ASH Presses for Action on Hematology Drug Shortages

The American Society of Hematology (ASH) is sounding a fresh alarm about ongoing supply problems with oncology drugs, saying this week that shortages of medicines used to treat patients with hematologic malignancies “have become critical and life-threatening.”

“An increasing number of physicians have been forced to take their patients off therapies midtreatment, delay treatment, choose alternative therapies that are less effective, and ration their remaining supplies of these therapies,” the society said in a statement posted on its Website.

ASH cited several drugs used to treat leukemia and lymphomas. The society is contacting pharmaceutical companies to gather information about the needed drugs and is working with lawmakers to seek remedies.

The expression of concern from ASH is the latest example of anxiety over nationwide drug shortages, which began in 2009 and rose to record levels by the end of last year, experts say. Approximately 75% of the shortages involve chemotherapy sterile injectables, FDA has reported.

The shortages have forced US institutions and practices to rethink protocols for the distribution of medications, while manufacturers continue to work toward rectification of the problems.

“There have been oncologic drug shortages going on for over a year,” according to Tatyana Feldman, MD, attending physician of the Lymphoma Division at John Theurer Cancer Center (JTCC) at Hackensack University Medical Center in New Jersey, who specializes in the treatment of lymphomas. “There have been over 10 different drugs on the ‘endangered species’ list, on and off, depending on situation. What is particularly troublesome is that these are deadly, but curable diseases, and not adhering to the schedule or regimen may jeopardize the outcomes.”

Some manufacturers have adequately addressed the problem, while others have not offered solutions. Bristol-Myers Squibb released one of its “endangered” agents, carmustine (BiCNU) in March, and, according to the FDA, the company anticipates no further supply issues.

Cytarabine, manufactured by APP (ARA-C) and Bedford Laboratories (Cytosar-U), is still in short supply. Cytarabine is used in combination with other drugs for remission induction in acute nonlymphocytic leukemia of adults and pediatric patients. It is also used to treat acute lymphocytic leukemia, the blast phase of chronic myelocytic leukemia, and as prophylaxis and treatment of meningeal leukemia. APP has limited supplies of ARA-C available. Bedford Laboratories has all requests for the Cytosar-U on back order.

The shortages have forced US institutions and practices to rethink protocols for the distribution of medications.

Thiotepa for Injection, also manufactured by Bedford, is used to treat lymphoma and cancers of the breast, ovary, bladder, and this drug is also in short supply. However, Adienne Pharma & Biotech, a company located in Italy, is coordinating with the FDA to increase the availability of Thiotepa, by initiating a temporary importation into the US market of Tepadina, a European Medicines Agency-approved version.

Tepadina contains the same active ingredient as the US-registered Thiotepa, but is provided in 2 different size vials—a 15-mg vial and a 100-mg vial. The 15-mg vial contains the same amount of active ingredient as the FDA-approved Thiotepa. According to an Adienne Pharma & Biotech press release, both vial sizes of Tepadina are a clinically acceptable substitute to the Thiotepa that is marketed in the US. The choice of vial size will depend on the specific indication and the patient.

Feldman said that the shortage has been very stressful for the staff and physicians at JTCC. “We have a certain policy in place. Since most of chemotherapy is done on schedule, our pharmacy gets the schedule several weeks in advance of when the chemotherapy is planned. Our pharmD makes sure that the pharmacy has it available. Each Friday an e-mail is sent to all the MDs and related professionals with the name of the medications on the shortage list, with a severity index.”

A measure intended to avoid future drug shortages, The Preserving Access to Life-Saving Medications Act (S-296), introduced by Senators Amy Klobuchar of Minnesota and Robert Casey, Jr, of Pennsylvania, proposes a warning system whereby manufacturers provide the FDA with a notification of discontinuation or prolonged interruption of a medication’s production.

The bill has been referred to committee. ASH has developed an advocacy campaign to encourage congressional support of S-296. The society has set up an ASH Advocacy Center (http://grassroots.hematology.org/blood/home/) to encourage oncologists and hematologists to contact their senators and relay to them the impact the shortage has had on their patients.