Shelf-Life Extension Of Azacitidine: A Cancer Centre Experience On Waste and Cost Reduction In The Treatment Of Myelodysplastic Syndromes

Azacitidine (AZA) is a nucleoside metabolic inhibitor indicated for the treatment of patients with myelodysplastic syndromes (MDS). In Canada, it is supplied as a lyophilized powder in 100-mg vials priced at 628 Canadian dollars (C$). The product monograph indicates that the reconstituted drug may be held under refrigerated conditions (2-8°C) for up to a maximum of 8 hours. At a recommended dosing of 75 mg/m² x 7 days and average body surface areas (BSA) ranging between 1.7-1.9 m², most patients require more than a single vial reconstituted each day resulting in a drug wastage that might range from 58-72 mg/patient/day. Without strategies to mitigate this wastage, up to 40-50% of the daily dosage for patients of average BSA is thus discarded. At our center, AZA acquisition costs are reimbursed by the provincial funding agency according to mg dispensed and administered (dollars/mg) and not for total vials used; the potential cost of drug wastage is substantial. Walker et al. (Can J Hosp Pharm 2012) recently demonstrated that AZA reconstituted in cold (4°C) sterile water, and stored at -20°C for up to 4 days retained more than 90% of its initial concentration. The Odette Cancer Centre has used this reconstitution and storage strategy since November 2011. In addition, ‘batching’ of AZA patients on the same days and at the same times is attempted wherever possible. We audited AZA prescription use and drug wastage over 1 year after adopting this strategy to determine if the anticipated drug wastage was actually minimized.

From December 2011 until November 2012 all patients with MDS treated with at least 1 cycle of AZA were identified via the Cancer Centre pharmacy database. Analysis of the prescribed and wasted doses of AZA was performed. We retrospectively retrieved the mean number of doses administered per patient and per cycle. The mean BSA was determined for all patients, and the mean dose per injection as well as the mean number of cycles per patient was calculated. The total amount of actual drug wastage (based on the pharmacy records) was compared to the projected amount of drug wastage without implementing the new strategy.

Thirty-one patients (mean BSA of 1.86 m²) received 1167 injections of AZA over 170 cycles of treatment (mean of 5.48 cycles per patient). The mean dose prescribed was 141.7 mg per injection (95% confidence interval 139.43-143.98). Over 12 months a total of 165,370 mg was dispensed at a cost of C$1,038,523.60. The projected amount of AZA that would have been dispensed without adopting the new strategy would have been 233,400 mg, representing potential drug wastage of 68,030 mg at a cost of C$427,228.40. With the mitigating strategies implemented, the actual amount of wasted drug was 2,400 mg at a cost of C$15,072. Expiry on shelf accounted for 52% of the drug wastage (1,240 mg). Drug expiry outside the freezer due to human error, patients failing to arrive on the day of treatment, freezer technical issues, or other causes accounted for 48% of the drug wastage. The average waste per patient per cycle of treatment due to drug expiry on shelf was only 7.3 mg at a cost of C$45.70. If a solitary patient (without patient batching) of average BSA 1.86 m²had been treated without our policy of cold (4°C) water reconstitution and freezing, the drug wastage (cost) would have been 425.6 mg (C$2,672.70)/7 day cycle. In contrast, cold (4°C) sterile water reconstitution with overnight freezing of vials and syringes would result in a drug wastage of 25.6 mg/7 day cycle (C$160.70), a 94% cost savings due to wastage.

Shelf-life extension with cold (4°C) sterile water reconstitution and freezing of vials and syringes is a simple policy that reduces the waste of AZA by 72-98%. This, in addition to other drug waste minimization strategies like patient batching can lead to significant reductions in drug expenditure and substantial cost-saving.

Charbonneau:Hospira: Honoraria; BD Medical: Honoraria; Sanofi: Honoraria; Hoffman LaRoche: Honoraria. Buckstein:Celgene: Honoraria, Research Funding.