HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use DACOGEN safely and effectively. See full prescribing information for DACOGEN. DACOGEN - ® (decitabine) for INJECTION ...
These highlights do not include all the information needed to use DACOGEN safely and effectively. See full prescribing information for DACOGEN.
DACOGEN ® (decitabine) for INJECTION
Initial U.S. Approval: 2006
INDICATIONS AND USAGE
DACOGEN is a nucleoside metabolic inhibitor indicated for 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. (
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DOSAGE AND ADMINISTRATION
There are two regimens for DACOGEN administration. With either regimen it is recommended that patients be treated for a minimum of 4 cycles; however, a complete or partial response may take longer than 4 cycles. (
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Treatment Regimen – Option 1
Administer DACOGEN at a dose of 15 mg/m 2 by continuous intravenous infusion over 3 hours repeated every 8 hours for 3 days. Repeat cycle every 6 weeks. ( 2.1)
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Treatment Regimen – Option 2
Administer DACOGEN at a dose of 20 mg/m 2 by continuous intravenous infusion over 1 hour repeated daily for 5 days. Repeat cycle every 4 weeks. ( 2.2)
DOSAGE FORMS AND STRENGTHS
Lyophilized powder in a single-dose vial, 50 mg/vial. (3)
CONTRAINDICATIONS
None (4)
WARNINGS AND PRECAUTIONS
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Neutropenia and thrombocytopenia: Perform complete blood counts and platelet counts. ( 5.1)
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Pregnancy: Can cause fetal harm. Advise women of potential risk to the fetus ( 5.2, 8.1)
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Women of childbearing potential and men with female partners of childbearing potential should use effective contraception and avoid pregnancy ( 5.3, 5.4)
ADVERSE REACTIONS
Most common adverse reactions (> 50%) are neutropenia, thrombocytopenia, anemia, and pyrexia. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Otsuka America Pharmaceutical, Inc. at 1-800-438-9927 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
See 17 for PATIENT COUNSELING INFORMATION.
Revised: 4/2016
FULL PRESCRIBING INFORMATION: CONTENTS*
Table of Contents
1 INDICATIONS AND USAGE
DACOGEN is indicated for treatment of patients with myelodysplastic syndromes (MDS) including previously treated and untreated, de novo and secondary MDS of all ...
DACOGEN is indicated for 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.
2 DOSAGE AND ADMINISTRATION
There are two regimens for DACOGEN administration. With either regimen it is recommended that patients be treated for a minimum of 4 cycles; however, a complete or partial response ...
There are two regimens for DACOGEN administration. With either regimen it is recommended that patients be treated for a minimum of 4 cycles; however, a complete or partial response may take longer than 4 cycles.
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.
2.1 Treatment Regimen – Option 1
DACOGEN is administered at a dose of 15 mg/m2 by continuous intravenous infusion over 3 hours repeated every 8 hours for 3 days. This cycle should be repeated every 6 weeks. Patients may be premedicated with standard anti-emetic therapy.
If hematologic recovery (ANC ≥ 1,000/μL and platelets ≥ 50,000/μL) from a previous DACOGEN treatment cycle requires more than 6 weeks, then the next cycle of DACOGEN therapy should be delayed and dosing temporarily reduced by following this algorithm:
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Recovery requiring more than 6, but less than 8 weeks − DACOGEN dosing to be delayed for up to 2 weeks and the dose temporarily reduced to 11 mg/m 2 every 8 hours (33 mg/m 2/day, 99 mg/m 2/cycle) upon restarting therapy.
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Recovery requiring more than 8, but less than 10 weeks − Patient should be assessed for disease progression (by bone marrow aspirates); in the absence of progression, the DACOGEN dose should be delayed up to 2 more weeks and the dose reduced to 11 mg/m 2 every 8 hours (33 mg/m 2/day, 99 mg/m 2/cycle) upon restarting therapy, then maintained or increased in subsequent cycles as clinically indicated.
2.2 Treatment Regimen – Option 2
DACOGEN is administered at a dose of 20 mg/m2 by continuous intravenous 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/μL platelets ≥ 50,000/μL).
2.3 Patients with Non-hematologic Toxicity
Following the first cycle of DACOGEN treatment, if any of the following non-hematologic toxicities are present, DACOGEN treatment should not be restarted until the toxicity is resolved: 1) serum creatinine ≥ 2 mg/dL; 2) SGPT, total bilirubin ≥ 2 times ULN; 3) and active or uncontrolled infection.
2.4 Instructions for Intravenous Administration
DACOGEN is a cytotoxic drug and caution should be exercised when handling and preparing DACOGEN. Procedures for proper handling and disposal of antineoplastic drugs should be applied. Several guidances on this subject have been published.1,,,4
DACOGEN should be aseptically reconstituted with 10 mL of Sterile Water for Injection (USP); upon reconstitution, each mL contains approximately 5.0 mg of decitabine at pH 6.7-7.3. Immediately after reconstitution, the solution should be further diluted with 0.9% Sodium Chloride Injection or 5% Dextrose Injection to a final drug concentration of 0.1 - 1.0 mg/mL. Unless used within 15 minutes of reconstitution, the diluted solution must be prepared using cold (2˚C - 8˚C) infusion fluids and stored at 2˚C - 8˚C (36˚F - 46˚F) for up to a maximum of 4 hours until administration.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if there is evidence of particulate matter or discoloration.
3 DOSAGE FORMS AND STRENGTHS
DACOGEN (decitabine) for Injection is supplied as a sterile, lyophilized white to almost white powder, in a single-dose vial, packaged in cartons of 1 vial. Each vial contains 50 mg ...
DACOGEN (decitabine) for Injection is supplied as a sterile, lyophilized white to almost white powder, in a single-dose vial, packaged in cartons of 1 vial. Each vial contains 50 mg of decitabine.
4 CONTRAINDICATIONS
None
None
5 WARNINGS AND PRECAUTIONS
5.1 Neutropenia and Thrombocytopenia - Treatment with DACOGEN is associated with neutropenia and thrombocytopenia. Complete blood and platelet counts should be ...
5.1 Neutropenia and Thrombocytopenia
Treatment with DACOGEN 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 [see Dosage and Administration (2.1, 2.2)]. Clinicians should consider the need for early institution of growth factors and/or antimicrobial agents for the prevention or treatment of infections in patients with MDS. Myelosuppression and worsening neutropenia may occur more frequently in the first or second treatment cycles, and may not necessarily indicate progression of underlying MDS.
5.2 Use in Pregnancy
DACOGEN can cause fetal harm when administered to a pregnant woman. Based on its mechanism of action, DACOGEN is expected to result in adverse reproductive effects. In preclinical studies in mice and rats, decitabine was teratogenic, fetotoxic, and embryotoxic. There are no adequate and well-controlled studies of DACOGEN in pregnant women. 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 while taking DACOGEN [see Use in Specific Populations (8.1)].
5.3 Use in Women of Childbearing Potential
Women of childbearing potential should be advised to avoid becoming pregnant while receiving DACOGEN and for 1 month following completion of treatment. Women of childbearing potential should be counseled to use effective contraception during this time [see Use in Specific Populations (8.1)]. Based on its mechanism of action, DACOGEN can cause fetal harm if used during pregnancy.
5.4 Use in Men
Men should be advised not to father a child while receiving treatment with DACOGEN, and for 2 months following completion of treatment [see Nonclinical Toxicology (13.1)]. Men with female partners of childbearing potential should use effective contraception during this time. Based on its mechanism of action, DACOGEN alters DNA synthesis and can cause fetal harm.
6 ADVERSE REACTIONS
6.1 Clinical Studies Experience - Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of ...
6.1 Clinical Studies Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Most Commonly Occurring Adverse Reactions: neutropenia, thrombocytopenia, anemia, fatigue, pyrexia, nausea, cough, petechiae, constipation, diarrhea, and hyperglycemia.
Adverse Reactions Most Frequently (≥ 1%) Resulting in Clinical Intervention in the Phase 3 Trials in the DACOGEN Arm:
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Discontinuation: thrombocytopenia, neutropenia, pneumonia, Mycobacterium avium complex infection, cardio-respiratory arrest, increased blood bilirubin, intracranial hemorrhage, abnormal liver function tests.
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Dose Delayed: neutropenia, pulmonary edema, atrial fibrillation, central line infection, febrile neutropenia.
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Dose Reduced: neutropenia, thrombocytopenia, anemia, lethargy, edema, tachycardia, depression, pharyngitis.
Discussion of Adverse Reactions Information
DACOGEN was studied in 3 single-arm studies (N = 66, N = 98, N = 99) and 1 controlled supportive care study (N = 83 DACOGEN, N = 81 supportive care ). The data described below reflect exposure to DACOGEN in 83 patients in the MDS trial. In the trial, patients received 15 mg/m2 intravenously every 8 hours for 3 days every 6 weeks. The median number of DACOGEN cycles was 3 (range 0 to 9).
Table 1 presents all adverse events regardless of causality occurring in at least 5% of patients in the DACOGEN group and at a rate greater than supportive care.
