Immutrex

Package leaflet: Information for the user

IMMUTREX

2.5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg, 17.5 mg, 20 mg, 22.5 mg, 25 mg, 27.5 mg and 30 mg
injection solution in pre-filled syringe
Methotrexate
Please read carefully this leaflet 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 may be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What IMMUTREX is and what it is used for

IMMUTREX 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.

IMMUTREX is indicated for the treatment of:

• active rheumatoid arthritis in adult patients;
• severe, active polyarticular forms of juvenile idiopathic arthritis inadequately responsive to non-steroidal anti-inflammatory drugs (NSAIDs);
• severe, recurrent, and disabling psoriasis inadequately responsive 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 when adequate treatment with other medications is not possible.

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 16 years of age. 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.
IMMUTREX 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, diarrhea, vomiting, or weight loss.

2. What you need to know before using IMMUTREX

Do not use IMMUTREX

• 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 IMMUTREX if:

• you are elderly or generally feel unwell and weak.
• you have liver function problems.
• you are dehydrated (loss of body water).

Special precautions for treatment with IMMUTREX
Methotrexate temporarily affects sperm and egg cell production, an effect which is reversible in most cases. Methotrexate may cause miscarriage and severe birth defects.
During treatment with methotrexate and for at least six months after treatment ends, women must avoid becoming pregnant. If you are a man, you must avoid fathering a child during treatment with methotrexate and for at least three months after treatment ends. Also refer to the section “Pregnancy, breastfeeding and fertility”.
Follow-up examinations and recommended precautions
Even when methotrexate is used at low doses, serious adverse effects may occur. To detect them early, your doctor must perform regular check-ups and laboratory tests.
Before starting therapy
Before starting treatment, you will undergo blood tests to assess whether you have a sufficient number of blood cells. In addition, your blood will be tested to evaluate liver function and to check for hepatitis. Serum albumin (a blood protein), hepatitis status (liver infection), and kidney function will also be monitored. Your doctor may decide to perform further liver tests, some of which may include imaging of your liver, while others may require a small tissue sample from the liver for closer examination. Your doctor may also ensure that you do not have tuberculosis and may perform a chest X-ray or lung function tests.
During treatment
Your doctor may carry out the following tests:

• examination of the oral cavity and pharynx to check for changes in the mucous membrane such as inflammation or ulceration
• blood tests / full blood count including blood cell counts and measurement of serum methotrexate levels
• blood tests to monitor liver function
• imaging tests to monitor liver condition
• liver biopsy (removal of a small liver tissue sample for closer examination)
• blood tests to monitor kidney function
• monitoring of the respiratory tract and, if necessary, lung function tests.

It is very important that you attend all scheduled appointments.
If any of these test results are significantly abnormal, your doctor will adjust your treatment accordingly.
Elderly patients
Elderly patients receiving methotrexate must be closely monitored by a doctor so that any adverse effects can be detected as early as possible.
Age-related impairment of liver and kidney function and low body reserves of folic acid require relatively low doses of methotrexate.
Other precautions
Cases of acute pulmonary hemorrhage have been reported in patients with rheumatic disease 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 affect the results of immunological tests. Chronic inactive infections may reactivate (e.g. herpes zoster [shingles], tuberculosis, hepatitis B or C). During treatment with IMMUTREX, vaccination with live vaccines must not be administered.
Methotrexate may increase skin sensitivity to sunlight. Avoid intense sun exposure and do not use sunbeds or tanning lamps without medical advice. To protect your skin from strong sunlight, wear appropriate clothing or use a sunscreen with a high protection factor.
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 possible side effect of IMMUTREX and may require discontinuation of treatment. If you experience diarrhea, discuss it with your doctor.
Certain brain disorders (encephalopathy/leukoencephalopathy) have occurred in cancer patients treated with methotrexate. Such side 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 IMMUTREX
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. Note that this also applies to medicines you may take in the future.
The effect of treatment may be altered if IMMUTREX is taken together with other medicines such as:

• antibiotics such as: tetracyclines, chloramphenicol, non-absorbable broad-spectrum antibiotics, penicillins, glycopeptides, sulfonamides, ciprofloxacin and cephalothin (medicines that prevent/treat certain infections).
• Penicillins may reduce methotrexate excretion, potentially increasing the risk of adverse effects.
• Non-steroidal anti-inflammatory drugs or salicylates (medicines for pain and/or inflammation such as acetylsalicylic acid, diclofenac and ibuprofen or pyrazolone derivatives).
• Probenecid (a medicine for gout).
• Weak organic acids such as loop diuretics (diuretic medicines).
• 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.
• Mercaptopurine (a cytostatic medicine).
• Retinoids (a medicine for psoriasis and other dermatological conditions).
• Theophylline (a medicine for bronchial asthma and other lung diseases).
• Certain medicines for stomach disorders such as omeprazole and pantoprazole.
• Hypoglycemics (medicines used to lower blood sugar).
• It is especially important that you inform your doctor if you are taking:
• metamizole (also known as novaminsulfone and dipyrone) (a medicine to relieve severe pain and/or fever).

Vitamin complexes containing folic acid may interfere with the treatment effect and should only be taken under medical supervision.
Vaccinations with live vaccines must be avoided.
IMMUTREX with food, drinks and alcohol
During treatment with IMMUTREX, alcoholic beverages, large quantities of coffee, caffeine-containing drinks, and black tea should be avoided.
Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before using this medicine.
Pregnancy
Do not use IMMUTREX 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 affecting the skull, face, heart and blood vessels, brain, and limbs. Therefore, it is very important that pregnant women or women planning pregnancy are not treated with methotrexate. Thus, in women of childbearing age, pregnancy must be ruled out before starting treatment by appropriate means, e.g. a pregnancy test.
During treatment with methotrexate and for at least six months after treatment ends, you must avoid pregnancy by using a reliable contraceptive method (see also section “Warnings and precautions”).
If you become aware or suspect you are pregnant during treatment, contact your doctor immediately for medical advice regarding the risk of harmful effects on the unborn child throughout the duration of treatment.
If you plan to become pregnant, you should consult your doctor, who may refer you to a specialist before the planned start of treatment.
Breastfeeding
Breastfeeding must be stopped before and during treatment with IMMUTREX.
Male fertility
Available data do not indicate an increased risk of birth defects or miscarriages if the father takes less than 30 mg of methotrexate per week. However, the risk cannot be completely excluded. Methotrexate may be genotoxic; that is, this medicine may cause genetic mutations. Methotrexate may affect sperm production and potentially cause birth defects. Therefore, while taking methotrexate and for at least three months after stopping treatment, you must avoid fathering a child or donating sperm.
Driving and using machines
Treatment with IMMUTREX may cause adverse reactions affecting the central nervous system, such as fatigue and dizziness. Therefore, your ability to drive or operate machinery may, in some cases, be impaired. If you feel tired or drowsy, you must not drive or operate machinery.
IMMUTREX contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially “sodium-free”.

3. How to use IMMUTREX

Important warning about the dose of IMMUTREX (methotrexate):
Use IMMUTREX once a week only for the treatment of rheumatoid arthritis,
polyarticular forms of severe juvenile idiopathic arthritis, psoriasis vulgaris, psoriatic arthritis, and
Crohn's disease. Overdosing with IMMUTREX (methotrexate) can be fatal. Read
paragraph 3 of this leaflet very carefully. If in doubt, consult your doctor or
pharmacist before taking this medicine.
Use this medicine exactly as instructed by your doctor. Check with your doctor or
pharmacist if you are unsure.
Your doctor will decide the dose, which will be adjusted to the individual patient. In general, treatment effects
are noticeable after 4–8 weeks of treatment.
IMMUTREX is administered by a doctor or under medical supervision, or by healthcare personnel, as an injection once a week only. Together with your doctor, decide on the day of the week for your weekly injection. IMMUTREX must be injected subcutaneously (under the skin).
Use in children and adolescents
Your doctor will determine the appropriate dosage for children and adolescents affected by polyarticular forms of juvenile idiopathic arthritis.
IMMUTREX is not recommended in children under 3 years of age due to limited experience in this age group.
Method of administration and duration of treatment
IMMUTREX is injected once a week only!
The duration of treatment is determined by your treating physician. Treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis vulgaris, psoriatic arthritis, and Crohn's disease with IMMUTREX is intended as long-term therapy.
At the beginning of treatment, IMMUTREX will be administered by medical personnel. However, your doctor may consider that you are able to learn how to self-administer IMMUTREX injections. In such a case, you will receive adequate training.
Under no circumstances should you attempt to self-inject without having received proper training.
Refer to the instructions for use at the end of this leaflet.
Handling and disposal must be carried out as for other cytotoxic preparations, in accordance with local regulations. Healthcare personnel who are pregnant must avoid handling and/or administering IMMUTREX.
If you use more IMMUTREX than you should
If you use more IMMUTREX than prescribed, contact your doctor immediately.
If you forget to use IMMUTREX
Do not use a double dose to make up for a forgotten dose.
If you stop using IMMUTREX
If you have any doubts about using this medicine, consult your doctor or pharmacist. If you stop treatment with IMMUTREX, contact your doctor immediately.
If you feel that the effect of IMMUTREX is too strong or too weak, inform your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The frequency and severity of side effects depend on the dose 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 will therefore prescribe blood tests to detect possible abnormalities in the blood (e.g. low white blood cell count, low platelet count and lymphoma) and changes 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: these may be signs of lung inflammation [common];
• Blood in saliva or after coughing: these may be signs of bleeding from the lungs [frequency not known];
• Signs of liver damage such as yellowing of the skin and whites of the eyes: methotrexate may cause chronic liver damage (liver cirrhosis), scarring of liver tissue (liver 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): these 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 happen when a blood clot breaks loose and blocks a blood vessel (thromboembolic event) [rare];
• Fever and severe deterioration in general condition, or sudden fever accompanied by sore throat or mouth inflammation, or urinary problems: methotrexate may cause a sudden drop in the number of certain types of white blood cells (agranulocytosis) and severe bone marrow suppression [very rare];
• Sudden bleeding, e.g. bleeding gums, blood in urine, vomiting blood or bruising: these 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, malaise, vomiting, confusion and sensitivity to light: these may indicate inflammation of the membranes surrounding the brain (acute aseptic meningitis) [very rare];
• Some brain disorders (encephalopathy/leukoencephalopathy) have been observed in cancer patients treated with methotrexate. Some side effects cannot be ruled out when methotrexate therapy is used to treat other conditions. Symptoms of such brain disorders may include mental confusion, movement disorders (ataxia), vision disturbances or memory problems [frequency not known];
• Severe skin rash or blisters (which may also appear in the mouth, eyes and genital area): these may be signs of a condition called Stevens-Johnson syndrome or 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 mouth mucosa, indigestion, malaise, loss of appetite, abdominal pain.
• Abnormal liver function test results (ASAT, ALAT, bilirubin, alkaline phosphatase).

Common: may affect up to 1 in 10 people

• Mouth ulcers, diarrhoea.
• Skin rash, skin redness, itching.
• Headache, fatigue, drowsiness.
• Reduced blood cell formation with decreased white blood cells and/or red blood cells and/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 skin sensitivity to sunlight, hair loss, increase in number of rheumatic nodules, skin ulcers, shingles, inflammation of blood vessels, herpes-like skin rashes, hives.
• Development of 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.
• Joint pain, muscle pain, reduced bone mass.

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

• Inflammation of the gums.
• Increased skin pigmentation, acne, bruising due to bleeding from blood vessels (ecchymoses, petechiae), allergic inflammation of blood vessels.
• Reduction in the number of antibodies in the blood.
• Infection (including reactivation of inactive chronic infections), red eyes (conjunctivitis).
• Mood swings (mood alterations).
• Visual disturbances.
• Inflammation of the membrane surrounding the heart, fluid accumulation in the membrane surrounding the heart, ventricular obstruction due to fluid in the membrane around the heart.
• Low blood pressure.
• Scarring of lung tissue (pulmonary fibrosis), shortness of breath and bronchial asthma, fluid accumulation in the membrane lining the lungs.
• Stress fractures.
• Electrolyte disturbances.
• Fever, delayed 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 around the nail folds (acute periungual tissue infection), deep infection of hair follicles (furunculosis), visible enlargement of small blood vessels.
• Local tissue damage (formation of sterile abscesses, changes in fatty tissue) at the injection site after intramuscular or subcutaneous administration.
• Pain, loss of strength or numbness or tingling/reduced sensitivity to stimulation, taste changes (metallic taste), seizures, paralysis, meningism.
• Visual disturbances, eye disorders of non-inflammatory origin (retinopathy).
• Loss of libido, impotence, enlargement of male breasts, 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 the available data:

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

Subcutaneous administration of methotrexate is locally well tolerated. Only mild local skin reactions have been observed, which decreased during treatment.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at www.aifa.gov.it/content/segnalazioni-reazioni-avvers e. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store IMMUTREX

Keep this medicine out of the sight and reach of children.
Store at a temperature not exceeding 25 °C.
Keep the pre-filled syringes in the outer carton to protect the medicine from light.
Do not use this medicine after the expiry date stated on the label and carton after EXP. The expiry date refers to the last day of that month.
For single use only. Any unused solution must be discarded.
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 IMMUTREX Contains

• The active substance is methotrexate.
• IMMUTREX 2.5 mg: Each 0.33 ml pre-filled syringe contains 2.5 mg of methotrexate.
• IMMUTREX 7.5 mg: Each 0.30 ml pre-filled syringe contains 7.5 mg of methotrexate.
• IMMUTREX 10 mg: Each 0.40 ml pre-filled syringe contains 10 mg of methotrexate.
• IMMUTREX 12.5 mg: Each 0.31 ml pre-filled syringe contains 12.5 mg of methotrexate.
• IMMUTREX 15 mg: Each 0.38 ml pre-filled syringe contains 15 mg of methotrexate.
• IMMUTREX 17.5 mg: Each 0.44 ml pre-filled syringe contains 17.5 mg of methotrexate.
• IMMUTREX 20 mg: Each 0.50 ml pre-filled syringe contains 20 mg of methotrexate.
• IMMUTREX 22.5 mg: Each 0.56 ml pre-filled syringe contains 22.5 mg of methotrexate.
• IMMUTREX 25 mg: Each 0.63 ml pre-filled syringe contains 25 mg of methotrexate.
• IMMUTREX 27.5 mg: Each 0.69 ml pre-filled syringe contains 27.5 mg of methotrexate.
• IMMUTREX 30 mg: Each 0.75 ml pre-filled syringe contains 30 mg of methotrexate.
• The other components are sodium chloride, sodium hydroxide, water for injectable preparations.

Description of the Appearance of IMMUTREX and Contents of the Package
IMMUTREX syringes contain a clear, yellow-orange solution free from visible particles.
Pack sizes:
IMMUTREX pre-filled syringes with fixed needle for subcutaneous injection and rigid protective cap, together with alcohol swabs, are available in packs of 1, 4, and 12 syringes.
The pre-filled syringes are equipped with a safety system designed to help prevent needle-stick injuries after use.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
LANOVA FARMACEUTICI S.r.l
Via Conca D’oro, 212
00141 Rome
Italy

Manufacturers
Biomedica Foscama Industria Chimico-Farmaceutica S.P.A
Via Morolense, 87
03013 Ferentino (FR)
and
S.C. Sindan-Pharma S.R.L
11 Ion Mihalache Blvd, Bucarest 1
Romania

Instructions for Use
Read these instructions carefully before starting the injection and always use the injection technique recommended by your doctor, pharmacist, or nurse.
For single use only. Any remaining solution must be discarded.
The solution must be clear and free from particles.
If you have any problems or questions, contact your doctor, pharmacist, or nurse.

Preparation
Choose a clean, well-lit, flat working surface.
Before starting, gather all the items you need:

• 1 pre-filled syringe of IMMUTREX
• 1 antiseptic wipe (alcohol swab) (supplied in the pack)

Wash your hands thoroughly. Before use, inspect the IMMUTREX syringe for any visible defects (or cracks).

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 stretch-marked skin. If you have psoriasis, try to avoid injecting directly into lesions or areas of raised, thickened, red, flaky, or otherwise affected skin.

Injecting the Solution

1. Remove the pre-filled methotrexate syringe from its packaging and read the patient information leaflet carefully. Take the pre-filled syringe out of the packaging at room temperature.
2. Disinfection: Choose an injection site and disinfect it with an antiseptic wipe, for example using the alcohol swab included in the pack. Allow the disinfectant to dry for at least 60 seconds.

3. Remove the plastic protective cap.

Carefully remove the plastic protective cap by pulling it straight off the syringe. If the cap is difficult to remove, gently twist it while pulling.
Important: Do not touch the needle of the pre-filled syringe!

4. Inserting the needle

Using two fingers, pinch a fold of skin and quickly insert the needle at a 90-degree angle.

Note: It is normal to see a small air bubble in the syringe. Do not attempt to remove this air bubble before injecting – doing so may result in loss of some of the medication.
Pre-filled syringes without needle safety protection system:

5. Injection

Fully insert the needle into the skin fold. Inject the liquid subcutaneously by slowly pushing the plunger all the way down to the end of the syringe. Keep a firm hold of the skin fold until the injection is complete.
Carefully withdraw the needle vertically.

To avoid injury, replace the needle cap using one hand and gently press the cap back into place.
Pre-filled syringes with needle safety protection system:
5. Injection
The IMMUTREX pre-filled syringe is equipped with a safety system designed to help prevent needle-stick injuries after use. The following instructions are specific to this safety system and may differ from instructions for other injection systems.
Fully insert the needle into the skin fold. Inject the liquid subcutaneously by slowly pushing the plunger all the way down to the end of the syringe. Keep a firm hold of the skin fold until the injection is complete.
Carefully withdraw the needle vertically, keeping your finger on the plunger.

…..
With the needle pointed away from yourself and others, activate the safety system by firmly pressing the plunger. The protective sheath will automatically cover the needle, and you will hear a click confirming activation of the shield.

6. Immediately dispose of the syringe in a sharps disposal container.

Methotrexate must not come into contact with the skin surface or mucous membranes. In case of contamination, the affected area must be immediately rinsed 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 must be carried out in accordance with local regulations for cytotoxic preparations. Healthcare personnel who are pregnant should avoid handling and/or administering IMMUTREX.