DBL Fluorouracil Adverse Reactions

The ratio between effective and toxic dose is small and therapy with fluorouracil is usually accompanied by some degree of adverse effects. Adverse effects of fluorouracil mainly result from its effects on rapidly dividing cells of normal tissue and its effects on the gastrointestinal tract and haematopoietic systems (see Precautions). Patients should be carefully observed and dosage adjustment may have to be made. Deaths have reported.
Gastrointestinal: The most pronounced and dose-limiting toxic effects of fluorouracil are on the normal, rapidly proliferating tissues of the bone marrow and the lining of the gastrointestinal tract.
Nausea and vomiting occur, and may be treated symptomatically. Other reported gastrointestinal symptoms are diarrhoea, stomatitis, proctitis, melaena gastrointestinal haemorrhage, gastrointestinal ulcer and oesophagitis, therefore the dose may require adjustment or therapy may need to be discontinued. Gastrointestinal side effects may be exacerbated if fluorouracil is given with folinic acid (leucovorin) (see Precautions).
Metabolism and nutrition disorders: Dehydration, decreased appetite.
Immune system disorders: Anaphylactic reaction, hypersensitivity.
Dermatological: Alopecia^a may be seen in a substantial number of cases, but is reversible. Nail disorders^b, dermatitis^c and hyperpigmentation of the nail beds and other body areas^d have been reported. Skin rashes and fissures have been associated with fluorouracil therapy. Palmar-Plantar Erythrodysaesthesia Syndrome^e, thrombophlebitis and asymptomatic hyperpigmentation over vascular channels have also been reported. Continuous-infusion fluorouracil may increase incidence and severity of palmar-plantar erythrodysaesthesia. Photosensitivity reaction.
Haematological: Leucopenia, primarily granulocytopenia commonly occurs. The nadir for white blood cell count usually occurs from the 9^th to the 14^th day after initiation of therapy, but may occur as late as the 25^th day. The count usually returns to normal by the 30^th day, Thrombocytopenia may also occur, with the lowest platelet counts occurring from the 7^th to the 17^th day of therapy. Bone marrow failure and pancytopenia may also occur.
Cardiovascular: There have been reports of chest pain, tachycardia^f, breathlessness, arrhythmia^f, ECG changes (ST segment changes), angina pectoris^f,g, myocardial ischaemia^f, myocardial infarction^f, cardiac shock^f, cardiac failure^f, myocarditis^f, cardiomyopathy^f, pericarditis^f, thrombophlebitis and haemorrhage after administration of fluorouracil. There have been reports of sudden death in patients readministered fluorouracil after a documented cardiovascular reaction.
Ocular: Systemic fluorouracil treatment has been associated with various types of ocular toxicity. Additionally several other reports have been noted including excessive lacrimation, dacryostenosis, visual changes and photophobia.
Neurological: Combination therapy with 5-fluorouracil and levamisole has been associated with leukoencephalopathy and multifocal inflammatory leukoencephalopathy^h (MILE) (see Precautions).
Neurotoxicity^h: Disorientation, confusion, euphoria, ataxia, nystagmus, headache, slurred speech, dizziness, unsteadiness, muscular weakness, acute cerebellar syndrome and occasionally, oculomotor disturbances, have occurred in patients receiving fluorouracil. These symptoms may persist after therapy is discontinued.
Infections and Infestations: Septic shock, sepsis, neutropenic sepsis, pneumonia, superinfection, urinary tract infection, catheter-related infection, cellulitis, pharyngitis and other infections.
Other: Local injection site reaction. Fever has also been reported. Rarely, anaphylaxis or generalised allergic reactions have occurred in patients receiving fluorouracil. Pyrexia and chest pain.
^a Reversible.
^b Such as partial or complete detachment of nails.
^c Manifests often as itchy maculopapular rash on the extremities.
^d Skin hyperpigmentation also refers to asymptomatic hyperpigmentation over vascular channels.
^e Observed in patients who received 5-fluorouracil and leucovorin bolus administration.
^f Listed cardiac disorders associated with 5-fluorouracil, may lead to cardiac arrest.
^g Observed in patients receiving high dose leucovorin and 5-fluorouracil bolus and continuous infusion.
^h Symptoms may persist after therapy is discontinued.