How drug shortages are affecting pediatrics
Delays in treatment, reliance on less familiar medications, key drugs rationed
- Copyright © 2011 by the American Academy of Pediatrics
An executive order signed by President Obama directs the Food and Drug Administration (FDA) to provide more oversight over drug shortages to alleviate this escalating problem that compromises patient safety and medical care.
The order signed in October instructs the FDA to urge manufacturers to provide advance notice of potential issues that could lead to drug shortages; expedite review of manufacturing changes that could prevent medicine shortages; and work with the Department of Justice to investigate possible price gouging and medication hoarding that may have occurred as a result of drug shortages.
Currently, 232 drugs are in short supply. This is more than the record-setting shortage of 211 drugs last year. It also is more than triple the amount in short supply in 2005, when the shortage began to worsen again following a steady improvement the previous five years, according to the University of Utah Drug Information Service.
Most of the drugs in low supply are sterile injectables. The pediatric areas most affected are anesthesia, chemotherapy, neonatology and rheumatology (see sidebar).
What’s driving the problem?
The FDA indicates that more than half of the injectable shortages are due to issues in production quality such as contamination, particulates or impurities discovered in medications. Other reasons given by the FDA for drug shortages include manufacturer delays or capacity issues, drug discontinuations, raw material issues, increase in demand in one medication due to shortage of another drug, loss of manufacturing sites, industry consolidation, and component problems or shortages.
In addition, older drugs may not be as profitable for manufacturers.
“It doesn’t surprise me that a lot of the drugs we are seeing in short supply are off-patent or older drugs,” said Constance S. Houck, M.D., FAAP, chair of the AAP Section on Anesthesiology and Pain Medicine Executive Committee and whose hospital has resorted to importing propofol from Germany because of a shortage of the drug in the United States.
“As a general rule, I think the pharmaceutical companies are more profit-driven and when these companies find that drugs — especially pediatric drugs — are expensive to manufacture and they’re not making enough money because the drugs are off-patent, then they don’t have the incentive to make sure the drugs are available,” Dr. Houck said.
The unavailability of drugs can lead to delays in treatment, less familiar medications being substituted for the more familiar drugs that are in short supply, rationing, or in some cases, death.
According to a survey by the American Hospital Association of 820 hospitals, 82% of hospitals had to delay some treatments, and more than three out of four started rationing or putting restrictions on drugs in short supply.
Dr. Houck said her hospital pharmacy started rationing low-supply drugs by distributing only the dosage needed for procedures rather than full vials.
“We have had to jump through a lot of hoops to get the medicines we need to care for patients and occasionally find ourselves having to use drugs we’re not as familiar with or don’t have as much research about because the drug we normally use isn’t available,” she said.
Eric J. Werner, M.D., FAAP, chair of the AAP Section on Hematology/Oncology Executive Committee, has seen cancer treatments delayed because drugs are unavailable.
Due to a lack of cytarabine, induction therapy treatment for acute myelogenous leukemia has been postponed for some patients. This has created angst for families who were prepared for their children to be hospitalized for several weeks to receive the treatment only to be told there would be a delay because of the drug shortage.
In addition, a shortage of several pediatric rheumatology drugs, including methotrexate, colchicines and anakinara, has given some patients no choice but to seek out the medicines from nontraditional sources, according to Kenneth M. Schikler, M.D., FAAP, chair of the AAP Section on Rheumatology Executive Committee.
In fact, a “gray market” of secondary vendors who purchase and stockpile short-supply medicines and sell them at inflated prices has emerged. A report from Premier, an alliance of hospitals and health care sites, indicates that the average markup for drugs sold by gray market vendors is 650%.
Another problem is that many manufacturers have not been required to notify the FDA of potential drug shortages nor have they been required to explain the reason for the shortage or how long it may last. Experience has shown that early notification can make a difference. In 2010, 38 shortages were prevented when manufacturers notified the FDA in advance, and 99 shortages have been prevented so far this year.
DeWayne M. Pursley, M.D., M.P.H., FAAP, chair of the AAP Section on Perinatal Pediatrics Executive Committee, recently provided testimony to the FDA on behalf of the Academy about the drug shortage problem. Several of the Academy’s recommendations that Dr. Pursley presented to the FDA were adopted into President Obama’s executive order. These include the importance of notification by drug companies about potential drug shortages; the need to broaden reporting of shortages; and the need to examine whether any secondary drug wholesalers or other market participants are hoarding medications or raising prices to gouge purchasers.
Steps for the future
The Academy made additional recommendations to the FDA that were not in the president’s executive order. These included:
develop and maintain a list of critical pediatric medications, including drugs used off-label;
establish the necessary amount of drugs needed to prevent shortages;
build on the existing Strategic National Stockpile, in which critical medications would be stockpiled;
develop a system for real-time, bi-directional exchange of information with providers because, in some cases, pediatricians are the first to learn about a change in supply;
generate and maintain a database of information about foreign and domestic manufacturers of critical drugs;
ensure fair and equitable distribution of drugs that are experiencing a shortage, discontinuance or interruption; and
determine and communicate alternative treatments more quickly.
Dr. Pursley also testified about the important role two laws, the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act, have played in relabeling more than 400 products with pediatric information. Despite the success of these laws, the use of products off-label in children is appropriate standard of care for pediatricians, and could be one reason physicians treating children have learned about some of these drug shortages.
“If anything, the drug shortage should be getting better because of drug regulations and increased pediatric labeling,” said Daniel A.C. Frattarelli, M.D., FAAP, chair of the AAP Committee on Drugs. “But it is a problem that is becoming more common and impacts almost everybody in some way.”
The AAP Washington, D.C., office is monitoring all legislative and regulatory activity related to pediatric drug shortages and will keep AAP members informed as the situation evolves.
Sampling of drugs used in pediatrics in short supply
total parenteral nutrition ingredients
vitamin A injection
To report a pediatric drug shortage or supply issue:
e-mail Tamar Magarik Haro in the AAP Department of Federal Affiars,