Fluorouracil Accord

Leaflet attached to the packaging: patient information

Fluorouracil Accord, 50 mg/mL, solution for injection or infusion

Fluorouracil

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any possible side effects not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet

• 1. What is Fluorouracil Accord and what is it used for
• 2. Important information before using Fluorouracil Accord
• 3. How to use Fluorouracil Accord
• 4. Possible side effects
• 5. How to store Fluorouracil Accord
• 6. Contents of the packaging and other information

1. What is Fluorouracil Accord and what is it used for

What is Fluorouracil Accord

The active substance of Fluorouracil Accord is fluorouracil. It is an anticancer medicine.
It is part of chemotherapy treatment.

What is Fluorouracil Accord used for

Fluorouracil Accord is used to treat many types of cancer, particularly colorectal, esophageal, pancreatic, stomach, head and neck, and breast cancer. It can be used in combination with other anticancer medicines and radiotherapy.
If there is no improvement or the patient feels worse, they should contact their doctor.

2. Important information before using Fluorouracil Accord

When not to use Fluorouracil Accord

• if the patient is allergic to fluorouracil or any of the other ingredients of this medicine (listed in section 6),
• in case of significant weakness due to prolonged illness,
• if the patient has a severe infection (e.g. shingles, chickenpox),
• if the cancer is benign,
• if the bone marrow has been damaged by the use of other types of anticancer treatment (including radiotherapy),
• if the patient is taking brivudine, sorivudine or their chemically related analogs (antiviral medicines). Fluorouracil should not be used within 4 weeks of stopping treatment with brivudine, sorivudine or their chemically related analogs.
• if the patient is breastfeeding,
• if the patient has severe liver disease,
• if the patient is homozygous for the dihydropyrimidine dehydrogenase (DPD) enzyme,
• if the patient has decreased activity/deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme

dihydropyrimidine dehydrogenase (DPD) deficiency. If any of the above situations apply to the patient, they should inform their doctor before using this medicine.

Warnings and precautions

Before starting treatment with Fluorouracil Accord, the patient should discuss it with their doctor, pharmacist or nurse.
Particular care should be taken:

• if the bone marrow is not producing blood cells properly (the doctor will perform a blood test to check this);
• if the patient has any kidney function disorders;
• if the patient has any liver function disorders, including jaundice (yellowing of the skin);
• if the patient has angina pectoris (chest pain) or has had heart disease in the past, as they may be more prone to angina or heart attack, or cardiac disorders during ECG examination;
• if the patient has undergone pelvic radiotherapy using high doses;
• if there has been metastasis to the bone marrow;
• in patients with poor general health and significant weight loss;
• if the patient has undergone surgery within the last 30 days;
• if the patient experiences side effects from the gastrointestinal tract (mouth ulcers, diarrhea, gastrointestinal bleeding) or bleeding in any location;
• if the patient has been diagnosed with partial DPD enzyme deficiency;
• if the patient has heart disease. The patient should tell their doctor if they experience chest pain during treatment.
• if a family member of the patient has partial or complete DPD enzyme deficiency.

DPD deficiency: DPD deficiency is a genetic disorder that usually does not cause any health problems until the patient receives certain medicines. If the patient has a DPD deficiency and takes Fluorouracil Accord, the risk of severe side effects (listed in section 4 - "Possible side effects") increases. It is recommended that the patient undergoes a test before starting treatment to check for DPD deficiency. If the patient has no activity of this enzyme, they should not be treated with Fluorouracil Accord. If the activity of this enzyme is reduced (partial enzyme deficiency), the doctor may prescribe a reduced dose of the medicine.
Even if the DPD deficiency test result is negative, severe and life-threatening side effects may still occur.
The patient should contact their doctor immediately if they are concerned about any side effects or if they notice any additional side effects not listed in this leaflet (see section 4: Possible side effects).
The patient should contact their doctor immediately if they experience any of the following symptoms: newly occurring confusion, disorientation or other mental disorders, balance or coordination disorders, vision disorders. These may be symptoms of encephalopathy, which can lead to coma and death if left untreated.
If any of the above situations apply to the patient, they should inform their doctor before using this medicine.
Fluorouracil may cause hypersensitivity to sunlight. This can cause severe skin reactions. To prevent this, the patient should avoid direct sunlight and not use a sunlamp or sunbed during treatment.
The patient should avoid exposure to UV radiation (e.g. natural sunlight, sunbed).
Treatment with fluorouracil may increase the likelihood of radiation-induced necrosis (tissue or skin death).
Administration of fluorouracil is associated with the occurrence of hand-foot syndrome, characterized by a tingling sensation in the hands and feet, which can turn into pain when holding objects or walking within a few days. The palms and soles become swollen and tender.

Fluorouracil Accord and other medicines

The patient should tell their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.
Particular care should be taken if the patient is taking/using other medicines, as some of them may interact with Fluorouracil Accord:

• Methotrexate, cyclophosphamide, cisplatin, vinorelbine (anticancer medicines)
• Metronidazole (antibiotic)
• Folinic acid (also known as calcium folinate, a medicine used to reduce the harmful effects of anticancer medicines)
• Allopurinol (a medicine used to treat gout)
• Cimetidine (a medicine used to treat stomach ulcers)
• Warfarin (an anticoagulant medicine)
• Interferon alpha (a medicine used to treat lymphomas and chronic hepatitis)
• Brivudine, sorivudine and other analogs (antiviral medicines)
• Phenytoin (a medicine used to treat epilepsy and/or seizures and irregular heartbeat)
• The patient should avoid live vaccines, as they can cause severe or life-threatening infections. The patient should avoid contact with people who have recently received a polio vaccine. Inactivated or killed vaccines can be administered; however, the response to them may be weakened.
• Radiation therapy
• Levamisole (a medicine used to treat parasitic infections)
• Tamoxifen (a medicine used to treat certain types of breast cancer)
• Clozapine (a medicine used to treat certain mental disorders) The patient should tell their doctor or pharmacist if they are taking or have recently taken these or any other medicines, including those available without a prescription.

Pregnancy, breastfeeding and fertility

Pregnancy
If the patient is pregnant or breastfeeding, thinks they may be pregnant or plans to have a child, they should consult their doctor before using this medicine.
Fluorouracil should only be used during pregnancy if the potential benefits outweigh the possible risk to the fetus. If the patient becomes pregnant during treatment, they should inform their doctor and seek genetic counseling.
Women must avoid becoming pregnant and use effective contraception during treatment with fluorouracil and for at least 6 months after its completion.
Breastfeeding
Since it is not known whether fluorouracil passes into human milk, breastfeeding should be discontinued before starting treatment with fluorouracil.
The patient should consult their doctor before using any medicine.
Fertility
Men treated with fluorouracil are advised not to plan to conceive a child during treatment and for 3 months after its completion.
Both men and women should consult their doctor about fertility before treatment, e.g. preservation of eggs or sperm, due to the possibility of irreversible infertility as a result of treatment.

Driving and using machines

The patient should not drive vehicles, operate machinery or use tools, as Fluorouracil Accord may cause side effects such as nausea and vomiting. It may also cause side effects related to the nervous system and lead to changes in vision. If the patient experiences any of these symptoms, they should not drive vehicles, operate machinery or use tools, as these symptoms may affect their ability to drive or operate machinery.

Fluorouracil Accord contains sodium

Fluorouracil Accord contains 7.78 mmol (178.2 mg) of sodium per maximum daily dose (600 mg/m2 body surface area). This should be taken into account for patients on a controlled sodium diet.

3. How to use Fluorouracil Accord

Recommended dose

The doctor will determine the appropriate dose of Fluorouracil Accord for the patient and how often it should be administered.
The dose used depends on the patient's overall health, body weight, recent surgical procedures, and liver and kidney function. In the first cycle of treatment, the dose can be administered once a day or at weekly intervals. In subsequent cycles of treatment, the dose can be administered depending on the patient's response to treatment. The patient may also receive combination treatment with radiotherapy.
Fluorouracil is not recommended for use in children due to insufficient data on safety and efficacy.
The medicine can be diluted with glucose solution, sodium chloride solution or water for injection before administration. The medicine should be administered intravenously by injection or infusion.

Using a higher dose of Fluorouracil Accord than recommended

Since the medicine is administered by a doctor or nurse, there is a low risk that the patient will receive too little or too much of the medicine. However, if there are any doubts, the patient should inform their doctor or nurse.
During and after treatment with Fluorouracil Accord, blood tests should be performed to check the number of blood cells. It may be necessary to stop using the medicine if the number of white blood cells is too low.
After an overdose of Fluorouracil Accord, the following symptoms may occur: nausea, vomiting, diarrhea, severe mucositis, ulcers and gastrointestinal bleeding.
If the patient has any further doubts about using this medicine, they should consult their doctor.

Missing a dose of Fluorouracil Accord

The patient should not take a double dose to make up for a missed dose.

4. Possible side effects

Like all medicines, Fluorouracil Accord can cause side effects, although not everybody gets them.

The patient should tell their doctor immediately if they experience any of the following:

• severe allergic reactions - may include sudden itchy rash (hives), swelling of hands, feet, ankles, face, lips or throat (which may cause difficulty in swallowing or breathing), the patient may feel weak,
• chest pain,
• bloody or tarry stools,
• mouth pain and ulcers,
• numbness, tingling and tremors of hands or feet,
• heart attack or other heart problems, such as rapid heartbeat and shortness of breath,
• symptoms of leukoencephalopathy (brain disease) - weakness, coordination disorders, difficulty thinking/speaking, vision/memory disorders, seizures, headaches,
• shortness of breath.

These side effects are very serious. The patient may need immediate medical attention.

If the patient experiences any of the following symptoms, they should tell their doctor as soon as possible:

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

• Sore throat
• Signs of myocardial ischemia in ECG
• Mysuppression (a disorder in which the bone marrow produces a reduced number of all types of blood cells [pancytopenia])
• Neutropenia and leukopenia (too few white blood cells in the blood)
• Thrombocytopenia (reduced platelet count, which reduces the blood's ability to clot)
• Severe decrease in granulocyte count in the blood (agranulocytosis)
• Anemia (reduced red blood cell count)
• Increased risk of infection due to immunosuppression
• Wheezing (bronchospasm)
• Nausea
• Vomiting
• Diarrhea
• Infections
• Loss of appetite
• Delayed wound healing
• Mucositis of the mouth, throat and gastrointestinal tract, including esophagus, rectum or anus
• Increased uric acid levels in the blood
• Nosebleeds
• Hair loss
• Hand-foot syndrome (toxic skin reaction with redness and swelling of hands and feet)
• Fatigue, tiredness and lack of energy
• General weakness

Common side effects (may affect up to 1 in 10 people)

• Blood infection (sepsis)
• Heart attack, angina pectoris (severe chest pain associated with insufficient blood flow to the heart)
• Low white blood cell count with fever
• Changes in ECG (electrocardiogram - a test that checks the heart rhythm and electrical activity)

Uncommon side effects (may affect up to 1 in 100 people)

• Heart rhythm disorders
• Heart failure
• Myocardial ischemia (reduced oxygen supply to the heart muscle)
• Myocarditis (inflammatory heart disease)
• Cardiomyopathy (a type of heart disease in which the heart muscle is abnormally enlarged, thickened and/or stiffened)
• Cardiogenic shock
• Low blood pressure
• Drowsiness
• Dehydration
• Liver cell damage
• Ulcers and gastrointestinal bleeding
• Exfoliative dermatitis (skin peeling)
• Gastrointestinal bleeding
• Nystagmus (rhythmic eye movements)
• Headache
• Dizziness
• Loss of balance and unsteadiness
• Parkinson's disease symptoms (progressive movement disorder characterized by tremors, stiffness and slow movements)
• Pyriformis syndrome
• Blood infection (sepsis)
• Skin inflammation
• Skin changes, such as dry skin, cracks, fissures, redness of the skin, itchy rash
• Skin rashes associated with certain infectious diseases
• Appearance of itchy blisters on the skin
• Photosensitivity
• Increased skin pigmentation
• Discoloration or depigmentation in the area of veins
• Nail pigmentation, nail bed disorders
• Paronychia (inflammation of the tissue surrounding the nail)
• Nail bed inflammation with pus formation and nail shedding
• Disorders of sperm or egg production
• Increased tear production
• Blurred vision
• Eye inflammation or redness of the eyeball and eyelid
• Eye movement disorders
• Conjunctivitis (eye redness)
• Optic neuritis (vision disorders caused by inflammation of the optic nerve)
• Double vision
• Decreased visual acuity
• Increased sensitivity to light and aversion to sunlight or being in well-lit rooms
• Narrowing of the tear ducts
• Eversion of the lower eyelid
• Euphoria

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

• Cerebral, intestinal or peripheral ischemia
• Poor blood circulation, which causes numbness and paleness of fingers and toes (Raynaud's syndrome)
• Hypersensitivity
• Phlebitis (vein inflammation caused by a blood clot)
• Severe allergic reaction affecting the whole body (anaphylaxis)
• Blood clots in blood vessels (in arteries or veins)
• Confusion or altered consciousness in relation to time, place or identity
• Confusion
• Kidney failure
• Changes in thyroid function - increased T4 and T3 (thyroxine and triiodothyronine) levels

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

• Cardiac arrest (sudden stop of heart rhythm and function)
• Sudden cardiac death (unexpected death due to heart disease)
• Leukoencephalopathy symptoms (a disease affecting the white matter of the brain), including ataxia (loss of coordination of muscle movements)
• Acute cerebellar syndrome
• Difficulty articulating words
• Partial or complete loss of ability to communicate verbally or in writing
• Unusual muscle weakness or fatigue
• Seizures or coma in patients taking high doses of 5-fluorouracil and in patients with DPD deficiency
• Gallbladder inflammation
• Liver cell damage (reported cases of death)

Frequency not known (cannot be estimated from available data)

• Blood poisoning (septic shock)
• Neutropenic sepsis (a life-threatening reaction to infection that can occur in patients with neutropenia - a low number of a certain type of white blood cell that acts as part of the immune system to fight infection)
• Pneumonia
• Urinary tract infection, bacterial infection of the urinary system
• Bacterial skin infection causing redness, swelling and pain in the affected area
• Decreased granulocyte count (a type of white blood cell)
• Decreased appetite
• Disorientation
• Fever
• Numbness or weakness of hands and feet
• Seizures
• Hyperammonemic encephalopathy (brain dysfunction caused by increased ammonia levels)
• Blood clots in the heart chambers that can rupture and block arteries in the body, which can cause a stroke or lack of blood flow to a limb
• Myocarditis
• Skin inflammation causing red, peeling patches, which may be accompanied by joint pain and fever (cutaneous lupus erythematosus)
• Heart disease characterized by chest pain, shortness of breath, dizziness, fainting, irregular heartbeat (stress cardiomyopathy)
• Bleeding
• Dark, sticky stool containing partially digested blood
• Chest pain
• Air accumulation in the intestinal wall
• A severe condition characterized by difficulty breathing, vomiting and abdominal pain with muscle spasms (lactic acidosis)
• A disease characterized by headache, disorientation, seizures and vision changes (posterior reversible encephalopathy syndrome)
• A severe complication of rapid tumor cell breakdown, causing a significant increase in uric acid, potassium and phosphate levels in the blood (tumor lysis syndrome)
• Discoloration at the injection site
• High levels of triglycerides (a type of fat) in the blood
• Pain, redness or swelling at the injection site, occurring during or shortly after injection or infusion (may be caused by improper injection into a vein)
• Thiamine deficiency and Wernicke's encephalopathy (brain damage caused by thiamine deficiency)
• Small intestine and colon inflammation causing pain and diarrhea, which can lead to tissue death (colitis, enteritis)

Reporting side effects

If the patient experiences any side effects, including any possible side effects not listed in this leaflet, they should tell their doctor or pharmacist. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices and Biocides of the Office for Registration of Medicinal Products, Medical Devices and Biocides, Al. Jerozolimskie 181C, 02-222 Warsaw, Tel: +48 22 49 21 301, Fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl. Side effects can also be reported to the marketing authorization holder. By reporting side effects, more information can be collected on the safety of the medicine.

5. How to store Fluorouracil Accord

Keep out of sight and reach of children.
Do not use this medicine after the expiry date stated on the label or carton after "EXP". The expiry date refers to the last day of the month.
Store below 25°C. Do not store in a refrigerator or freeze.
Store the vial in the outer packaging to protect from light.
For single use only. Dispose of any unused medicine.
Shelf life after dilution
Chemical and physical stability of the medicine has been demonstrated for 24 hours at 25°C after dilution in 5% glucose solution or 0.9% sodium chloride solution for injection or water for injection for a Fluorouracil Accord concentration of 0.98 mg/mL.
From a microbiological point of view, the medicine should be used immediately. If the solution is not administered immediately, the responsibility for the storage time and conditions before administration lies with the healthcare professional.
The storage time should not exceed 24 hours at a temperature of 2°C to 8°C, unless the solution has been diluted under controlled and validated aseptic conditions.

• In case of a brown or dark yellow discoloration of the solution, it should not be used.
• The medicine should not be used if the container is damaged or if particles and/or crystals are visible.

Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Fluorouracil Accord contains

• The active substance is fluorouracil.
• The other ingredients are water for injection, sodium hydroxide and hydrochloric acid.

What Fluorouracil Accord looks like and contents of the pack

1 mL of solution contains 50 mg of fluorouracil (in the form of sodium salt formed in situ).
Fluorouracil Accord solution for injection or infusion is a clear, colorless to pale yellow solution, which comes in a colorless glass type I vial with a rubber stopper and an aluminum flip-off cap, in a cardboard box.
Each 5 mL vial contains 250 mg of fluorouracil.
Each 10 mL vial contains 500 mg of fluorouracil.
Each 20 mL vial contains 1000 mg of fluorouracil.
Each 50 mL vial contains 2500 mg of fluorouracil.
Each 100 mL vial contains 5000 mg of fluorouracil.
Not all pack sizes may be marketed.

Marketing authorization holder

Accord Healthcare Polska Sp. z o.o.
Taśmowa 7
02-677 Warsaw
Tel: +48 22 577 28 00

Manufacturer/Importer

Accord Healthcare Polska Sp. z o.o.
Lutomierska 50
95-200 Pabianice
Poland
Accord Healthcare Single Member S.A.
64th Km National Road Athens Lamia
32009 Schimatari
Greece

This medicine is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Date of last revision of the leaflet: February 2025

Information intended for healthcare professionals only:

INSTRUCTIONS FOR USE, PREPARATION OF THE MEDICINE FOR USE AND DISPOSAL OF FLUOROURACIL ACCORD

PROCEDURES REQUIRED FOR CYTOTOXIC MEDICINES MUST BE FOLLOWED
Fluorouracil Accord should only be administered by or under the direct supervision of a doctor qualified and experienced in the use of chemotherapeutic agents in the treatment of cancer.
Fluorouracil Accord should be prepared for administration by qualified personnel who have been trained in the safe handling of the medicine.
Preparation of the medicine should only be carried out in aseptic conditions or in a designated area.
In case of spillage, personnel preparing the product should wear gloves and a face mask, protect their eyes, wear a disposable gown and wipe up the spilled liquid with a well-absorbing material, which should be placed in a designated area. The surface should be cleaned and any contaminated materials should be placed in a bag or container designated for spilled cytotoxic agents and sealed for incineration.

Contamination

Fluorouracil is irritating, contact with skin and mucous membranes should be avoided.
In case of contact with the skin or eyes, the affected area should be rinsed with plenty of water or saline solution. To treat transient skin burning, a hydrocortisone cream 1% can be applied. If the solution gets into the eyes, respiratory tract or is ingested, medical advice should be sought.

First aid

Eye contact: immediately rinse with water and seek medical advice.
Skin contact: carefully wash with water and soap. Contaminated clothing should be removed.
Inhalation, ingestion: seek medical advice.

Disposal of the medicine

Syringes, containers, absorbent materials, solution and any other contaminated materials should be placed in a thick plastic bag or other impermeable container labeled as cytotoxic waste, and then incinerated at a temperature of not less than 700°C.
Chemical inactivation can be achieved with 5% sodium hypochlorite solution for 24 hours.

Instructions for preparation:

a) Chemotherapeutic agents should only be prepared for administration by personnel who have been trained in the safe handling of the medicine.
b) Procedures such as dissolving the powder and transferring to syringes should only be carried out in a designated area.
c) Personnel performing these procedures should wear appropriate protective clothing, two pairs of gloves: latex and protective PVC (PVC should be worn over latex), which prevents the penetration of various anticancer agents, and protect their eyes. Luer Lock syringes and connectors should always be used when preparing and administering cytotoxic products.
d) Pregnant women are advised to avoid contact with chemotherapeutic agents.
e) Before disposing of the medicine, the patient should familiarize themselves with local regulations.
Instructions for use
Fluorouracil Accord can be administered by intravenous injection (bolus), infusion or continuous infusion.

Incompatibilities

Fluorouracil Accord is incompatible with calcium folinate, carboplatin, cisplatin, cytarabine, diazepam, doxorubicin, droperidol, filgrastim, gallium nitrate, methotrexate, metoclopramide, morphine, ondansetron, parenteral nutrition, vinorelbine and other anthracyclines.
Since the prepared solutions are alkaline, they should not be mixed with medicines or products with acidic pH.
As compatibility studies have not been conducted, the medicine should not be mixed with other medicinal products.

Shelf life and storage

Shelf life of unopened vials
2 years. For single use only. Dispose of any unused medicine.
Store below 25°C. Do not store in a refrigerator or freeze.
Store the container in the outer packaging to protect from light.
In case of a precipitate forming due to low temperature, the precipitate should be dissolved by heating the vial contents to 60°C with vigorous shaking. The solution should be allowed to cool to room temperature before use. The medicine should be discarded if the solution turns brown or dark yellow.
Shelf life after dilution
In use: Chemical and physical stability of the medicine has been demonstrated for 24 hours at 25°C after dilution in 5% glucose solution or 0.9% sodium chloride solution for injection or water for injection for a Fluorouracil Accord concentration of 0.98 mg/mL.
From a microbiological point of view, the medicine should be used immediately. If the solution is not administered immediately, the responsibility for the storage time and conditions before administration lies with the healthcare professional.
The storage time should not exceed 24 hours at a temperature of 2°C to 8°C, unless the solution has been diluted under controlled and validated aseptic conditions.