Developers Restart Methotrexate Production Following Shortage

According to findings reported by American Society of Health-System Pharmacists (ASHP), methotrexate injections at 25 mg/mL, 2 mL, 10 mL, and 40 mL preservative-free vials were on back order at Accord following manufacturing delays.

Developer Accord Healthcare has renewed production of the frequently used agent methotrexate during an ongoing shortage of oncology agents in the United States, according to a press release from Reuters.¹

Resumed production of the injectable chemotherapy agent may increase access to treatment for patients with pediatric acute lymphoblastic leukemia, breast cancer, lung cancer, and specific subtypes of head and neck cancers. The FDA previously announced its goal to identify new manufacturers to mitigate the methotrexate shortage in June 2023.

According to findings reported by American Society of Health-System Pharmacists (ASHP), methotrexate injections at 25 mg/mL, 2 mL, 10 mL, and 40 mL preservative-free vials were on back order at Accord following manufacturing delays.² Additionally, other manufacturers including Fresenius Kabi, Pfizer, Teva, and Hikma had methotrexate injections on back order due to increased demand amid the ongoing chemotherapy shortages in the United States.

In terms of navigating the limited supply of methotrexate in the country, the ASHP recommended administering alternative, patient-specific agents based on renal function, liver function, and type and location of the neoplasm, although the organization cautioned that methotrexate could not be substituted for any one single agent. Institutions were also advised to monitor methotrexate supplies prior to initiating chemotherapeutic regimens, and switching to alternative combinations in the case of inadequate resources.

The organization also advised for practices to save preservative-free methotrexate for intrathecal administration and to consult Hematology/Oncology specialists to receive patient- and neoplasm-specific treatment recommendations. Another recommendation included employing treatment with oral methotrexate for indications outside of oncology.

Current shortages of chemotherapeutic agents including methotrexate, carboplatin, and cisplatin are believed to be linked to an FDA inspection of a manufacturing plant.³ After failing to reach the quality standards established by the regulatory agency, the facility halted production of the aforementioned drugs; resolving these concerns has become an ongoing priority.

According to findings from a survey conducted by the National Comprehensive Cancer Network (NCCN) Best Practices Committee across 27 NCCN Member Institutions within the United States in May 2023, 93% of practices reported a shortage of carboplatin.^3,4 Results from the survey also spotlighted a lack of adequate cisplatin supplies, according to 70% of the surveyed institutions.

Additional findings from the survey highlighted that 100% of practices were able to keep patients on cisplatin with no delays or claim denials. Moreover, 64% of surveyed practices were able to continue administering carboplatin to patients who were already receiving the agent.

The FDA sought to mitigate the chemotherapy drug shortages by importing these agents from alternative sources. For instance, the regulatory agency arranged an agreement with Chinese manufacturers to temporarily import cisplatin in May 2023.⁵ Moreover, the agency made an effort to relabel these products and add English labels to packaging as means of ensuring safety for buyers.³

References

1. Accord resumes production of cancer drug methotrexate amid supply shortage. News release. Reuters. November 7, 2023. Accessed November 8, 2023. https://yhoo.it/3QRh3EY
2. Methotrexate injection. American Society of Health-System Pharmacists. November 8, 2023. Accessed November 8, 2023. https://bit.ly/3u5XKix
3. Cancer drug shortage 2023: commitment to our community. News release. University of Utah Huntsman Cancer Institute. July 5, 2023. Accessed November 8, 2023. https://bit.ly/3QPSfNM
4. NCCN releases statement addressing ongoing chemotherapy shortages; shares survey results finding more than 90% of cancer centers are impacted. News release. National Comprehensive Cancer Network. June 7, 2023. Accessed November 8, 2023. https://prn.to/40szN0M
5. Temporary importation of CISplatin injection with non-U.S. labeling to address drug shortage. FDA. May 24, 2023. Accessed November 8, 2023. https://shorturl.at/eiPQZ