoid fathering a child or donating semen.

Driving and using machines
Treatment with Reumaflex may cause adverse reactions affecting the central nervous system, such as fatigue and dizziness. Therefore, the ability to drive a vehicle and/or operate machinery may, in some cases, be impaired. If you feel tired or drowsy, you must not drive or operate machinery.

Reumaflex contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per dose, i.e. it is practically "sodium-free".

3. How to use Reumaflex

Important warning regarding the dosage of Reumaflex (methotrexate):
In the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis, psoriatic arthritis, and
Crohn's disease, Reumaflex must be used only once a week. Excessive use of
Reumaflex (methotrexate) can be fatal. Please read paragraph 3 of this leaflet very carefully.
If in doubt, consult your doctor or pharmacist before taking this medicine.
Always use this medicine exactly as instructed by your doctor. If you have any doubts, consult
your doctor or pharmacist.
Your doctor will determine the dosage, which must be tailored to the individual patient. The effects of
treatment are generally noticeable after 4–8 weeks.
Reumaflex is administered by a doctor or under medical supervision, or by healthcare professionals, as an injection under the skin (subcutaneous injection) only once a week. Together with your doctor, decide on the specific day of the week for your weekly injection.

Use in children and adolescents
Your doctor will determine the appropriate dosage for children and adolescents with polyarticular forms of juvenile idiopathic arthritis.
Reumaflex is not recommended for children under 3 years of age due to limited experience with use in this age group.

Method of administration and duration of treatment
Reumaflex is administered by subcutaneous injection once a week only!
The duration of treatment is determined by your treating physician. Treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis vulgaris, and psoriatic arthritis with Reumaflex is intended as long-term therapy.
At the beginning of treatment, Reumaflex will be administered by medical personnel. However, your doctor may consider that you are able to learn how to self-administer Reumaflex subcutaneous injections.
In such a case, you will receive adequate training.
Under no circumstances should you attempt to self-inject without having received adequate training.
Refer to the instructions for use at the end of this package leaflet.
Handling and disposal must be carried out as for other cytotoxic preparations, in accordance with local regulations. Healthcare workers who are pregnant should avoid handling and/or administering Reumaflex.
Methotrexate must not come into contact with the skin surface or mucous membranes. In case of contamination, the affected area must be immediately rinsed thoroughly with plenty of water.

If you use more Reumaflex than you should
If you use more Reumaflex than prescribed, contact your doctor immediately.

If you forget to use Reumaflex
Do not use a double dose to make up for the missed dose.

If you stop using Reumaflex
If you discontinue treatment with this medicine, contact your doctor immediately.
If you feel that the effect of Reumaflex is too strong or too weak, inform your doctor or pharmacist.

4. Possible side effects

Like all medicines, Reumaflex can cause side effects, although not everyone experiences them.
The frequency and severity of side effects depend on the dosage and frequency of administration.
Since serious side effects may occur even at low doses, it is important that your doctor performs regular monitoring.

Your doctor should therefore prescribe blood tests to detect any possible abnormalities (e.g. reduced white blood cell count, reduced platelet count, lymphoma) and abnormalities in kidney and liver function.

Contact your doctor immediately if you notice any of the following symptoms, which may indicate serious, potentially life-threatening side effects requiring urgent specific treatment:

• Persistent dry cough without phlegm, shortness of breath, and fever may be signs of a lung infection [common];
• Blood in saliva or after coughing; this could indicate pulmonary bleeding [frequency not known];
• Signs of liver damage such as yellowing of the skin and whites of the eyes: methotrexate may cause chronic liver damage (hepatic cirrhosis), scar tissue formation in 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 rashes including red, itchy skin, swelling of 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 hands, ankles, feet, or changes in frequency of urination, reduced urine output (oliguria), or absence of urine (anuria): may be signs of kidney failure [rare];
• Signs of infection, e.g. fever, chills, pain, sore throat: methotrexate may increase susceptibility 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 general condition, or sudden fever accompanied by sore throat or inflamed mouth, or urinary problems: methotrexate may cause a sudden decrease in certain white blood cells (agranulocytosis) and severe bone marrow suppression [very rare];
• Sudden bleeding, e.g. bleeding gums, blood in urine, vomiting blood, or bruising: may be signs of a severe decrease in platelet count due to severe bone marrow suppression [very rare];
• Symptoms such as severe headache often associated with fever, neck stiffness, nausea, vomiting, disorientation, and sensitivity to light may indicate inflammation of the membranes surrounding the brain (acute aseptic meningitis) [very rare];
• Some brain changes (encephalopathy/leukoencephalopathy) have occurred in patients with tumors treated with methotrexate. These side effects cannot be excluded when methotrexate is used to treat other diseases. Signs of such brain changes may include altered mental status, uncoordinated movements (ataxia), vision or memory disturbances [frequency not known];
• Severe skin rash or blisters (may also appear in mouth, eyes, and genitals): may be signs of a very rare condition called Stevens-Johnson syndrome or scalded skin syndrome (toxic epidermal necrolysis/Lyell’s syndrome) [very rare].

Other side effects may also occur, listed below:
Very common: may affect more than 1 in 10 people

• Inflammation of the lining of the mouth, indigestion, malaise, loss of appetite, abdominal pain
• Abnormal results in certain blood tests (AST, ALT, bilirubin, alkaline phosphatase)

Common: may affect up to 1 in 10 people

• Mouth ulcers, diarrhea
• Skin rash, redness of the skin, itching
• Headache, fatigue, drowsiness
• Reduced production of blood cells with decreased white and/or red blood cells and/or platelets

Uncommon: may affect up to 1 in 100 people

• Sore throat
• Intestinal inflammation, vomiting, pancreatitis, black stools, gastrointestinal ulcers and bleeding
• Increased sensitivity to light, hair loss, increase in number of rheumatic nodules, skin ulcers, shingles (herpes zoster), inflammation of blood vessels, herpes-like skin rashes, hives (urticaria)
• Onset of diabetes mellitus
• Dizziness, confusion, depression
• Decreased serum albumin
• Reduced number of all blood cells and platelets
• Inflammation and ulceration of the urinary bladder or vagina, reduced kidney function, urinary problems (urination difficulties)
• Joint pain, muscle pain, reduced bone mass

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

• Gum inflammation
• Increased skin pigmentation, acne, bruising due to bleeding from blood vessels (ecchymoses, petechiae)
• Allergic inflammation of blood vessels
• Reduced number of antibodies in the blood
• Infection (including reactivation of inactive chronic infections), eye redness (conjunctivitis)
• Mood swings (mood alterations)
• Visual disturbances
• Inflammation of the membrane surrounding the heart, fluid accumulation in the membrane surrounding the heart, obstruction of heart filling due to fluid in the membrane lining the heart
• Low blood pressure
• Scar tissue formation in the lungs (pulmonary fibrosis), shortness of breath and bronchial asthma, fluid accumulation in the membrane lining the lungs
• Stress fracture
• Electrolyte disturbances
• Fever, impaired wound healing

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

• Acute toxic dilation of the intestine (toxic megacolon)
• Increased nail pigmentation, inflammation of nail cuticles (acute paronychia), deep infection of hair follicles (furunculosis), visible enlargement of capillaries
• Local tissue damage at injection site (formation of sterile abscesses, changes in fatty tissue)
• Pain, loss of strength, or numbness, tingling/lessened sensitivity to stimulation, taste changes (metallic taste), seizures, paralysis, meningism
• Non-inflammatory eye disorders (retinopathy)
• Loss of libido, impotence, enlargement of male breast glands, abnormal sperm formation (oligospermia), menstrual disorders, vaginal discharge
• Enlargement of lymph nodes (lymphoma). Lymphoproliferative disorders (excessive growth of white blood cells)

Frequency not known: cannot be estimated from available data:

• Increase in number of certain white blood cells
• Nosebleeds
• Protein in urine
• Feeling of weakness
• Bone damage in the jaw/mandible (secondary to excessive growth of white blood cells)
• Tissue destruction at injection site
• Skin redness and peeling
• Swelling

Subcutaneous administration of methotrexate is generally well tolerated locally. Only mild local skin reactions have been observed, which tend to diminish during treatment.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor or pharmacist. You may also report side effects directly via the Italian Medicines Agency (Agenzia Italiana del Farmaco) – website: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Reumaflex

Keep this medicine out of the sight and reach of children.
.
Store below 25 °C.
Keep the pre-filled syringes in the outer cardboard box to protect them from light.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of that month.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Reumaflex contains

• The active substance is methotrexate. 1 ml of solution contains methotrexate disodium equivalent to 50 mg of methotrexate.
• The other components are sodium chloride, sodium hydroxide, water for injections.

Description of the appearance of Reumaflex and contents of the pack
Pre-filled syringes of Reumaflex contain a clear yellowish-brown solution.
For packs containing only syringes with a safety system, the syringe is equipped with a safety system to prevent needle-stick injuries and reuse of the needle.
The following pack sizes are available:

• Pre-filled syringes with fixed subcutaneous needle and graduated markings, packed in blisters containing 0.15 ml, 0.20 ml, 0.25 ml, 0.30 ml, 0.35 ml, 0.40 ml, 0.45 ml and 0.50 ml of injectable solution, in packs of 1, 4, 6, 12 and 24 pre-filled syringes with safety system.
• Pre-filled syringes with fixed subcutaneous needle and graduated markings, packed in blisters, 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, in calendar packs of 6 and 12 pre-filled syringes with safety system.

Not all pack sizes may be marketed.
Marketing Authorization Holder:
Alfasigma S.p.A. - Via Ragazzi del ’99, n. 5 - 40133 Bologna (BO)
Manufacturer:
medac Gesellschaft für klinische Spezialpräparate mbH
Theaterstr. 6
22880 Wedel
Germany
Tel: +49 4103 8006 0
Fax: +49 4103 8006 100
This medicinal product is authorized in the Member States of the European Economic Area under the following names:

• Austria, Belgium, Czech Republic, Finland, Greece, Hungary, Iceland, Netherlands, Slovakia, Slovenia, Spain, Sweden: Metoject
• Denmark, Estonia, Latvia, Lithuania, Norway, Poland and Portugal: Metex
• Germany: metex
• Italy: Reumaflex

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Instructions for subcutaneous use
Reumaflex is administered by a subcutaneous injection once weekly only. Read these instructions carefully before starting the injection and always use the injection technique recommended by your doctor, pharmacist or nurse.
For any problems or questions, contact your doctor, pharmacist or nurse.
Preparation
Choose a flat, clean and well-lit working surface.
Wash your hands thoroughly.
Remove the pre-filled syringe of methotrexate from the packaging and read the package leaflet carefully. Take the pre-filled syringe out of the packaging at room temperature.
Before use, check the Reumaflex syringe for any defects in appearance (or cracks). If a small air bubble is visible in the solution, this will not affect the dose or harm you.
Injection site

The best injection sites are:

• upper thigh,
• abdomen, excluding the area around the navel.
• If you have assistance for the injection, it may also be administered into the back of the upper arm, just below the shoulder.
• Change the injection site with each injection. This can help reduce the risk of developing irritation at the injection site.
• Never inject into areas of delicate, bruised, red, hard, scarred or stretch-marked skin. If you suffer from psoriasis, try not to inject directly into lesions or into raised, thickened, red or flaky areas of skin or lesions.

Injecting the solution

1. Choose an injection site and clean the chosen injection site area

and its surroundings (with water and soap or disinfectant).

2. Remove the plastic protective cap

.

Carefully remove the grey plastic protective cap by pulling it straight off the syringe. If the cap is difficult to remove, gently rotate it while pulling outward.
Important: Do not touch the needle of the pre-filled syringe!
Note:
Once the cap has been removed, administer the injection
immediately

3. Inserting the needle

Pinch the skin with two fingers and quickly insert the needle into the skin at a 90-degree angle.

4. Injection

Insert the needle completely into the skin fold. Push the plunger slowly and inject the liquid under the skin. Keep holding the skin fold firmly until the injection is complete.
Carefully remove the needle vertically.

5. Dispose of the used syringe, including the needle, in a sharps container. Do not place it in household waste.

Methotrexate must not come into contact with the skin surface or mucous membranes. If this occurs, immediately rinse thoroughly with plenty of water.
If you or someone near you is accidentally injured by the needle, consult a doctor immediately and do not use the pre-filled syringe.
Disposal and other handling
Handling and disposal of this medicinal product and the pre-filled syringe must comply with local requirements. Healthcare personnel who are pregnant should avoid handling and/or administering Reumaflex.
.

Instructions for subcutaneous use
Reumaflex is administered by a subcutaneous injection once weekly only. Read these instructions carefully before starting the injection and always use the injection technique recommended by your doctor, pharmacist or nurse.
For any problems or questions, contact your doctor, pharmacist or nurse.
Preparation
Choose a flat, clean and well-lit working surface.
Wash your hands thoroughly.
Remove the pre-filled syringe of methotrexate with safety system from the packaging and read the package leaflet carefully.
Take the pre-filled syringe out of the packaging at room temperature.
Before use, check the Reumaflex syringe for any defects in appearance (or cracks). If a small air bubble is visible in the solution, this will not affect the dose or harm you.
Injection site

The best injection sites are:

• upper thigh,
• abdomen, excluding the area around the navel.
• If you have assistance for the injection, it may also be administered into the back of the upper arm, just below the shoulder.
• Change the injection site with each injection. This can help reduce the risk of developing irritation at the injection site.
• Never inject into areas of delicate, bruised, red, hard, scarred or stretch-marked skin. If you suffer from psoriasis, try not to inject directly into lesions or into raised, thickened, red or flaky areas of skin or lesions.

Injecting the solution
.

3. Needle insertion

Grasp a skin fold with two fingers and quickly insert
the needle into the skin at a 90-degree angle.

4. Injection

Insert the needle completely into the skin fold. Push the
plunger slowly and inject the liquid subcutaneously.

5. Needle removal

Note: The safety mechanism triggered by removing the protective cap can only be activated
when the syringe has been completely emptied by fully depressing the plunger to the end of its travel.
.

6. Dispose of the used syringe, including the needle, in a sharps waste container. Do not place it in household waste.

Methotrexate must not come into contact with the skin surface or mucous membranes. If this
occurs, immediately rinse thoroughly with abundant water.
If you or someone near you is injured by the needle, consult a doctor immediately and do not use the
pre-filled syringe.
Disposal and other handling
Handling and disposal of this medicinal product and the pre-filled syringe must comply
with local requirements. Healthcare personnel who are pregnant must refrain from
handling and/or administering Reumaflex.
.