Teva Pharmaceutical Industries, a leading domestic manufacturer of the sedative, has told the FDA that it will stop producing the product. The decision, which comes on the heels of a $356 million jury award involving use of the company’s drug in Nevada, means that the shortage of propofol likely will become even more aggravating for clinicians, experts said.
Propofol has long been the injected anesthetic of choice in hospitals for both surgery and intensive care applications, and the loss of Teva’s product from the market leaves only two U.S. companies, APP Pharmaceuticals (Diprivan) and Hospira, producing the medication in the United States. However, Hospira has had its own troubles with propofol and has not been shipping the product for more than two months.Denise Bradley, a spokeswoman for Teva, said the decision to stop producing propofol was financial. “The product is difficult to manufacture and has little to no profitability.”
Ms. Bradley said Teva, which hasn’t been making or shipping propofol since mid-April, has not determined what product it will manufacture in the Irvine, Calif., facility where the company produced the sedative.
“We are aware that Teva has announced its discontinuation of propofol,” said Crystal Rice, an FDA spokeswoman. “We continue to work actively with the remaining two manufacturers, APP and Hospira, to ensure that adequate supplies of the drug are available. APP has been covering the majority of the market and we are working with them on increasing supplies further, and Hospira is also working to return to the market as quickly as possible.”
Teva and Hospira have been plagued by manufacturing difficulties since last July that curtailed stocks of propofol by 25% or more. In late 2009, the FDA allowed APP, a division of the European firm Fresenius Kabi Group, to import a version of propofol to ease the shortage. That product, Propoven, has a slightly different chemical makeup from domestic formulations of the drug, but is thought to act similarly in the body.
Despite that decision, hospitals continue to complain of problems with obtaining adequate supplies of propofol. As a result, many anesthesiologists have been forced to switch to alternative sedatives with which they may have less experience. However, supply woes also have affected several other anesthesia-related drugs, including thiopental (Pentothal, Hospira) and certain neuromuscular blocking agents.
A Year's Worth of Problems
Teva’s woes began in mid-July, when the company recalled lots of propofol after at least 20 patients who received the drug fell ill with flu-like symptoms. The company announced that it had discovered high levels of endotoxin in vials of the sedative pulled from the affected lots.
In October, Hospira notified customers that it was recalling batches of propofol and Liposyn, an IV fat emulsion with which propofol is administered, after discovering metal particles in the products.
Hospira eventually restarted production, but in March it recalled its propofol shipments and stopped producing the drug when metal particles were once again detected in the medication.
Daniel Rosenberg, a Hospira spokesman, said the two recalls involved unrelated equipment and manufacturing problems and that it was unclear when the company would resume selling the drug.
“We have made improvements to the manufacturing process for propofol and have begun manufacturing again. However, we haven't released the newly manufactured product because our manufacturing changes are being reviewed by the FDA,” Mr. Rosenberg said. “We will release the product once we have the agency’s approval. We can't speculate on the timing.”
Mr. Rosenberg said Hospira has received no reports of patient harm linked to the glitches.
Teva’s plans to stop making propofol were first reported by the Wall Street Journal. The company could not immediately be reached for comment.
Early this month, a jury in Las Vegas awarded Henry Chanin $500 million in a verdict against Teva and Baxter Healthcare, whom it had previously found guilty of product liability issues surrounding propofol. Mr. Chanin had contracted hepatitis C during an endoscopic procedure for which he received propofol administered through a re-used syringe. The two companies are appealing the judgment.
Ms. Bradley said Teva’s decision “has nothing to do with the Las Vegas trial. That situation was a case of blatant disregard of product labeling.”
Favorable Profile of Action and Safety Makes Replacing Drug Difficult
Marc E. Koch, MD, MBA, president and CEO of Somnia Inc., a major group anesthesia practice based in New Rochelle, N.Y., said the loss of a supply of propofol “creates a problem” for all anesthesiologists regardless of where they work. “Very few medications are quick on/quick off and have almost no side effects,” Dr. Koch said.
For those reasons, Dr. Koch estimated that between “95% to 100%” of the roughly 250,000 anesthetics Somnia clinicians perform each year involve propofol. Now, he added, clinicians may have to resort to barbiturate-based agents with less favorable profiles. “It’s going to be a really tough period for all anesthesia providers,” he said.
Bona E. Benjamin, RPh, director of medication-use quality improvement for the American Society of Health-System Pharmacists (ASHP), called the loss of Teva’s propofol “concerning” and said hospitals could feel the effects in their coffers.
“ASHP surveyed members in late April on budget implications,” Ms. Benjamin said. “Over 80% responded that the shortage had increased costs ‘somewhat’ or ‘significantly.’ Some pharmacy departments are preparing propofol in ready-to-administer doses for anesthesia, an extremely labor-intensive process due to the short beyond-use dating of propofol,” she said. “So, yes, budgets are adversely affected."
Some hospitals and anesthesia groups also have reported price gouging on the part of suppliers, who have taken advantage of short supplies to raise the price on propofol. Dr. Koch, for example, said his company had paid 10 times the usual price for the drug, although he stopped short of calling the hike a gouge.
“I am highly concerned about the prospects of losing Teva as a manufacturer of propofol,” said Tricia A. Meyer, PharmD, MS, director of the Department of Pharmacy and assistant professor of anesthesiology at Scott and White Hospital at Texas A&M Health Science Center, in Temple. “When we were struggling to cope with propofol supply disruptions over the past few months, we used all three current suppliers—Teva, Hospira and APP. If one company had shortages, we’d attempt to order from the others to fill the gap. Now, with Teva pulling out, that flexibility will be gone.”
Dr. Meyer said that Teva's decision to stop manufacturing propofol will severely erode her hospital's flexibility in purchasing the sedative. Such flexibility, she stressed, is crucial for a drug that is “one of the most frequently used products in any hospital—it’s widely used not only in the operating room and in ambulatory surgery, but also in the emergency department and particularly in the ICU.”
Having access to multiple suppliers also provides an important hedge against drug shortages related to FDA sanctions.
“If one plant has a manufacturing issue—as Teva did in 2009—that may cause a supply disruption,” Dr. Meyer said. In these cases, “it helps to have other suppliers available." Having Teva out of the market, she noted, limits a hospital's ability to turn to alternative sources "and may extend the current propofol shortage or potentially even make it worse.”
Dr. Meyer urged Teva “to consider the practitioner” when devising a plan for leaving the propofol market. “I would like to see Teva work closely with FDA and the other propofol suppliers to ensure a smooth transition, with steps taken to ensure adequate supplies of [the sedative] for health care providers,” she said. “This may be a six- to eight-month transition period.”
Ms. Bradley said Teva did consider the needs of clinicians, but ultimately chose to bow out of the market for propofol. “We do understand clinician concerns, but felt we could not manufacture this product any longer,” she said.
Additional reporting by David Bronstein.
