Decitex Dosage/Direction for Use

MODE OF ADMINISTRATION: Decitabine must be initiated under the supervision of physicians experienced in the use of chemotherapeutic agents. Complete blood and platelet count should be performed regularly, as clinically indicated and prior to each treatment cycle.
Decitabine is administered by intravenous infusion. A central venous catheter is not required. For instructions on reconstitution and dilution of the medicinal product before administration, see Instructions for Use and Handling and Disposal under Cautions for Usage.
RECOMMENDED DOSE: There are 2 regimens recommended for decitabine administration. A 5-Day dosing regimen in the treatment of AML, and a 3-Day or 5-Day dosing regimen in the treatment of MDS. With either regimen, it is recommended that patients be treated for a minimum of 4 cycles; however, a response may take longer than 4 cycles to be obtained. Treatment may be continued as long as the patient shows response, continues to benefit or exhibits stable disease, i.e., in the absence of overt progression.
If after 4 cycles, the patient's hematological values (e.g., platelet count or absolute neutrophil count), 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 non-responder and alternative therapeutic options to decitabine should be considered.
Pre-medication for the prevention of nausea and vomiting is not routinely recommended but may be administered if required.
Treatment Regimen in Acute Myeloid Leukemia: In a treatment cycle, decitabine is administered at a dose of 20 mg/m² body surface area by intravenous infusion over 1 hour repeated daily for 5 consecutive days (i.e., a total of 5 doses per treatment cycle). The total daily dose must not exceed 20 mg/m² and the total dose per treatment cycle must not exceed 100 mg/m². The cycle should be repeated every 4 weeks depending on the patient's clinical response and observed toxicity. If a dose is missed, treatment should be resumed as soon as possible. It is possible to use this regimen in an outpatient setting.
Treatment Regimen in Myelodysplastic Syndromes: 3-Day Dosing Treatment Regimen in MDS: In a treatment cycle, decitabine is administered for 3 consecutive days at a fixed dose of 15 mg/m² body surface area over a 3-hour period every 8 hours (i.e., a total of 9 doses per treatment cycle). This cycle is repeated approximately 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.
5-Day Dosing Treatment Regimen in MDS: In a treatment cycle, decitabine is administered at a dose of 20 mg/m² body surface area by intravenous infusion over 1 hour repeated daily for 5 consecutive days (i.e., a total of 5 doses per treatment cycle). The total daily dose must not exceed 20 mg/m² and the total dose per treatment cycle must not exceed 100 mg/m². The cycle should be repeated every 4 weeks depending on the patient's clinical response and observed toxicity. If a dose is missed, treatment should be resumed as soon as possible. It is possible to use this regimen in an outpatient setting.
Management of Myelosuppression and Associated Complications: Myelosuppression and adverse events related to myelosuppression (thrombocytopenia, anemia, neutropenia, and febrile neutropenia) are common in both treated and untreated patients with AML and MDS. Complications of myelosuppression include infections and bleeding. Treatment may be modified in patients experiencing myelosuppression and associated complications as described as follows: In AML: Treatment may be delayed at the discretion of the treating physician, if the patient experiences myelosuppression-associated complications, such as those described as follows: Febrile neutropenia (temperature ≥38.5°C and absolute neutrophil count <1000/μL).
Active viral, bacterial or fungal infection (i.e., requiring intravenous anti-infectives or extensive supportive care).
Hemorrhage (gastrointestinal, genito-urinary, pulmonary with platelets <25000/μL or any central nervous system hemorrhage).
Treatment with decitabine may be resumed once these conditions have improved or have been stabilized with adequate treatment (anti-infective therapy, transfusions, or growth factors).
Dose reduction is not recommended.
In MDS: 5-Day Dosing Regimen: Dose reduction is not recommended in this clinical setting to optimize patient benefit, dose should be delayed as follows: Dose Regimen Modifications in the First 3 Cycles: During the first cycles of treatment, Grade 3 and 4 cytopenias are common and may not represent progression of MDS. Pre-treatment cytopenias may not improve until after Cycle 3.
For the first 3 cycles, to optimize patient benefit in the setting of moderate neutropenia (absolute neutrophil count <1000/μL), all attempts should be made to maintain full dose treatment at the standard treatment cycle interval. Concomitant antimicrobial prophylaxis as per institutional guidelines can be administered until recovery of granulocytes to above 500/μL. Clinicians should also consider the need for early administration of growth factors during this time for the prevention or treatment of infections in patients with MDS.
Similarly, to optimize patient benefit in the setting of moderate thrombocytopenia (platelet count <25000/μL), all attempts should be made to maintain full dose treatment at the standard treatment cycle interval with concomitant administration of platelet transfusions in case of bleeding events.
Dose Regimen Modifications After Cycle 3: Dose should be delayed in case of the following toxicities considered to be at least possibly related to the treatment: Severe myelosuppression-associated complications (infections not resolving with adequate anti-infective therapy, bleeding not resolving with adequate treatment).
Prolonged myelosuppression defined as a hypocellular marrow (5% or less cellularity) without evidence of disease progression for 6 weeks or more after the start of a course of therapy.
If recovery (absolute neutrophil count >1000/μL and platelets >50000/μL) requires more than 8 weeks, the patient should be discontinued from the treatment of drug and assessed for disease progression (by bone marrow aspirate) within 7 days after the end of 8 weeks. For patients who have been treated for at least 6 cycles, and who continue to derive benefit from the therapy, a prolonged delay beyond 8 weeks can be allowed, in the absence of progression, at the discretion of the treating physician.
3-Day Dosing Regimen: Dose Regimen Modifications in the First 3 Cycles: During the first cycles of treatment, Grade 3 and 4 cytopenias are common and may not represent progression of MDS. Pre-treatment cytopenias may not improve until after Cycle 3.
For the first 3 cycles, to optimize patient benefit in the setting of moderate neutropenia (absolute neutrophil count <1000/μL), all attempts should be made to maintain full dose treatment at the standard treatment cycle interval. Concomitant antimicrobial prophylaxis as per institutional guidelines can be administered until recovery of granulocytes to above 500/μL.
Clinicians should also consider the need for early administration of growth factors during this time for the prevention or treatment of infections in patients with MDS.
Similarly, to optimize patient benefit in the setting of moderate thrombocytopenia (platelet count <25000/μL), all attempts should be made to maintain full dose treatment at the standard treatment cycle interval with concomitant administration of platelet transfusions in case of bleeding events.
Dose Regimen Modifications After Cycle 3: If hematologic recovery (absolute neutrophil count >1000/μL and platelets >50000/μL) from a previous decitabine treatment cycle, with persistent cytopenia(s) being considered related to drug administration, requires more than 6 weeks, then the next cycle of decitabine therapy should be delayed and dosing reduced by the algorithm as follows. All dose reductions that occur should remain in effect for the duration of the chemotherapy; there should be no dose re-escalation.
Recovery requiring more than 6 weeks, but less than 8 weeks - decitabine dosing to be delayed for up to 2 weeks and the dose reduced to 11 mg/m² every 8 hours (33 mg/m²/day, 99 mg/m²/cycle) upon restarting therapy.
Recovery requiring more than 8 weeks, but less than 10 weeks - the decitabine dose should be delayed up to 2 more weeks and the dose reduced to 11 mg/m² every 8 hours (33 mg/m²/day, 99 mg/m²/cycle) upon restarting therapy, then maintained in subsequent cycles as clinically indicated.
Recovery requiring more than 10 weeks - Patient should be discontinued from the treatment of drug and assessed for disease progression (by bone marrow aspirates) within 7 days after the end of 10 weeks. However, for patients who have been treated for at least 6 cycles, and who continue to derive benefit from the therapy, a prolonged delay beyond 10 weeks can be allowed, in the absence of progression, at the discretion of the treating physician.
Special populations: Pediatrics: The safety and effectiveness in pediatric patients with MDS have not been reported.
Treatment of pediatric patients with AML is not recommended because decitabine was not reported to be effective in this patient population.
Hepatic impairment: Studies in patients with hepatic impairment have not been reported. The need for dosage adjustment in patients with hepatic impairment has not been evaluated. If worsening hepatic function occurs, patients should be carefully monitored (see PRECAUTIONS and Pharmacology: Pharmacokinetics under Actions).
Renal impairment: Studies in patients with renal impairment have not been reported; however, data from reported clinical trials that included patients with mild-moderate impairment indicated no need for dosage adjustment. Patients with severe renal impairment were excluded from these reported trials (see Pharmacology: Pharmacokinetics under Actions).