Ready-to-Dilute Cyclophosphamide Injections Obtain FDA Approval

Ready-to-Dilute Cyclophosphamide Injections Obtain FDA Approval

The FDA has approved the new drug application for ready-to-dilute 200 mg/mL vial cyclophosphamide injection to treat patients across multiple cancer types, including malignant lymphoma, multiple myeloma, and various types of leukemia, according to a news release from manufacturer Nevakar.¹

The intention behind injectable therapeutics is to offer formulas that are easier to administer. In the announcement, manufacturers asserted that the current method of mixing many anticancer therapeutics remains suboptimal. Cancer therapies often require tedious preparation before they can be administered, as such, the time it can take to prepare some therapies leads to unwanted delays in administration and increase the risk of contamination—because these molecules degrade easily.

In the patent for the product, inventors noted that, historically, the only commercially available formulations of cyclophosphamide were solid. The product is available as both a dry powder or lyophilized powders, which on reconstitution with water needs to be used immediately, and when reconstituted with 0.9% sodium chloride injection is only stable for 24 hours at room temperature or up to 6 days in a refrigerator. If the solution is diluted with sodium 0.45% sodium chloride injection it, once again, is only stable for 24 hours at room temperature and up to 6 days when refrigerated. If diluted with 5% dextrose injection or combination with 5% dextrose plus 0.9% sodium chloride injection, it is stable up to 24 hours at room temperature and only 36 hours when refrigerated.²

Of note, nursing professionals face higher exposure risks when the mixing times are greater. In the patent, it is noted that when cyclophosphamide is handled as either a dry powder or lyophilizate, it needs to dissolve before it is removed for injection and administered to a patient. When the vial is accessed with a syringe to add the solubilizing liquid vehicle, and when it is extracted for administration, small quantities of the drug become airborne. Even when nurses are diligent with their personal protection equipment, inhalation of these aerosols is a concern.²

“[We] believe that cyclophosphamide ready-to-dilute multi dose injection serves a very important need in oncology therapy,” Sriram Ramanathan, MS, MBA, chief executive officer of Nevakar Injectables, said in the release. “The product is available in two configurations, 500 mg / 2.5 mL and 1 gram / 5 mL vials to provide the health care providers with flexibility to use based on patient needs. Our simple and elegant formulation contains no unnecessary additives and benefits both providers and patients, as it minimizes waste, is easy to prepare, and reduces the risk of dosing error and product exposure.”¹

Cyclophosphamide is indicated for patients with malignant lymphomas, including Hodgkin's disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, and Burkitt's lymphoma, along with multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, ovarian adenocarcinoma, retinoblastoma, and breast carcinoma. Patients should not receive this treatment if they demonstrate a hypersensitivity to the product, or if they have urinary outflow obstruction.³

The most common adverse events associated with cyclophosphamide include neutropenia, febrile neutropenia, fever, alopecia, nausea, vomiting, and diarrhea.³

References

1. Nevakar injectables announces FDA approval of cyclophosphamide RTD solution. News release. NevakarInjectables. July 3, 2023. Accessed July 6, 2023. https://nevakar.com/nevakar-injectables-announces-fda-approval-of-cyclophosphamide-rtd-solution/#:~:text=(%E2%80%9CNevakar%E2%80%9D)%2C%20a,mL%20vials%20for%20use%20in
2. Shaik RA, Saha A, Garikipati J, et al. Dr. Reddy’s Laboratories Limited. Stable liquid formulations of cyclophosphamide and processed to prepare the same. US 11,382,923 B2. July 12, 2022. Accessed July 6, 2023. https://patentimages.
3. Cyclophosphamide injection. Prescribing information. Ingenus Pharmaceuticals, LLC; 2022. Accessed July 6, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212501s000lbl.pdf