SILVER SPRING, MD. – With their increasing prevalence, drug shortages in the United States have led to delays in treatment, forced the use of less effective alternatives, and encouraged a burgeoning gray market that sells tough-to-obtain medications at highly inflated prices, according to stakeholders gathered at a recent FDA meeting.
Shortfalls in drug supply have increased in the United States, with 178 shortages of products reported in 2010, up from 61 in 2005, according to Dr. Edward Cox, coordinator of the FDA's drug shortage program. Disproportionately affected are generic drugs and sterile injectable products; the latter accounted for two-thirds of the shortages last year.
About half of the injectable shortages were caused by problems with product quality, followed by manufacturing delays (21%) and discontinuations (11%), and other issues including an increase in demand created by another shortage, he said at the meeting.
As with older generic drugs, there's little financial incentive to produce older sterile injectables such as propofol, which sell for as little as 48 cents for a 20-mL vial. In such cases, manufacturing glitches can often convince companies to pull the plug on a product, creating shortages.
Most hospitals aren't immune. A June 2011 survey of 820 nonfederal, short-term, acute care hospitals by the American Hospital Association found that almost 99% had experienced one or more drugs shortages in the first 6 months of 2011; 44% reported at least 21 shortages during that time. In addition, nearly half reported experiencing drug shortages on a daily basis, 40% on a weekly basis, and 13% on a monthly basis.
Almost all these hospitals (96%) had experienced shortages of anesthesia for surgery, followed by drugs used for emergency care (91%), cardiovascular care (90%), GI/nutrition (89%), pain management (88%), infectious disease (83%), and oncology (66%).
Drug shortages have hit the fields of oncology and anesthesiology particularly hard, often causing the delay or postponement of clinical trials of cancer treatments.
Shortages of propofol and succinylcholine have been common. Dr. Frederick Blum, past president of the American College of Emergency Physicians, who practices in Morgantown, W. Va., described being told there was no succinylcholine available when he recently requested it as he was about to intubate a trauma patient. When he asked for the next best drug, it wasn't available either because supply had been depleted from the succinylcholine shortage. A third, less-than-ideal alternative was found. But Dr. Blum said that after 30 years of practice, during which time he probably has used succinylcholine thousands of times, he left that shift shaking his head about the need to resort to using a third-choice drug.
Before the shortage of succinylcholine was resolved earlier this year, shortages of the agent also resulted in postponed surgeries at Veterans Administration Medical Centers.
Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society, noted that many generic cancer drugs are in short supply. Such drugs, developed years ago, often are inexpensive and “remain mainstays of many currently available and effective cancer treatment programs,” he said.
Generic cancer drugs that are in short supply include fluorouracil (5-FU), paclitaxel, daunorubicin, cytarabine, bleomycin, and cisplatin.
In many cases, such shortages are causing patients to have to travel further to get the drugs they need. Alternatively, they are treated with second- and third-line therapies that are not necessarily as effective, Dr. Lichtenfeld said. Many adult and pediatric trials of cancer treatments have been suspended when supply of the active control drug is no longer available, he added, and ACS is regularly contacted by patients and families who are looking for medications in short supply.
Exacerbating a shortage situation is the emergence of gray markets that trigger hoarding, he said.
Dr. Laura Porter of the Colon Cancer Alliance said that there have been shortages of 5 of 22 drugs used to treat for colon cancer, including 5-FU and leucovorin. Of the five, four are generic drugs. Last year, there were eight manufacturers of irinotecan, another drug used to treat colon cancer; today, there are only two, and the FDA has asked another company to start manufacturing the colon cancer agent.
At St. Jude Children's Research Hospital, Memphis, 1-4 drug shortages were reported every month in 2009, but in 2011, an average of 22 shortages have been reported every month, peaking at 28 in July. Notable shortages over the past year have included every component of total parenteral nutrition (TPN) and multivitamin injections, with the latter resulting in a hospitalization of a patient who could not take oral multivitamins and developed neurotoxicity and a thiamine deficiency, said James Hoffman, Pharm. D., the hospital's medication outcomes and safety officer.