Reumaflex

PACKAGE LEAFLET: INFORMATION FOR THE USER

Reumaflex 50 mg/ml injectable solution, 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 their symptoms are the same as yours, because it could be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, contact 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 compound 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, recurring 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 disease onset.
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 diseases of the liver or kidneys 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 using 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 with methotrexate. See also section “Pregnancy, breastfeeding and fertility”.
Follow-up examinations and precautions
Even though methotrexate is used at low doses, serious adverse effects may occur. To detect them early, your doctor must perform 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 check liver function and to detect hepatitis. Furthermore, serum albumin levels (a blood protein), the status of hepatitis infections (liver infections), and kidney function will be assessed.
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 mucosal changes 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.
• Small liver tissue biopsy for closer examination.
• Blood tests to monitor kidney function.
• Monitoring of respiratory tract, and, if necessary, pulmonary 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 doctor 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 performed.
Radiation dermatitis and sunburn may reappear during methotrexate therapy (recall reaction). Psoriatic lesions may worsen following concomitant use of ultraviolet radiation and methotrexate.
Swollen 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.
Some brain disorders (encephalopathy/leukoencephalopathy) have occurred in patients with cancer treated with methotrexate. These adverse effects cannot be excluded 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 also applies to any medicines you may take in the future.
The effect of treatment may be altered if Reumaflex is administered 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/treat 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 adverse 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
• Cyclosporines (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 compromise the treatment effect and should only be taken 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 women who are pregnant or planning a pregnancy are not treated with methotrexate.
In women of childbearing age, any possibility of pregnancy must be excluded using appropriate measures, for example by performing a pregnancy test before starting treatment. During methotrexate treatment 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 plan a pregnancy, 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 dose of methotrexate below 30 mg/week. However, the risk cannot be completely excluded. Methotrexate may be genotoxic. This means that the medicine
may cause genetic mutations. Methotrexate may affect sperm production, possibly 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. 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 decide the dosage, which must be adjusted to the individual patient. In general, treatment effects
are noticeable after 4–8 weeks.
Reumaflex is administered by a doctor or under medical supervision, or by healthcare personnel, as a subcutaneous injection (under-the-skin injection) only once a week. Together with your doctor, decide which day of the week you will receive 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 the medicine 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 long-term therapy.
At the beginning of treatment, Reumaflex will be administered by medical personnel. However, your doctor may determine 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 leaflet.
Handling and disposal must comply with local regulations for cytotoxic agents. Pregnant healthcare personnel 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 carries out regular monitoring.
Your doctor should therefore prescribe blood tests to detect 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 lung infection [common];

• Blood in saliva or after coughing; this could indicate pulmonary bleeding [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 or reduced (oliguria) or absence of urine (anuria): may be signs of kidney failure [rare]

• Signs of infection, e.g. fever, chills, aches, 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 drop 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 drop in platelet count due to severe bone marrow suppression [very rare]

• Symptoms such as severe headache often associated with fever, neck stiffness, nausea, vomiting, confusion, and sensitivity to light may indicate inflammation of the membranes surrounding the brain (acute aseptic meningitis) [very rare]

• Some brain alterations (encephalopathy/leukoencephalopathy) have occurred in cancer patients treated with methotrexate. These side effects cannot be excluded when methotrexate is used to treat other conditions. Signs of such brain alterations may include altered mental status, uncoordinated movements (ataxia), vision or memory disturbances [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, diarrhoea,
• Skin rash, redness of the skin, itching,
• Headache, fatigue, drowsiness,
• Reduced production of blood cells leading to decreased white blood cells and/or red blood cells and/or platelets.

Uncommon: may affect up to 1 in 100 people

• Sore throat,
• Intestinal inflammation, vomiting, pancreatitis, black stools, gastrointestinal ulcers and bleeding,
• Increased sensitivity to light, hair loss, increase in number of rheumatoid nodules, skin ulcers, shingles (herpes zoster), blood vessel inflammation, herpes-like skin rashes, hives,
• Onset of type 2 diabetes mellitus,
• Dizziness, confusion, depression,
• Decreased serum albumin,
• Reduction in 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, poor 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 (formation of sterile abscesses, changes in fatty tissue) at the injection site.
• Pain, loss of strength, or numbness, tingling/lessened sensation to stimulation, taste changes (metallic taste), seizures, paralysis, meningism.
• Non-inflammatory eye disorders (retinopathy).
• Loss of libido, impotence, enlargement of male mammary 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 the urine.
• Feeling of weakness.
• Bone damage in the jaw/mandible (secondary to excessive white blood cell growth).
• Destruction of tissue at the injection site.
• Skin redness and peeling.
• Swelling.

Subcutaneous administration of methotrexate is locally well tolerated. Only mild local skin reactions have been observed, which diminished during treatment.
Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the Italian Medicines Agency - 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 carton 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 no longer required. 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 device, 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 device.
• 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 device.

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

.

Instructions for Subcutaneous Use
Reumaflex is administered by a single injection under the skin 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 work surface.
Wash your hands thoroughly.
Remove the pre-filled methotrexate syringe from the packaging and read the package leaflet carefully.
Remove the pre-filled syringe from its packaging at room temperature.
Before use, inspect 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 on 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 stretched skin (striae). If you have psoriasis, try to avoid injecting directly into lesions or raised, thickened, red, or flaky areas of skin or lesions.

Injecting the Solution

1. Choose an injection site and clean the chosen site and surrounding area (with water and soap or a 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 twist it while pulling outward.
Important: Do not touch the needle of the pre-filled syringe!
Note:
Once the cap is 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 subcutaneously. 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 dispose of it with household waste.

Methotrexate must not come into contact with the skin surface or mucous membranes. If this occurs, rinse immediately 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. Pregnant healthcare personnel should avoid handling and/or administering Reumaflex.
.

Instructions for Subcutaneous Use
Reumaflex is administered by a single injection under the skin 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 work surface.
Wash your hands thoroughly.
Remove the pre-filled methotrexate syringe with safety device from the packaging and read the package leaflet carefully.
Remove the pre-filled syringe from its packaging at room temperature.
Before use, inspect 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 on 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 stretched skin (striae). If you have psoriasis, try to avoid injecting directly into lesions or 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

Fully insert the needle into the skin fold. Slowly push
the plunger 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 pushing the plunger to the end of its travel.
.
6. Dispose of the used syringe, including the needle, in a sharps disposal 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 injured with 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.
.