Decitabine

DECITABINE- decitabine injection, powder, lyophilized, for solution
BluePoint Laboratories

1 INDICATIONS AND USAGE

Decitabine for Injection is indicated for treatment of adult 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

2.1 Recommended Dosage

Pre-Medications and Baseline Testing

Consider pre-medicating for nausea with antiemetics
Conduct baseline laboratory testing: complete blood count (CBC) with platelets, serum hepatic panel, and serum creatinine.

Decitabine for Injection Regimen Options

Three Day Regimen

Administer Decitabine for Injection at a dose of 15 mg/m2 by continuous intravenous infusion over 3 hours repeated every 8 hours for 3 days. Repeat cycles every 6 weeks upon hematologic recovery (ANC at least 1,000/µL and platelets at least 50,000/µL) for a minimum of 4 cycles. A complete or partial response may take longer than 4 cycles. Delay and reduce dose for hematologic toxicity [see Dosage and Administration (2.2)].

Five Day Regimen

Administer Decitabine for Injection at a dose of 20 mg/m2 by continuous intravenous infusion over 1 hour daily for 5 days. Delay and reduce dose for hematologic toxicity [see Dosage and Administration (2.2)]. Repeat cycles every 4 weeks upon hematologic recovery (ANC at least 1,000/µL and platelets at least 50,000/µL) for a minimum of 4 cycles. A complete or partial response may take longer than 4 cycles.

Patients with Renal or Severe Hepatic Impairment

Treatment with Decitabine for Injection has not been studied in patients with pre-existing renal or hepatic impairment. For patients with pre-existing renal or hepatic impairment. For patients with pre-existing renal or hepatic impairment, consider the potential risks and benefits before initiating treatment with Decitabine for Injection.

2.2 Dosage Modifications for Adverse Reactions

Hematologic Toxicity

If hematologic recovery from a previous Decitabine for Injection treatment cycle requires more than 6 weeks, delay the next cycle of Decitabine for Injection therapy and reduce Decitabine for Injection dose temporarily by following this algorithm:

Recovery requiring more than 6, but less than 8 weeks – delay Decitabine for Injection dosing for up to 2 weeks and reduce the dose temporarily to 11 mg/m2 every 8 hours (33 mg/m2 /day, 99 mg/m2 /cycle)) upon restarting therapy.
Recovery requiring more than 8, but less than 10 weeks – Perform bone marrow aspirate to assess for disease progression. In the absence of progression, delay Decitabine for Injection dosing up to 2 more weeks and reduce the dose to 11 mg/m2 every 8 hours (33mg/m2 /day, 99mg/m2 /cycle) upon restarting therapy, then maintain or increase dose in subsequent cycles as clinically indicated.

Non-Hematologic Toxicity

Delay subsequent Decitabine for Injection treatment for any the following non-hematologic toxicities and do not restart until toxicities resolve:

Serum creatinine greater than or equal to 2 mg/dL
Alanine transaminase (ALT), total bilirubin greater than or equal to 2 times upper limit of normal (ULN)
Active or uncontrolled infection

2.3 Preparation and Administration

Decitabine for Injection is a cytotoxic drug. Follow special handling and disposal procedures1.

Aseptically reconstitute Decitabine for Injection with room temperature (20o C to 25 o C) 10 mL of Sterile Water for Injection, USP. Upon reconstitution, the final concentration of the reconstituted Decitabine for Injection solution is 5 mg/mL. You must dilute the reconstituted solution with 0.9% Sodium Chloride Injection or 5% Dextrose Injection prior to administration. Temperature of the diluent (0.9% Sodium Chloride Injection or 5% Dextrose Injection) depends on time of administration after preparation.

For Administration Within 15 Minutes of Preparation

If Decitabine for Injection is intended to be administered within 15 minutes from the time of preparation, dilute the reconstituted solution with room temperature (20o C — 25 o C) 0.9% Sodium Chloride Injection or 5% Dextrose Injection to a final concentration of 0.1 mg/mL to 1 mg/mL. Discard unused portion.

For Delayed Administration

If Decitabine for Injection is intended to be administered after 15 minutes of preparation, dilute the reconstituted solution with cold (2o C to 8o C) 0.9% Sodium Chloride Injection or 5% Dextrose Injection to a final concentration of 0.1mg/mL to 1 mg/mL. Store at 2o C to 8 o C for up to 4 hours. Diluted stored solution must be used within 4 hours from the time of preparation. Discard unused portion.

Use the diluted, refrigerated solution within 4 hours from the time of preparation or discard.

Parental 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

For Injection: 50mg of decitabine as a sterile, white to almost white lyophilized powder, in a single-dose vial for reconstitution.

4 CONTRAINDICATIONS

None

5 WARNINGS AND PRECAUTIONS

5.1 Myelosuppression

Fatal and serious myelosuppression occurs in Decitabine for Injection-treated patients. Myelosuppression (anemia, neutropenia, and thrombocytopenia) is the most frequent cause of Decitabine for Injection dose reduction, delay and discontinuation. Neutropenia of any grade occurred in 90% of Decitabine for Injection-treated patients with grade 3 or 4 occurring in 87% of patients. Grade 3 or 4 febrile neutropenia occurred in 23% of patients. Thrombocytopenia of any grade occurred in 89% of patients with grade 3 or 4 occurring in 85% of patients. Anemia of any grade occurred in 82% of patients. Perform complete blood count with platelets at baseline, prior to each cycle, and as needed to monitor response and toxicity. Manage toxicity using dose-delay, dose-reduction, growth factors, and anti-infective therapies as needed [see Dosage and Administration (2.2)]. 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 Embryo-Fetal Toxicity

Based on findings from human data, animal studies and its mechanism of action, Decitabine for Injection can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) and Nonclinical Toxicology (13.1)]. In preclinical studies in mice and rats, decitabine caused adverse developmental outcomes including embryo-fetal lethality and malformations. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception while receiving Decitabine for Injection and for 6 months following the last dose. Advise males with female partners of reproductive potential to use effective contraception while receiving treatment with Decitabine for Injection, and for 3 months following the last dose [see Use in Specific Populations (8.1, 8.3)].

6 ADVERSE REACTIONS

The following clinically significant adverse reactions are described elsewhere in the labeling:

Myelosuppression [see Warnings and Precautions (5.1)]

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