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FLUOROURACIL is a brand name for Fluorouracil. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Fluorouracil Injection 25 mg/ml, solution for injection, may be used alone or in combination, for its palliative action in the management of common malignancies particularly cancer of the colon and breast, either as single agent or in combination with other cytotoxic agents.
Verbatim from this product's MHRA label. Tap a section to expand.
Routes of administration:
Fluorouracil Injection can be given by intravenous injection or intravenous or intra- arterial infusion.
Adults:
Selection of an appropriate dose and treatment regime depends upon the condition of the patient, the type of carcinoma being treated and whether fluorouracil is to be administered alone or in combination with other therapy. 8 – 1 gram.
It is customary to calculate the dose in accordance with the patient’s actual bodyweight unless there is obesity, oedema or some other form of abnormal fluid retention such as ascites. In this case, ideal weight is used as the basis for calculation.
Reduction of the dose is advisable in patients with any of the following: 1. Cachexia. 2. Major surgery within preceding 30 days. 3. Reduced bone marrow function. 4. Impaired hepatic or renal function.
ADULT DOSE:
The following regimens have been recommended for use as a single agent: Initial Treatment: This may be in the form of an infusion or an injection, the former usually being preferred because of lesser toxicity. 9 % NaCl injection and given over 4 hours.
Alternatively the daily dose may be infused over 30 – 60 minutes or may be given as a continuous infusion over 24 hours. The infusion may be repeated daily until there is evidence of toxicity or a total dose of 12 – 15 g has been reached.
Intravenous Injection: 12 mg/kg bodyweight may be given daily for 3 days and then, if there is no evidence of toxicity, 6 mg/kg on alternate days for three further doses. An alternative regime is 15 mg/kg as a single intravenous injection once a week throughout the course.
5 mg/kg bodyweight daily may be given by 24-hour continuous intra-arterial infusion.
Maintenance Therapy:
An initial intensive course may be followed by maintenance therapy providing there are no significant toxic effects. In all instances, toxic side effects must disappear before maintenance therapy is started. The initial course of fluorouracil can be repeated after an interval of 4 – 6 weeks from the last dose or, alternatively, treatment can be continued with intravenous injections of 5 – 15 mg/kg bodyweight at weekly intervals.
Summary of the safety profile The most commonly reported undesirable effects are gastrointestinal complaints like diarrhoea, nausea and mucositis. Leukopenia is also very common and the precautions described above should be followed.
Frequency assessment:
Very common (≥ 1/10) Common (≥ 1/100, < 1/10) Uncommon (≥ 1/1,000, < 1/100) Rare (≥ 1/10,000, < 1/1,000) Very rare (< 1/10,000), not known Infections and infestations Very common Infections Uncommon Sepsis Blood and lymphatic system disorders Very common Myelosuppression (Onset: 7-10 days, Nadir: 9-14 days, Recovery: 21-28 days), neutropenia, leukopenia, granulocytopenia, thrombocytopenia, agranulocytosis, anemia, pancytopenia Common Febrile Neutropenia Immune system disorders Very common Immunosuppression Rare Generalized allergic reactions, anaphylactic reaction, anaphylactic shock Endocrine disorders Rare Increase of T4 (total thyroxin), increase of T3 (total trijodthyronin) Metabolism and nutrition disorders Very common Hyperuricemia Uncommon Dehydration Not known Lactic acidosis, tumour lysis syndrome, hypertriglyceridaemia, vitamin B1 deficiency Psychiatric disorders Uncommon Euphoria Rare Confusion Very rare Disorientation Nervous system disorders Uncommon Nystagmus, headache, dizziness, symptoms of Parkinson's disease, pyramid signs, somnolence, opticus neuritis Rare Extrapyramidalmotoric disturbances, cerebellar disturbances, cortical disturbances, peripheral neuropathy Very rare leuko-encephalopathy including ataxia, acute cerebellar syndrome, dysarthria, confusion, disorientation, myasthenia, aphasia, convulsion or coma Not known Hyperammonaemic encephalopathy, posterior reversible encephalopathy syndrome (PRES), Wernicke’s encephalopathy Eye disorders Common Conjunctivitis Uncommon Excessive lacrimation, blurred vision, eye movement disturbance, diplopia, decrease in visual acuity, photophobia, blepharitis, ectropion, dacryostenosis Cardiac disorders Very common Ischaemic ECG abnormalities Common Angina pectoris-like chest pain, tachycardia Uncommon Arrhythmia, myocarditis, myocardial ischaemia, cardiac failure, myocardial infarction, dilatative cardiomyopathy, cardiac shock Very rare Cardiac arrest, sudden cardiac death Not known Pericarditis, stress cardiomyopathy (takotsubo syndrome) Vascular disorders Uncommon Hypotension Rare Vasculitis, cerebral ischaemia, intestinal ischaemia, peripheral ischaemia, Raynaud’s phenomenon, thromboembolism, thrombophlebitis/vein tracking Respiratory, thoracic and mediastinal disorders Very common Bronchospasm, epistaxis Uncommon Dyspnea Gastrointestinal disorders Very common Gastrointestinal adverse events are very common and may be life-threatening.
It is recommended that fluorouracil should only be given by, or under the strict supervision of, a qualified physician who is conversant with the use of potent antimetabolites and has the facilities for regular monitoring of clinical, biochemical and haematological effects during and after administration.
All patients should be admitted to hospital for initial treatment. The ratio between effective and toxic dose is small and therapeutic response is unlikely without some degree of toxicity. Care must be taken therefore, in the selection of patients and adjustment of dosage.
Treatment should be stopped in case of severe toxicity. Haematotoxicity Adequate treatment with fluorouracil is usually followed by leukopenia, the lowest white blood cell (WBC) count commonly being observed between the 7th and 14th day of the first course, but occasionally being delayed for as long as 20 days.
The count usually returns to normal by the 30th day. Daily monitoring of platelet and WBC count is recommended and treatment should be stopped if platelets fall below 100,000 per mm³ or the WBC count falls below 3,500 per mm³. If the total count is less than 2,000 per mm³, and especially if there is granulocytopenia, it is recommended that the patient be placed in protective isolation in the hospital and treated with appropriate measures to prevent systemic infection.
Gastrointestinal toxicity Treatment should also be stopped at the first sign of oral ulceration or if there is evidence of gastrointestinal side effects such as stomatitis, diarrhoea, bleeding from the GI tract or haemorrhage at any site.
Cardiotoxicity Cardiotoxicity has been associated with fluoropyrimidine therapy, including myocardial infarction, angina, arrhythmias, myocarditis, cardiogenic shock, sudden death, stress cardiomyopathy (takotsubo syndrome) and electrocardiographic changes (including very rare cases of QT prolongation).
g. 5 for drug interaction).
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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This sequence constitutes a course of therapy. Some patients have received up to 30 g at a maximum rate of 1 g daily. A more recent alternative method is to give 15 mg/kg IV once a week throughout the course of treatment. This obviates the need for an initial period of daily administration.
In combination with Irradiation:
Irradiation combined with fluorouracil has been found to be useful in the treatment of certain types of metastatic lesions in the lungs and for the relief of pain caused by recurrent, inoperable growth. The standard dose of fluorouracil should be used.
CHILDREN:
No recommendations are made regarding the use of fluorouracil in children.
ELDERLY:
Fluorouracil should be used in the elderly with similar considerations as with normal adult doses.
Mucositis (stomatitis, oesophagitis, pharyngitis, proctitis), anorexia, watery diarrhoea, nausea, vomiting Uncommon Gastrointestinal ulceration, gastrointestinal hemorrhage Not known Pneumatosis intestinalis, enterocolitis, colitis (including necrotising colitis) Hepatobiliary disorders Uncommon Liver cell damage Very rare Liver necrosis (cases with fatal outcome), biliary sclerosis, cholecystitis Skin and subcutaneous tissue disorders Very common Alopecia, palmar-plantar erythrodysaesthesia syndrome (hand-foot syndrome) has been noted with protracted and high dose continuous infusion.
The syndrome begins with dysaesthesia of the palms and soles that progress to pain and tenderness. There is associated symmetrical swelling and erythema of the hand and foot. g. g. diffuse superficial blue pigmentation, nail hyperpigmentation, nail dystrophy, pain and thickening of the nail bed, paronychia), onycholysis, recall phenomenon Not known Cutaneous lupus erythematosus Renal and urinary disorders Very rare Renal failure Reproductive system and breast disorder Uncommon Spermatogenesis and ovulation disorder General disorders and administration site conditions Very common Fever, delayed wound healing, fatigue, malaise, weakness Not known Local reaction caused by extravasation (pain, swelling, erythema) Description of selected adverse reactions Cardiotoxic adverse events mostly occur during or within hours following the first treatment cycle.
There is an increased risk of cardiotoxicity in patients with previous coronary heart disease or cardiomyopathy. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play Apple App Sore.
These adverse events are more common in patients receiving continuous infusion of 5-fluorouracil rather than bolus injection. Prior history of coronary artery disease may be a risk factor for some cardiac adverse reactions. Care should therefore be exercised in treating patients who experienced chest pain during courses of treatment, or patients with a history of heart disease.
Cardiac function should be regularly monitored during treatment with fluorouracil. In case of severe cardiotoxicity the treatment should be discontinued. Encephalopathy Cases of encephalopathies (including hyperammonaemic encephalopathy, leukoencephalopathy, posterior reversible encephalopathy syndrome [PRES], Wernicke’s encephalopathy) associated with 5-fluorouracil treatment have been reported from post-marketing sources.
Signs or symptoms of encephalopathy are altered mental status, confusion, disorientation, coma or ataxia. If a patient develops any of these symptoms withhold treatment and test serum ammonia and vitamin B1 levels immediately. In case of elevated serum ammonia levels or vitamin B1 deficiency initiate appropriate therapy.
Hyperammonaemic encephalopathy often occurs together with lactic acidosis. Caution is necessary when administering fluorouracil to patients with renal and/or hepatic impairment. Patients with impaired renal and/or hepatic function may have an increased risk for hyperammonaemia and hyperammonaemic encephalopathy.
Tumour lysis syndrome Cases of tumour lysis syndrome associated with fluorouracil treatment have been reported from post-marketing sources. g. with renal impairment, hyperuricemia, high tumour burden, rapid progression) should be closely monitored.
g. hydration, correction of high uric acid levels) should be considered. 2). Patients with DPD deficiency are therefore at increased risk of fluoropyrimidines- related toxicity, including for example stomatitis, diarrhoea, mucosal inflammation, neutropenia and neurotoxicity.
DPD-deficiency related toxicity usually occurs during the first cycle of treatment or after dose increase. 5% of Caucasians). 3). Partial DPD deficiency Partial DPD deficiency is estimated to affect 3-9% of the Caucasian population. Patients with partial DPD deficiency are at increased risk of severe and potentially life-threatening toxicity.
A reduced starting dose should be considered to limit this toxicity. DPD deficiency should be considered as a parameter to be taken into account in conjunction with other routine measures for dose reduction. Initial dose reduction may impact the efficacy of treatment.
In the absence of serious toxicity, subsequent doses may be increased with careful monitoring. Testing for DPD deficiency Phenotype and/or genotype testing prior to the initiation of treatment with Fluorouracil Injection 25 mg/ml is recommended despite uncertainties regarding optimal pre-treatment testing methodologies.
Consideration should be given to applicable clinical guidelines. Impaired kidney function can lead to increased blood uracil levels resulting in an increased risk for misdiagnosis in patients with DPD deficiency with moderate or severe renal impairment.
Genotypic characterisation of DPD deficiency Pre-treatment testing for rare mutations of the DPYD gene can identify patients with DPD deficiency. 1236G>A/HapB3 can cause complete absence or reduction of DPD enzymatic activity. Other rare variants may also be associated with an increased risk of severe or life-threatening toxicity.
Certain homozygous and compound heterozygous mutations […]