METOTRESSATO 25 mg /Ml Инъекционный Раствор

Содержание инструкции

1. Metotressato Teva 25 mg/ml injectable solution, 100 mg/ml injectable solution
   1. What is Metotressato Teva and what is it used for
   2. What you need to know before using Metotressato Teva
   3. How to use Metotressato Teva
   4. Possible side effects
   5. How to store Metotressato Teva
   6. Contents of the pack and other information

Metotressato Teva 25 mg/ml injectable solution, 100 mg/ml injectable solution

Generic medicine

Read this leaflet carefully before you use this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as you, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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

1. What is Metotressato Teva and what is it used for

Metotressato Teva contains methotrexate, a substance capable of inhibiting the growth of certain tumors.
This medicine is used in the treatment of tumors such as choriocarcinoma, destructive chorioadenoma,
vesicular or hydatidiform mole.
It is also used alone or in combination with other drugs for the treatment of tumors at the
level:

• of connective tissue (sarcoma);
• of the blood and lymphatic system (lymphomas and in particular in cases of acute leukemia, lymphoblastic leukemia in children and stage III and IV lymphosarcoma in children);
• of the head and neck (cervico-facial carcinomas);
• of the breast;
• of the lung;
• of the cervix.

2. What you need to know before using Metotressato Teva

Do not use Metotressato Teva

• if you are allergic to the active ingredient or to any of the other ingredients of this medicine (listed in section 6);
• if you suffer or have suffered from severe liver dysfunction (severe hepatic insufficiency);
• if you suffer or have suffered from severe kidney dysfunction (severe renal insufficiency);
• if you suffer or have suffered from severe alterations at the blood level (such as bone marrow hypoplasia, thrombocytopenia, severe anemia, leukopenia);
• if you are an alcoholic;
• if you have an ongoing infectious disease;
• if you suffer from a disease that alters your immune system (immunodeficiency syndrome);
• if you are pregnant or breastfeeding (see section “Pregnancy and breastfeeding”);
• if you have lesions or wounds in your mouth or at the level of the stomach or intestinal wall (ulcers);
• if you are going to undergo vaccination with vaccines consisting of live microorganisms (see section “Warnings and precautions”).

Warnings and precautions
Consult your doctor, pharmacist or nurse before using Metotressato Teva.
Metotressato Teva must only be administered by a doctor specializing in the use of anticancer drugs,
who therefore knows the characteristics of this medicine.
Tell your doctor if:

• you have problems with your liver or kidneys;
• you have chronic liver infections (e.g. hepatitis B or C), as these infections may reactivate, worsen or cause death;
• you have problems with the bone marrow with a consequent reduction in the number of white blood cells, red blood cells and platelets in the blood;
• you have signs or symptoms of an ongoing infection (e.g. fever);
• you have lesions or wounds at the level of the stomach or duodenal mucosa (peptic ulcer);
• you suffer from an inflammatory bowel disease (ulcerative colitis);
• you have inflammation at the level of the mouth (ulcerous stomatitis);
• you are dehydrated or suffer from conditions that can cause dehydration (vomiting, diarrhea and stomatitis);
• you are very elderly or very young and/or debilitated;
• you have tumor lysis syndrome, i.e. disorders due to rapid death of tumor cells;
• you have a deficiency of folic acid (a vitamin) and other similar substances;
• you have recently undergone or are undergoing radiotherapy;
• you have patchy hair loss (alopecia);
• you have diabetes;
• you are severely overweight;
• you have an abnormal accumulation of fluid in the abdomen or pleura (the cavity located between the lungs and the chest wall);
• you have lung problems;
• you experience headache, back pain, neck stiffness, fever, seizures, paralysis, loss of muscle coordination (ataxia), irritability, confusion, drowsiness, dementia, coma or any other sign of brain problems;
• you have lesions on the skin or mucous membranes or are diagnosed with bone necrosis;
• you experience swollen lymph nodes. This may be a symptom of the onset of lymphomas that usually regress after discontinuation of treatment with Metotressato Teva.

Keep in mind that during treatment with this medicine, symptoms of
toxicity (which can be fatal) or serious adverse reactions (such as an increased risk of developing
bacterial infections) may occur, so the doctor may decide to reduce the dose or stop the
treatment. In case of severe bone marrow depression, blood or platelet transfusions may be necessary.
If, during treatment, you experience undesirable effects such as
diarrhea, inflammation of the mouth, vomiting, muscle cramps, skin reactions, cough or difficulty in
breathing, immediately inform your doctor as it may be necessary to interrupt the
treatment (see also section 4 “Stop treatment and immediately consult your
doctor”) and establish supportive therapy. Inform your doctor if you experience these symptoms.
In addition, during treatment with Metotressato Teva, the doctor will regularly examine your mouth and
throat to check that there are no lesions of the mucosa.
If you, your partner or the person assisting you notice the onset or worsening of neurological symptoms,
including general muscle weakness, visual disturbances, changes in thinking, memory and orientation, resulting in confusion and personality changes, immediately consult your doctor as these may be symptoms of a very rare and serious brain infection
called progressive multifocal leukoencephalopathy (PML).
The toxicity associated with the use of methotrexate increases in case of dehydration, reduced excretion
of the medicine at the kidney level, in case of folate deficiency (B vitamins) or in case of
concurrent radiotherapy. As a preventive measure, to reduce the risk of dehydration, it is recommended to drink plenty of water during
treatment with Metotressato Teva. The doctor may also
prescribe the administration of sodium bicarbonate or other alkalinizing drugs (to reduce the acidity
of the urine).

Metotressato Teva can decrease the response of the immune system and affect the response to
vaccinations, which may be less effective. In addition, during treatment with this
medicine it is preferable that you do not undergo vaccination with live vaccines because you may
develop infections.
If you experience lung symptoms during treatment with Metotressato Teva,
immediately consult your doctor as it may be necessary to interrupt the treatment and
perform specific tests.
Methotrexate can make the skin more sensitive to sunlight. Avoid exposure to the sun or the use
of sunbeds or solariums without a doctor's advice. To protect the skin from intense sun exposure,
wear appropriate clothing or use a sunscreen with a high protection factor.

Renal function
Methotrexate can cause damage to the kidneys, which can also lead to acute renal failure. The doctor, if he should find problems with the kidneys during therapy with
this medicine, will assess a reduction of the dose or suspension of the treatment, at least until
his renal functions are not improved or returned to normal.

Hepatic function
Methotrexate can cause alterations at the liver level, such as transient and asymptomatic
increase of some liver enzymes and alterations of liver function tests, which may require
suspension of treatment. Persistence of problems at the liver level or decrease of albumin levels in the blood may be manifestations of severe hepatic toxicity. You may
have to undergo a thorough examination of the liver (biopsy) to rule out the onset of serious
diseases (tissue alterations, fibrosis or hepatic cirrhosis), especially after prolonged use of
the medicine.

Laboratory tests
Even if methotrexate is used at low doses, serious adverse effects can occur. To detect them in time, the doctor must perform monitoring tests and laboratory tests.
Due to the possible suppressive effect of Metotressato Teva on bone marrow function, which
can occur suddenly at any time and even at low doses, periodic blood tests may be necessary
during oncological therapy with this medicine.
Before starting treatment:
The doctor will subject you to blood tests to verify that you have a sufficient number of blood cells.
Your blood will also be analyzed to check liver function and to
find out if you have hepatitis. In addition, serum albumin (a protein in the blood) and
the function of your liver and kidneys will be checked. The doctor may also check if you have tuberculosis and
may perform a chest X-ray or a pulmonary function test. It is possible that
the doctor will prescribe other tests if he deems it necessary.
During treatment:
Depending on the state of health before taking methotrexate and based on your response to
the drug, the doctor may prescribe you periodically the following checks:

• blood tests/complete blood count with number of blood cells and measurement of serum methotrexate levels;
• blood and urine tests, to check the function of your liver, kidneys, the onset of possible toxic effects and therefore a possible suspension of treatment;
• examination of the oral cavity and pharynx for alterations of the mucous membrane such as inflammation or ulceration;
• imaging to monitor the condition of the liver;
• monitoring of the respiratory tract and, if necessary, pulmonary function tests.

In addition, if administered high doses for long periods of time, it may be
necessary to subject you to more in-depth examinations to verify the functioning of your bone marrow
(aspirate) and the correct state of health of your liver (biopsy).
It is very important that you show up for the performance of these scheduled tests.
If any of these tests should return significant results, the doctor will adjust the treatment
accordingly.

Children
Children must be carefully monitored in order to identify the optimal dose of this
medicine and to identify possible adverse effects promptly.

Elderly
Elderly patients treated with methotrexate must be carefully monitored by a doctor
so that possible adverse effects can be detected as soon as possible.
The age-related impairment of hepatic and renal function and the low reserves of folic acid in old age require a relatively low dose of methotrexate.

Other medicines and Metotressato Teva
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicine.

Some medicines can increase the toxic effects of methotrexateif taken
simultaneously.
The doctor will carefully assess the medicines you are taking and will exercise particular caution with the simultaneous administration of this medicine and:

• non-steroidal anti-inflammatory drugs (NSAIDs) including salicylates (such as aspirin) and phenylbutazone;
• phenytoin and diphenylhydantoin, used for the treatment of epilepsy;
• leucovorin(folinic acid) and vitamin preparationscontaining folic acid;
• drugs toxic to the liver (such as leflunomide, azathioprine, retinoidsand sulfasalazine);
• probenecid, used to reduce uric acid levels in the blood;
• antibiotics such as penicillins, sulfonamides, tetracyclines, pristinamycin, chloramphenicol, ciprofloxacinand other antibiotics antagonists of folates (such as trimethoprim, sulfamethoxazole). Penicillinsand sulfonamidescan reduce the excretion of methotrexate causing a potential increase in undesirable effects;
• proton pump inhibitors (such as omeprazole, pantoprazole, lansoprazole), used to protect the gastric mucosa;
• cisplatin, mercaptopurine, cytarabine and L-asparaginase, used against some types of cancer;
• theophylline, used for the treatment of some respiratory diseases (asthma);
• para-aminobenzoic acid, essential for protein metabolism;
• triamterene, used to lower blood pressure by increasing urine production;
• amiodarone, used against heart rhythm anomalies;
• metamizole(also known as novaminsulfon or dipyrone), used against acute pain and/or fever.

Drugs that have a pharmacological activity similar to that of methotrexate, such as pyrimethamine
(medicine used for the treatment and prevention of malaria), must NOT be taken
together with this medicine.
Tell your doctor if you have recently undergone a transfusion with concentrated red blood cells (red blood cells),
if you are undergoing radiotherapy or a therapy for psoriasis or mycosis fungoides involving
the use of xanthotossin(a medicine) and ultraviolet radiation.
If you are to undergo anesthesia with nitrous oxide, tell the doctor that you are being treated with
Metotressato Teva.

Metotressato Teva with alcohol
Avoid drinking alcohol during treatment with this medicine, as it can increase the effect
toxic exerted by the medicine on the liver

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant or are planning a pregnancy, or if you are breastfeeding with
breast milk, ask your doctor or pharmacist for advice before using this medicine.
Pregnancy
Do not use Metotressato Teva during pregnancy. Methotrexate can 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 patients who are pregnant or who
are planning a pregnancy are not treated with methotrexate.
In women of childbearing potential, the possibility of an ongoing pregnancy must be excluded, for example with
performing pregnancy tests before starting treatment.
Do not use Metotressato Teva if you are trying to become pregnant. During treatment with methotrexate
and for at least 6 months after its completion, you should avoid pregnancy by ensuring, therefore, to use an effective contraceptive method throughout the entire period (see also the
paragraph “Warnings and precautions”).
If you become pregnant during treatment or suspect you are expecting a baby, contact your doctor
as soon as possible. If you become pregnant during treatment, you will be provided with advice 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
Metotressato Teva passes into breast milk and can cause serious unwanted effects in the baby.
Stop breastfeeding with breast milk if you need to start therapy with this medicine (see also the
paragraph “Do not use Metotressato Teva”).
Fertility
Metotressato Teva can cause impaired fertility in men, inducing oligospermia
(reduced number of sperm), and in women (menstrual disorders).

Male fertility
Methotrexate can have a genotoxic effect, i.e. it can cause genetic mutations. Methotrexate
can affect sperm production, which is associated with the possibility of birth defects.
During treatment with methotrexate and for at least 3 months after its completion, you should
avoid procreation or donating semen. Because treatment with methotrexate at higher doses
commonly used in cancer treatment can cause infertility and genetic mutations, it may be advisable for male patients treated with methotrexate doses
greater than 30 mg/week to consider sperm preservation before
starting treatment (see also the paragraph “Warnings and precautions”).

Driving and using machines
If you need to drive a vehicle or use machinery, ask your doctor first
because Metotressato Teva may alter your ability to drive vehicles or use machinery due to the
side effects that may occur (e.g. dizziness and/or fatigue).

Metotressato Teva contains sodium
Metotressato Teva 25 mg/ml injectable solution

• 2 ml vial:contains less than 1 mmol (23 mg) of sodium per 2 ml, i.e. essentially “sodium-free”.
• 20 ml vial:contains approximately 93 mg of sodium (main component of table salt) per 20 ml. This is equivalent to 4.6% of the maximum recommended daily intake with the diet of an adult.

Metotressato Teva 100 mg/ml injectable solution

• 10 ml vial: contains approximately 101 mg of sodium (main component of table salt) per 10 ml. This is equivalent to 5.06% of the maximum recommended daily intake with the diet of an adult.
• 50 ml vial: contains approximately 506 mg of sodium (main component of table salt) per 50 ml. This is equivalent to 25.3% of the maximum recommended daily intake with the diet of an adult.

3. How to use Metotressato Teva

Use this medicine following the instructions of your doctor or pharmacist exactly. If you have
any doubts, consult your doctor or pharmacist.

This medicine must be administered in hospital or clinic under the supervision of
experienced doctors.
Administration may occur via intramuscular, intravenous, intrathecal, intra-arterial or
intraventricular route depending on the type of tumor to be treated.
The doctor may decide to administer methotrexate alone or in combination with other
medicines or other types of therapy (radiotherapy or surgery).
The doctor will determine the dose and frequency of administration of this medicine based on the type and
severity of the disease or based on your condition.
In case of high dose administration, you will also be administered calcium leucovorin to relieve
the undesirable effects of Metotressato Teva.
Dosage

The doctor will carefully evaluate the dose to prescribe to you as the administration of doses

that are not correct has sometimes led to fatal cases of intoxication.
The dose of medication that will be administered to you will in fact be established based on the disease to
be treated, the route of administration, your health conditions, age, weight and
body surface area.

If you use more Metotressato Teva than you should
The symptoms of an overdose caused by taking an excessive dose of medication
administered via the intrathecal route are generally: headache, nausea and vomiting, seizures or
convulsions, acute toxic encephalopathy, cerebellar dislocation (cerebellar herniation), increased
intracranial pressure, death.
The doctor will subject you to periodic checks to monitor the levels of methotrexate in the blood.
Calcium folinate is the antidote used to neutralize the immediate toxic effects of methotrexate
and in addition to this, other additional therapies may be necessary such as blood transfusions and renal
dialysis, hydration and alkalization of the urine, rapid drainage of cerebrospinal fluid and
ventriculo-lumbar perfusion.

If you stop taking Metotressato Teva
Do not stop treatment with Metotressato Teva without consulting your doctor. If you have any
doubts about the use of this medicine, contact your doctor, pharmacist or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Stop treatment and contact your doctor immediatelyif you experience:

• widespread infection of the whole body (sepsis);
• reactivation of pre-existing hepatitis B infection;
• worsening of pre-existing hepatitis C infection;
• lymphoma (blood cancer);
• severe allergic reactions (anaphylactoid reactions);
• paralysis of one side of the body (hemiparesis), of a group of muscles (paresis) or of the lower part of the body (paraplegia);
• brain diseases (encephalopathy/leukoencephalopathy, arachnoiditis);
• temporary or permanent loss of vision, severe visual disturbances;
• interstitial pneumonia;
• ulcers and bleeding of the stomach and intestines, perforation of the intestine;
• non-infectious peritonitis (inflammation of the membrane lining the abdominal organs);
• acute liver inflammation (acute hepatitis);
• severe skin reaction such as rash and skin ulceration, redness, blisters, pustules, skin necrosis or peeling (Stevens-Johnson syndrome, toxic epidermal necrolysis, skin ulceration);
• increased susceptibility to bone fractures, bone tissue death (osteonecrosis);
• fetal malformations or death, abortion.

Other side effects may be:

Very common (may affect more than 1 in 10 people)

• excessive decrease in the number of blood cells called platelets (thrombocytopenia);
• reduction of white blood cells in the blood (leukopenia);
• abdominal pain;
• inflammation of the mouth (stomatitis);
• nausea;
• loss of appetite;
• vomiting;
• inflammation of the mucous membranes (mucositis);
• increased levels of liver enzymes.

Common (may affect up to 1 in 10 people)

• herpes zoster infections;
• alteration of bone marrow function, responsible for the production of blood cells (bone marrow depression);
• excessive decrease in red blood cells (anemia);
• reduction in the number of all cells present in the blood (pancytopenia);
• headache;
• sensation of numbness and tingling reduced normal sensitivity to stimulation (paresthesia/ hypoesthesia);
• pneumonia;
• severe form of pneumonia, sometimes fatal (interstitial pneumonia);
• erythematous rash;
• itching;
• feeling unwell;
• reduced muscle strength (asthenia).

Very rare frequency for low-dose methotrexate.

Uncommon (may affect up to 1 in 100 people)

• infections, also serious (sometimes fatal);
• lower urinary tract infection (cystitis);
• vaginal infection;
• increased predisposition to infections (increased susceptibility to infections);
• tumor originating in the lymphatic system (lymphoma, including reversible lymphoma); reduced activity of the bone marrow that produces blood cells (bone marrow failure);
• severe allergic reactions (anaphylactic reaction, anaphylactoid reaction);
• diabetes mellitus;
• dizziness;
• partial loss of motor function of one half of the body (hemiparesis);
• convulsions;
• progressive brain disease of varying severity (encephalopathy/leukoencephalopathy);
• inflammation of blood vessels (vasculitis);
• chronic disease characterized by progressive loss of lung function (pulmonary fibrosis);
• accumulation of fluid in the cavity between the lungs and the inner part of the chest (pleural effusion);
• lesions and wounds to the intestinal mucosa (intestinal ulcer);
• gastrointestinal bleeding;
• diarrhea;
• inflammation of the pancreas (pancreatitis);
• excessive accumulation of fat in the liver (steatosis);
• development of scar tissue in the liver (hepatic fibrosis);
• severe liver dysfunction (liver cirrhosis);
• urticaria;
• skin reactions similar to sunburn due to increased skin sensitivity to sunlight (photosensitivity);
• severe skin reactions such as Stevens Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome);
• pigmentation abnormalities;
• hair loss (alopecia);
• joint pain (arthralgia);
• pain localized in one or more muscles (myalgia);
• reduced bone density (osteoporosis);
• impaired kidney function (renal failure, nephropathy);
• difficulty urinating (dysuria);
• lesions to the vagina (vaginal ulceration);
• fetal malformation;
• fever;
• decreased levels of albumin in the blood.

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

• excessive inflammatory response of the body to a generalized infection (sepsis);
• inflammation of the pharynx (pharyngitis);
• inflammation of the gum tissue (gingivitis);
• larger than normal red blood cells due to vitamin B12 or folic acid deficiency (megaloblastic anemia);
• mood changes;
• temporary impairment of cognitive abilities;
• partial loss of muscle motility (paresis);
• speech disorders (dysarthria and aphasia);
• drowsiness;
• eye irritation;
• visual disturbances;
• blurred vision;
• hypotension;
• formation of blood clots (thromboembolic event including arterial thrombosis, cerebral thrombosis, thrombophlebitis, deep vein thrombosis and pulmonary embolism, retinal vein thrombosis);
• inflammation of the small intestine (enteritis);
• passage of blood with stools (melena);
• lesions to the stomach and intestines (gastrointestinal ulcer);
• toxicity to the liver causing damage (hepatotoxicity);
• impaired liver function (acute hepatitis);
• a rare rheumatic disease called rheumatoid nodulosis;
• appearance of bruises (ecchymosis);
• acne;
• multiforme erythema;
• lesions and wounds to the skin (skin ulcer);
• recurrence of a chronic inflammatory skin disease called psoriasis;
• painful detachment of psoriatic plaques;
• abortion;
• formation of nodules;
• stress fractures.

Lesions may worsen following exposure to the sun.

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

• pneumonia from Pneumocystis jirovecii;
• infection caused by a bacterium of the genus Nocardia(nocardiosis);
• infection caused by a fungus of the genus Histoplasma(histoplasmosis);
• lung infection caused by a fungus of the genus Cryptococcus(Cryptococcosis);
• liver infection (hepatitis from herpes simplex);
• disseminated herpes simplexinfection;
• deep infection of hair follicles (furuncle);
• metabolic alterations resulting from the destruction of tumor cells, with the consequent release of substances into the blood (tumor lysis syndrome);
• lymphoproliferative disorders (excessive growth of white blood cells);
• insufficient production in the bone marrow of all types of blood cells (aplastic anemia);
• severe reduction in the number of white blood cells in the blood (neutropenia);
• enlargement of the lymph nodes (lymphadenopathy);
• decreased levels of gammaglobulins in the blood (hypogammaglobulinemia);
• loss of sexual desire;
• sensory disturbances (unusual cranial sensations);
• cranial nerve disorders (cranial nerve disorder);
• inflammation of the eyes (conjunctivitis);
• loss of vision, even temporary (blindness);
• inflammatory disease affecting a membrane surrounding the heart called the pericardium (pericarditis);
• excessive accumulation of fluid in the membrane lining the heart (pericardial effusion);
• lung disease resulting from injury to the tissue lining the alveoli (interstitial lung disease);
• emission of blood from the mouth (hematemesis);
• reduction in liver volume as a result of a decrease in the number and size of individual cells that compose it (hepatic atrophy);
• death of liver cells with consequent loss of its functionality (hepatic necrosis);
• dilation of superficial capillaries, which become visible on the skin (telangiectasia);
• variation of nitrogen levels (azotemia) in the blood;
• presence of blood in the urine (hematuria);
• impotence;
• infertility;
• lower than normal sperm count (oligospermia);
• vaginal secretions;
• alterations in the formation of eggs (ovogenesis) or sperm (spermatogenesis);
• death, sudden death;

Not known (frequency cannot be estimated based on available data)

• bone damage in the mandible/jaw (secondary to excessive growth of white blood cells);
• redness and exfoliation of the skin/exfoliative dermatitis;
• infection (including fatal sepsis);
• Cytomegalovirus infection (including Cytomegalovirus pneumonia);
• reactivation of hepatitis B infection;
• worsening of hepatitis C infection;
• decrease in the number of a type of white blood cells in the blood called granulocytes (agranulocytosis);
• increase in the number of a type of white blood cells in the blood called eosinophils (eosinophilia);
• increased pressure of the fluid around the brain and spinal cord (increased intracranial pressure), brain damage (neurotoxicity), inflammation of the membranes surrounding the brain (arachnoiditis);
• paralysis of the lower part of the body (paraplegia);
• loss of responsiveness to stimuli (stupor), disorders of coordination of movements (ataxia), dementia;
• inflammation of the alveoli of the lungs (alveolitis), difficulty breathing (dyspnea), chest pain, lack of oxygen in the body (hypoxia), cough;
• intestinal perforation, inflammation of the membrane lining the abdominal organs (non-infectious peritonitis), inflammation of the tongue (glossitis);
• liver problems (liver failure);
• drug reaction with eosinophilia and systemic symptoms, characterized by an increase in the number of a type of white blood cells (eosinophils) in the blood (eosinophilia) and systemic symptoms;
• skin irritation (dermatitis), red spots on the skin (petechiae);
• presence of protein in the urine (proteinuria);
• fetal death;
• problems with the genitals and urinary tract (urogenital dysfunction);
• swelling (edema);
• chills, fatigue;
• reactions at the injection site;
• necrosis (death of cellular tissue) at the injection site.

Description of selected adverse reactions following intrathecal administration of methotrexate
The acute formis an acute inflammation of the meninges (arachnoiditis) which manifests with headache, back or shoulder pain, stiff neck and fever.
The subacute formmay manifest with partial and generally transient loss of muscle motility (paresis), partial loss of motor skills of the upper or lower limbs (paraparesis), complete loss of motor skills of the lower limbs (paraplegia) or complete loss of motor function (paralysis) and cerebellar dysfunction.
The chronic formis a leukoencephalopathy, of varying severity, which manifests with irritability, confusion, lack of coordination of muscles (ataxia), strong increase in muscle tone (spasticity), occasional seizures, dementia, drowsiness, coma and rarely death.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. You can also report side effects directly through 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 Metotressato Teva

Keep this medicine out of the sight and reach of children.
Store at a temperature below 25°C and in the original package to protect the medicine
from light.
Do not use this medicine after the expiry date which is stated on the pack after “Exp.”. The expiry
date refers to the last day of that month.
Do not dispose of any medicine in waste water or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Metotressato Teva contains

Metotressato Teva 25 mg/ml injectable solution

• The active ingredient is methotrexate. Each ml of solution contains 25 mg of methotrexate. One vial of 2 ml contains 50 mg of methotrexate. One vial of 20 ml contains 500 mg of methotrexate.
• The other ingredients are sodium chloride, sodium hydroxide, dilute hydrochloric acid, water for injections.

Metotressato Teva 100 mg/ml injectable solution

• The active ingredient is methotrexate. Each ml of solution contains 100 mg of methotrexate. One vial of 10 ml contains 1 g of methotrexate. One vial of 50 ml contains 5 g of methotrexate.
• The other ingredients are sodium hydroxide, dilute hydrochloric acid, water for injections.

Description of the appearance of Metotressato Teva and contents of the pack

Metotressato Teva 25 mg/ml injectable solution
Metotressato Teva is packaged in a glass vial of 2 ml or 20 ml.

Metotressato Teva 100 mg/ml injectable solution
Metotressato Teva is packaged in a glass vial of 10 ml or 50 ml.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder
Teva Italia S.r.l. - Piazzale Luigi Cadorna, 4 – 20123 Milano

Manufacturer
Pharmachemie B.V. - Swensweg, 5 - Haarlem 2031GA, (Netherlands)