Patient Information Leaflet

Fluorouracil Accord 50 mg/ml Injectable Solution or for Infusion EFG

Read this leaflet carefully before you start using the medicine because it contains important information for you.

• Keep this leaflet, as you may need to read it again.

• If you have any questions, consult your doctor or pharmacist or nurse.

• This medicine has been prescribed for you only and should not be given to others, even if they have the same symptoms as you, as it may harm them.

• If you experience any side effects, consult your doctor or pharmacist or nurse,even if they are not listed in this leafletSee section 4.

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

2. What you need to know before starting to use Fluorouracil Accord

3. How to use Fluorouracil Accord

4. Possible side effects

5. Storage of Fluorouracil Accord

6. Contents of the pack and additional information

What is Fluorouracilo Accord

Fluorouracilo Accord contains the active ingredient fluorouracilo. It is a cancer medication. It is part of chemotherapy.

What is Fluorouracilo Accord used for

Fluorouracilo Accord is used to treat many common types of cancer, especially cancers of the large intestine, esophagus, pancreas, stomach, head, neck, and breast. It may be used in combination with other cancer medications or radiation therapy.

You should talk to your doctor if you do not get better or if you get worse.

No use Fluorouracilo Accord

• If you are allergic to fluorouracil or any of the other components of this medication (listed in section 6).
• If you are in a state of severe weakness due to a long illness.
• If you have a severe infection (e.g. chickenpox, shingles, or measles).
• If your cancer is not malignant.
• If your bone marrow has been damaged due to other cancer treatments (including radiation therapy).
• If you are taking brivudin, sorivudin, or their chemically related analogs (antiviral medications). Fluorouracil should not be used in the 4 weeks following treatment with brivudin, sorivudin, or their chemically related analogs.
• If you are breastfeeding.
• If you have severe liver disease.
• If you are homozygous for the dihydropyrimidine dehydrogenase (DPD) enzyme.
• If you have reduced or deficient activity of the dihydropyrimidine dehydrogenase (DPD) enzyme.

Inform your doctor if any of the above apply before using this medication.

Warnings and Precautions

Consult your doctor, pharmacist, or nurse before starting to use Fluorouracil Accord.Be especially careful with Fluorouracil Accord:

• If your bone marrow does not produce normal blood cells (your doctor will perform a blood test to check this)
• If you have kidney problems.
• If you have any liver problems, including jaundice (yellow skin).
• If you have had angina (chest pain) or have a history of heart disease, as you are more likely to have a heart attack or show signs of heart problems during an ECG test
• If you have received high-dose radiation in the pelvis.
• If the tumors have spread (metastasis) to your bone marrow
• If you have poor overall health and have lost a lot of weight
• If you have had surgery in the last 30 days
• If you have gastrointestinal (GI) adverse reactions (oral ulcers, diarrhea, gastrointestinal bleeding) or bleeding in any other area.
• If you know you have partial deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme activity.
• If you have heart problems. Inform your doctor if you experience chest pain during treatment.
• If you are a relative of someone with partial or complete deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme.

Dihydropyrimidine dehydrogenase (DPD) deficiency: DPD deficiency is a genetic condition that is not usually related to health problems, unless you are being treated with certain medications. If you have a DPD deficiency and take Fluorouracil Accord, you will have a higher risk of experiencing severe adverse effects (listed in section 4, Possible adverse effects). It is recommended that you undergo a test to detect DPD deficiency before starting treatment. If you have no enzyme activity, you should not take Fluorouracil Accord. If you have reduced enzyme activity (partial deficiency), your doctor may prescribe a reduced dose. Although the test results for DPD deficiency are negative, you may still experience severe and potentially life-threatening adverse effects.

Contact your doctor immediately if you are concerned about any of the adverse effects or if you notice any additional adverse effects not mentioned in the leaflet (see section 4 Possible adverse effects).

Contact your doctor immediately if you experience the following signs or symptoms: new onset of confusion, disorientation, or alteration of mental state, difficulty with balance or coordination, visual disturbances. These may be signs of encephalopathy that can lead to coma and death if not treated.

Inform your doctor if any of the above situations apply before using this medication.

Fluorouracil can cause sensitivity to sunlight. This can result in increased skin reactions. To avoid this, try to stay out of direct sunlight as much as possible while using it and do not use a sunlamp or tanning bed.

Avoid exposure to ultraviolet radiation (e.g. natural sunlight, tanning salon).

Treatment with fluorouracil may increase the risk of necrosis (death of tissue or skin) caused by radiation after radiation therapy.

The administration of fluorouracil has been associated with the development of hand-foot syndrome, characterized by a tingling sensation in the hands and feet, which can evolve over a few days to pain when gripping objects or walking. The palms of the hands and soles of the feet swell and become sensitive.

Use of Fluorouracil Accord with other medications

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.

• You need to be especially careful if you are taking/using other medications, as some may interact with the fluorouracil injection: Methotrexate, cyclophosphamide, cisplatin, vinorelbine (a cancer medication)
• Metronidazole (an antibiotic)
• Folic acid (also known as calcium folinate or leucovorin calcium - used to reduce the harmful effects of cancer medications)
• Alopurinol (used to treat gout)
• Cimetidine (used to treat stomach ulcers)
• Warfarin (used to treat blood clots)
• Interferon alpha (used in the treatment of lymphomas and chronic hepatitis)
• Brivudin, sorivudin, or their chemically related analogs (antiviral medications)
• Phenytoin (used to control epilepsy, seizures, and also heart arrhythmias)
• Avoid live vaccines, as they can cause severe or life-threatening infections. Avoid contact with people who have recently been treated with the polio vaccine. Inactivated or killed vaccines may be administered; however, the response may be affected
• Levamisole (a medication to treat worm infections)
• Tamoxifen (used in some types of breast cancer)
• Clozapine (used in psychiatric disorders)

Inform your doctor or pharmacist if you are taking or have taken recently these or other medications, even those purchased without a prescription.

Pregnancy, breastfeeding, and fertility

Pregnancy

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a child, consult your doctor before taking this medication.

Fluorouracil should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. If pregnancy occurs during treatment, inform your doctor and seek genetic counseling.

Women should avoid becoming pregnant and use a highly effective contraceptive method during treatment with Fluorouracil and for at least 6 months after.

Breastfeeding

Since it is unknown whether fluorouracil passes into breast milk, you should discontinue breastfeeding before treatment with Fluorouracil injectable.

Consult your doctor before taking any medication.

Fertility

It is recommended that men treated with Fluorouracil not have children during treatment and for 3 months after completing treatment.

Both men and women should seek advice on fertility, such as egg or sperm preservation before treatment, due to the possibility of irreversible infertility caused by therapy.

Driving and operating machinery

Do not drive or operate machinery because fluorouracil may cause adverse effects such as nausea and vomiting. It may also cause nervous system events and changes in vision. If you experience any of these effects, do not drive or operate tools or machinery, as it may impair your 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). This should be taken into account by patients on a sodium-controlled diet.

Recommended Dose

Your doctor will determine the correct dose of Fluorouracil injectable solution or for infusion for you and how often you should receive it.

The dose of the medication you will receive will depend on your overall health, your body weight, if you have recently undergone surgery, and the condition of your bone marrow, liver, and kidneys. The first treatment cycle may be administered daily or at weekly intervals. Subsequent cycles may be administered according to your response to treatment. You may also receive treatment in combination with radiation therapy.

Fluorouracil is not recommended for use in children due to insufficient data on safety and efficacy.

Before administration, the medication may be diluted with a glucose solution, saline solution, or water for injectable preparations. You will be administered through a vein as a normal injection or as a slow infusion (infusion).

If You Use More Fluorouracil Accord Than You Should

Since this medication will be administered by a doctor or nurse, it is unlikely that you will receive too much or too little; however, speak with your doctor or nurse if you have any concerns.

You will have blood tests performed during and after treatment with Fluorouracil Accord to monitor blood cell levels, and it may be necessary to stop treatment if your white blood cell count is too low.

Overdose of fluorouracil may cause nausea, vomiting, diarrhea, severe mucositis, and gastrointestinal ulcers and bleeding. If you have any doubts about the use of this medication, ask your doctor.

If You Forget to Use Fluorouracil Accord

Do not take a double dose to make up for the missed dose.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

If you experience any of the following side effects, consult your doctor immediately:

• Severe allergic reaction – you may experience itching (urticaria), swelling of the hands, feet, ankles, face, lips, mouth, or throat (which could cause difficulty swallowing or breathing) or feel like you are going to faint.
• Chest pain
• Stools with blood or black
• Mouth pain or appearance of ulcers
• Numbness, tingling, or tremors in the hands or feet
• Myocardial infarction or other heart problems such as rapid heart rate and shortness of breath
• Symptoms of leukoencephalopathy (brain disease) weakness, coordination problems with arms and legs, difficulty thinking or speaking, vision or memory problems, seizures, headaches
• Difficulty breathing

These are very serious side effects. You may need urgent medical attention.

If you experience any of the following, contact your doctor as soon as possible:

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

• Throat irritation
• Inadequate blood supply to the heart, as shown by the ECG
• Mielosupresión (a disorder in which the bone marrow produces a reduced number of all types of blood cells [pancitopenia])
• Neutropenia and leucopenia (an abnormally low level of types of white blood cells in the blood)
• Trombocitopenia (a reduced number of platelets in the blood that reduces blood clotting ability)
• A severe drop in circulating granulocytes (agranulocytosis)
• Anemia (a condition in which red blood cells are reduced)
• Increased risk of infection due to immunosuppression
• Wheezing (bronchospasm)
• Nausea
• Vomiting
• Diarrhea
• Infections
• Delayed wound healing
• Inflammation of the mucous membrane lining any of the structures of the mouth, throat, and digestive tract, e.g. esophagus (throat), rectum, or anus
• Increased uric acid in the blood
• Nasal bleeding
• Hair loss
• Hand-foot syndrome (toxic skin reaction with redness and swelling of hands and feet)
• Fatigue, tiredness, and lack of energy
• Discomfort

Rare: may affect up to 1 in 100 people:

• Atrial fibrillation
• Myocardial infarction
• Myocardial ischemia (reduction of oxygen supply to the heart)
• Myocarditis (inflammatory disease of the heart muscle)
• Myocardial dilatation (a type of heart disease in which the heart muscle is abnormally large, thick, and/or hardened)
• Cardiac shock
• Hypotension
• Drowsiness
• Dehydration
• Liver cell damage
• Gastrointestinal ulcer and bleeding
• Peeling of the skin
• Gastrointestinal bleeding
• Eye movements (nystagmus)
• Headache
• Dizziness
• Sensations of imbalance and instability
• Symptoms of Parkinson's disease (a progressive movement disorder marked by tremors, rigidity, slow movements)
• Pyramidal signs
• Blood infection (sepsis)
• Dermatitis (inflammation of the skin)
• Skin changes. E.g. dry skin, erosion with fissures, skin redness, maculopapular and pruritic skin rash (a skin rash with red bumps and itching)
• A skin rash accompanying certain infectious diseases
• Appearance of hives that cause itching on the skin
• Sensitivity to light (photosensitivity)
• Pigmentation of the skin
• Pigmentation in stripes or depigmentation near the veins
• Nail pigmentation, thickening of the nail bed
• Paronychia (inflammation of the tissue surrounding the fingernails)
• Inflammation of the nail matrix with pus formation and nail detachment
• Disorders of sperm or ovulation
• Increased tear secretion
• Blurred vision
• Inflammation or redness of the conjunctiva and lower eyelid
• Eye movement disorder
• Red eyes (conjunctivitis)
• Optic neuritis (a vision disorder characterized by inflammation of the optic nerve)
• Diplopia (double vision)
• Reduced visual acuity
• Excessive sensitivity of the eyes to light, aversion to sunlight and well-lit places
• Narrowing of the tear duct that drains tears from the eye (dacryostenosis)
• Eversion of the eyelid (ectropion)
• Euphoria

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

• Inadequate blood supply to the brain, intestines, and peripheral organs (extremities)
• Poor blood circulation that causes numbness and paleness of the fingers and toes (Raynaud's syndrome)
• Hypersensitivity
• Inflammation of the veins caused by a blood clot
• Severe allergic reaction throughout the body (anaphylaxis)
• Formation of blood clots in blood vessels, both in veins and arteries
• Confusion or disorder of consciousness, especially related to time, place, or identity
• Confusion
• Renal failure
• Changes in thyroid function - increased T4 and T3 (total thyroxine and triiodothyronine)

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

• Cardiac arrest (sudden cessation of heartbeats and cardiac function)
• Sudden cardiac death (unexpected death due to cardiac problems)
• Symptoms of leukoencephalopathy (brain diseases that affect the white matter of the brain), including ataxia (loss of ability to coordinate muscle movement)
• Acute cerebellar syndrome
• Difficulty articulating words
• Partial or total loss of verbal or written communication ability
• Abnormal muscle weakness or fatigue
• Convulsion or coma in patients who have received high doses of 5-fluorouracil or in patients with dihydropyrimidine dehydrogenase (DPD) deficiency
• Inflammation of the gallbladder
• Liver cell damage (fatal outcome)

Unknown: the frequency cannot be estimated from available data:

• Blood poisoning (septic shock)
• Neutropenic sepsis (potentially fatal reaction to an infection that can occur in patients with neutropenia, i.e. low levels of a type of white blood cell that forms part of the immune system and fights infections in the blood)
• Pulmonary infection
• Urinary tract infection, bacterial infection of the urinary system
• Bacterial skin infection that causes redness, swelling, and pain in the affected area.
• Reduced number of granulocytes, a type of white blood cell
• Loss of appetite
• Disorientation
• Fever
• Numbness or weakness of arms and legs
• Seizures
• Hyperrammonemic encephalopathy (cerebral dysfunction caused by elevated ammonia)
• Thrombi in the heart cavities that could detach and obstruct blood vessels in the body, for example, causing a stroke or inadequate blood supply to a limb.
• Inflammation of the heart muscle.
• Inflammation of the skin that causes red, scaly patches possibly accompanied by joint pain and fever (cutaneous lupus erythematosus [CLE])
• Cardiac disease that manifests with chest pain, difficulty breathing, dizziness, fainting, irregular heartbeats (stress cardiomyopathy)
• Bleeding
• Dark, sticky stools containing partially digested blood
• Chest pain
• Air in the intestinal wall
• Severe disorder that manifests with difficulty breathing, vomiting, and abdominal pain with muscle cramps (lactic acidosis)
• Disorder characterized by headache, confusion, seizures, and changes in vision (posterior reversible encephalopathy syndrome [PRES])
• Severe complication with rapid degradation of cancer cells that causes elevated levels of uric acid, potassium, and phosphate (tumor lysis syndrome)
• Decoloration at the injection site
• Elevated triglyceride levels in the blood, a type of fat
• Pain, redness, or swelling at the injection site during, or shortly after, the injection/infusion (this may be due to the injection not penetrating correctly into the vein)
• Vitamin B1 deficiency and Wernicke encephalopathy (brain damage caused by vitamin B1 deficiency)
• Inflammation of the small and large intestines causing pain and diarrhea, which can cause death of intestinal tissue (colitis, enterocolitis)

Reporting of adverse reactions:

If you experience any type of adverse reaction, consult your doctor or pharmacist, even if it is a possible adverse reaction that does not appear in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: https://www.notificaRAM.es. By reporting adverse reactions, you can contribute to providing more information on the safety of this medicine.

• Keep this medication out of the sight and reach of children.
• Do not use this medication after the expiration date that appears on the label and packaging after CAD. The expiration date is the last day of the month indicated.
• Store below25°C. Do not refrigerate or freeze.
• Store in the original packaging to protect it from light.

Single use. Dispose of any unused medication.

Validity period after dilution

Physical-chemical stability has been demonstrated under usage conditions for 24 hours at25°Cwith 5% glucose injections or 0.9% sodium chloride or injectable water with a fluorouracil concentration of 0.98 mg/ml. However, from a microbiological standpoint, the product should be used immediately. If not used immediately, the storage times under usage conditions and the conditions prior to use will be the responsibility of the user.

• Do not use if the solutionshowsa brown or dark yellow color.
• Do not use if it warns that the packaging is damaged or particles/crystals are visible.
• Do not dispose of the medication in the trash or down the drain. All materials used for preparation and administration, or that have come into contact with cisplatin in any way, must be disposed of in accordance with local cytotoxic requirements.

Composition of Fluorouracil Accord

The active ingredient of Fluorouracil Accord is fluorouracil.

The other components are water for injection, sodium hydroxide, and hydrochloric acid.

Appearance of the product and contents of the container

Each ml of solution contains 50 mg of fluorouracil (as sodium salt formed in situ).

The injectable or infusion solution of fluorouracil is a transparent, colorless to pale yellow solution conditioned in a type I glass vial with a rubber stopper.

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.

Only some sizes of packaging may be commercially available.

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center

Moll de Barcelona, s/n

Edifici Est, 6th floor

08039 Barcelona

Responsible for manufacturing

Accord Healthcare Polska Sp.z o.o.,

ul. Lutomierska 50,95-200 Pabianice,

Poland

or

Accord Healthcare Single Member S.A.

64th Km National Road Athens,

Lamia, Schimatari, 32009,

Greece

This medicinal product has been authorized in the Member States of the European Economic Areawith the following names

Last review date of this leaflet: February 2025

The detailed information of this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/)

This information is intended solely for doctors or healthcare professionals

INSTRUCTIONS FOR USE/GUIDE FOR HANDLING, PREPARATION, AND DISPOSAL FOR THE USE OF FLUOROURACIL ACCORD

Cytotoxic handling guidelines

Fluorouracil should only be administered by a doctor or under the supervision of a qualified doctor with experience in the use of chemotherapeutic drugs for cancer treatment.

Fluorouracil Accord should only be prepared by professionals who have been trained in the safe preparation of the same. The preparation should be carried out in a laminar flow cabinet or a dedicated room for the handling of cytotoxics.

If the medication spills, the operators should use gloves, facial masks, eye protection, and a disposable apron and clean the spilled material with an absorbent material stored in the area for that purpose. The area should be cleaned afterwards and all contaminated material should be deposited in a cytotoxic waste bag or container and sealed for incineration.

Contamination

Fluorouracil Accord is irritating, and contact with the skin and mucous membranes should be avoided.

In case of contact with the skin or eyes, the affected area should be washed with plenty of water or normal saline solution. A 1% hydrocortisone cream may be used to treat transient skin irritation. Medical advice should be sought if the eyes are affected or if the preparation is inhaled or ingested.

First aid

Contact with the eyes: wash immediately with plenty of water and consult a doctor.

Contact with the skin: wash thoroughly with water and soap and remove contaminated clothing.

Inhalation or ingestion: consult a doctor.

Disposal

Needles, containers, absorbent materials, solutions, and other contaminated materials should be placed in a thick plastic bag or other impermeable container, marked as cytotoxic waste, and incinerated at a minimum temperature of 700°C.

Chemical inactivation can be achieved with 5% sodium hypochlorite for 24 hours.

Preparation guidelines

a) Chemotherapeutic drugs should only be prepared for administration by professionals who have been trained in the safe use of the preparation.

b) Operations such as reconstituting the powder and transferring to syringes should only be carried out in the designated area.

c) The personnel performing these procedures should be adequately protected with special clothing, two pairs of gloves (one of latex and one of PVC; with the first one underneath the PVC one) to cover the different permeabilities to the various antineoplastics, and protective glasses. For the preparation and administration of cytotoxic products, syringes and accessories with Luer Lock closure should always be used.

d) Pregnant employees should not handle chemotherapeutic drugs.

e) Refer to local guidelines before starting.

Instructions for use

Fluorouracil Accord can be administered by intravenous injectionas a bolus, perfusion, or continuous perfusion.

Incompatibilities

Fluorouracil is incompatible with calcium folinate, carboplatin, cisplatin, cytarabine, diazepam, doxorubicin, droperidol, filgrastim, gallium nitrate, methotrexate, metoclopramide, morphine, ondansetron, parenteral nutrition, vinorelbine, and other anthracyclines.

The formulated solutions are alkaline and it is recommended to avoid mixing with acidic drugs or preparations.

Given the absence of compatibility studies, this medicinal product should not be mixed with any other medicinal product.

Shelf life and storage

Shelf life of unopened vials

2 years. Single use only. Dispose of any unused medicinal product.

Store below 25°C. Do not refrigerate or freeze.

Store the container in the outer packaging to protect it from light.

In case of formation of a precipitate as a result of exposure to low temperatures, heat to 60°C and agitate the product vigorously to redisolve it. Let it cool to room temperature before use. Dispose of the medicinal product if the solution turns yellow or brown.

Shelf life after dilution

In use: physical and chemical stability has been demonstrated under use conditions for 24 hours at 25°C with glucose 5% injections or sodium chloride 0.9% or water for injection with a fluorouracil concentration of 0.98 mg/ml.

From a microbiological point of view, the product should be used immediately. If not used immediately, the storage times under use conditions and the conditions prior to use will be the responsibility of the user.