Azacord Dosage/Direction for Use

Recommended Dosage: First Treatment Cycle: The recommended starting dose of azacitidine for the first treatment cycle, for all patients regardless of baseline hematology laboratory values, is 75 mg/m² subcutaneously or intravenously, daily for 7 days. Patients should be premedicated for nausea and vomiting.
Subsequent Treatment Cycles: Cycles should be repeated every 4 weeks. The dose may be increased to 100 mg/m² if no beneficial effect is seen after 2 treatment cycles and if no toxicity other than nausea and vomiting has occurred. It is recommended that patients be treated for a minimum of 4 to 6 cycles. However, complete or partial response may require additional treatment cycles. Treatment may be continued as long as the patient continues to benefit. Patients should be monitored for hematologic response and renal toxicities [Precautions], and dosage delay or reduction as described as follows may be necessary.
Dosage Adjustment Based on Hematology Laboratory Values: For patients with baseline (start of treatment) WBC ≥3.0x10⁹/L, ANC ≥1.5x10⁹/L, and platelets ≥75.0x10⁹/L, adjust the dose as in Table 1, based on nadir counts for any given cycle: See Table 1.

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For patients whose baseline counts are WBC <3.0x10⁹/L, ANC <1.5x10⁹/L, or platelets <75.0x10⁹/L, dose adjustments should be based on nadir counts and bone marrow biopsy cellularity at the time of the nadir as shown in Table 2, unless there is clear improvement in differentiation (percentage of mature granulocytes is higher and ANC is higher than at onset of that course) at the time of the next cycle, in which case the dose of the current treatment should be continued. (See Table 2.)

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If a nadir as defined in the table previously has occurred, the next course of treatment should be given 28 days after the start of the preceding course, provided that both the WBC and the platelet counts are >25% above the nadir and rising. If a >25% increase above the nadir is not seen by day 28, counts should be reassessed every 7 days. If a 25% increase is not seen by day 42, then the patient should be treated with 50% of the scheduled dose.
Route of Administration: Route of administration is subcutaneous or intravenous.
Preparation of AZACITIDINE: Azacitidine is a cytotoxic drug. If reconstituted azacitidine comes into contact with the skin, immediately and thoroughly wash with soap and water. If it comes into contact with mucous membranes, flush thoroughly with water. The azacitidine vial is single-use and does not contain any preservatives. Unused portions of each vial should be discarded properly. Do not save any unused portions for later administration.
Instructions for Subcutaneous Administration: Azacitidine should be reconstituted aseptically with 4 mL sterile water for injection. The diluent should be injected slowly into the vial. Vigorously shake or roll the vial until a uniform suspension is achieved. The suspension will be cloudy. The resulting suspension will contain azacitidine 25 mg/mL. Do not filter the suspension after reconstitution.
Preparation for Immediate Subcutaneous Administration: Doses greater than 4 mL should be divided equally into 2 syringes. The product may be held at room temperature for up to 1 hour, but must be administered within 1 hour after reconstitution.
Preparation for Delayed Subcutaneous Administration: The reconstituted product may be kept in the vial or drawn into a syringe. Doses greater than 4 mL should be divided equally into 2 syringes. The product must be refrigerated immediately. When azacitidine for injection is reconstituted using water for injection that has not been refrigerated, the reconstituted product may be held under refrigerated conditions (2°-8°C, 36°-46°F) for up to 8 hours. When azacitidine for injection is reconstituted using refrigerated (2°-8°C, 36°-46°F) water for injection, the reconstituted product may be stored under refrigerated conditions (2°- 8°C, 36°-46°F) for up to 22 hours. After removal from refrigerated conditions, the suspension may be allowed to equilibrate to room temperature for up to 30 minutes prior to administration.
Subcutaneous Administration: To provide a homogeneous suspension, the contents of the dosing syringe must be re-suspended immediately prior to administration. To re-suspend, vigorously roll the syringe between the palms until a uniform, cloudy suspension is achieved.
Azacitidine suspension is administered subcutaneously. Doses greater than 4 mL should be divided equally into 2 syringes and injected into 2 separate sites. Rotate sites for each injection (thigh, abdomen, or upper arm).
Suspension Stability: Azacitidine reconstituted for subcutaneous administration may be stored for up to 1 hour at 25°C (77°F) or for up to 8 hours between 2°C and 8°C (36°F and 46°F).
Instructions for Intravenous Administration: Reconstitute the appropriate number of azacitidine vials to achieve the desired dose. Reconstitute each vial with 10 mL sterile water for injection. Vigorously shake or roll the vial until all solids are dissolved. The resulting solution will contain azacitidine 10 mg/mL. The solution should be clear. Parenteral drug product should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Withdraw the required amount of azacitidine solution to deliver the desired dose and inject into a 50-100 mL infusion bag of either 0.9% Sodium Chloride Injection or Lactated Ringer's Injection.
Intravenous Administration: Azacitidine solution is administered intravenously. Administer the total dose over a period of 10-40 minutes. The administration must be completed within 1 hour of reconstitution of the azacitidine vial.
Solution Stability: Azacitidine reconstituted for intravenous administration may be stored at 25°C (77°F), but administration must be completed within 1 hour of reconstitution.