Azacitidine is available as a lyophilized powder in single-use (preservative-free) vials in a formulation containing 100 mg of azacitidine and 100 mg of mannitol.3325 Azacitidine (Actavis) also is available as a lyophilized powder in single-use (preservative-free) vials in a formulation containing 100 mg of azacitidine with sucrose 170 mg, monosodium phosphate monohydrate, and disodium hydrogen phosphate dihydrate.3326
To prepare a suspension of azacitidine for subcutaneous administration from either formulation, the powder contents of one vial should be reconstituted by slowly injecting 4 mL of sterile water for injection into the vial.3325; 3326 The vial should be shaken vigorously or rolled until a uniform, cloudy suspension results.3325; 3326 The suspension will have a final azacitidine concentration of 25 mg/mL.3325; 3326
To prepare a solution of azacitidine for intravenous administration from either formulation, each 100-mg vial of azacitidine should be reconstituted with 10 mL of sterile water for injection.3325; 3326 Vials should be vigorously shaken or rolled until all solids are dissolved and a clear solution results.3325; 3326 The solution will have a final azacitidine concentration of 10 mg/mL.3325; 3326 The appropriate dose of the reconstituted solution should be withdrawn from the vial and diluted in 50 to 100 mL of sodium chloride 0.9% or Ringer’s injection, lactated.3325; 3326
Trade Name(s)
Vidaza
Azacitidine may be administered subcutaneously as a suspension or intravenously as a solution.3325; 3326
Prior to subcutaneous administration, the reconstituted suspension may be allowed to come to room temperature for up to 30 minutes if it has been refrigerated.3325; 3326 The suspension should be resuspended immediately prior to subcutaneous administration by vigorously rolling the container between the palms until a uniform, cloudy suspension is achieved.3325; 3326 For doses exceeding a volume of 4 mL of the reconstituted suspension, the total dose should be divided equally into 2 syringes and injected into 2 separate sites.3325; 3326 Injection sites should be rotated.3325; 3326
For intravenous infusion, the final diluted solution should be administered over 10 to 40 minutes.3325; 3326
As with other toxic drugs, applicable special handling and disposal procedures for azacitidine should be followed.3325; 3326
Azacitidine is a white to off-white powder.3325; 3326 Intact vials should be stored at controlled room temperature.3325; 3326
The reconstituted suspension of azacitidine intended for immediate subcutaneous administration may be held at 25°C for up to 1 hour, but must be administered within 1 hour after reconstitution.3325; 3326 One manufacturer recommends administration of the reconstituted suspension within 45 minutes of preparation when intended for immediate use.3327
Stability of the reconstituted suspension intended for delayed subcutaneous administration differs between the two formulations of azacitidine;3325; 3326 the sucrose-containing formulation (Actavis) has demonstrated improved stability of the reconstituted suspension compared with the original mannitol-containing formulation.3328 If either formulation of the reconstituted suspension is intended for delayed subcutaneous administration, the suspension must be stored in the refrigerator immediately following reconstitution, either in the vial or drawn into a syringe.3325; 3326 For the mannitol-containing formulation, when cold sterile water for injection (stored at 2 to 8°C) is used for reconstitution, the resulting suspension may be stored at 2 to 8°C for up to 22 hours; when sterile water for injection that has not been refrigerated is used for reconstitution, the resulting suspension may be stored at 2 to 8°C for only up to 8 hours.3325 For the sucrose-containing formulation, when cold sterile water for injection (stored at 2 to 8°C) is used for reconstitution, the resulting suspension may be stored at 2 to 8°C for up to 30 hours; when sterile water for injection that has not been refrigerated is used for reconstitution, the resulting suspension may be stored at 2 to 8°C for only up to 12 hours.3326
When cold sterile water for injection is used for reconstitution, some authors have noted that sterile water for injection in glass bottles and ampuls of various sizes stored at 2 to 8°C quickly increased in temperature within 15 minutes after removal from refrigeration, which could potentially impact the subsequent stability of the drug.3329 To combat this problem, these authors have suggested freezing 20-mL ampuls of sterile water for injection and thawing them for 30 minutes prior to use.3329 After thawing, ampuls should be agitated for 30 seconds prior to removing the volume needed for reconstitution.3329
If either formulation is reconstituted to a solution and further diluted for intravenous infusion, administration of the diluted solution for infusion must be completed within 1 hour of reconstitution.3325; 3326
Azacitidine (Celgene) 10-mg/mL solution and 25-mg/mL suspension prepared with room temperature sterile water for injection and stored in glass vials at 23°C demonstrated less than 10% loss in 2.4 hours;3330 when prepared with cold (4°C) sterile water for injection and stored in glass vials at 4°C, this formulation demonstrated less than 10% loss in 1 day.3330
pH Effects
Maximum stability of azacitidine has been reported at a pH ranging from 6.5 to 7.741; 969
Temperature Effects
Azacitidine is very sensitive to temperature,3329; 3330 degrading quickly at room temperature.3325; 3326
Freezing Solutions
Azacitidine (National Cancer Institute) 0.5- and 2-mg/mL solutions prepared with ice-cold (specific temperature not defined) Ringer’s injection, lactated and stored in 50-mL polypropylene syringes (Becton Dickinson) were stable for 2 weeks at -20°C followed by 1 hour at room temperature after thawing over 30 to 45 minutes.1519
Azacitidine (Celgene) 10-mg/mL solution prepared with cold (4°C) sterile water for injection and stored in glass vials and polypropylene syringes (Becton Dickinson) at -20°C demonstrated little to no loss in 23 days.3330
Freezing Suspensions
Azacitidine (Celgene) 25-mg/mL suspension prepared with cold (4°C) sterile water for injection and stored in glass vials and polypropylene syringes (Becton Dickinson) at -20°C demonstrated little to no loss in 23 days.3330
Azacitidine (Celgene) 25-mg/mL suspension prepared with ice-cold water (specific temperature not defined) and stored in polypropylene syringes for 8 days at -20°C followed by thawing at room temperature (i.e., 23 to 25°C) for 30 minutes with or without subsequent storage for 8 hours at 2 to 8°C demonstrated a loss of less than 5%.3331 Neither changes in color of the suspension nor partial dissolution of the suspension was noted throughout the study.3331
Syringes
Azacitidine (Celgene) 10-mg/mL solution and 25-mg/mL suspension prepared with cold (4°C) sterile water for injection and stored in polypropylene syringes (Becton Dickinson) at 4°C demonstrated less than 10% loss in 1 day.3330
Filtration
Filtration of azacitidine suspension could result in removal of the drug; the suspension should not be filtered.3325; 3326
For a list of references cited in the text of this monograph, search the monograph titled References.