Methotrexate Doc Generici

Package leaflet: Information for the patient

METOTREXATO DOC Generici

2.5 mg solution for injection in pre-filled syringe
7.5 mg solution for injection in pre-filled syringe
10 mg solution for injection in pre-filled syringe
12.5 mg solution for injection in pre-filled syringe
15 mg solution for injection in pre-filled syringe
17.5 mg solution for injection in pre-filled syringe
20 mg solution for injection in pre-filled syringe
22.5 mg solution for injection in pre-filled syringe
25 mg solution for injection in pre-filled syringe
27.5 mg solution for injection in pre-filled syringe
30 mg solution for injection in pre-filled syringe
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 others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What METOTREXATO DOC Generici is and what it is used for

METOTREXATO DOC Generici 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 defense mechanism)
• has anti-inflammatory effects.

METOTREXATO DOC Generici is indicated for the treatment of:

• active rheumatoid arthritis in adult patients;
• severe, active polyarticular forms of juvenile idiopathic arthritis, when treatment with non-steroidal anti-inflammatory drugs (NSAIDs) has been inadequate;
• severe, recurring, and disabling psoriasis that does not respond adequately to other therapies such as phototherapy, PUVA, and retinoids, as well as severe psoriatic arthritis in adult patients;
• mild to moderate Crohn's disease in adult patients, in cases where adequate treatment with other medications 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.
METOTREXATO DOC Generici 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 METOTREXATE DOC Generics

Do not use METOTREXATE DOC Generics

• 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 METOTREXATE DOC Generics if:

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

Follow-up examinations and recommended safety measures
Even when used at low doses, serious adverse effects may occur with METOTREXATE DOC Generics. To detect them early, your doctor must carry out monitoring tests and laboratory examinations.

Before starting therapy
Before beginning treatment, a blood sample must be taken to check that you have an adequate number of blood cells. Your blood will also be tested to assess liver function and to detect possible hepatitis. In addition, serum albumin levels (a blood protein), hepatitis status (liver infection), and kidney function will be checked. Your doctor may also decide to perform further liver tests, some of which may include imaging of your liver, while others may require small tissue samples 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 perform the following tests:

• Examination of the oral cavity and pharynx to check for mucosal changes or ulcerations
• Blood tests / complete blood count with blood cell counts and measurement of serum methotrexate levels
• Blood tests to monitor liver function
• Imaging tests to monitor liver condition
• Small tissue samples taken from the liver 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 these scheduled examinations.
If any of these test results are abnormal, your doctor will adjust your treatment accordingly.

Elderly patients
Elderly patients receiving methotrexate must be closely monitored by a doctor so that possible adverse effects can be detected as early as possible.
Age-related impairment of liver and kidney function, as well as reduced body stores of vitamin folic acid in older age, require a relatively low dose of methotrexate.
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 can affect the immune system and vaccination outcomes. It may also influence the results of immunological tests. Chronic inactive infections may reactivate (e.g. herpes zoster [shingles], tuberculosis, hepatitis B or C). During treatment with METOTREXATE DOC Generics, vaccination with live vaccines must not be administered.

If you, your partner, or caregiver notice the onset or worsening of neurological symptoms, including general muscle weakness, vision disturbances, changes in thinking, memory, or 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).

Radiation dermatitis and sunburn may reappear during methotrexate therapy (recall reaction). Psoriatic lesions may worsen following 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 METOTREXATE DOC Generics and requires interruption of therapy. If you experience diarrhea, discuss it with your doctor.

Some brain disorders (encephalopathy / leukoencephalopathy) have occurred in cancer patients treated with methotrexate. It cannot be excluded that these side effects may also occur when methotrexate is used to treat other diseases.

Special precautions for treatment with METOTREXATE DOC Generics
Methotrexate temporarily affects sperm and egg production, an effect that is reversible in most cases. Methotrexate may cause miscarriage and severe birth defects. If you are a woman, you must avoid pregnancy while taking methotrexate and for at least 6 months after stopping treatment. If you are a man, you must avoid fathering a child while taking methotrexate and for at least 3 months after stopping treatment. See also section “Pregnancy, breastfeeding and fertility”.

Other medicines and METOTREXATE DOC Generics
Tell 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 METOTREXATE DOC Generics 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 that prevent/treat certain infections).
• Non-steroidal anti-inflammatory drugs or salicylates (medicines for pain and/or inflammation, e.g. acetylsalicylic acid, diclofenac and ibuprofen or pyrazolones)
• Probenecid (medicine for gout)
• Weak organic acids such as loop diuretics (diuretic medicines)
• 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
• Mercaptopurine (a cytostatic medicine)
• Retinoids (medicine for psoriasis and other dermatological conditions)
• Theophylline (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 impair the treatment effect and should only be taken under medical supervision.

Penicillins
Penicillins may reduce methotrexate excretion, potentially increasing side effects.

Vaccinations with live vaccines must be avoided.

METOTREXATE DOC Generics with food, drinks and alcohol
During treatment with METOTREXATE DOC Generics, 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, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before using this medicine.

Pregnancy
Do not use METOTREXATE DOC Generics 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 those planning pregnancy are not treated with methotrexate. In women of childbearing age, pregnancy must be ruled out using adequate measures, for example by performing a pregnancy test before starting treatment. You must avoid pregnancy using reliable contraceptive methods throughout the entire period of methotrexate use and for at least 6 months after stopping treatment (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 have a child, you should consult your doctor, who will refer you to a specialist before the planned start of treatment.

Breastfeeding
Breastfeeding must be stopped before and during treatment with METOTREXATE DOC Generics.

Male fertility
Available evidence does not indicate an increased risk of birth defects or miscarriage if the father takes a methotrexate dose below 30 mg/week. However, the risk cannot be completely excluded. Methotrexate may be genotoxic, meaning it may cause genetic mutations. Methotrexate may affect sperm production and potentially cause 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 METOTREXATE DOC Generics may cause adverse reactions affecting the central nervous system, such as fatigue and dizziness. Therefore, your 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.

METOTREXATE DOC Generics contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is practically “sodium-free”.

3. How to use METOTREXATO DOC Generici

Important warning about the dose of METOTREXATO DOC Generici:
In the treatment of rheumatoid arthritis, psoriasis, polyarticular forms of juvenile idiopathic arthritis, and
Crohn's disease, METOTREXATO DOC Generici must be taken only once a week.
Excessive use of METOTREXATO DOC Generici can be fatal. Please 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. If you have any doubts, consult your doctor or pharmacist.
Your doctor will decide the dose, which will be tailored to the individual patient. Generally, the effects of treatment become apparent after 4–8 weeks of therapy.
METOTREXATO DOC Generici is administered by a doctor or under medical supervision, or by healthcare personnel, as an injection once a week only. Decide together with your doctor on which day of the week to administer the weekly injection. METOTREXATO DOC Generici must be injected subcutaneously (under the skin).
At the beginning of treatment, METOTREXATO DOC Generici will be administered by medical
personnel.
However, your doctor may determine that you are capable of learning how to self-inject METOTREXATO DOC Generici. In such a case, you will receive adequate training. Under no circumstances should you attempt to self-inject without having received proper training.
Use in children and adolescents
The appropriate dose for children and adolescents with polyarticular forms of juvenile idiopathic arthritis will be determined by the doctor.
METOTREXATO DOC Generici 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
METOTREXATO DOC Generici is injected once a week!
The duration of treatment is determined by the treating physician. Treatments for rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis vulgaris, psoriatic arthritis, and Crohn's disease with METOTREXATO DOC Generici are long-term therapies.
Handling and disposal must be carried out as for other cytotoxic preparations, in accordance with local regulations. Healthcare personnel who are pregnant should refrain from handling and/or administering METOTREXATO DOC Generici.
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 METOTREXATO DOC Generici than you should
If you use more METOTREXATO DOC Generici than prescribed, contact your doctor immediately.
If you forget to use METOTREXATO DOC Generici
Do not take a double dose to make up for a missed dose.
If you stop treatment with METOTREXATO DOC Generici
If you stop treatment with METOTREXATO DOC Generici, contact your doctor immediately.
If you feel that the effect of METOTREXATO DOC Generici 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 everyone 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 should therefore prescribe blood tests to detect possible abnormalities (e.g. low white blood cell count, low platelet count, 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: may be signs of lung inflammation [common];
• Blood in saliva or coughed up;
• 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 the liver (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, reduced (oliguria) or absent urine (anuria): may be signs of kidney failure [rare];
• Signs of infection, for example fever, chills, aches, sore throat: methotrexate may increase susceptibility to infections. Serious infections such as a specific type of pneumonia ( Pneumocystis carinii pneumonia) or blood poisoning ( sepsis ) [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 blood clot breaks loose and blocks a blood vessel (thromboembolic event) [rare];
• Fever and severe worsening of general condition, or sudden fever accompanied by sore throat or mouth sores, or urinary problems: methotrexate may cause a sudden drop in certain white blood cells (agranulocytosis) and severe bone marrow suppression [very rare];
• Sudden bleeding, for example 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, feeling unwell, vomiting, confusion and sensitivity to light: may indicate inflammation of the membranes surrounding the brain (acute aseptic meningitis) [very rare];
• Some brain disorders (encephalopathy/leukoencephalopathy) have occurred in cancer patients treated with methotrexate. It cannot be ruled out that these side effects may also occur when methotrexate is used to treat other diseases. Signs of such brain disorders may include: mental status changes, movement disorders (ataxia), visual disturbances, or memory problems [not known];
• Severe skin rash or skin blistering (may also appear in mouth, eyes and genitals): 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

• Mouth inflammation, indigestion, nausea (feeling unwell), loss of appetite, abdominal pain.
• Abnormal liver function tests (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.
• Intestinal inflammation, vomiting, pancreatitis, black and tarry stools, gastrointestinal ulcers and bleeding.
• Increased sensitivity to light, hair loss, increase in number of rheumatoid nodules, skin ulcers, shingles, inflammation of blood vessels, herpes-like skin rashes, hives.
• Onset of diabetes mellitus.
• Dizziness, confusion, depression.
• Decrease in serum albumin.
• Reduction in number of 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

• Gum inflammation.
• Increased skin pigmentation, acne, skin bruising due to bleeding from blood vessels (ecchymoses, petechiae), allergic inflammation of blood vessels.
• Reduction in number of antibodies in the blood.
• Infection (including reactivation of inactive chronic infection), red eyes (conjunctivitis).
• Mood changes (emotional instability).
• Visual disturbances.
• Inflammation of the membrane surrounding the heart, fluid accumulation in the membrane around the heart, obstruction of heart filling 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, 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 around the nail folds, furunculosis (deep infection of hair follicles), visible enlargement of small blood vessels (capillaries).
• Local tissue damage (formation of sterile abscesses, changes in fatty tissue) at the injection site after intramuscular or subcutaneous administration.
• Vision disorders, pain, loss of strength, or numbness, tingling/lessened sensation to stimulation, taste changes (metallic taste), seizures, paralysis, severe headache accompanied by fever.
• Retinopathy (eye disorders of non-inflammatory origin).
• Loss of libido, impotence, enlargement of male breast glands (gynaecomastia), abnormal sperm formation, menstrual disorders, vaginal discharge.
• Enlargement of lymph nodes (lymphoma).
• Lymphoproliferative disorders (excessive growth of white blood cells).

Frequency not known: cannot be estimated based on available data:

• Increase in number of certain types of white blood cells.
• Nosebleeds.
• Skin redness and peeling.
• Protein in urine.
• Feeling of weakness.
• Bleeding from the lungs.
• Bone damage in the jaw/mandible (secondary to excessive growth of white blood cells).
• Tissue destruction at the injection site, 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 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 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 METOTREXATE DOC Generici

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 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 remaining solution must be discarded.
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 METOTREXATO DOC Generici contains
The active substance is methotrexate.
METOTREXATO DOC Generici 2.5 mg:
each 0.33 ml pre-filled syringe contains 2.5 mg of methotrexate
METOTREXATO DOC Generici 7.5 mg:
each 0.30 ml pre-filled syringe contains 7.5 mg of methotrexate
METOTREXATO DOC Generici 10 mg:
each 0.40 ml pre-filled syringe contains 10 mg of methotrexate
METOTREXATO DOC Generici 12.5 mg:
each 0.31 ml pre-filled syringe contains 12.5 mg of methotrexate
METOTREXATO DOC Generici 15 mg:
each 0.38 ml pre-filled syringe contains 15 mg of methotrexate
METOTREXATO DOC Generici 17.5 mg:
each 0.44 ml pre-filled syringe contains 17.5 mg of methotrexate
METOTREXATO DOC Generici 20 mg:
each 0.50 ml pre-filled syringe contains 20 mg of methotrexate
METOTREXATO DOC Generici 22.5 mg:
each 0.56 ml pre-filled syringe contains 22.5 mg of methotrexate
METOTREXATO DOC Generici 25 mg:
each 0.63 ml pre-filled syringe contains 25 mg of methotrexate
METOTREXATO DOC Generici 27.5 mg:
each 0.69 ml pre-filled syringe contains 27.5 mg of methotrexate
METOTREXATO DOC Generici 30 mg:
each 0.75 ml pre-filled syringe contains 30 mg of methotrexate.
The other components are sodium chloride, sodium hydroxide for pH adjustment, water for
injections.

Description of the appearance of METOTREXATO DOC Generici and contents of the pack
METOTREXATO DOC Generici syringes contain a clear, yellow-orange solution free from visible particles.
Packaging:
Pre-filled syringes of METOTREXATO DOC Generici with fixed injection needle, rigid protective cap and alcohol swabs are available in packs of 1 and 4 syringes.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
DOC Generici Srl, Via Turati 40, 20121 Milano
Manufacturer:
Actavis Italy S.p.A., Via Pasteur 10, Nerviano (Milano)
S.C. Sindan-Pharma S.R.L, 11 Ion Mihalache Blvd, Bucharest, 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.
For 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 METOTREXATO DOC Generici
• 1 disinfectant swab (alcohol-impregnated swab) (supplied in the pack)
  Wash your hands thoroughly. Before use, check the METOTREXATO DOC Generici 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 in the back of the upper arm, just below the shoulder.
• Change the injection site for 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 not to inject directly into lesions or into raised, thickened, red, flaky or otherwise affected skin areas.

Injecting the solution

1. Remove the pre-filled methotrexate syringe from its packaging and read the package leaflet carefully. Take the pre-filled syringe out of the packaging at room temperature.
2. Disinfection
   Choose an injection site and disinfect it with a disinfectant swab, for example using the alcohol-impregnated 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 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 into the skin at a 90-degree angle.

Note: It is normal to have 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.

5. Injection
   Insert the needle completely into the skin fold. Inject the liquid subcutaneously by slowly pushing the plunger all the way down to the end of the syringe. Keep holding the skin fold firmly until the injection is complete.
   Carefully remove the needle vertically.

To prevent injury, replace the needle cap using one hand and gently press the cap back into place.

6. Immediately dispose of the syringe in a sharps 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 accidentally injured with 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 as for other cytotoxic preparations, in accordance with local regulations. Healthcare personnel who are pregnant should avoid handling and/or administering METOTREXATO DOC Generici.