Potency and stability of compounded cyclophosphamide: a pilot study

Abstract

Compounding of drugs for use in veterinary oncology is becoming increasingly common. We obtained 15 mg cyclophosphamide capsules from five different compounding pharmacies and performed potency analyses at two time points, as well as stability at 60 days. Potency results for four out of five and zero out of five (4/10) samples analysed were inadequate. Stability at 60 days was acceptable for all but one sample. This pilot study raises several important points of concern when compounding chemotherapy in dogs and cats. Further studies are necessary to solidify this data. Collaboration between pharmacists, veterinarians and regulatory bodies is needed to ensure safe and accurate delivery of compounded drugs to client-owned animals.

The addition of metronomic chemotherapy does not improve outcome for canine splenic haemangiosarcoma

“…Recent studies (Burton et al . , Robat & Budde , KuKanich et al . ) found that compounded drugs may contain suboptimal levels and the concentration of a compounded drug can vary more than 10% of the intended dose.…”

Potency and stability of compounded formulations of chlorambucil, melphalan and cyclophosphamide

“…The variability in potency and stability of compounded drugs could potentially arise from a number of factors including the drugs being compounded, whether the compounding is performed from the FDA‐approved product or a bulk substance, the compounding technique and storage duration and conditions. A previous study evaluating the potency and stability of compounded cyclophosphamide demonstrated that 4 of 10 samples of compounded cyclophosphamide evaluated were <90% of labelled concentration at initial testing, with a fifth sample with a potency of <90% of labelled concentration after a 60‐day stability period . All samples of compounded cyclophosphamide obtained in this study were within 90%‐110% of labelled concentration both at baseline and at the 6‐week time point; however, 3 samples had decreases in potency of 6.2%, 7.5% and 12.6% over the 6‐week period.…”

“…Despite wide use clinically, the potency and stability of compounded oral chemotherapy drugs have not been extensively evaluated to date. A recent publication demonstrated that 40% of samples of compounded cyclophosphamide had an actual potency that was greater than ±10% the labelled concentration of drug; 1 sample had a potency of <10% of labelled concentration 60 days after receipt, indicating that stability of compounded chemotherapy drugs may be an issue as well . This study raises further concern that compounded chemotherapy agents may not be as stable or as potent as their FDA‐approved product.…”

Glutathione‐S‐transferase‐theta genotypes and the risk of cyclophosphamide toxicity in dogs

“…An important limitation of the current study was the variation in CP dosing among individual dogs, with a mix of oral pulse (~250 mg/m 2 q2‐4 weeks) and metronomic (~15 mg/m 2 q24h) protocols. Actual pulse dosages varied based on tablet size, and many of the metronomic doses were compounded, which could affect the potency of dose given . Without measuring plasma or urinary concentrations of CP and its metabolites, we could not account for variability in dosing from imprecisely compounded formulations.…”

“…Actual pulse dosages varied based on tablet size, and many of the metronomic doses were compounded, which could affect the potency of dose given. 29 Without measuring plasma or urinary concentrations of CP and its metabolites, we could not account for variability in dosing from imprecisely compounded formulations. In addition, we did not collect urine-specific gravity data, which could influence SHC risk.…”