Presenter: Quan Li, BCOP, BCPS, PharmD, MedStar Washington Hospital Center, Washington, DC
Co-Author: Tonya Wright, PharmD, MedStar Washington Hospital Center, Washington, DC
BACKGROUND: Cyclophosphamide has been available only as a lyophilized powder in a single-dose vial for a long time, and it requires labor-intensive reconstitution. A new liquid formulation of cyclophosphamide was recently approved in a multidose vial for convenient use. However, this new formulation has alcohol as an excipient. Many clinicians are leery to use the new formulation because of the safety concerns regarding the alcohol.
OBJECTIVE: To determine if the new formulation of alcohol-containing cyclophosphamide has more central nervous system (CNS) and liver adverse events than the lyophilized powder formulation of cyclophosphamide.
METHOD: A multicenter, retrospective chart review was conducted of oncology patients who received cyclophosphamide, either in the lyophilized powder formulation or the alcohol-containing formulation, from April 1, 2021, to December 31, 2021. The exclusion criteria were patient age <18 years, having advanced liver damage, having liver or brain metastases, or having liver or brain cancer. The primary end points were changes to liver function tests and CNS side effects that happen within 21 days of receiving the cyclophosphamide dose. The secondary end points were treatment delays >7 days or treatment-related hospitalizations.
RESULTS: A total of 97 patients were in the lyophilized powder group and 134 patients were in the alcohol-containing group. The lyophilized powder group was predominately white (52.6%), and the alcohol-containing group was predominately black or African American (64.2%; P <.001). In all, 68% of the patients in the lyophilized powder group and 85.8% of patients in the alcohol-containing group were women (P = .001). No significant differences were seen between the 2 groups for changes to liver function tests (AST, P = .179; ALT, P = .460). The incidence of CNS symptoms was similar between the groups (50.5% in the lyophilized powder group vs 50% in the alcohol-containing group; P = .938). For the secondary outcomes, the treatment delay rate was 3% in both groups, but the hospitalization rate was higher in the lyophilized powder group than in the alcohol-containing group (16.5% vs 6%, respectively; P = .01).
CONCLUSION: The liquid, alcohol-containing formulation of cyclophosphamide had similar CNS and liver side effects to the lyophilized powder formulation of cyclophosphamide. The use of the liquid, alcohol-containing formulation of cyclophosphamide in adults could be encouraged with close monitoring.
- Cyclophosphamide injection, for intravenous use [prescribing information]. Orlando, FL: Ingenus Pharmaceuticals; May 2013. www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf. Accessed August 5, 2021.
- Cyclophosphamide injection, for intravenous use [prescribing information]. Orlando, FL: Ingenus Pharmaceuticals; July 2020. www.accessdata.fda.gov/drugsatfda_docs/label/2020/212501s000lbl.pdf. Accessed August 6, 2021.
- IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Cyclophosphamide. Lyon, France: International Agency for Research on Cancer; 2012. www.ncbi.nlm.nih.gov/books/NBK304336/. Accessed April 30, 2022.
- Costardi JVV, Nampo RAT, Silva GL, et al. A review on alcohol: from the central action mechanism to chemical dependency. Rev Assoc Med Bras (1992). 2015;61:381-387.
- Casaurancq M-C, Labat V, Bertrand L, et al. Cyclophosphamide reconstituted in advance: could Drug Cam provide a solution? www.gerpac.eu/cyclophosphamide-reconstituted-in-advance-could-drug-cam-r-provide-a-solution. Accessed April 15, 2022.
- European Medicines Agency Committee for Medicinal Products for Human Use. Information for the package leaflet regarding ethanol used as an excipient in medicinal products for human use. November 22, 2019. www.ema.europa.eu/en/documents/scientific-guideline/information-package-leaflet-regarding-ethanol-used-excipient-medicinal-products-human-use_en.pdf. Accessed May 12, 2022.