The most common and serious side effects of fluorouracil are bone marrow toxicity and gastrointestinal symptoms.
The evaluation of undesirable effects is based on the following information on frequency: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000), Not known (cannot be estimated from the available data).
Blood and lymphatic system disorders:
Very common: Myelosuppression (leucopenia, neutropenia, thrombocytopenia), anaemia, epistaxis.
Common: Febrile neutropenia.
Very rare: Agranulocytosis, pancytopenia.
Immune system disorders:
Very common: lmmunosuppression with elevated infection rate.
Rare: Generalised allergic reactions up to anaphylactic shock.
Not known: Increase in total thyroxine (T4) and total triiodothyronine (T3) in serum without increase in free T4 and TSH and without clinical signs of hyperthyroidism.
Metabolism and nutrition disorders:
Very common: Hyperuricaemia.
Nervous system disorders:
Uncommon: Nystagmus, headache, vertigo, parkinsonian symptoms, pyramidal signs, euphoria.
Rare: Peripheral neuropathy (in combination with radiotherapy).
Very rare: Dysgeusia, (leuko-)encephalopathy with symptoms such as ataxia, speech impediments, confusion, impaired orientation, myasthenia, aphasia, seizures or coma after infusion of high doses of fluorouracil or in patients with dihydropyrimidine dehydrogenase deficiency, respectively.
Uncommon: Excessive lacrimation, blurred vision, disorders of ocular motility, optic neuritis, diplopia, reduced visual acuity, photophobia, conjunctivitis, blepharitis, ectropion due to scars, lacrimal fibroses.
Very common: ECG alterations typical for ischaemia.
Common: Angina pectoris-like chest pain.
Uncommon: Arrhythmia, myocardial infarction, myocardial ischaemia, myocarditis, cardiac insufficiency, dilative cardiomyopathy, cardiogenic shock.
Very rare: Cardiac arrest, sudden cardiac death.
Not known: Cerebral, intestinal and peripheral ischaemia, Raynaud's syndrome, thromboembolism.
Respiratory, thoracic and mediastinal disorders:
Very common: Bronchospasm.
Very common: Gastrointestinal side effects (potentially life-threatening) such as mucositis (stomatitis, pharyngitis, oesophagitis, proctitis), anorexia, (watery) diarrhoea, nausea and vomiting (see also Precautions).
Uncommon: Dehydration, sepsis as well as ulcerations and haemorrhages in the gastrointestinal tract, sloughing.
Uncommon: Liver cell damage, stoneless cholecystitis.
Very rare: Liver necroses (partially fatal).
Skin and subcutaneous tissue disorders:
Very common: Alopecia, delayed wound healing, hand-and-foot syndrome (see as follows) associated with dysaesthesia as well as reddening, swelling, pain and desquamation of the skin in palms and soles.
Uncommon: Exanthemas, skin alterations (dry skin, erosions/fissures, erythema, pruritic maculopapular rash), dermatitis, urticaria, photosensitivity, hyperpigmentation of the skin, striated hyperpigmentation or depigmentation in the area of the venous course, ungual alterations (e.g. diffuse superficial blue pigmentation, hyperpigmentation, onychodystrophy, pain and thickening of the nail bed, paronychia), onycholysis.
General disorders and administration site conditions:
Very common: Exhaustion, general asthenia, fatigue, lack of impulse, fever.
Description of selected adverse events: Blood and lymphatic system disorders:
Myelosuppression is one of the dose-limiting side effects (see also Dosage & Administration and Precautions).
The degree (NCI grades I - IV) of myelosuppression depends on the mode of administration (i.v. bolus injection or i.v. continuous infusion) and the dose.
Neutropenia occurs after each therapeutic cycle with i.v. bolus injection at adequate dose. The nadir is generally reached between the 9th and 14th day of treatment, sometimes also until the 20th day of treatment; normal values usually after day 30.
Cardiotoxic side effects mostly occur during or few hours after the first therapeutic cycle.
Patients with pre-existing coronary heart disease or cardiomyopathy are at aggravated risk of developing cardiotoxic side effects.
Gastrointestinal side effects:
The severity (NCl grades I-IV) of gastrointestinal side effects depends on the dose and the mode of administration. In i.v. continuous infusion, stomatitis more likely proves to be dose-limiting than myelosuppression.
Skin and subcutaneous tissue disorders:
The so-called hand-and-foot syndrome associated with dysaesthesia as well as reddening, swelling, pain and desquamation of the skin in palms and soles is very common after i.v. continuous infusion and common after i.v. bolus injection.