Fluorouracil

Registered South African indications:

• Carcinoma of the breast 
• Carcinoma of gastro-intestinal tract
• Hepatoma
• Carcinoma of the ovary
• Carcinoma of the cervix
• Carcinoma of the urinary bladder
• Carcinoma of the prostate
• Carcinoma of the pancreas
• Carcinoma of the oropharyngeal areas

Contraindications

• Hypersensitivity to the active ingredient or any of the excipients
• Pregnancy
• Breastfeeding
• Seriously debilitated patients
• Suffering from bone marrow depression after radiotherapy or treatment with other antineoplastic agents
• Potentially serious infection
• Not for management of non-malignant disease
• Poor nutritional states
• Known complete absence of dihydropyrimidine dehydrogenase (DPD) activity
• Have been treated with brivudine, sorivudine or their chemically related analogues, which are potent inhibitors of the enzyme dihydropyrimidine dehydrogenase (DPD), which degrades fluorouracil. Fluorouracil must not be taken within 4 weeks of treatment with brivudine, sorivudine or their chemically related analogues

Cautions

• Renal impairment
• Hepatic impairment
• Elderly
• Recent major surgery
• History of cardiac disease and risk factors thereof
• Encephalopathy
• Patients who have had high-dose pelvic radiation
• Patients on a controlled sodium diet
• Coadministration with folinic acid
• Live vaccines
• Should be administered under the supervision of an experienced cancer chemotherapy physician

Forms avail. in SA and covered in this monograph: inj

Carcinoma of the breast
Carcinoma of gastro-intestinal tract
Hepatoma
Carcinoma of the ovary
Carcinoma of the cervix
Carcinoma of the urinary bladder
Carcinoma of the prostate
Carcinoma of the pancreas
Carcinoma of the oropharyngeal areas

Consult specialist for dosages and regimens

Not established for use in children

Pregnancy

• Contraindicated
• There are no adequate and well-controlled studies in pregnant women, however, foetal defects and miscarriages have been reported
• Women of childbearing potential should be advised to avoid becoming pregnant and use an effective method of contraception during treatment with fluorouracil and up to 6 months afterward
• If the drug is used during pregnancy, or if the patient becomes pregnant while taking the drug, the patient should be fully informed of the potential hazard to the foetus and genetic counseling is recommended
• Fluorouracil should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus

Breastfeeding

• Contraindicated
• Since it is not known whether fluorouracil passes into breast milk, breast-feeding must be discontinued if the mother is treated with fluorouracil

Fertility

• Men treated with fluorouracil are advised not to father a child during and for up to 6 months following cessation of treatment. Advice on conservation of sperm should be sought prior to treatment because of the possibility of irreversible infertility due to therapy with fluorouracil

Renal Impairment

• Caution; dose adjustment recommended
• Consult Oncology specialist for any possible dose adjustments and regimens

Hepatic Impairment

• Caution; dose adjustment recommended

Elderly

• Caution; no dose adjustment recommended

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Euphoria
• Confusional state 
• Disorientation
• Nystagmus
• Headache
• Dizziness
• Symptoms of Parkinson's disease
• Pyramidal signs
• Somnolence
• Encephalopathy
• Ataxia
• Acute cerebellar syndrome
• Dysarthria
• Myasthenia
• Aphasia
• Convulsion 
• Coma
• Peripheral neuropathy 

Cardiovascular Disorders

• Cerebral ischaemia
• Intestinal ischaemia
• Peripheral ischemia
• Raynaud's syndrome
• Thromboembolism
• Thrombophlebitis
• Hypotension
• ECG changes
• Angina pectoris-like chest pain
• Arrhythmia
• Myocardial infarction
• Myocardial ishchaemia dilative cardiomyopathy
• Cardiac arrest 
• Sudden cardiac death

Gastrointestinal Disorders

• Diarrhoea
• Nausea and vomiting 
• Anorexia 
• Stomatitis 
• Proctitis
• Oesophagitis
• Gastrointestinal ulcerations
• Gastrointestinal bleeding 

Skin and Subcutaneous Tissue Disorders

• Alopecia 
• Palmar-plantar erythrodysesthesia syndrome 
• Dermatitis
• Pigmentation
• Changes in nails 
• Dry skin
• Fissure erosion
• Erythema
• Pruritic maculopapular rash
• Exanthema
• Photosensitivity
• Hyperpigmentation of the skin
• Streaky hyperpigmentation 
• Depigmentation near the veins

Immune, Blood and Lymphatic System Disorders

• Myelosuppression
• Leucopenia
• Pancytopenia 
• Thrombocytopenia
• Agranulocytosis
• Anaemia
• Hypersensitivity reactions
• Anaphylactic reactions
• Allergic reactions

Sensory Disorders

• Ocular toxicity
• Excessive lacrimation
• Dacryostenosis
• Visual changes 
• Photophobia

Others

• Weakness
• Fever
• Vein discolouration proximal to injection sites

• Folinic acid
• Leucovorin
• Nucleoside analogues
• Sorivudine 
• Brivudine
• Antimetabolites (e.g. methotrexate)
• Metronidazole
• Cimetidine
• Warfarin 
• Levamisole 
• Phenytoin 
• Clozapine
• Interferon alfa
• Allopurinol
• Thiazide diuretics
• Myelosuppressive agents
• Live vaccines
• Poliomyelitis virus
• Cisplatin
• Cytostatic agents and irradiation therapy
• Vinorelbine

• Full blood count

Specific cases may require

• Renal function
• Hepatic function

Injection 50mg/ml - EML (Section 21) 

• This drug should be administered only under the supervision of a qualified physician with extensive experience in cytotoxic treatment

Fluorouracil is a pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. Fluorouracil may also interfere with RNA synthesis.

Injection (per ml) 50mg

• Abic Fluorouracil (Pharmachemie)
• 5-Fluorouracil-Faulding (Pharmaplan)
• Floracor (Accord)
• Fluracedyl (Teva Pharmaceuticals)

Injection (per 5ml) 250mg

• Fluracedyl 250 Mg (Teva Pharmaceuticals)

Injection (per 10ml) 500mg

• Abic Fluorouracil (Pharmachemie)
• Fluroblastin (Pfizer) originator 
• Fluracedyl (Teva Pharmaceuticals)

Injection (per 20ml) 1000mg

• Fluracedyl 1000 Mg (Teva Pharmaceuticals)

Injection (per 100ml) 5000mg

• Fluracedyl 5000 Mg (Teva Pharmaceuticals)

Also available in the following form: Ointment