Fluorouracil medac

Package Leaflet: Information for the User

Fluorouracil medac, 50 mg/ml, Solution for Injection

Fluorouracil

Read all of this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Pack

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

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

Fluorouracil is an anticancer medicine belonging to the group of antimetabolites.
Fluorouracil medac, solution for injection, is used in the treatment of colorectal and breast cancer. It can be used in combination with other anticancer medicines.

2. Important information before using Fluorouracil medac

When not to use Fluorouracil medac

• if you are allergic (hypersensitive) to fluorouracil or any of the other ingredients of this medicine (listed in section 6);
• if your bone marrow has been damaged by previous treatment (including radiotherapy);
• if the tumor is benign;
• if you have severe liver function disorders;
• if you have a severe infection (e.g., shingles, chickenpox);
• if you are severely weakened due to prolonged treatment or other anticancer therapies (e.g., radiotherapy);
• if you are breastfeeding;
• if you have a complete deficiency of the enzyme dihydropyrimidine dehydrogenase (DPD);
• if you are currently being treated with or have been treated with brivudine in the last 4 weeks as part of the treatment for shingles or chickenpox.

Warnings and precautions

Before starting treatment with Fluorouracil medac, discuss with your doctor or pharmacist:

• if you have a low white blood cell count (your doctor will monitor your blood count);
• if you have gastrointestinal side effects (mouth ulcers, diarrhea, gastrointestinal bleeding) or bleeding from any site;
• if you have angina pectoris (worsening heart condition due to sudden chest pain attacks);
• if you have a history of heart disease;
• if you have heart disorders. You should inform your doctor if you experience chest pain during treatment;
• if you have been diagnosed with a partial deficiency of the enzyme dihydropyrimidine dehydrogenase (DPD);
• if a family member has a partial or complete deficiency of the enzyme dihydropyrimidine dehydrogenase (DPD);
• if you are being treated with brivudine or if you have received such treatment in the last 4 weeks;
• if you are taking phenytoin to prevent seizures;
• if you have kidney disease;
• if you have liver disease, including jaundice (yellowing of the skin);
• if you have been exposed to sunlight for a long time. Sunlight is not recommended due to the risk of photosensitivity;
• if you have received pelvic irradiation with high doses;
• if you have received live vaccines;
• if you are taking folic acid or receiving folic acid. Folic acid may increase the risk of toxicity associated with fluorouracil, especially in elderly and weakened patients.

DPD deficiency: DPD deficiency is a genetic disorder that usually does not cause any health problems until the patient receives certain medications. If you have a DPD deficiency and are taking Fluorouracil medac, the risk of severe side effects (listed in section 4 - "Possible side effects") increases. It is recommended that a test be performed before starting treatment to check for DPD deficiency. If you have no activity of this enzyme, you should not be treated with Fluorouracil medac. If the activity of this enzyme is reduced (partial enzyme deficiency), your doctor may prescribe a reduced dose of the medicine. Even if the DPD deficiency test result is negative, severe and life-threatening side effects can still occur.
You should contact your doctor immediately if you experience any of the following symptoms:
new 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.
Treatment should be started in a hospital. Before the first administration, the patient should undergo blood tests and other necessary examinations to ensure that they can be treated with fluorouracil.
You should inform your doctor immediately if you experience chest pain during treatment.

Fluorouracil medac and other medicines

Tell your doctor about all medicines you are taking now or have recently taken, even those that are available without a prescription, as well as any medicines you plan to take. This is especially important because taking more than one medicine at the same time can enhance or weaken their effects.

Do not take brivudine (an antiviral medicine used to treat shingles or chickenpox) at the same time as taking Fluorouracil medac (including during periods when Fluorouracil medac is not being taken).

If you have taken brivudine, you must wait at least 4 weeks after stopping brivudine before starting to take Fluorouracil medac.

See the section "When not to use Fluorouracil medac".
Interactions with fluorouracil and the following medicines are known:

• allopurinol (used to treat gout)
• certain medicines used to treat cancer
• radiotherapy
• leucovorin (also known as folic acid - used in anticancer therapies and to treat folic acid deficiency)
• phenytoin (used to treat epilepsy)
• cimetidine (used to treat heartburn and gastrointestinal ulcers)
• metronidazole (used to treat infections)
• interferon alfa 2a (used to treat cancer or hepatitis)
• thiazides (e.g., hydrochlorothiazide)
• cyclophosphamide (an anticancer medicine)
• methotrexate (used to treat cancer or autoimmune diseases)
• warfarin (used to prevent blood clots)
• levamisole (a medicine used to treat parasitic infections)
• clozapine (used to treat schizophrenia)
• anthracyclines (an anticancer medicine, e.g., epirubicin, doxorubicin, daunorubicin)
• tamoxifen (an anticancer medicine)
• vinorelbine (an anticancer medicine)
• live vaccines should be avoided
• cisplatin (an anticancer medicine).

Tell your doctor about any of the above medicines you are taking or have taken recently, so that your doctor can decide whether to start treatment with fluorouracil.

Pregnancy, breastfeeding, and fertility

Pregnancy
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine.
Fluorouracil should only be used during pregnancy if the potential benefits outweigh the potential risks to the fetus. Women of childbearing age should not become pregnant during treatment. Women of childbearing age must use effective contraception during treatment with this medicine and for at least 6 months after the end of treatment.
If you become pregnant during treatment, you must inform your doctor and consult a genetic counseling center.
Breastfeeding
Since it is not known whether fluorouracil passes into breast milk, breastfeeding should be stopped before starting treatment with Fluorouracil medac.
Fertility
Men should avoid fathering a child during and for 3 months after treatment with Fluorouracil medac. Before starting treatment, you should seek advice on sperm storage, considering the possibility of irreversible infertility due to treatment with Fluorouracil medac.
Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Do not drive or operate machinery, as fluorouracil can cause side effects such as nausea and vomiting. It can also cause neurological side effects and changes in vision. If you experience any of these symptoms, you should not drive or operate machinery, as they may impair your ability to drive or operate machinery.

Fluorouracil medac contains sodium

10 ml vial
The medicine contains 82.37 mg of sodium (the main component of common salt) per 10 ml vial.
This corresponds to 4.12% of the maximum recommended daily intake of sodium in the diet for adults.
20 ml vial
The medicine contains 164.75 mg of sodium (the main component of common salt) per 20 ml vial.
This corresponds to 8.24% of the maximum recommended daily intake of sodium in the diet for adults.
100 ml vial
The medicine contains 823.75 mg of sodium (the main component of common salt) per 100 ml vial.
This corresponds to 41.19% of the maximum recommended daily intake of sodium in the diet for adults.
The medicine can be diluted. The sodium content from the diluent should be taken into account when calculating the total sodium content in the prepared solution. For accurate information on the sodium content in the solution used for dilution, refer to the package leaflet of the diluent used.

3. How to use Fluorouracil medac

If fluorouracil is used at home, it is essential to follow the doctor's, nurse's, or pharmacist's instructions. If the packaging is damaged and fluorouracil has leaked, contact a nurse or pharmacist. If fluorouracil comes into contact with the skin, wash the affected area thoroughly with water and soap and contact a doctor, nurse, or pharmacist. Do not clean up spilled fluorouracil without first contacting a nurse or pharmacist.
Fluorouracil medac is administered by intravenous injection or infusion (drip or pump). It can also be administered as an intra-arterial infusion if the patient is in the hospital.
Dosage depends on the type of cancer and whether other medicines are being administered. It also depends on blood test results and the patient's condition.
Doses of up to 15 mg/kg body weight, but not more than 1 g (1,000 mg) per day, are used.
Initially, treatment may be given at 1-day intervals or with weekly breaks. The doctor will decide on further treatment based on the patient's response to treatment.

Using more than the recommended dose of Fluorouracil medac

This medicine will be given to you by a doctor or nurse. There is a small chance that you may receive too little or too much of the medicine, but if you have any doubts, inform your doctor or nurse.
Symptoms
If you receive too much fluorouracil, you may experience nausea, vomiting, diarrhea, severe mouth ulcers, and bleeding from the stomach and intestines.
Treatment
During and after fluorouracil therapy, blood tests will be performed to check the number of cells. It may be necessary to stop using the medicine if the number of white blood cells becomes too low.
If you have any further questions about the use of this medicine, ask your doctor.

Missing a dose of Fluorouracil medac

Contact a nurse or pharmacist immediately if the required dose of the medicine is not administered or if you are taking the medicine at home and there are problems with the pump.

Stopping treatment with Fluorouracil medac

After the end of treatment, you may experience fatigue and some side effects associated with fluorouracil.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Before starting treatment, your doctor will inform you about the expected effects and potential risks associated with fluorouracil.

You should tell your doctor immediately if you experience any of the following:

• if you see blood in your stool
• if you have pain or ulcers in your mouth
• if you experience chest pain
• if you experience shortness of breath.

If severe mouth ulcers (ulcers in the mouth and/or throat), mucositis, diarrhea, neutropenia (increased risk of infection), or neurotoxicity occur during the first cycle of treatment, it may be related to DPD deficiency (see section 2: "Warnings and precautions").
Very common side effects (may affect more than 1 in 10 people):

• infections
• changes in blood cell count (decreased number of white blood cells, neutrophils, granulocytes, red blood cells, and/or platelets [in test results])
• severe decrease in the number of white blood cells in the blood
• immunosuppression
• increased uric acid levels in the blood
• abnormal ECG with signs of ischemia (insufficient blood supply to the organ, usually due to a blocked artery)
• difficulty breathing due to bronchospasm
• nasal bleeding
• gastrointestinal inflammation (esophagitis, pharyngitis, proctitis)
• loss of appetite
• watery diarrhea
• nausea
• vomiting
• hair loss
• redness on the palms of the hands and soles of the feet (palmar-plantar erythrodysesthesia syndrome)
• fever
• delayed wound healing
• fatigue
• malaise
• weakness

Diarrhea and infections occur quite frequently, but your doctor may prescribe medicines to reduce these symptoms.
Hair usually grows back after the end of fluorouracil therapy.
Fluorouracil affects blood cells, so you will need to have blood tests both during and after treatment.
Common side effects (may affect up to 1 in 10 people):

• low white blood cell count with fever
• eye inflammation
• increased heart rate (tachycardia)

Tell your doctor or nurse if you experience dizziness, rapid pulse, or shortness of breath.
Uncommon side effects (may affect up to 1 in 100 people):

• severe infections (sepsis)
• dehydration
• euphoria
• uncontrolled and rhythmic eye movements
• headache
• dizziness
• Parkinson's disease symptoms (e.g., dizziness, abnormal movements)
• neurological symptoms (pyramidal symptoms)
• drowsiness
• optic neuritis (vision disorders caused by optic nerve inflammation)
• excessive tearing
• vision changes (e.g., blurred vision, eye movement disorders, double vision, decreased visual acuity, sensitivity to light)
• blepharitis
• ectropion (outward turning of the lower eyelid)
• stenosis or blockage of the tear ducts
• irregular heartbeat, myocarditis, myocardial ischemia (reduced blood supply to the heart muscle), heart failure, myocardial infarction, cardiomyopathy, cardiac shock
• low blood pressure
• liver cell damage
• skin inflammation, redness, and rash
• skin changes (e.g., dry skin, presence of cracks and fissures, redness, itchy rash)
• photosensitivity
• hyperpigmentation or hypopigmentation of the skin
• uneven discoloration or depigmentation in the area of the veins
• nail changes (e.g., unusual blue discoloration of the nail plate, discoloration, lack of growth, pain, and thickening of the nail matrix, paronychia)
• disorders of sperm or egg production

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

• generalized allergic reaction
• severe allergic reaction (anaphylactic) or shock
• increased levels of thyroid hormones (T3 and T4)
• confusion
• brain and peripheral nerve damage
• vasculitis (inflammation of blood vessels)
• circulatory disorders (reduced blood supply to the brain, limbs, or intestines [cerebral ischemia, peripheral ischemia, intestinal ischemia], Raynaud's syndrome)
• blood clots in blood vessels, which can occur in arteries or veins (thromboembolic disease)
• phlebitis (thrombophlebitis)
• pain or discoloration along the vein into which fluorouracil was administered

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

• disorientation
• brain disease symptoms (leukoencephalopathy), e.g., uncertainty of movement, speech disorders, confusion, disorientation, weakness, loss of speech, seizures (convulsions), loss of consciousness
• sudden cardiac arrest (sudden stop of heart rhythm and function)
• sudden cardiac death (unexpected death due to heart disease)
• liver cell damage (cases leading to death)
• slowly progressing destruction of small bile ducts
• cholecystitis
• renal failure

Frequency not known (frequency cannot be estimated from the available data):

• hyperammonemic encephalopathy (brain disorders caused by increased ammonia levels)
• pericarditis (inflammation of the fibrous sac surrounding the heart)
• skin inflammation causing red, scaly patches, which may be accompanied by joint pain and fever (cutaneous lupus erythematosus)
• heart disease characterized by chest pain, shortness of breath, dizziness, fainting, and arrhythmias (stress cardiomyopathy)
• air accumulation in the intestinal wall
• a serious 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 serious complication leading to rapid breakdown of cancer cells, causing a significant increase in uric acid, potassium, and phosphate levels in the blood (tumor lysis syndrome)
• 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)
• vitamin B1 deficiency and Wernicke's encephalopathy (brain damage caused by vitamin B1 deficiency)
• inflammation of the small and large intestine, causing pain and diarrhea, which can lead to tissue death (colitis, enteritis)

Fluorouracil can cause confusion, which usually resolves after the end of treatment. You should inform your doctor if you experience this symptom.
Circulatory disorders can lead to numbness or paleness (limbs), pain (gastrointestinal tract), paralysis, or speech problems (brain).
During and after fluorouracil treatment, one or more side effects may occur. You should inform your doctor about any side effects.

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, you should tell your doctor, pharmacist, or nurse. You can also report side effects directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products: Al. Jerozolimskie 181C, PL-02-222 Warsaw, tel.: +48 22 49-21-301, fax: +48 22 49-21-309, website: https://smz.ezdrowie.gov.pl
You can also report side effects to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Fluorouracil medac

Keep this medicine out of the sight and reach of children.
Do not store above 25 °C. Do not refrigerate or freeze.
Store in the original package in a cardboard box.
Do not use this medicine after the expiry date stated on the carton. The expiry date refers to the last day of the month stated.

6. Contents of the pack and other information

What Fluorouracil medac contains

The active substance is fluorouracil. 1 ml of the solution contains 50 mg of fluorouracil.
Other ingredientsare: sodium hydroxide and water for injections.

What Fluorouracil medac looks like and contents of the pack

Fluorouracil medac, solution for injection, is a clear, colorless or almost colorless solution, stored in a colorless glass vial with a rubber stopper coated with a fluoropolymer (chlorobutyl rubber) and an aluminum cap.
Each vial contains 10 ml (20 ml or 100 ml) of the solution for injection.
1 or 10 vials in a cardboard box.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

medac
Gesellschaft für klinische Spezialpräparate mbH
Theaterstr. 6
22880 Wedel
Germany

Date of last revision of the leaflet: 11/2024

Information intended for healthcare professionals only:
Instructions for storage, use, preparation, and disposal of Fluorouracil medac
The medicine should be used immediately after preparation.
If it is not used immediately, it should be stored for no more than 24 hours at a temperature between 2 °C and 8 °C.
If a precipitate forms due to exposure to low temperature, it should be redissolved by heating the solution to 40 °C, shaking vigorously at the same time.
Before administration, the medicine should be cooled to body temperature.
The solution for injection should be prepared in a designated area, on a easily cleanable surface or on a single-use, absorbent material (paper), covered with a non-permeable plastic material. Protective eyewear, gloves, a mask, and a gown should be used. Syringes and infusion sets should be disposed of carefully to avoid any spillage. All materials used to dissolve and administer the medicine should be disposed of in accordance with the applicable procedure.
Any remaining solution after use should be disposed of. The waste disposal procedure should take into account the cytotoxic properties of the product.