Generic Name: Decitabine
Class: Antineoplastic Agents
Chemical Name: 4-Amino-1-(2-deoxy-β-d-erythro-pentofuranosyl)-1,3,5-triazin-2(1H)-one
Molecular Formula: C8H12N4O4
CAS Number: 2353-33-5
Uses for Dacogen
Used in patients with previously treated or untreated, de novo or secondary MDS of all French-American-British (FAB) subtypes (i.e., refractory anemia [RA], RA with ringed sideroblasts [RARS], RA with excess blasts [RAEB], RAEB in transformation to leukemia [RAEB-T], chronic myelomonocytic leukemia [CMML]) and International Prognostic Scoring System (IPSS) risk groups with scores of ≥0.5 (i.e., intermediate-1, intermediate-2, and high-risk groups).1 3 4
Dacogen Dosage and Administration
Consult specialized references for procedures for proper handling and disposal of antineoplastic drugs.1
Consider premedicating with an antiemetic to prevent nausea and vomiting.1
For solution compatibility information, see Compatibility under Stability.
Administer by IV infusion.1
Immediately after reconstitution, dilute appropriate dose in an appropriate volume (e.g., 50–250 mL) of 0.9% sodium chloride, 5% dextrose, or lactated Ringer’s injection to yield a final concentration of 0.1–1 mg/mL.1 3
Rate of Administration
Administer by continuous IV infusion over 3 hours.1
Withhold therapy if Scr ≥2 mg/dL, serum ALT or total bilirubin concentration ≥2 times the ULN, or if active or uncontrolled infection occurs; delay subsequent cycles until recovery occurs.1 (See Adequate Patient Evaluation and Monitoring under Cautions.)
Dosage Modification for Hematologic Toxicity
Dosage modification is based on time to hematologic recovery (i.e., ANC ≥1000/mm3, platelet count ≥50,000/mm3) from previous treatment cycle.1
Hematologic recovery >6 to <8 weeks from previous treatment cycle: Delay next treatment cycle up to 2 weeks and temporarily reduce dosage at the start of the next cycle to 11 mg/m2 every 8 hours for 3 consecutive days (total dosage during treatment cycle: 99 mg/m2).1
Hematologic recovery >8 to <10 weeks from previous treatment cycle: Evaluate for disease progression (i.e., by bone marrow aspirates).1 If no disease progression, delay next treatment cycle up to 2 more weeks and reduce dosage to 11 mg/m2 every 8 hours for 3 consecutive days (total dosage during treatment cycle: 99 mg/m2).1 Reduced dosage may be maintained or increased in subsequent treatment cycles as clinically indicated.1
Routine dosage reduction not required.3
Possible decreased elimination; dosage reduction may be necessary.3
Cautions for Dacogen
Known hypersensitivity to decitabine.1
Fetal/Neonatal Morbidity and Mortality
May cause fetal harm; teratogenicity and embryolethality demonstrated in animals.1 Women should avoid pregnancy during therapy; men should not father child during therapy and for 2 months after therapy.1 If used during pregnancy or if patient becomes pregnant during therapy, apprise of potential fetal hazard.1
Risk of dose-limiting and potentially fatal myelosuppression, manifested commonly as severe neutropenia, severe thrombocytopenia, and anemia.1 Myelosuppression may occur more frequently in the first and second treatment cycles and may not indicate progression of underlying MDS.1
Delay or reduce dosage for subsequent cycles based on hematologic recovery.1 (See Dosage Modification for Hematologic Toxicity under Dosage and Administration.)
Adequate Patient Evaluation and Monitoring
Perform CBC and platelet counts prior to each treatment cycle and periodically thereafter.1
Category D.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
Not known whether decitabine is distributed into milk; discontinue nursing or the drug.1
Safety and efficacy not established.1
Safety and efficacy in those ≥65 years of age similar to that in younger adults; however, increased sensitivity to the drug in some geriatric individuals cannot be ruled out.1
Not studied in patients with hepatic impairment.1
Not studied in patients with renal impairment.1
Common Adverse Effects
Neutropenia, thrombocytopenia, anemia, fatigue, pyrexia, nausea, cough, petechiae, constipation, diarrhea, hyperglycemia.1
Interactions for Dacogen
No formal drug interaction studies to date; however, in vitro studies suggest that decitabine is not a substrate for CYP enzymes and is unlikely to inhibit or induce CYP enzymes.1
Following IV administration, decitabine rapidly enters cells by a nucleoside-specific transport mechanism; distributed into body fluids and crosses the blood-brain barrier.5
Plasma Protein Binding
Converted intracellularly to an active 5′-triphosphate metabolite.1 5 Also undergoes deamination by cytidine deaminase, principally in the liver, as well as granulocytes, intestinal epithelium, and whole blood.1
Biphasic; terminal half-life is approximately 0.51 hour.1
Powder for Injection
25°C (may be exposed to 15–30°C).1
Dilute immediately after reconstitution.1 Solutions diluted in cold (2–8°C) infusion fluids may be stored at 2–8°C for up 7 hours.1 Solutions diluted in infusion fluids that are not cold must be used within 15 minutes of reconstitution.1
For information on systemic interactions resulting from concomitant use, see Interactions.
Dextrose 5% in water1
Ringer’s injection, lactated1
Sodium chloride 0.9%1
Exert its antineoplastic effect by incorporating into DNA and inhibiting DNA methyltransferase, thereby causing hypomethylation of DNA.1 3 4 5 Does not appear to cause major suppression of DNA synthesis.1
Hypomethylation may restore normal function to genes silenced by aberrant DNA methylation (e.g., tumor suppressor genes) that are critical for cellular differentiation, proliferation, senescence, and apoptosis.1 5
Cell-cycle specific, acting principally in the S phase of the cell cycle; does not inhibit progression of cells from G1 into S phase.5
Advice to Patients
Importance of women informing clinicians immediately if they are or plan to become pregnant or plan to breast-feed.1 Advise women to avoid pregnancy during therapy and advise men not to father a child during and for 2 months following discontinuance of therapy.1 Necessity of advising pregnant women of the risk to the fetus.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., liver or kidney disease).1
Importance of informing patients of other important precautionary information. (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
AHFS DI Essentials. © Copyright, 2004-2015, Selected Revisions May 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
1. MGI Pharma, Inc. Dacogen (decitabine) prescribing information. Bloomington, MN; 2006 May.
2. Food and Drug Administration. Orphan designation pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act. (P.L. 97-414). Rockville, MD; From FDA website (). Accessed 2006 Jul 13.
3. MGI Pharma, Inc., Bloomington, MN: Personal communication.
4. Kantarjian H, Issa JP, Rosenfeld CS et al. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer. 2006; 106:1794-803. [PubMed 16532500]
5. Momparler RL. Pharmacology of 5-Aza-2’-deoxycytidine (decitabine). Semin Hematol. 2005; 42:S9-16. [PubMed 16015507]
6. Kantarjian HM, Issa JP. Decitabine dosing schedules. Semin Hematol. 2005; 42:S17-22.
7. Myelodysplastic syndromes. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2006 Aug 24.