VIAL (powder for solution for injection): 1.
Must be administered under the supervision of physicians experienced in the treatment of MDS. Pre-medication for the prevention of nausea and vomiting is not routinely recommended but may be administered if required.
There are two administration regimens. With either regimen, it is recommended that patients be treated for a minimum of 4 cycles; however, a complete or partial remission may take longer than 4 cycles to be obtained.
If after 4 cycles, the patient's hematological values (e.g., platelet counts or absolute neutrophil count [ANC]), have not returned to pre-treatment levels or if disease progression occurs (peripheral blast counts are increasing or bone marrow blast counts are worsening), the patient may be considered to be a nonresponder and alternative therapeutic options should be considered. Complete blood counts and platelet counts should be performed as needed to monitor response and toxicity, but at a minimum, prior to each cycle. Liver chemistries and serum creatinine should be obtained prior to initiation of treatment.
Treatment Regimen Option 1: Administration is at a dose of 15 mg/m2
body surface by continuous I.V. infusion over 3 hours repeated every 8 hours for 3 days. This cycle should be repeated every 6 weeks depending on the patient's clinical response and observed toxicity. The total daily dose must not exceed 45 mg/m2
and the total dose per treatment cycle must not exceed 135 mg/m2
. If a dose is missed, treatment should be resumed as soon as possible. Patients may be premedicated with standard anti-emetic therapy.
Treatment Regimen Option 2: Administration is at a dose of 20 mg/m2
by continuous I.V. infusion over 1 hour repeated daily for 5 days. This cycle should be repeated every 4 weeks. Patients may be premedicated with standard anti-emetic therapy. If myelosuppression is present, subsequent treatment cycles of Dacogen should be delayed until there is hematologic recovery (ANC> 1,000/mcL platelets> 50,000mcL).
See prescribing information for management of grade 3-4 myelosuppression.
Patients with non-hematologic toxicity: Following treatment with either regimen, if the following non-hematological toxicities occur, the next cycle of therapy should be withheld until levels return to within the normal range or baseline: Alanine aminotransferase (ALT) or total bilirubin greater than or equal to 2 times the upper limit of normal; Active viral or bacterial infection that is not controlled by concomitant anti-infective therapy. See prescribing information for full details.
Treatment of patients with myelodysplastic syndromes (MDS) including previously treated and untreated, de novo and secondary MDS of all French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia) and Intermediate-1, Intermediate-2, and high-risk International Prognostic Scoring System groups.
Patients with a known hypersensitivity to decitabine or any of the excipients. Pregnancy, lactation.
Treatment is associated with neutropenia and thrombocytopenia. Complete blood and platelet counts should be performed as needed to monitor response and toxicity, but at a minimum, prior to each dosing cycle. After administration of the recommended dosage for the first cycle, treatment for subsequent cycles should be adjusted.
: The safety and effectiveness have not been established.
: No overall differences in safety or effectiveness were observed between these subjects and younger subjects.
: Caution should be exercised and patients should be monitored closely for signs of toxicity.
Pregnancy and lactation
: Contraindicated: If this drug is used during pregnancy, or if a patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant. Men should be advised not to father a child while receiving treatment with Dacogen, and for two months following completion of treatment. Lactation is contraindicated, therefore if treatment is required, breastfeeding must be discontinued. See prescribing information for full details.
Neutropenia, thrombocytopenia, anemia, fatigue, pyrexia, nausea, cough, petechiae, constipation, diarrhea, and hyperglycemia. See prescribing information for full details.
Given its low in vitro plasma protein binding (<1%), decitabine is unlikely to displace co-administered drugs from their plasma protein binding. See prescribing information for full details.