Fluorouracil Accord 50 mg/ml solution for injection or for infusion EFG: detailed information

Patient Information Leaflet

Introduction

Package leaflet: Information for the patient

Fluorouracil Accord 50 mg/ml solution for injection or infusion EFG

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

Keep this leaflet, as 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 and must not be given to other people, even if they have the same symptoms as you. It could harm them.
If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if the effects are not listed in this leaflet. See section 4.

Leaflet contents:

What Fluorouracil Accord is and what it is used for
What you need to know before using Fluorouracil Accord
How to use Fluorouracil Accord
Possible adverse effects
How to store Fluorouracil Accord
Contents of the pack and other information

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

What Fluorouracil Accord is

Fluorouracil Accord contains the active substance fluorouracil. It is an anticancer medicine and part of chemotherapy treatment.

What Fluorouracil Accord is used for

Fluorouracil Accord is used to treat many common types of cancer, especially cancers of the colon, esophagus, pancreas, stomach, head, neck, and breast. It may be used in combination with other anticancer medicines or radiotherapy.

You should speak with your doctor if you do not feel better or if you feel worse.

2. What you need to know before using Fluorouracil Accord

Do not use Fluorouracil Accord

if you are allergic to fluorouracil or to any of the other components of this medicine (listed in section 6).
if you are in a severe state of weakness due to a prolonged illness.
if you have a serious infection (e.g., chickenpox, shingles or herpes zoster).
if your cancer is not malignant.
if your bone marrow has been damaged due to previous cancer treatments (including radiotherapy).
if you are taking brivudine, sorivudine, or their chemically related analogues (antiviral medicines). Fluorouracil must not be used within 4 weeks of treatment with brivudine, sorivudine, or their chemically related analogues.
if you are breastfeeding.
if you have severe liver disease.
if you are homozygous for the enzyme dihydropyrimidine dehydrogenase (DPD).
if you have reduced activity or deficiency of the enzyme dihydropyrimidine dehydrogenase (DPD).

Inform your doctor if any of the above apply to you before using this medicine.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting treatment with Fluorouracil Accord. Take special care with Fluorouracil Accord:

if your bone marrow does not produce blood cells normally (your doctor will perform a blood test to check this).
if you have kidney problems.
if you have any liver problems, including jaundice (yellowing of the skin).
if you have experienced angina (chest pain) or have a history of heart disease, as you may be more likely to experience angina attacks or heart attacks, or show signs of heart problems during an ECG test.
if you have received pelvic radiation at a high dose.
if tumours have spread (metastasized) to your bone marrow.
if you are generally unwell and have lost a lot of weight.
if you have had surgery within the last 30 days.
if you experience gastrointestinal (GI) adverse reactions (oral ulceration (stomatitis), diarrhoea, gastrointestinal bleeding) or bleeding at any other site.
if you know you have partial deficiency of 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 enzyme dihydropyrimidine dehydrogenase (DPD).

DPD deficiency: DPD deficiency is a genetic condition that usually does not cause health problems unless you are being treated with certain medicines. If you have DPD deficiency and take Fluorouracil Accord, you have a higher risk of experiencing serious adverse effects (listed in section 4, Possible side effects). It is recommended that you be tested for DPD deficiency before starting treatment. If you have no enzyme activity, you must not take Fluorouracil Accord. If you have reduced enzyme activity (partial deficiency), your doctor may prescribe a lower dose. Even if the test result for DPD deficiency is negative, serious and potentially fatal adverse effects may still occur.

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

Contact your doctor immediately if you experience any of the following signs or symptoms: new onset confusion, disorientation, or changes in mental status, difficulty with balance or coordination, or visual disturbances. These could be signs of encephalopathy, which may lead to coma and death if not treated.

Inform your doctor if any of the above situations apply to you before using this medicine.

Fluorouracil may cause increased sensitivity to sunlight. This may result in an increased risk of skin reactions. To avoid this, you should avoid direct sunlight as much as possible while using this medicine and must not use sunlamps or sunbeds.

Exposure to ultraviolet radiation (e.g., natural sunlight, tanning salons) should be avoided.

Treatment with fluorouracil may increase the likelihood of necrosis (tissue or skin death) caused by radiation following radiotherapy.

Administration of fluorouracil has been associated with hand-foot syndrome, characterised by tingling sensations in the hands and feet, which may progress within days to pain when handling objects or walking. The palms of the hands and soles of the feet may swell and become tender.

Using Fluorouracil Accord with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

Special care is needed if you are taking/using other medicines, as some may interact with fluorouracil injection:
Metotrexate, cyclophosphamide, cisplatin, vinorelbine (a cancer medicine)
Metronidazole (an antibiotic)
Folinic acid (also known as calcium folinate or leucovorin calcium – used to reduce harmful effects of cancer medicines)
Allopurinol (used to treat gout)
Cimetidine (used to treat stomach ulcers)
Warfarin (used to treat blood clots)
Interferon alfa (used in the treatment of lymphomas and chronic hepatitis)
Brivudine, sorivudine, or their chemically related analogues (antiviral medicines)
Phenytoin (used to control epilepsy, seizures, and also heart arrhythmias)
Live vaccines should be avoided, as they may cause serious or fatal infections. You should also avoid contact with people who have recently received the oral polio vaccine. Inactivated or killed vaccines may be administered; however, the immune response may be reduced.
Levamisole (a medicine used to treat worm infections)
Tamoxifen (used in certain types of breast cancer)
Clozapine (used in psychiatric disorders)

Inform your doctor or pharmacist if you are taking or have recently taken any of these or other medicines, including those obtained 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 baby, consult your doctor before taking this medicine.

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 immediately and seek genetic counselling.

Women must avoid becoming pregnant and use a highly effective method of contraception during treatment with Fluorouracil and for at least 6 months after treatment ends.

Breastfeeding

As it is unknown whether fluorouracil passes into breast milk, breastfeeding must be discontinued before treatment with injectable Fluorouracil.

Seek advice from your doctor before taking any medicine.

Fertility

Men treated with Fluorouracil are advised not to father a child during treatment and for at least 3 months after treatment ends.

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

Driving and using machines

Do not drive or operate machinery because fluorouracil may cause adverse effects such as nausea and vomiting. It may also cause adverse events affecting the nervous system and changes in vision. If you experience any of these effects, do not drive or operate tools or machines, as your ability to drive or operate machinery may be impaired.

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 consideration by patients on a controlled sodium diet.

3. How to use Fluorouracil Accord

Recommended dose

Your doctor will determine the correct dose of Fluorouracil for injection or infusion and how often it should be administered.

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

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

Prior to administration, the medicine may be diluted with glucose solution, saline solution, or water for injectable preparations. It will be administered through a vein either as a standard injection or as a slow intravenous infusion (perfusion).

If you use more Fluorouracil Accord than you should

Since this medicine 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 during and after treatment with Fluorouracil Accord to monitor your blood cell levels, and it may be necessary to stop treatment if your white blood cell count becomes too low.

Nausea, vomiting, diarrhea, severe mucositis, and gastrointestinal ulcers and bleeding may occur if you receive too much fluorouracil. If you have any questions about the use of this medicine, ask your doctor.

If you forget to use Fluorouracil Accord

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

4. Possible adverse effects

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

If you experience any of the following adverse 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 containing blood or black stools
mouth pain or development of ulcers
numbness, tingling, or trembling in the hands or feet
myocardial infarction or other heart problems such as increased heart rate and shortness of breath
symptoms of leukoencephalopathy (brain disease): weakness, coordination problems in arms and legs, difficulty thinking or speaking, vision or memory problems, seizures, headaches
difficulty breathing

These are very serious adverse effects. You may require 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 on ECG tracing
Myelosuppression (a disorder in which the bone marrow produces a reduced number of all types of blood cells [pancytopenia])
Neutropenia and leucopenia (abnormally low levels of certain types of white blood cells in the blood)
Thrombocytopenia (reduced number of platelets in the blood, leading to reduced blood clotting ability)
Severe drop in circulating granular white blood cells (agranulocytosis)
Anaemia (a condition in which red blood cells are reduced)
Increased risk of infection due to immunosuppression
Wheezing (bronchospasm)
Nausea
Vomiting
Diarrhoea
Infections
Delayed wound healing
Inflammation of the mucous lining of any structures in the mouth, throat, and digestive tract, e.g. oesophagus (throat), rectum or anus
Increased uric acid 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
Malaise

Common: may affect up to 1 in 10 people:

Blood infection (sepsis)
Heart attack, angina (severe chest pain associated with inadequate blood supply to the heart)
Low white blood cell count accompanied by fever
Changes in ECG (electrocardiogram: tests to check the rhythm and electrical activity of the heart).

Uncommon: may affect up to 1 in 100 people:

Cardiac arrhythmia
Heart attack
Myocardial ischaemia (reduced oxygen supply to the heart)
Myocarditis (inflammatory disease of the heart muscle)
Dilated cardiomyopathy (a type of heart disease in which the heart muscle is abnormally large, thick, and/or stiff)
Cardiogenic shock
Hypotension
Somnolence
Dehydration
Hepatocellular liver damage
Gastrointestinal ulcer and bleeding
Skin peeling
Gastrointestinal haemorrhage
Rhythmic eye movements (nystagmus)
Headache
Dizziness
Sensations of imbalance and instability
Symptoms of Parkinson's disease (a progressive movement disorder characterized by tremors, stiffness, and slow movements)
Pyramidal signs
Blood infection (sepsis)
Skin inflammation (dermatitis)
Skin disorders, e.g. dry skin, erosion with fissures, skin redness, maculopapular and pruritic rash (a skin rash with red bumps and itching)
A skin rash associated with certain infectious diseases
Appearance of itchy hives on the skin
Light sensitivity (photosensitivity)
Hyperpigmentation of the skin
Band-like hyperpigmentation or depigmentation near 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 lining of the white part of the eye and the inner surface of the eyelid
Eye movement disorder
Red eyes (conjunctivitis)
Optic neuritis (vision disorder characterized by inflammation of the optic nerve)
Double vision
Reduced visual acuity
Excessive sensitivity of the eyes to light, aversion to sunlight and well-lit places
Narrowing of the tear drainage duct from the eye (dacryostenosis)
Eyelid turning outward (ectropion)
Euphoria

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

Inadequate blood flow to the brain, intestines, and peripheral organs (extremities)
Poor blood circulation causing numbness and pallor in fingers and toes (Raynaud's syndrome)
Hypersensitivity
Vein inflammation due to blood clot (phlebitis)
Severe, whole-body allergic reaction (anaphylaxis)
Blood clot formation in blood vessels, both in veins and arteries
Mental confusion or disturbance of consciousness, particularly regarding time, place, or identity
Confusion
Renal failure
Changes in thyroid function – increase in T4 and T3 (total thyroxine and triiodothyronine)

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

Cardiac arrest (sudden cessation of heartbeat and cardiac function)
Sudden cardiac death (unexpected death due to heart problems)
Symptoms of leukoencephalopathy (diseases affecting the brain's white matter), including ataxia (loss of ability to coordinate muscle movements)
Acute cerebellar syndrome
Difficulty articulating words
Partial or complete loss of ability to communicate verbally or in writing
Abnormal muscle weakness or fatigue
Seizure 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 (with fatal outcome)

Unknown: frequency cannot be estimated from available data:

Blood poisoning (septic shock)
Neutropenic sepsis (a potentially life-threatening response to infection that may occur in patients with neutropenia, i.e., low levels of a type of white blood cell involved in the immune system and fighting infections in the blood)
Pulmonary infection
Urinary tract infection, bacterial infection of the urinary system
Bacterial skin infection causing redness, swelling, and pain in the infected area
Reduced number of granulocytes, a type of white blood cell
Decreased appetite
Disorientation
Fever
Numbness or weakness in arms and legs
Seizures
Hyperammonaemic encephalopathy (brain dysfunction caused by elevated ammonia levels)
Blood clots in the heart chambers that could dislodge and block arteries in the body, potentially causing stroke or impaired blood flow to a limb
Inflammation of the heart muscle (myocarditis)
Skin inflammation causing scaly red patches, possibly accompanied by joint pain and fever (cutaneous lupus erythematosus [CLE])
Heart disease presenting with chest pain, difficulty breathing, dizziness, fainting, and irregular heartbeats (stress cardiomyopathy)
Haemorrhage
Dark, tarry stools containing partially digested blood
Chest pain
Air in the intestinal wall
Severe disorder presenting with difficulty breathing, vomiting, and abdominal pain with muscle cramps (lactic acidosis)
Condition characterized by headache, confusion, seizures, and vision changes (reversible posterior encephalopathy syndrome [RPES])
Serious complication involving rapid breakdown of cancer cells leading to elevated levels of uric acid, potassium, and phosphate (tumour lysis syndrome)
Discoloration at the injection site
Elevated blood triglyceride levels, a type of fat
Pain, redness, or swelling at the infusion site during or shortly after injection/infusion (may be due to improper venous placement of the injection)
Vitamin B1 deficiency and Wernicke's encephalopathy (brain damage caused by vitamin B1 deficiency)
Inflammation of the small and large intestine causing pain and diarrhoea, which may lead to intestinal tissue death (colitis, enterocolitis)

Reporting of adverse effects:

If you experience any adverse effects, consult your doctor or pharmacist, even if they are possible side effects not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicinal Products: https://www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Fluorouracil Accord

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and packaging following EXP. The expiry date refers to the last day of the month indicated.
Store below 25°C. Do not refrigerate or freeze.
Keep in the original packaging to protect from light.

For single use only. Any unused medicinal product must be discarded.

Period of validity after dilution

Physicochemical stability has been demonstrated under in-use conditions for 24 hours at 25°C in 5% glucose injections, 0.9% sodium chloride or water for injections, 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 and conditions prior to use are the responsibility of the user.

Do not use if the solution has a brown or dark yellow colour.
Do not use if the container is damaged or if particles/crystals are visible.
Do not dispose of medicines via household waste or down the drain. All materials used in the preparation and administration, or that have come into contact with cisplatin in any way, must be disposed of in accordance with local requirements for cytotoxic agents.

6. Contents of the container and other information

Composition of Fluorouracil Accord

The active substance is fluorouracil.

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

Appearance of the product and contents of the container

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

The fluorouracil injectable or perfusion solution is a clear, colourless to pale yellow solution contained in a clear 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 container sizes may be marketed.

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center

Moll de Barcelona, s/n

Edifici Est, 6th floor

08039 Barcelona, Spain

Manufacturer

Accord Healthcare Polska Sp. z o.o.,

ul. Lutomierska 50, 95-200 Pabianice,

Poland

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 Area under the following names

Member State	Medicinal product name
Austria	Fluorouracil Accord 50 mg/ml, solution for injection or infusion
Belgium	Fluorouracil Accord Healthcare 50 mg/ml, solution for injection or perfusion/ solution for injection or infusion/ solution for injection or infusion
Czech Republic	Fluorouracil Accord 50 mg/ml, injectable/infusion solution
Denmark	Fluorouracil Accord, injection and infusion solution, concentrate
Estonia	Fluorouracil Accord 50 mg/ml, injection or infusion solution
Finland	Fluorouracil Accord 50 mg/ml, injection or infusion solution/ solution for injection and infusion
Ireland	Fluorouracil 50 mg/ml, Solution for Injection or Infusion
Italy	Fluorouracil AHCL 50 mg/ml, Solution for Injection or Infusion
Spain	Fluorouracil Accord 50 mg/ml injectable solution or for perfusion EFG
Sweden	Fluorouracil Accord 50 mg/ml, solution for injection and infusion
Latvia	Fluorouracil Accord 50 mg/ml, solution for injection or infusion
Lithuania	Fluorouracil Accord 50 mg/ml, concentrate for injection or infusion solution
Poland	Fluorouracil Accord
Portugal	Fluorouracil Accord
Slovak Republic	Fluorouracil Accord 50 mg/ml, solution for injection or infusion
Netherlands	Fluorouracil Accord 50 mg/ml, solution for injection or infusion
United Kingdom	Fluorouracil 50 mg/ml, Solution for Injection or Infusion
Bulgaria	Fluorouracil Accord 50 mg/ml Solution for Injection or Infusion
Cyprus	Fluorouracil 50 mg/ml, Solution for Injection or Infusion
Germany	Fluorouracil Accord 50 mg/ml, concentrate for injection or infusion solution
Hungary	Fluorouracil Accord 50 mg/ml, solution for injection or infusion
Iceland	Fluorouracil Accord 50 mg/ml, solution for injection or infusion
Malta	Fluorouracil 50 mg/ml, Solution for Injection or Infusion
Norway	Fluorouracil Accord 50 mg/ml concentrate for infusion solution
Romania	Fluorouracil Accord 50 mg/ml, injectable or perfusable solution
Slovenia	Fluorouracil Accord 50 mg/ml, solution for injection or infusion

Date of the most recent review of this summary: February 2025

Detailed information on this medicine is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/)

This information is intended for healthcare professionals only

INSTRUCTIONS FOR USE / HANDLING, PREPARATION AND DISPOSAL GUIDELINES FOR FLUOROURACIL ACCORD

Cytotoxic handling guidelines

Fluorouracil must only be administered by a physician or under the supervision of a qualified physician experienced in the use of chemotherapeutic agents for cancer treatment.

Fluorouracil Accord must only be prepared by healthcare professionals trained in its safe preparation. Preparation must be carried out in a laminar airflow cabinet or in a dedicated area for handling cytotoxic agents.

In the event of a spill, personnel must wear gloves, face masks, eye protection, and disposable gowns, and clean up the spill using absorbent material stored in the designated area. The area should then be cleaned thoroughly, and all contaminated materials must be placed in a cytotoxic waste bag or container, sealed, and incinerated.

Contamination

Fluorouracil Accord is irritating; contact with skin and mucous membranes must be avoided.

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

First aid

Eye contact: Immediately rinse thoroughly with water and consult a physician.

Skin contact: Wash thoroughly with soap and water and remove contaminated clothing.

Inhalation or ingestion: Seek medical advice immediately.

Disposal

Syringes, containers, absorbent materials, solutions, and all other contaminated materials must be placed in a thick plastic bag or other impermeable container clearly labeled as cytotoxic waste and incinerated at a minimum temperature of 700°C.

Chemical inactivation can be achieved using 5% sodium hypochlorite over 24 hours.

Preparation guidelines

Chemotherapeutic agents must only be prepared for administration by trained professionals familiar with safe handling procedures.
Procedures such as powder reconstitution and transfer into syringes must only be performed in a designated area.
Personnel performing these procedures must wear appropriate protective clothing, two pairs of gloves (a latex glove under a PVC glove) to protect against different permeabilities of various antineoplastic agents, and protective goggles. Luer Lock syringes and accessories must always be used when preparing and administering cytotoxic products.
Pregnant healthcare workers are advised not to handle chemotherapeutic agents.
Refer to local guidelines before beginning.

Instructions for use

Fluorouracil Accord may be administered by intravenous injection as a bolus, infusion, or continuous infusion.

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 formulations are alkaline and mixing with acidic drugs or preparations should be avoided.

Due to the absence of compatibility studies, this medicine must not be mixed with any other medicinal product.

Shelf life and storage

Shelf life of unopened vials

2 years. For single use only. Any unused medicine must be discarded.

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

Keep the container in the outer packaging to protect from light.

If a precipitate forms due to exposure to low temperatures, warm the product to 60°C and shake vigorously to re-dissolve. Allow to cool to room temperature before use. Discard the medicine if the solution turns yellow or brown.

Shelf life after dilution

In-use stability: Physicochemical stability has been demonstrated for 24 hours at 25°C when diluted with 5% glucose injection, 0.9% sodium chloride injection, or water for injections, with a fluorouracil concentration of 0.98 mg/ml.

From a microbiological standpoint, the product should be used immediately. If not used immediately, the storage duration and conditions prior to use are the responsibility of the user.