Methotrexate Shortage Appears to Have Been Averted

A severe shortage of preservative-free methotrexate that threatened to deprive thousands of cancer patients of necessary treatment appears to have been averted, but the problem is one that has become all too familiar.

Preservative-free methotrexate has been used for 6 decades to treat acute lymphoblastic leukemia (ALL), the most common childhood cancer, and osteogenic sarcoma, a form of bone cancer. These conditions require such high doses of the drug that a preservative-free version must be used or else respiratory problems, organ damage, or even paralysis can result. The cure rate for ALL patients is 90% with proper administration of the drug, and there is no alternative treatment.

The current crisis was triggered by the shutdown last November of 4 Ohio factories by Ben Venue Laboratories Inc, 1 of the 4 manufacturers of generic preservative-free methotrexate, after the company failed an FDA inspection for problems including moldy walls and rusty machinery. As of early this week, hospitals warned that they were on track to run out of the drug within a few weeks.

In response, the FDA has pushed the 3 remaining manufacturers of the drug to pick up the slack. According to the Associated Press, this pressure has born fruit: Mylan Inc is working to increase its manufacturing capacity and will ship some of its emergency reserve of small vials of the drug; Hospira Inc has increased its production but is grappling with a shortage of the drug’s active ingredient; and Sandoz plans to ship some of the drug later this month. In addition, APP Pharmaceuticals LLC, which manufactures a form of methotrexate with preservatives, is trying to get approval to make a preservative-free version.

Concern that needy patients would be deprived of preservative-free methotrexate emerged in a US Senate hearing yesterday when Senator Ron Wyden (D, OR) told Health and Human Services Secretary Kathleen Sebelius that he had been contacted by the father of a 3-year-old girl who could not get the drug, the Wall Street Journal reported. Sebelius assured Wyden that the shortage would be remedied within 2 weeks. The Journal also reported that Ben Venue would release supplies of the drug produced before its factories were shut down.

Methotrexate is just 1 of 283 drugs currently in short supply, according to the AP, including 27 new shortages this year and 215 that began in 2010 or 2011 and continue to this day. Indeed, Ben Venue’s shutdown has also led to a severe shortage of Doxil, a drug for ovarian and breast cancer, of which it was the sole manufacturer. (The FDA is looking into licensing a foreign manufacturer to attend to this shortage.)

To learn more, check out our recent coverage of drug shortages:

Drug Shortages Grab Congress' Attention (Dec. 5, 2011)

Playing the Blame Game over Shortages of ADHD Drugs (Jan. 30, 2012)