Cytarine Adverse Reactions

The following adverse events have been reported in association with cytarabine therapy.
Frequencies are defined using the following convention: 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).
Undesirable effects from cytarabine are dose-dependent. Most common are gastrointestinal undesirable effects. Cytarabine is toxic to the bone marrow, and cause haematological undesirable effects.
Infection and infestations: Uncommon: Sepsis (immunosuppression).
Blood and lymphatic system disorders: Common: Anaemia, megaloblastosis, leucopenia, thrombocytopenia.
Not known: Reticulocytopenia.
These appear to be more evident after high doses and continuous infusions; the severity depends on the dose of the drug and schedule of administration.
Gastrointestinal disorders: Common: Dysphagia, abdominal pain, nausea, vomiting, diarrhea, oral/anal inflammation or ulceration.
Uncommon: Oesophagitis, oesophageal ulceration, pneumatosis cystoides intestinalis, necrotising colitis, peritonitis.
Not known: Gastrointestinal haemorrhage, pancreatitis.
Nausea and vomiting occur and are generally more frequent following rapid intravenous infusion than with continuous IV infusion of the drug.
Skin and subcutaneous tissue disorders: Common: Reversible undesirable effects to the skin, such as erythema, bullous dermatitis, urticarial, vasculitis, alopecia.
Uncommon: skin ulceration, pruritus, burning pain of palms and soles.
Very rare: Neutrophilic eccrine hidradenitis.
Not known: Rash, freckling, skin bleeding.
Renal and urinary disorders: Common: Renal impairment, urinary retention.
Not known: Renal dysfunction.
General disorders and administration site conditions: Common: Fever, thrombophlebitis at the site of injection.
Uncommon: Cellulitis at the injection site.
Not known: Chest pain, irritation or sepsis at the injection site, mucosal bleeding.
Cardiac disorders: Uncommon: Pericarditis.
Very rare: Arrhythmia.
Hepatobiliary disorders: Common: Reversible effects on the liver with increased enzyme levels.
Not known: Hepatic dysfunction and jaundice.
Metabolism and nutrition disorders: Common: Anorexia, hyperuricaemia.
Nervous system disorders: Common: At high doses cerebellar or cerebral influence with deterioration of the level of consciousness, dysarthria, nystagmus.
Uncommon: Headache, peripheral neuropathy, paraplegia at intrathecal administration.
Not known: Dizziness, neuritis or neural toxicity and pain, neurotoxicity rash.
Eye disorders: Common: Reversible haemorrhagic conjunctivitis (photophobia, burning, visual disturbance, increased lacrimation), keratitis.
Not known: Conjunctivitis.
Respiratory, thoracic and mediastinal disorders: Uncommon: Pneumonia, dyspnea, sore throat.
Musculoskeletal and connective tissue disorders: Uncommon: Myalgia, joint pain.
A Cytarabine Syndrome (immunoallergic effect) is characterized by fever, myalgia, bone pain, occasionally chest pain, exanthema, maculopapular rash, conjunctivitis, nausea and malaise. It usually occurs 6-12 hours after administration. Corticosteroids have been shown to be beneficial in treating or preventing this syndrome. If the symptoms of the syndrome are serious enough to warrant treatment, corticosteroids should be contemplated. If treatment is effective, therapy with cytarabine may be continued.
Adverse effects due to high dose cytarabine treatment, other than those seen with conventional doses include: Blood and lymphatic system disorders: Hematological toxicity has been seen as profound pancytopenia which may last 15-25 days along with more severe bone marrow aplasia than that observed at conventional doses.
Nervous system disorders: After treatment with high doses of cytarabine, symptoms of cerebral or cerebellar influence like personality changes, affected alertness, dysarthria, ataxia, tremor, nystagmus, headache, confusion, somnolence, dizziness, coma, convulsions, etc. The incidence in elderly (>55 years) may be even higher. Other predisposing factors are impaired liver and renal function, previous CNS treatment (e.g., radiotherapy) and alcohol abuse. CNS disturbances are in the most cases reversible.
The risk of CNS toxicity increases if the cytarabine treatment - given as high dose i.v.- is combined with another CNS toxic treatment such as radiation therapy or high dose of a cytotoxic agent.
Eye disorders: Reversible corneal lesion and haemorrhagic conjunctivitis have been described. These phenomena can be prevented or decreased by installation of corticosteroid eye drops.
Gastrointestinal disorders: Especially in treatment with high doses of cytarabine, more severe reactions may appear in addition to common symptoms. Intestinal perforation or necrosis with ileus and peritonitis have been reported. Pancreatitis has also been observed after high-dose therapy.
Hepatobiliary disorders: Liver abscesses, hepatomegaly and Budd-Chiari-syndrome (hepatic venous thrombosis) have been observed after high-dose therapy.
Respiratory, thoracic and mediastinal disorders: Clinical signs as present in pulmonary oedema/ARDS may develop, particularly in high-dose therapy.
Reproductive system and breast disorders: Amenorrhoea and azoospermia.
Others: Following cytarabine therapy, cardiomyopathy and rhabdomyolysis have been reported. The gastrointestinal undesirable effects are reduced if cytarabine is administered as infusion. Local glucocorticoids are recommended as prophylaxis of haemorrhagic conjunctivitis.