FLUOROURACILE 1 Г/20 МЛ Инфузионный раствор

Содержание инструкции

1. Fluorouracile Teva 250 mg/5 ml solution for infusion, 500 mg/10 ml solution for infusion, 1 g/20 ml solution for infusion, 5 g/100 ml solution for infusion
   1. What is Fluorouracile Teva and what is it used for?
   2. What you need to know before you use Fluorouracile Teva
   3. How to use Fluorouracile Teva
   4. Possible side effects
   5. How to store Fluorouracile Teva
   6. Package contents and other information

Fluorouracile Teva 250 mg/5 ml solution for infusion, 500 mg/10 ml solution for infusion, 1 g/20 ml solution for infusion, 5 g/100 ml solution for infusion

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 their symptoms are the same as yours, 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 Fluorouracile Teva is and what it is used for
• 2. What you need to know before you use Fluorouracile Teva
• 3. How to use Fluorouracile Teva
• 4. Possible side effects
• 5. How to store Fluorouracile Teva
• 6. Contents of the pack and other information

1. What is Fluorouracile Teva and what is it used for?

Fluorouracile Teva contains fluorouracil, a substance capable of inhibiting and combating the growth of
tumors, used in the treatment of breast cancer, the second part of the intestine
(colon and rectum), stomach and pancreas.
This medicine is used in patients who cannot be operated on or treated by other means.
See your doctor if you do not feel better or if you feel worse.

2. What you need to know before you use Fluorouracile Teva

Do not use Fluorouracile 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 are seriously debilitated (e.g. malnourished);
• if your bone marrow function, i.e. the ability of your bone marrow to produce functioning blood cells, is reduced, for example, due to previous chemotherapy or radiotherapy treatment;
• if you have serious ongoing infections (e.g. Herpes zoster, chickenpox);
• if you are being treated with or have been treated in the last 4 weeks with brivudine, sorivudine and analogues (antiviral drugs);
• if you know you have no activity of the dihydropyrimidine dehydrogenase (DPD) enzyme;
• if you have a mutation defined as “homozygous” for the dihydropyrimidine dehydrogenase (DPD) enzyme;
• if your tumor is not malignant;
• if you have severe liver dysfunction;
• if you are breastfeeding.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking Fluorouracile Teva, in
particular:

• if you have heart problems. Tell your doctor even if you experience chest pain during treatment;
• if you know you have a partial deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme activity;
• if you have a family member with partial or complete deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme activity.

DPD Deficiency: DPD deficiency is a genetic condition that generally does not associate with
health problems, unless you take certain medications. If you have a DPD deficiency and take
Fluorouracile Teva, you are at higher risk of developing severe side effects (listed in
section 4 “Possible side effects”). It is recommended to perform DPD deficiency tests
before starting treatment. Do not take Fluorouracile Teva if you have no enzymatic activity.
If you have reduced enzymatic activity (partial deficiency) your doctor may prescribe a lower
dose. Even if the results of the DPD deficiency tests are negative, serious or potentially life-threatening
side effects may still occur.
Contact your specialist immediately if you experience the following signs or symptoms: new onset of
confusion, disorientation or altered mental status, difficulty with balance or
coordination, visual disturbances. These could be signs of encephalopathy that can lead to coma
and death if not treated.
The doctor will need to pay particular attention and carefully assess whether to subject you to treatment with
Fluorouracile Teva if you are a patient who:

• previously underwent high-dose radiation therapy in the pelvic area (lower part of the trunk, corresponding to the pelvis);
• previously underwent treatment with alkylating antitumor drugs;
• has widespread metastases in the bone marrow;
• has reduced kidney or liver function including jaundice (yellowing of the skin).

Fluorouracile Teva must only be administered by a doctor specializing in the use of
antitumor drugs, or under their supervision.
You will need to be hospitalized, at least during the initial treatment cycle, for possible toxic effects
that this drug can cause. In fact, despite adequate dose adjustment and
careful assessment of your clinical condition, it is rare for treatment with Fluorouracile Teva to be
effective without developing any symptoms of toxicity. In the most severe cases, gastrointestinal bleeding (hemorrhage), signs of toxicity to the blood and even death can occur, for this
reason the doctor may decide to discontinue therapy with this medicine. Furthermore, any
condition that may increase your stress level, interfere with your nutritional status or
affect your bone marrow function increases the toxicity of the medicine (see also the section
“Other medicines and Fluorouracile Teva”).
During the treatment period with Fluorouracile Teva, you should not undergo any
vaccinations, to avoid the onset of serious or fatal reactions (see also the section “Other
medicines and Fluorouracile Teva”) and you should avoid prolonged exposure to sunlight due to the
risk of photosensitivity.
During the treatment period with Fluorouracile Teva, your doctor will subject you to frequent blood tests
to assess your blood count, i.e. the number of red blood cells and white blood cells and
platelets present in your blood.
If you experience even one of the following symptoms, treatment with Fluorouracile Teva will be
immediately discontinued:

• oral ulcers and gastrointestinal side effects such as inflammation of the oral cavity or pharynx (stomatitis and esophagitis);
• reduction in the number of white blood cells (leukopenia with white blood cell count less than
• 3500) too rapid or excessive;
• uncontrollable vomiting;
• frequent bowel movements, diarrhea and watery stools;
• gastrointestinal ulcers and bleeding;
• decrease in the number of platelets (thrombocytopenia);
• widespread bleeding (hemorrhage);
• heart problems;
• nervous system disorders.

The administration of fluorouracil has been associated with the onset of a condition known as
“ hand-foot syndrome” (palmo-plantar erythrodysesthesia; see also the section “Possible side
effects”). This syndrome is characterized by a tingling sensation in the hands and feet
that can degenerate within a few days into pain when grasping objects or walking. The
palms of the feet and hands become swollen, presenting skin irritation, sometimes with
scaling symmetrically. Discontinuation of therapy leads to a gradual resolution
within 5-7 days.
In addition, during treatment with this medicine, an alteration of some blood values may occur: decrease in white blood cells and platelets (leukopenia), increase in alkaline phosphatase,
transaminases, bilirubin and lactic dehydrogenase, as well as decrease in
plasma albumin.
In addition, the concentration of 5-hydroxyindoleacetic acid in the urine may increase.

Children
The use of fluorouracil is not recommended in children due to insufficient safety and
efficacy data.

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

You must not take brivudine, sorivudine and analogues (antiviral medicines for the treatment of
shingles or chickenpox) at the same time as treatment with fluorouracil
(even during break periods when no fluorouracil tablets are taken).
If you have taken brivudine, sorivudine and analogues you must wait at least 4 weeks after stopping their use before starting fluorouracil therapy. See also the section “Do
not use Fluorouracile Teva”.
The following medicines can increase the toxic effects of fluorouracil:

• calcium folinate/folinic acid;
• immunosuppressant/myelosuppressant drugs, including radiation therapy:sometimes prescribed together with or consecutively to fluorouracil to increase the effectiveness of therapy. In this case, the dose may need to be reduced.

It is also important to keep in mind that fluorouracil therapy can lower your normal immune defenses
and therefore alter your response to any vaccinations ( vaccines with killed viruses/live attenuated viruses). For this reason, the doctor will carefully assess whether and when to vaccinate you. In addition, if someone who is in close contact with you wants to get a
vaccine containing the polio virus (orally), they should discuss this decision with the doctor and possibly ask this person to postpone the vaccination until your health conditions improve.
Patients with leukemia in remission should not receive vaccines containing live attenuated viruses
before three months from their last chemotherapy session.
Also, tell your doctor or pharmacist if you are taking the following medicines, as they affect
the effect of fluorouracil:

• allopurinol(used to treat gout);
• cimetidine(used to treat stomach ulcers);
• metronidazole(an antibiotic);
• interferon(an antiviral);
• blood-thinning medicines (anticoagulants), e.g. warfarin;
• thiazide diuretics (to treat high blood pressure);
• levamisole(a medicine used to treat infections);
• tamoxifen, cyclophosphamide(antitumor medicines);
• clozapine(an antipsychotic medicine);
• phenytoin(a medicine used to control epilepsy/seizures and irregular heartbeat);
• vinorelbine(an antitumor medicine);
• methotrexate(an antitumor medicine);
• leucovorin(a medicine also called calcium folinate, used to reduce the harmful effects of antitumor medicines).

Diagnostic tests
During treatment with Fluorouracile Teva, an increase in some enzymes
called alkaline phosphatase, transaminases, lactic dehydrogenase, and bilirubin may occur, detectable through
blood tests, and 5-hydroxyindoleacetic acid (5-HIAA), detectable through urine tests. A decrease in
plasma protein, albumin, may also occur.

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 for advice before using this medicine.

Pregnancy
Fluorouracil should only be used during pregnancy if the potential benefit justifies the
potential risk to the fetus.
If you are a woman of childbearing potential, you should use effective contraceptive measures during the administration of
this drug and for up to 6 months after treatment. If pregnancy occurs during treatment,
you should contact your doctor, who will inform you of the potential risks to the fetus and seek genetic counseling
from a specialist.

Breastfeeding
Fluorouracil is strictly contraindicated in breastfeeding women. It is not known whether
fluorouracil passes into breast milk, therefore breastfeeding must be discontinued before
treatment with Fluorouracile Teva.

Fertility
If you are a man, you should avoid conceiving a child during treatment and for up to 3 months after
stopping treatment with Fluorouracile Teva. Semen preservation is recommended
before treatment due to the possibility of irreversible infertility due to fluorouracil therapy.

Driving and using machines
Do not drive or use machines because fluorouracil can cause side effects such as nausea and vomiting.
It can also cause adverse effects on the nervous system and visual disturbances. If you are affected by any
of these effects, do not drive and do not use tools or machinery, as the drug may alter your
ability to drive vehicles or use machinery.

Fluorouracile Teva contains sodium
This medicine contains 8.2 mg of sodium per ml, i.e. 164 mg of sodium per maximum dose of
1000 mg of fluorouracil (20 mL), equivalent to 8.23% of the recommended daily intake
with the diet of an adult.

3. How to use Fluorouracile Teva

Fluorouracile Teva will be administered to you via infusion by qualified healthcare personnel.
The dose will be established by the doctor, as it must be calculated with the utmost precision
based on your body weight, your general health conditions (any recent surgeries you may have
undergone and the function of your liver and kidneys) and the therapeutic plan defined for your
clinical condition.
The dose may then be modified based on your response to the first treatment cycle.
During treatment, you will undergo regular medical examinations and checks to establish the correct
progress of the therapy.
If you are elderly and your kidney function is reduced, the doctor will reduce the dose of the medicine.
The normally recommended doses are:

Initial dosage
The recommended dose is 12 mg/kg of body weight once a day, for 4 days. The daily
dose should not exceed 800 mg. The doctor may decide to continue the
administration of the drug even beyond 4 days, based on your individual response and your
conditions.
In patients at risk and those particularly debilitated, the recommended dose is 6 mg/kg per
day, for 3 days. The total daily dose should not exceed 400 mg. The doctor may
decide to continue the administration of the drug even beyond 3 days, based on your response
individual and your conditions.

Maintenance therapy
Therapy may continue with the initial dosage in cases where toxicity does not represent a
problem, repeating the administration every 30 days from the last treatment.
In case of toxicity, when the signs of it have diminished, the recommended dose is:

• 10 - 15 mg/kg per week in a single administration. The total weekly dose should not exceed 1 g.

In patients at risk and those particularly debilitated, the dose will be reduced.
In any case, the dosage administered in each treatment cycle will be adjusted based on the reactions
that occurred during the previous treatment.

Infusion
The doctor will decide the dosage most suitable for your conditions and the drug will be administered
through a slow injection (infusion) directly into a vein. A sequence of injections
constitutes a "cycle" of therapy. The interval between two treatment cycles should be 4 - 6
weeks.

If you use more Fluorouracile Teva than you should
Given the conditions of administration, it is unlikely that you will take more Fluorouracile Teva than
you should. However, please consider that the following reactions may occur if you receive
an excessive dose of fluorouracil: nausea, vomiting, diarrhea, inflammation of the stomach wall
and intestines with possible bleeding (gastrointestinal ulcerations) and decreased
bone marrow function (the ability of the bone marrow to produce blood cells). If these conditions occur,
treatment will be discontinued and supportive measures will be instituted. Your health status will be monitored for at least 4 weeks.

If you stop taking Fluorouracile Teva
Ask your doctor for advice if you intend to stop treatment.
If you have any doubts about the use of this medicine, ask your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
Therapy with fluorouracil will be discontinued if signs of severe toxicity due to the
drug should appear.
If severe stomatitis (ulcers in the mouth and/or throat), inflammation of the mucous membranes,
diarrhea, neutropenia (increased risk of infections), or neurotoxicity occur during the first cycle of
treatment, this may be caused by DPD deficiency (see Section 2 “Warnings and precautions”).
If any of the following occurs, tell your doctor immediately:

• chest pain;
• shortness of breath.

Possible side effects may include:

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

• infections;
• insufficient bone marrow function (bone marrow failure);
• reduction in the number of white blood cells called neutrophils (neutropenia);
• reduction in the number of platelets (thrombocytopenia);
• reduction in the number of white blood cells (leukopenia);
• reduction in the number of white blood cells called granulocytes (agranulocytosis);
• anemia;
• reduction in the number of all blood cells (pancytopenia);
• inflammation in the oral cavity (stomatitis), esophagus (esophagitis), pharynx (pharyngitis), rectum and anus (proctitis);
• diarrhea, nausea and vomiting;
• increased uric acid in the blood (hyperuricemia);
• loss or lack of appetite (anorexia);
• reduction in normal immune defenses (immunosuppression);
• hair loss, especially in women (alopecia);
• tingling sensation in the hands and feet that can develop into pain within days when gripping objects or walking (palmo-plantar erythrodysesthesia, also known as “hand-foot syndrome”);
• delayed wound healing;
• discomfort, weakness (asthenia) and fatigue;
• nosebleeds (epistaxis);
• abnormal constriction of the bronchial muscles (bronchospasm);
• ischemic abnormalities in the electrocardiogram (insufficient blood supply to an organ, usually due to a blocked artery).

Common (may affect up to 1 in 10 people)

• inflammation of the tongue (glossitis), stomach lining (gastritis) and intestinal lining (enteritis, duodenitis and duodenal ulcer);
• abdominal pain;
• low levels of white blood cells accompanied by fever (febrile neutropenia);
• skin inflammation (dermatitis);
• chest pain similar to that associated with insufficient blood supply to the heart (angina pectoris).

Uncommon (may affect up to 1 in 100 people)

• bacterial infection in the bloodstream or body tissues (sepsis);
• irregular heartbeat (arrhythmia); myocardial infarction; lack of oxygen to the heart muscle (myocardial ischemia); inflammatory disease of the heart muscle (myocarditis); heart failure; heart disease in which the heart muscle is abnormally thickened, enlarged and/or stiffened (restrictive cardiomyopathy); cardiac shock;
• inflammation of the stomach and intestinal wall with possible bleeding (gastrointestinal ulcerations and hemorrhages);
• shedding of the gastrointestinal mucosa;
• dehydration;
• oscillating, rhythmic and involuntary eye movements (nystagmus);
• headache;
• feeling of imbalance and instability (dizziness);
• symptoms of Parkinson's disease (a progressive movement disorder characterized by tremors, rigidity, slow movements);
• central motor type syndrome (pyramidal syndrome);
• drowsiness;
• dry skin, erosion of skin fissures, redness of the skin, itchy maculopapular rash (rash starting on the lower extremities and progressing to the arms and then to the chest); rash; appearance of itchy blisters on the skin (urticaria); photosensitivity; skin hyperpigmentation;
• hyperpigmentation or depigmentation near the veins;
• nail pigmentation, nail dystrophy, nail bed disorder; inflammation of the tissue surrounding the nails (paronychia); inflammation of the nail matrix with pus formation and nail shedding (onycholysis);
• tearing; blurred vision; altered eye movements; optic neuritis (a vision disorder characterized by inflammation of the optic nerve); double vision (diplopia); decreased visual acuity; excessive sensitivity to light (photophobia); inflammation or redness of the lining of the white of the eye (conjunctivitis) and the edge of the eyelid (blepharitis); lower eyelids turned outward (ectropion); blockage of the tear duct (acquired dacryostenosis);
• euphoria;
• disorder of ovarian or sperm production (azoospermia);
• low blood pressure (hypotension);
• damage to liver cells (hepatocellular injury).

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

• insufficient blood circulation in the intestine (intestinal ischemia), in the brain (cerebral ischemia) and in the peripheral organs (peripheral ischemia);
• kidney failure;
• hypersensitivity; severe allergic reaction throughout the body (anaphylaxis); anaphylactic shock;
• confusion;
• formation of a blood clot in the blood vessels that can affect arteries or veins (thromboembolism); inflammation of the veins with subsequent formation of blood clots (thrombophlebitis);
• discoloration of the fingers of the hands and feet and occasionally other areas (Raynaud's phenomenon);
• increased total thyroxine (T4) and total triiodothyronine (T3).

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

• sudden cessation of heartbeat and cardiac function (cardiac arrest); sudden death due to heart problems (sudden cardiac death);
• symptoms of leukoencephalopathy (a disease affecting the white matter of the brain) including ataxia (loss of the ability to coordinate muscle movements);
• brain injury (acute cerebellar syndrome that may persist even after treatment is discontinued);
• difficulty articulating speech (dysarthria);
• partial or total loss of the ability to communicate verbally or use written language (aphasia);
• seizures or coma;
• muscle weakness;
• disorientation;
• damage to liver cells (cases with fatal outcome); slow and progressive destruction of the bile ducts (biliary sclerosis); inflammation of the gallbladder (cholecystitis, even without gallstones).

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

• formation of thrombi in one of the ventricles of the heart (cardiac ventricular thrombosis);
• inflammation of the membrane lining the heart, called the pericardium (pericarditis); alteration of the structure of the liver (intra- and extrahepatic sclerosis);
• drowsiness (lethargy);
• impaired vision;
• dilation of blood vessels (aneurysm);
• reduced blood flow (ischemia);
• blockage of blood vessels (arterial thrombosis, embolism);
• bleeding at the infusion cannula site;
• obstruction of the infusion cannula;
• development of rheumatic diseases (fibromyalgia);
• abscess;
• infections at the cannula insertion site;
• alterations in the electrocardiogram;
• hyperammonemic encephalopathy (brain dysfunction caused by high levels of ammonia);
• numbness or weakness of the arms and legs) peripheral neuropathy;
• fever;
• alteration of the color of the vein near the injection sites;
• difficulty breathing, such as shortness of breath (dyspnea);
• skin inflammation causing scaly red patches and may occur with joint pain and fever (cutaneous lupus erythematosus (CLE));
• heart disease that presents with chest pain, shortness of breath, dizziness, fainting, irregular heartbeat (stress cardiomyopathy);
• air in the intestinal wall;
• a serious condition presenting with difficulty breathing, vomiting and abdominal pain with muscle cramps (lactic acidosis);
• a condition characterized by headache, confusion, seizures and visual disturbances (reversible posterior encephalopathy syndrome (PRES));
• a serious complication with rapid degradation of tumor cells causing high levels of uric acid, potassium and phosphate (tumor lysis syndrome);
• high levels of triglycerides, a type of fat;
• pain, redness or swelling at the infusion site during or shortly after injection/infusion (likely due to the injection not entering the vein correctly);
• vitamin B1 deficiency and Wernicke encephalopathy (brain damage caused by vitamin B1 deficiency);
• inflammation in the small and large intestine causing pain and diarrhea, which can lead to death of intestinal tissue (colitis, enterocolitis).

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please tell your
doctor, pharmacist or nurse. 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 Fluorouracile Teva

Store at a temperature between 15°C and 25°C. Store in the original package to
protect the medicine from light.
Keep this medicine out of the sight and reach of children.
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 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 Fluorouracile Teva contains

Fluorouracile Teva 250 mg/5 ml solution for infusion
The active ingredient is fluorouracil. One vial contains 250 mg of fluorouracil.

Fluorouracile Teva 500 mg/10 ml solution for infusion
The active ingredient is fluorouracil. One vial contains 500 mg of fluorouracil.

Fluorouracile Teva 1 g/20 ml solution for infusion
The active ingredient is fluorouracil. One vial contains 1 g of fluorouracil.

Fluorouracile Teva 5 g/100 ml solution for infusion
The active ingredient is fluorouracil. One vial contains 5 g of fluorouracil.
The other ingredients are sodium hydroxide, hydrochloric acid, water for injections.

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

Fluorouracile Teva 250 mg/5 ml solution for infusionis presented in a pack containing one
5 ml glass vial.

Fluorouracile Teva 500 mg/10 ml solution for infusionis presented in a pack containing one
10 ml glass vial.

Fluorouracile Teva 1 g/20 ml solution for infusionis presented in a pack containing one
20 ml glass vial.

Fluorouracile Teva 5 g/100 ml solution for infusionis presented in a pack containing one
100 ml glass vial.

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 - 2031 GA Haarlem (Netherlands)
The following information is intended exclusively for healthcare professionals.

Dosage and administration
Medicines administered parenterally must be visually inspected for the presence of particles or
changes in colour before handling and administration.
The fluorouracil solution for intravenous infusion may change colour during storage; the
validity and safety of the product are not compromised.
If a precipitate forms in the solution due to exposure to low temperatures,
heat to 60°C and shake vigorously; cool to body temperature before use.

Compatibility
Fluorouracile Teva can be diluted with 0.9% sodium chloride injection or 5% dextrose injection. The resulting solution is stable for 48 hours if stored at room temperature, protected
from light.

Incompatibility
Do not mix fluorouracil injection with intravenous infusion additives or other chemotherapeutic agents.

Special precautions for handling
As with all cytotoxic preparations, particular care must be taken to ensure correct and
safe handling.

• 1. Only adequately trained personnel may handle the medicine. Pregnant women must not handle the medicine.
• 2. Handling must be carried out in a designated area, in a vertical laminar flow hood. The work surface must be covered with a disposable, laminated absorbent paper.
• 3. Suitable protective clothing must be worn, for example plastic gloves, safety glasses and a mask. If contact occurs with the eyes, wash them under running water or with saline solution.
• 4. Luer-lock fittings must be applied to all syringes and equipment. Any spraying of the solution can be reduced by using needles with a wide internal diameter and needles with an air vent.
• 5. All unused materials, needles, syringes, vials and other items that have been in contact with cytotoxic drugs must be kept separate, placed in tightly closed polypropylene bags and incinerated at a temperature above 1000°C. Excreta must be treated similarly. Liquid waste must be disposed of with a large amount of water.