ation has been reported (see section 4.4).
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via:
United Kingdom
Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store
4.9 Overdose
There is no specific antidote for cytarabine overdose. Cessation of therapy followed by management of ensuing bone marrow depression including whole blood or platelet transfusion and antibiotics as required.
Twelve doses of 4.5 g/m2 by IV infusion over one hour every 12 hours induces irreversible and fatal central nervous system toxicity.
Cytarabine may be removed by haemodialysis.
5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Pyrimidine analogues, ATC code: L01BC01
Mechanism of action
Cytarabine (ARA-C) is metabolised in vivo to ARA-CTP phosphorylated compound. This competitively inhibits DNA polymerase and may also inhibit certain acid kinase enzymes. Primarily the drug acts as a false nucleoside and competes for enzymes involved in the conversion of cytidine nucleotide to deoxycytidine nucleotide and also incorporation into the DNA.
Cytarabine has no effect on non-proliferating cells nor on proliferating cells unless in the S phase. It is a cell cycle specific antineoplastic drug.
5.2 Pharmacokinetic properties
Absorption
Oral administration is ineffective due to rapid deamination in the gut. Cytidine deaminase is concentrated in the liver and intravenous doses show biphasic elimination with half-lives of approximately 10 minutes and 1-3 hours.
Elimination
After 24 hours 80% of a dose has been eliminated either as the inactive metabolite or as the unchanged cytarabine, mostly in urine but some in bile.
Distribution
CSF levels of 50% of plasma levels are achieved with intravenous infusion. Intrathecal dosing results in slower elimination (T1/2 2-11 hours).
Cytarabine is rapidly and widely distributed into tissues, crosses the blood brain barrier and also the placenta.
5.3 Preclinical safety data
There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
6. Pharmaceutical particulars
6.1 List of excipients
Water for Injections
Hydrochloric Acid (for pH adjustment)
Sodium Hydroxide (for pH adjustment)
6.2 Incompatibilities
Solutions of cytarabine have been reported to be incompatible with various drugs, i.e. carbenicillin sodium, cephalothin sodium, fluorouracil, gentamicin sulphate, heparin sodium, hydrocortisone sodium succinate, insulin-regular, methylprednisolone sodium succinate, nafacillin sodium, oxacillin sodium, penicillin G sodium. However, the incompatibility depends on several factors (e.g. concentrations of the drug, specific diluents used, resulting pH, temperature). Specialised references should be consulted for specific compatibility information.
6.3 Shelf life
Before use: 18 months
In use: Chemical and physical in-use stability has been demonstrated for 7 days at room temperature.
From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions a |
