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Decitabine

(British Approved Name, US Adopted Name, rINN)

Drug Nomenclature

International Nonproprietary Names (INNs) in main languages (French, Latin, Russian, and Spanish):

DecitabineSynonyms: 5-Aza-2´-deoxycytidine; DAC; Decitabina; NSC-127716
BAN: Decitabine
USAN: Decitabine
INN: Decitabine [rINN (en)]
INN: Decitabina [rINN (es)]
INN: Décitabine [rINN (fr)]
INN: Decitabinum [rINN (la)]
INN: Децитабин [rINN (ru)]
Chemical name: 4-Amino-1-(2-deoxy-β-d-erythro-pentofuranosyl)-1,3,5-triazin-2(1H)-one
Molecular formula: C8H12N4O4 =228.2
CAS: 2353-33-5

Adverse Effects, Treatment, and Precautions

For general discussions see Antineoplastics. The most common adverse effect of decitabine is myelo-suppression, which may be severe and dose-limiting. Fatalities have been reported. Other common adverse effects include fatigue, pyrexia, gastrointestinal disturbances, petechiae, and hyperglycaemia. Cardiorespiratory arrest, increased blood bilirubin, intracranial haemorrhage, abnormal liver function tests, pulmonary oedema, atrial fibrillation, central line infection, or febrile neutropenia may force treatment to be stopped or delayed. Other adverse effects which may be dose-limiting include lethargy, oedema, tachycardia, depression, or pharyngitis.

Pharmacokinetics

On intravenous dosage decitabine exhibits biphasic disposition. Plasma protein binding is negligible. The exact route of metabolism and excretion is not known; one pathway appears to be deamination by cytidine deaminase, which is found principally in the liver, but also in granulocytes, the intestinal epithelium, and whole blood. A terminal elimination half-life of about 0.5 hours has been reported after a 72-hour infusion.

Uses and Administration

DecitabineDecitabine is an antineoplastic antimetabolite structurally related to cytarabine. It is reported to cause DNA hypomethylation by the inhibition of DNA methyltransferase, which has the potential to alter gene expression (reactivate silent genes) and limit disease progression and resistance. Decitabine is used in the treatment of myelodysplastic syndromes. It is given by intravenous infusion over 3 hours, diluted to a final concentration of 0.1 to 1 mg/mL in sodium chloride 0.9%, glucose 5%, or lactated Ringer’s injection.

The recommended dose is 15 mg/m every 8 hours for 3 days; this 3-day cycle is repeated every 6 weeks, for a minimum of 4 cycles. Treatment may be continued as long as the patient continues to benefit. If haematological recovery from a cycle is incomplete, cycle length may be increased to as much as every 10 weeks and the dose reduced to 11 mg/m every 8 hours upon restarting therapy; this dose may be maintained or increased in subsequent cycles as clinically indicated. Decitabine treatment should also be delayed if serum creatinine is 2 mg per 100 mL or greater, or if total bilirubin is 2 or more times the upper limit of normal, or if the patient has an active or uncontrolled infection.

Decitabine is also under investigation for the treatment of chronic myeloid leukaemia and acute myeloid leukaemia. It is also reported to increase fetal haemoglobin in patients with sickle-cell disease.

Proprietary Preparations

United States of America (US and USA): Dacogen.

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