50 mg / ml solution for injection / infusion
fluorouracil
What Fluorouracil Accord is and what it is used for
The name of your medicine is Fluorouracil Accord 50 mg/ml, solution for injection or infusion, but for the rest of this leaflet, it will be called Fluorouracil Accord.
What Fluorouracil Accord is
Fluorouracil Accord contains the active substance fluorouracil. It is a cancer medicine.
What Fluorouracil Accord is used for
Fluorouracil Accord is used to treat many common cancers, especially colon cancer, esophageal cancer, pancreatic cancer, stomach cancer, head and neck cancer, and breast cancer. It can be used in combination with other drugs for cancer and radiation.
Fluorouracil contained in the Fluorouracil Accord may also be approved for the treatment of other diseases not mentioned in this leaflet. Ask your doctor, pharmacist, or other healthcare professional if you have any further questions, and always follow their instructions.
What you need to know before using Fluorouracil Accord
Do not use Fluorouracil Accord
- If you are allergic (hypersensitive) to fluorouracil or any of the other ingredients of Fluorouracil Accord (listed in section 6).
- If you have a serious infection (eg herpes zoster, chickenpox).
- If your tumor is not malignant.
- If you are severely weakened by long-term illness.
- If your bone marrow has been damaged by other treatments (including radiation).
- If you are taking brivudine, sorivudine, or analogs (medicines for viral diseases).
- If you are pregnant or breastfeeding.
- If you have severe hepatic impairment.
- If you have identical pairs of dihydropyrimide dehydrogenase (DPD ) enzyme genes.
- If you know that you are completely devoid of enzyme activity a dihydropyrimide dehydrogenase (DPD) (total DPD deficiency).
Warnings and cautions
Talk to your doctor, pharmacist, or nurse before using Fluorouracil Accord. Take special care with Fluorouracil Accord:
- if you have too few white blood cells (you will have to take blood samples to check this)
- if you have a sore mouth, fever or bleeding somewhere or feel weak (these symptoms may be because your blood contains a very low number of blood cells )
- if you have kidney problems
- if you have liver problems, including jaundice (yellowish skin)
- if you have heart problems. Tell your doctor if you feel chest pain during treatment.
- if you have decreased activity or a deficiency of DPD enzyme (dihydropyrimide dehydrogenase).
- if you have received high doses of radiation in the pelvic area.
- if you have gastrointestinal side effects ( stomatitis, diarrhea, gastrointestinal bleeding) or bleeding anywhere.
- if you know that the enzyme dihydropyrimide dehydrogenase (DPD) is partially inactive in you.
- if you have heart problems. Tell your doctor if you feel chest pain during treatment.
- if the enzyme a dihydropyrimide dehydrogenase (DPD) is partially or completely inactive in someone in your family.
DPD Deficiency: DPD deficiency is a congenital condition that is not usually associated with health problems unless you use certain medications. If you have DPD deficiency and are taking Fluorouracil Accord, you have an increased risk of serious side 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, do not take Fluorouracil Accord. If you have reduced enzyme activity ( partial deficiency), your doctor may prescribe a lower dose. Serious and life-threatening side effects may still occur even if your test result for DPD deficiency is negative.
Contact healthcare professionals immediately if you experience the following signs or symptoms: new onset of confusion, disorientation or otherwise altered mental status, problems with balance or coordination, visual disturbances. These can be signs of brain disease that can lead to coma and death if left untreated.
Other medicines and Fluorouracil Accord
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
- Methotrexate (an anticancer medicine)
- Metronidazole (an antibiotic/infectious drug)
- Calcium leucovorin (also called calcium folinate – used to reduce the harmful effects of anticancer medicines)
- Allopurinol (used to treat gout )
- Cimetidine (used to treat stomach ulcers )
- Warfarin (used to treat blood clots)
- Interferon-alpha 2a; brivudine, sorivudine and its analogs (medicines for viral diseases)
- Cisplatin (an anti-cancer drug)
- Phenytoin (used to treat epilepsy/seizures and irregular heartbeat)
- Vaccines
- Vinorelbine (an anticancer medicine)
- Cyclophosphamide (an anticancer medicine)
- Levamisole (a medicine used to treat machine infection)
- Tamoxifen (an anticancer medicine)
The above drugs affect the action of fluorouracil.
Pregnancy, breastfeeding, and fertility
You must not take this medicine if you are pregnant or planning to become pregnant. If you are a woman of childbearing potential, you must use an effective method of contraception while you are taking this medicine and for at least 6 months afterward. If you become pregnant during treatment, you must inform your doctor and should take advantage of the opportunity for genetic counseling.
As it is not known whether fluorouracil is excreted in human milk, breast-feeding must be discontinued if the mother is treated with drugs containing fluorouracil.
If you are a man, you should avoid becoming the father of a child during treatment and for 6 months afterward. You are advised to apply for sperm preservation before treatment as there is a possibility that treatment with Fluorouracil Accord causes persistent infertility.
Ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines
Fluorouracil can cause side effects such as nausea and vomiting. Therefore do not drive and do not use machines. It can also have unwanted effects on the nervous system and vision changes. You should not drive or use machines if you have these symptoms.
You are responsible for assessing whether you are fit to drive a motor vehicle or perform work that requires increased vigilance. One of the factors that can affect your ability in these respects is the use of drugs due to their effects and/or side effects. Descriptions of these effects and side effects can be found in other sections. Read all the information in this leaflet for guidance. If you are not sure, talk to your doctor or pharmacist.
Fluorouracil Accord contains sodium
Fluorouracil Accord contains 7.78 mmol (178.2 mg) sodium per maximum daily dose (600 mg / m 2 ). This should be considered by patients on a low-salt diet.
3. How to use Fluorouracil Accord
The dose of medicine you receive depends on your medical condition, your body weight, whether you have recently had surgery, and how well your liver and kidneys are functioning. It also depends on your blood test results. Your first course of treatment may consist of a daily dose or one dose a week.
Additional treatment regimens may be given depending on how you respond to the treatment. You can also get the medicine in combination with radiation therapy.
The medicine can be diluted with a glucose solution, sodium chloride solution, or water for injections before you get it. You receive the medicine in a vein, either as a regular injection or as a slow drip ( infusion ).
If you take more Fluorouracil Accord then you should
This medicine is given to you under medical supervision, so it is unlikely that you will get too little or too much. If you still have questions, or if e.g. a child ingested the medicine by mistake, contact a doctor, hospital, or the Poison Information Center for risk assessment and advice.
Blood samples will be taken during and after treatment with Fluorouracil Accord to check the number of white blood cells. Treatment may need to be stopped if the number of white blood cells becomes too low.
The following symptoms may occur in patients who have received too much fluorouracil: Nausea, vomiting, diarrhea, severe mucositis (ulcers in the oral mucosa), and ulcers or bleeding in the gastrointestinal tract. If you have any further questions on the use of this product, ask your doctor.
4. Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
If any of the following occur, tell your doctor immediately:
- severe allergic reaction – you may suddenly have an itchy rash ( hives ), swelling of your hands, feet, ankles, face, lips, mouth, or throat (which may make it difficult to swallow or breathe) and you may feel dizzy
- chest pain
- your stool is bloodstained or black
- you get a sore mouth or a sore mouth
- numbness, tingling, or tremors in the hands or foot pulse increase and you feel short of breath
- you feel confused or unsteady on your feet, have problems with coordination in arms and legs, difficulty thinking / speaking, problems with vision/memory
- chest pain
- shortness of breath.
These are serious side effects. You may need urgent medical attention.
| Very common side effects (may affect more than 1 user in 10): | ||
|---|---|---|
| • ECG changes of the ischemic type (caused by lack of oxygen) | • Neutropenia (abnormally low levels of neutrophils, a type of white blood cell, in the blood) | • Leukopenia (abnormally low white blood cell count ) |
| • Anemia (lack of red blood cells in the circulation) • High fever and a drastic reduction of neutrophils, a type of white blood cell, in the blood • Inflammation of the rectum or rectal opening | Pancytopenia (drastic reduction or cessation of bone marrow blood cell production) • Inflammation of the mucous membranes of the oral cavity and gastrointestinal tract • Loss of appetite | Reduced blood cell production • Pharyngitis ( inflammation of the lining of the throat) • Watery diarrhea • Hair loss (especially in women) • Hand-foot syndrome; a harmful skin reaction • Fatigue |
| • Nausea • Delayed wound healing Weakness • Inflammation in any part of the oral mucosa Elevated levels of uric acid in the blood | • Vomiting • Nasal blood • Inflammation of the esophagus • Infection is |
| Common side effects are (may affect up to 1 in 10): |
|---|
| • Angina pectoris (chest pain: severe chest pain due to the insufficient blood supply to the heart)Low white blood cell count with fever |
| Uncommon side effects (may affect up to 1 in 100 people): | ||
|---|---|---|
| • Abnormal heart rhythm | • Heart attack | • Myocardial ischemia (decreased oxygen supply to the heart muscle) |
| • myocarditis ( inflammation of the heart muscle) | • Heart failure | Dilated cardiomyopathy (enlarged, thickened, and/or hardened heart muscle) |
| • Shock caused by severe heart failure | • Low blood pressure | • Sleepiness |
| • Dehydration | • Infection, caused by bacteria, in the blood or body tissues | • Ulcers or bleeding in the gastrointestinal tract, skin flaking |
| • Involuntary twitching eye movements | • Headache | The feeling of imbalance and instability |
| • Symptoms similar to those of Parkinson’s disease (a progressive movement disorder characterized by tremors, stiffness, slow movements) | • Pyramidal symptoms (such as loss of fine motor skills and reflex disorders) | • Feeling of well-being |
| • Skin inflammation | • Skin changes, e.g. dry skin, cracks, skin loss, redness, itchy maculopapular rash (a rash that started on the legs and continued to the arms and then up to the chest) | • A skin rash that accompanies certain infectious diseases |
| • Emergence of itchy streaks on the skin | • Light sensitivity | • Hyperpigmentation |
| Streaked hyperpigmentation or depigmentation near the veins | • Nail changes (eg diffuse superficial blue pigmentation, hyperpigmentation, nail dystrophy (a condition that makes nails thin, uneven, and sometimes bent in two different directions), pain and thickening of the nail bed a | • Paronychia ( inflammation in the tissue around fingernail) |
| • Connective tissue inflammation in the nail with wart formation and nail loss | Disrupted sperm or egg production | |
| • Increased tear flow | • Blurred vision | • inflammation or redness on the membrane (conjunctiva) covering the white of the eye and the back of the lid. |
| • Disorder of the eye movements | • Optic neuritis (visual disturbance caused by inflammation of the optic nerve ) | • Double vision |
| • Decreased visual acuity | • Extreme light sensitivity and avoidance of sunlight and brightly lit places | • Eye disease with chronic inflammation of the eyelid stripe |
| • The lower eyelid is facing outwards | • Blocked tear ducts | • Layer or mass of dead tissue separated from surrounding living tissue, such as in wounds, injury, or inflammation. |
| • Damage to liver cells• Euphoria/elation |
| Rare side effects (may affect up to 1 in 1,000 people): | ||
|---|---|---|
| Insufficient blood supply to the brain, intestines, and peripheral organs | Discoloration of fingers and toes, and in some cases also other parts of the body | Generalized allergic reaction occurrence of a blood clot in artery or vein |
| Swelling ( inflammation ) in the vein caused by a blood clot | Severe allergic reaction involving the whole body ( anaphylaxis ) | Dilation of blood vessels throughout the body with a drop in blood pressure as a result |
| Confusion states can occur which then disappear | Increase in T4 (total thyroxine ), increase in T3 (total triiodothyronine) |
| Very rare side effects are (may affect up to 1 in 10 000 users): | ||
|---|---|---|
| • Cardiac arrest (sudden cessation of heartbeat and heart function) | • Sudden cardiac death (unexpected death due to heart problems) | Symptoms such as leukoencephalopathy (a disease affecting the white matter of the brain) including ataxia (loss of muscle coordination ability) |
| • Difficulty articulating words | • Confusion | |
| • Mental confusion or impaired awareness, especially about time, space, and identity | • Acute cerebellar syndrome | • Abnormal muscle weakness or muscle fatiguePartial or total loss of the ability to use or understand the language. |
| • Seizures or coma in patients receiving high- dose 5-fluorouracil and in patients with dihydropyrimidine dehydrogenase deficiency | • Kidney failure | • Damage to liver cells (isolated cases with fatal outcome)• Disorientation |
| • Inflammation of the gallbladder | Slow increasing degradation of the small bile ducts | • Cardiac arrest |
Has been reported (occurs in an unknown number of users):
- fever
- numbness or weakness in the arms and legs
- discoloration of the vein at the injection site
- high heart rate and shortness of breath
- hyperammonemia encephalopathy (an impaired function of the brain due to increased levels of ammonia)
5. How to store Fluorouracil Accord
- Keep this medicine out of the sight and reach of children.
- Do not use this medicine after the expiry date which is stated on the label and carton after EXP. The expiration date is the last day of the specified month.
- Do not store above 25 ° C. Store in a cold place. Do not freeze.
- Store the bottle in the outer carton. Sensitive to light.
- For single use only. Discard unused
Shelf life after dilution
Chemical and physical in-use stability has been demonstrated for 24 hours at 25 ° C with 5% glucose solution or 0.9% sodium chloride solution or water for injections with a fluorouracil concentration of 0.98 mg/ml. From a microbiological point of view, however, the solution should be used immediately. If the solution is not used immediately, the user is responsible for the storage conditions and the length of the storage time for the product during use.
- The product should be discarded if it appears brown or dark yellow in the solution.
- Do not use the product if the bottle is damaged or particles/crystals are visible.
- Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.
6. Contents of the packaging and other information
Content declaration
The active substance in Fluorouracil Accord is fluorouracil.
The other ingredients are water for injections, sodium hydroxide, and hydrochloric acid.
What the medicine looks like and the contents of the pack
1 ml of solution contains 50 mg of fluorouracil (in the form of sodium salt formed in situ ).
Fluorouracil Accord for injection and infusion is a clear, colorless, or almost colorless solution in a Type I clear glass bottle with a rubber seal.
One 5 ml vial contains 250 mg of fluorouracil.
One 10 ml vial contains 500 mg of fluorouracil.
One 20 ml vial contains 1000 mg of fluorouracil.
One 50 ml vial contains 2500 mg of fluorouracil.
One 100 ml vial contains 5000 mg of fluorouracil.
Not all pack sizes may be marketed.
Marketing Authorization Holder and Manufacturer
Marketing Authorisation Holder
Accord Healthcare BV
Winthontlaan 200
3526 KV Utrecht
Netherlands
Manufacturer
Accord Healthcare Limited
Sage House,
319 Pinner Road,
North Harrow,
Middlesex,
HA1 4HF,
UK
Accord Healthcare Polska Sp.z oo,
ul. Lutomierska 50,95-200 Pabianice, Poland