usions or injections. Myelosuppression is biphasic and nadirs at 7-9 and 15-24 days. Evidence of bone marrow improvement may be expected 7-64 (mean 28) days after the beginning of treatment.
Paediatric population: Children appear to tolerate higher doses of cytarabine than adults, and where the range of doses is given, children should receive the higher dose.
Elderly: No data is available to suggest that a change in dose is necessary in the elderly. However, the elderly patient is more susceptible to toxic reactions and therefore particular attention should be paid to drug induced leukopenia, thrombocytopenia and anaemia.
Method of administration
Cytarabine 100 mg/ml Injection is a ready to use injection and can be administered by the intravenous and subcutaneous routes. Cytarabine 100 mg/ml Injection should not be administered by the intrathecal route due to the slight hypertonicity of this formulation. (See section 4.8).
4.3 Contraindications
Hypersensitivity to cytarabine or to any of the excipients listed in 6.1.
Anaemia, leukopenia and thrombocytopenia of non-malignant aetiology (e.g. bone marrow aplasia), unless the benefits outweigh the risk.
Degenerative and toxic encephalopathies, especially after the use of methotrexate or treatment with ionizing radiation.
During pregnancy, cytarabine should only be administrated on strict indication, where the benefits of the drug to the mother should be weighed against possible hazards to the foetus.
4.4 Special warnings and precautions for use
Cytarabine is a potent bone marrow suppressant. Therapy should be started cautiously in patients with pre-existing drug-induced bone marrow suppression. Patients receiving the drug should be kept under close medical supervision. Leucocyte and platelet counts should be performed frequently and daily during induction. Bone marrow examinations should be performed frequently after blasts have disappeared from the peripheral blood.
Facilities should be available for management of complications, possibly fatal, of bone marrow suppression (infection resulting from granulocytopenia and other impaired body defences, and haemorrhage secondary to thrombocytopenia).
One case of anaphylaxis that resulted in cardiopulmonary arrest and necessitated resuscitation has been reported. This occurred immediately after intravenous cytarabine was administered.
Severe and at times fatal central nervous system (CNS), gastrointestinal (GI) and pulmonary toxicity (different from that seen with conventional therapy regimens of cytarabine) has been reported following some experimental cytarabine dose schedules. These reactions include reversible corneal toxicity; cerebral and cerebellar dysfunction, usually reversible; somnolence; convulsion; severe gastrointestinal ulceration including pneumatises cysteroides intestinalis, leading to peritonitis; sepsis and liver abscess; and pulmonary oedema.
The risk of CNS toxicity increases if high dose cytarabine is given in combination with another CNS toxic treatment such as radiation therapy or in patients who have previously had CNS treatment as chemotherapy intrathecally. Rarely, neurological effects such as severe spinal cord toxicity even leading to necrotising encephalopathy, quadriplegia and paralysis and blindness have been reported with cytosine arabinoside and have been predominantly associated with intrathecal administration. Isolated cases have also been reported with |
