Arasid-100/Arasid-500/Arasid-1000 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 gastro-intestinal undesirable effects. Cytarabine is toxic to the bone marrow, and causes haematological undesirable effects.
Infections and infestations: Uncommon: Sepsis (immunosuppression), cellulitis at injection site.
Not Known: Pneumonia, liver abscess.
Neoplasm benign, malignant and unspecified (Incl. cysts and polyps): Uncommon: Lentigo.
Blood and lymphatic system disorders: Common: Anaemia, megaloblastosis, leucopenia, thrombocytopenia.
Not Known: Reduced reticulocytes.
The severity of these reactions is dose and schedule dependent. Cellular changes in the morphology of bone marrow and peripheral smears can be expected.
Immune system disorders: Uncommon: Anaphylaxis.
Not known: Allergic oedema.
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.
Not known: Neural toxicity, neuritis, dizziness.
Eye disorders: Common: Reversible haemorrhagic conjunctivitis (photophobia, burning, visual disturbance, increased lacrimation), keratitis.
Not known: Conjunctivitis (may occur with rash).
Cardiac disorders: Uncommon: Pericarditis.
Very rare: Arrhythmia.
Respiratory, thoracic and mediastinal disorders: Uncommon: Pneumonia, dyspnea, sore throat.
Gastrointestinal disorders: Common: Dysphagia, abdominal pain, nausea, vomiting, diarrhoea, oral/anal inflammation or ulceration.
Uncommon: Esophagitis, esophageal ulceration, pneumatosis cystoides intestinalis, necrotising colitis, peritonitis.
Not known: Pancreatitis.
Hepatobiliary disorders: Common: Reversible effects on the liver with increased enzyme levels.
Uncommon: Jaundice.
Not known: Hepatic dysfunction.
Skin and subcutaneous tissue disorders: Common: Reversible undesirable effects to the skin, such as erythema, bullous dermatitis, urticaria, vasculitis, alopecia.
Uncommon: Skin ulceration, pruritus, burning pain of palms and soles.
Very rare: Neutrophilic eccrine hidradenitis.
Not known: Freckling, rash.
Musculoskeletal and connective tissue disorders: Uncommon: Myalgia, arthralgia.
Renal and urinary disorders: Common: Renal impairment, urinary retention.
General disorders and administration site conditions: Common: Fever, thrombophlebitis at the injection site.
Uncommon: Chest pain.
Cytarabine (Ara-C) Syndrome: (Immunoallergic effect): Fever, myalgia, bone pain, occasional chest pain, exanthema, conjunctivitis and nausea may occur 6-12 h after start of therapy. Corticosteroids may be considered as prophylaxis and therapy. If they are effective, therapy with cytarabine may be continued.
Adverse effects due to high dose cytarabine treatment, other than those seen with conventional doses include: Hematological toxicity: Seen as profound Pancytopenia which may last 15-25 days along with more severe bone marrow aplasia than that observed at conventional doses.
Infections and infestations: Sepsis, liver abscess.
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. appear in 8-37 % of treated patients. Peripheral motor and sensory neuropathies have also been reported with high dose therapy. 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.-combined with another CNS toxic treatment such as radiation therapy or high dose.
Corneal and conjunctival toxicity: Reversible lesion of corneal and haemorrhagic conjunctivitis have been described. These phenomena can be prevented or decreased by installation of corticosteroid eye drops.
Skin and subcutaneous tissue disorders: Skin rash leading to desquamation, alopecia.
Viral, bacterial, fungal, parasitic, or saprophytic infections, in any location in the body, may be associated with the use of Cytarabine alone or in combination with other immunosuppressive agents following immunosuppressant doses that affect cellular or humoral immunity. These infections may be mild, but can be severe.
A Cytarabine syndrome has been described. It is characterised by fever, myalgia, bone pain, occasionally chest pain, maculopapular rash, conjunctivitis and malaise. It usually occurs 6-12 hours following drug 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 as well as continuation of therapy with Cytarabine.
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.
Liver abscesses, hepatomegaly, Budd-Chiari-syndrome (hepatic venous thrombosis) and pancreatitis 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. The reaction is probably caused by an alveolar capillary injury. It is difficult to make an assessment of frequencies (stated as 10-26 % in different publications), since the patients usually have been in relapse where other factors may contribute to this reaction.
Others: Following cytarabine therapy, cardiomyopathy and rhabdomyolysis have been reported. One case of anaphylaxis that resulted in cardiopulmonary arrest and required resuscitation has been reported. This occurred immediately after the intravenous administration of cytarabine.
The gastro-intestinal undesirable effects are reduced if cytarabine is administered as infusion. Local glucocorticoids are recommended as prophylaxis of haemorrhagic conjunctivitis.
Amenorrhoea and azoospermia (See Use in Pregnancy & Lactation).
Cytarabine is not recommended for intrathecal use; however, the following side-effects have been reported with such use. Expected systemic reactions: bone marrow depression, nausea, vomiting. Occasionally, severe spinal cord toxicity even leading to quadriplegia and paralysis, necrotising encephalopathy, blindness and other isolated neurotoxicities have been reported.