Xpreza 100 Dosage/Direction for Use

Xpreza 100 treatment should be initiated and monitored under the supervision of a physician experienced in the use of chemotherapeutic agents. Patients should be premedicated with anti-emetics for nausea and vomiting.
Posology: First treatment Cycle: The recommended starting dose for the first treatment cycle, for all patients regardless of baseline haematology laboratory values, is 75 mg/m² of body surface area, injected subcutaneously or intravenously, daily for 7 days. Patients should be premedicated for nausea and vomiting. Complete blood counts, liver chemistries and serum creatinine should be obtained prior to first dose.
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 (see Precautions) and dosage delay or reduction as described as follows may be necessary.
Dose adjustment due to haematological Laboratory values: For patients with baseline (start of treatment) WBC ≥3.0 x10⁹/L, ANC ≥1.5 x10⁹/L, and platelets ≥75.0 x10⁹/L, adjust the dose as follows, based on nadir counts for any given cycle: See Table 5.

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Patients without reduced baseline blood counts are WBC <3.0 x 10⁹/L and ANC <1.5 x 10⁹/L, and platelets <75.0 x 10⁹/L dose adjustments should be based on nadir counts and bone marrow biopsy cellularity at the time of the nadir as noted as follows, 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 6.)

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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.
Dosage Adjustment Based on Renal Function and Serum Electrolytes: If unexplained reductions in serum bicarbonate levels to <20 mEq/L occur, the dosage should be reduced by 50% on the next course. Similarly, if unexplained elevations of BUN or serum creatinine occur, the next cycle should be delayed until values return to normal or baseline and the dose should be reduced by 50% on the next treatment course.
Use in Geriatric Patients: Azacitidine and its metabolites are known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
Method of administration and Preparation: Reconstituted Xpreza 100 should be injected subcutaneously (insert the needle at a 45-90° angle) using a 25-gauge needle into the upper arm, thigh or abdomen.
Doses greater than 4 mL should be injected into two separate sites.
Injection sites should be rotated. New injections should be given at least 2.5 cm from the previous site and never into areas where the site is tender, bruised, red, or hardened.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Subcutaneous Preparation: Xpreza 100 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.
Preparation for Immediate Subcutaneous Administration: Doses greater than 4 mL should be divided equally into 2 syringes. The product may be held at 25°C 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, and may be held under refrigerated conditions (2ºC-8ºC, 36ºF-46ºF) for up to 8 hours. When azacitidine is reconstituted using refrigerated (2ºC-8ºC, 36ºF-46ºF) water for injection, the reconstituted product may be stored under refrigerated conditions (2ºC-8ºC, 36ºF-46ºF) 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). New injections should be given at least one inch from an old site and never into areas where the site is tender, bruised, red, or hard.
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). When Azacitidine for injection is reconstituted using refrigerated (2°C to 8°C) water for injections, the chemical and physical in-use stability of the reconstituted medicinal product has been demonstrated at 2°C to 8°C for 22 hours.
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 Solution Incompatibility: Azacitidine is incompatible with 5% Dextrose solutions, Hespan, or solutions that contain bicarbonate. These solutions have the potential to increase the rate of degradation of Azacitidine and should therefore be avoided.
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.