Used for conditions such as metastatic ovarian and bladder cancer, cisplatin has been in shortage since March 6 due to manufacturing delays and increased demand, according to Accord and Fresenius Kabi, respectively, ASHP reports. WG Critical Care, Hikma, and Teva gave no reason for the scarcity. The manufacturers said they anticipate release dates of this month to late April.
ASHP reported the fluorouracil shortage on March 14, with supplier Fresenius Kabi citing increased demand and Accord and Sagent providing no reason. Fluorouracil is used for cancers in locations such as the colon, breast, pancreas, and stomach. Estimated resupply dates range from this month to June.
The Food and Drug Administration (FDA) reported the Pluvicto shortage on March 7, saying the drug is expected to be unavailable for 4 months. "There are challenges in meeting demand, and no therapeutic equivalents are available," the FDA said.
In a February letter to patients, Novartis said it is working to increase Pluvicto production at two new manufacturing plants when they receive anticipated FDA approval in about 4 to 6 months. The company said the nuclear drug is made in small batches at a manufacturing facility in Italy, with only a 5-day window for each dose to reach its patient and no possibility of stockpiling.
"Any interruption in the process—either caused by unplanned manufacturing events, weather-related shipping delays, or the challenges associated with importing a nuclear medicine into the U.S.—can result in doses not arriving in time," the letter said. "When that happens, impacted doses must be rescheduled and remade, causing the need to also reschedule other patient doses behind them."
In the meantime, Novartis said, it won't take new orders and will prioritize supplying patients who have already received their first doses. Patients awaiting first doses will be rescheduled. The FDA approved Pluvicto in March 2022.
Jonathan McConathy, MD, PhD, of the University of Alabama at Birmingham, told the Wall Street Journal that some patients who would have benefitted from Pluvicto won't receive it in time. "People will die from this shortage, for sure," he said.
No definitive end in sight
While cancer centers and hospital officials told Endpoints News that they have been able to cope with the shortages of methotrexate, cisplatin, and fluorouracil thus far, the lack of definite resupply dates is worrisome.
"At the end of the day, the supply is what the manufacturer has," said Emily Pherson, Johns Hopkins Hospital assistant director of medication use policy and clinical informatics. "And the fact that we're at the point where we're getting it directly means that there could be a risk the supply runs out and that we would have to look towards alternative strategies."
The paucity of methotrexate for intravenous infusion or spinal injection is especially troublesome, experts said, because, in addition to treating acute lymphoblastic leukemia, it is used to treat conditions such as bone cancer and non-Hodgkin's lymphoma.
"Like so many hospitals, we face these types of considerations," Yoram Unguru, a pediatric hematologist and oncologist at Children's Hospital at Sinai and Baltimore, said. While he said he was hopeful the hospital can continue to buy the drug, the shortage results in "time diverted from other important hospital tasks, which increases risk that care will be affected and, of course, sizable financial cost."