When performing certain procedures, many otolaryngologists use succinylcholine, a neuromuscular blocking agent, to help them monitor the facial nerve.
“We need a rapid-onset but short-acting muscle relaxant so that we can paralyze the patient for intubation but not have them paralyzed for the duration of the surgery,” said David Steward, MD, associate professor of otolaryngology and director of the Division of Thyroid/Parathyroid at the University of Cincinnati College of Medicine.
There’s just one problem: Otolaryngologists might not be able to get the drug. Succinylcholine is one of some 160 drugs currently listed by the American Society of Health-System Pharmacists (ASHP) as affected by a nationwide shortage of prescription medications.
“Drug shortages have been occurring for decades, but the situation is much worse now than it has ever been before,” said Allen Vaida, PharmD, executive vice president of the Institute for Safe Medication Practices (ISMP). As of the end of 2010, the University of Utah’s Drug Information Service, which tracks medication shortages, lists 211 drugs as being in short supply or unavailable for at least part of the year. That compares to 166 in 2009 and 149 in 2008. It’s more than double the number listed in short supply just five years ago.
The current shortage involves many different types of medications, mostly hospital-based: chemotherapy drugs, antibiotics, anti-anxiety drugs, parenteral nutrition preparations and a number of others. But, in their hospital and office-based surgical practices, otolaryngologists have mostly been affected by shortages in anesthesia and analgesia medications such as succinylcholine, propofol and tetracaine.
“We had a particularly bad shortage of succinylcholine a couple of months back, which seems to have lessened right now,” Dr. Steward said. “But for nearly six months, our hospital had extremely limited supplies; either it was totally unavailable, or we could get it only in very limited quantities. We were noticing that the anesthesiologists were using it exceedingly sparingly, because they were trying to save what little they had. They wouldn’t use it unless it was absolutely necessary. Or in some cases, the anesthesia staff would use a subtherapeutic dose of a longer-acting muscle relaxant, in order to get it to wear off more quickly.”
Propofol, another anesthesia drug that has been in short supply over the past year, is also well suited for otolaryngology procedures. “It’s an excellent, very quick-on and quick-off IV anesthetic. I like it a lot for the procedures that I do,” Dr. Steward said. “The anesthesiologist can titrate the drug either using a pump or with small boluses, in order to keep the patient asleep just for the length of the procedure. As soon as the case is over, we can wake them up and extubate them without having to wait a long time as we have to do with narcotics and inhalation agents, which tend to stick around longer.”
Propofol is back in most pharmacy cabinets now, but the situation is far from ideal. The shortage originally began because two of the three U.S. manufacturers of the drug had problems in their plants, one related to sterility and the other having to do with metal particles in the compound. The U.S. Food and Drug Administration (FDA) ultimately cleared both manufacturers to restart propofol production, but one elected not to.
“So the supply was significantly impaired—right at the time of the worst of the economy—and it never really came back,” said Mauricio Gonzalez, MD, assistant professor of anesthesiology at Boston Medical Center. “The FDA issued an emergency dispensation that allowed us to get propofol from Europe, and a large amount of the supply is now coming from there. The problem is that all manufacturers have different preparations in terms of their inactive ingredients and the media used for suspension of the drug, and you really don’t know which brand you’ll have from week to week.”
Another drug popular for certain otolaryngology procedures recently disappeared from the market altogether. Production of tetracaine, known by the brand name Pontocaine, was discontinued in mid-2010 by its sole manufacturer, Hospira.
“This was a long-acting topical anesthetic agent that was very useful for office-based laryngeal procedures,” said Gregory Grillone, MD, associate professor and vice chair of the department of otolaryngology-head and neck surgery at Boston Medical Center. “I used topical Pontocaine for anesthetizing the surface of the larynx and the surrounding areas during procedures such as flexible endoscopy and lasering of a polyp or lesion, or for a biopsy. It was a much better topical anesthetic than the conventional varieties we are now forced to use, such as lidocaine and novocaine, which are not quite as potent or as long-lasting.”
The implications of ongoing drug shortages can be far more severe than just frustration or inconvenience. Switching from one drug to another usually means an entirely different dosage and side effect profile, which leaves the door open to medical errors. According to a survey done by the ISMP last fall, in at least six cases, patients have died because of mix-ups and dosing errors related to medication shortages. Even when the outcomes haven’t been so dire, a number of patients have experienced adverse events, ranging from respiratory problems to blood clots to hemorrhage.
“We had a very limited supply of morphine last year, which we use frequently with ENT patients,” Dr. Gonzalez said. “So we had to substitute hydromorphone, which is seven to 10 times more potent. That’s very risky when you’re not used to the dosage. Every time we have a shortage and have to change the way we practice, it’s not just forcing us to choose a drug that might be more costly or not do the job quite as well, but it’s also opening the door for accidents.”
And hospitals, physicians and pharmacists never know what’s coming next. “Neostigmine, a drug we use to reverse the effects of certain muscle relaxants, went short a couple of weeks ago,” Dr. Gonzalez said. “We were told at 4 p.m. on one day that we’d run out the next day, so we had to scramble to find options. There is another drug we can use [Enlon-Plus], which is as good but pretty expensive, so we hadn’t used it for decades. They were able to get it in, but then I had to in-service 115 people overnight on how to use this drug, because none of them had used it in 10 years.”
There’s no one culprit; rather, a confluence of factors seems to be behind the sudden medication supply crisis. Many of the drugs running short are generics, which offer no real incentive for a manufacturer to get into the game, so there may be only a handful of suppliers—or even just one. When one supplier shuts down production temporarily, perhaps because of contamination in the supply chain, or due to a shortage of raw materials, the other suppliers, if any, may be hard pressed to ramp up production in time, Vaida says.
Meanwhile, about 80 percent of the raw materials for many drugs come from overseas at a time when there is a great deal of unrest going on. The economic downturn of 2008-2009 also played a role, putting pressure on companies to quickly shut down product lines should they become less profitable. “All of these factors have come to a head at the same time,” Vaida said.
So what can be done? According to ASHP, the American Society of Anesthesiologists (ASA) and the American Society of Clinical Oncology (ASCO), drug manufacturers should be required to notify the FDA ahead of time when they anticipate a slowdown or an interruption in the supply of a certain drug. Right now, manufacturers usually don’t have to give any early warning of an impending shortage.
If you learn of a shortage, ASHP wants to know about it. Bona Benjamin, ASHP’s director of medication-use quality improvement said to report shortages at ashp.org/shortages. “It’s not restricted; anyone can report a shortage if they know that one is pending,” she said. “We can make sure that the FDA knows about it. They’ve told us that sometimes our notifications have been their first alert to a shortage. This gives them more latitude to get plans in place.”
Senators Amy Klobuchar (D-Minn.) and Bob Casey (D-Pa.) have introduced a bill that has been called an important first step to resolving the drug shortage crisis. The Preserving Access to Life-Saving Medications Act (SB 296) requires prescription drug manufacturers to give early notification to the FDA of any incident that would likely result in a drug shortage. “Last year the FDA actually averted over 30 drug shortages when they had advance communication about them,” Vaida said. “If they know beforehand, the FDA can work with manufacturers on quality issues, fast track inspections and work with other manufacturers to see if they can take up some of the slack.”
But that’s only one step, he added. ASHP, which hosted a summit meeting on the drug shortage in November 2010, has taken the lead in bringing together groups of physicians, pharmacists and others involved in the issue, including manufacturers, group purchasing organizations, third-party payers and professional societies such as ASA and ASCO (because chemotherapy and anesthesia drugs have been among the hardest hit).
“They’re working on supply and raw materials, regulatory issues and distribution issues, hoping to address some of the other factors that lead to shortages,” Vaida said. “But in the meantime, a lot of the unpredictability is still going on. We don’t know what will be short when. Nobody has a good handle on what is going to hit next.”