Drug shortages raise new fears about patient care
From the December ACP-ASIM Observer, copyright © 2001 by the American College of Physicians-American Society of Internal Medicine.
By Phyllis Maguire
Across the country, physicians are reporting a phenomenon they say has become all too frequent: phone calls from pharmacists and drug suppliers claiming that a drug they've prescribed is not available.
Just a few years ago, such phone calls might cause hostility. What kind of incompetence, physicians used to ask, would lead pharmacies and distributors to run out of drugs?
Today, however, physicians know that drug shortages are an increasingly common—and troublesome—feature of medical practice. As a result, doctors are learning to scramble to find alternatives for everything from beta-blockers and fungicides to hard-to-find antibiotics like oxacillin, gentamicin and penicillin G.
Worse yet, drug shortages are becoming much more frequent because of factors ranging from natural disasters to bottom-line marketing decisions. Ten years ago, shortages were rare and only cropped up with drugs used by relatively few patients, like the cancer drug vincristine. Now, pharmacists and physicians must cope with dozens of shortages each year.
Hospitals have run out of certain anesthetics and now ration the intravenous multivitamin with thiamine solution that physicians use for alcoholic hepatitis and GI bleeds. Dexamethasone and other corticosteroids-used to treat everything from arthritis to asthma to the swelling associated with brain tumors-are in critically short supply. And office-based physicians say they haven't seen any tetanus diptheria vaccine in months.
As shortages grow, physicians worry about the potential effects on patient care. The lack of tetanus vaccine and of corticosteroids, for example, affects many patients. And even smaller-scale shortages raise the specter that physicians who must use unfamiliar drugs might prescribe the wrong dose and harm patients.
Patient care problems
Shortages can be a nuisance for physicians, who get disrupted by calls from pharmacists or patients looking for a suitable alternative. Switching drugs then leads to more calls or office visits to monitor a patient's new regimen-and then even more effort to get patients back on the original medication once it becomes available again.
Besides the hassle, however, physicians worry about the clinical effects of switching medications. "There's always the chance that you'll over- or undertreat" with a new medication, said Yul D. Ejnes, FACP, a general internist with Coastal Medical Inc. in Cranston, R.I., and Governor for the College's Rhode Island Chapter. When physicians have to switch beta-blockers because of a shortage, for example, he said, "You run the risk of not controlling the patient's blood pressure as well during the transition."
Shortages can also force physicians to tailor or forego certain procedures. Denver hospitalist Kelly L. Lepkowski, ACP-ASIM Member, said she wasn't able to order ventilation-perfusion scans for months because of a shortage in a medication necessary for the procedure. Instead, she had to use CT angiograms to evaluate pulmonary emboli, a procedure that costs more and is not suitable for patients with renal failure.
Harmon H. Davis II, FACP, a pulmonologist in Cheyenne, Wyo., and Governor for the College's Wyoming Chapter, said he has had to resort to more expensive alternatives to get around the sodium oxacillin shortage. But he is even more troubled by the national shortage of succinylcholine, a muscle relaxant used for intubations. (Earlier this year, one of his main alternatives—rapacuronium—was taken off the market.) While the hospital where Dr. Davis works still has succinylcholine in stock, he said he is very concerned.
"Besides intubations, we also do bilevel ventilation, where we use succinylcholine to temporarily paralyze the patient," Dr. Davis said. "If the drug goes away, it will imperil our ability to use that form of ventilation."
Physicians are also troubled by the potential for poor outcomes, particularly with influenza and tetanus. (See "Problems with flu vaccine supplies: déjà vu all over again?" below.) Tetanus diptheria vaccine is in such short supply that the vaccine's sole manufacturer is selling it only to hospitals, critical care units and public health facilities.
"It's worrisome," Joseph Y. Bordelon, FACP, an internist with Acadiana Medicine Clinic in Opelousas, La., said about the shortage. Because he must now refer patients to a nearby public clinic for tetanus shots, he said he sometimes finds patients who work in offshore drilling need an injection on the weekend, when that clinic is closed.
"The patient heads out to work offshore for a couple of weeks," Dr. Bordelon continued. "That's a long time to wait for a tetanus shot."
And physicians are increasingly disturbed by the medical errors and quality control problems that can occur as a result of shortages. The ongoing shortage of corticosteroids, for instance, led a physician in northern California to order a batch of betamethasone to be prepared by a local compounding pharmacy this summer. The product ended up being contaminated with bacteria-and linked to the deaths of three patients who contracted bacterial meningitis after being injected.
The Institute for Safe Medication Practices (ISMP) in Huntingdon Valley, Pa., has reported overdoses requiring cardiac resuscitations during last year's fentanyl shortage. In each case, the wrong dose of a substitute painkiller, sufentanil, was prescribed. (See www.ismp.org/MSAarticles/ShortageSurvey.html for more information.)
Who's in charge?
One problem is that no one—including the FDA—is in charge of managing drug shortages, nor is there any early warning system to let physicians and pharmacists know that a drug may soon be scarce. Instead, physicians use an informal network of drug shortage alerts—with much of the information coming from physicians themselves.
The FDA does maintain a drug shortage Web site that it began posting a year and a half ago (www.fda.gov/cder/drug/shortages/). However, the site lists only shortages of drugs the agency deems "medically necessary." To meet that definition, drugs must be used for a "serious" disease or condition and have no alternate supplier or therapeutic alternative.
An FDA spokesperson explained that the agency does not require drug makers to give advance notice about potential shortages, unless the company is the sole manufacturer of a "medically necessary" product. As a result, the FDA gets much of its information on shortages from physicians, pharmacists, consumers and professional organizations like the American Society of Health-System Pharmacists (ASHP), a trade association in Bethesda, Md., that has taken the lead in reporting drug shortages and recommended substitutes. (See www.ashp.org/shortage/#shortages.)
The ASHP in turn gets its information from the Drug Information Service at the University of Utah Hospitals and Clinics in Salt Lake City. "Our most reliable initial source of information is our own buying staff," said Linda S. Tyler, PharmD, the service's pharmacy manager. "They tell us when they're not getting drugs they've ordered. We then see how much of the drug we have and start working with the manufacturer."
That work, Dr. Tyler said, can be frustrating. Often, a drug maker's own customer service division isn't informed about manufacturing problems within the company. Dr. Tyler's service has tracked shortages through weekly phone calls to a manufacturer, for instance, only to learn months later that the product had in fact been discontinued.
The fact that drug shortages are much more common also makes tracking more difficult. National shortages were "very rare" in the late 1980s, Dr. Tyler said, and occurred only two or three times a year in the early 1990s.
Those figures jumped in the mid-1990s to 10 or 15 a year, Dr. Tyler explained. Last year, the University of Utah's service reported about 25 shortages. By October 2001, it had already tracked more than 35 shortages this year.
Analysts say many factors are behind those trends. Natural disasters can interrupt the flow of raw materials, and processing changes can derail production.
Concerns about bovine diseases, for instance, led drug companies to switch from beef to plant proteins in corticosteroids, which necessitated a new round of FDA approvals. That change is partly to blame for the dexamethasone and methylprednisolone shortages.
The ongoing trend toward consolidation among drug companies can result in new mega-corporations trimming their product lines. And manufacturers routinely discontinue old products to make way for new ones, while shareholder pressures regularly lead drug companies to stop making products that don't generate enough profit.
Experts say profitability concerns led Wyeth-Ayerst to stop producing tetanus vaccine products. When a second producer also dropped out of the market, Aventis Pasteur became the sole producer of adult tetanus vaccines. As a result, the company has had to greatly expand its production facilities to fill the need. (According to an Aventis Pasteur spokesperson, full supply and backlog of adult tetanus diphtheria vaccine should be available by mid-2002.)
Manufacturers aren't the only ones to blame. As health plans limit the drugs on their formularies and hospitals tighten spending by cutting drug inventories, national drug shortages can often have an acute local impact. While many hospitals once had a two-week inventory of drugs, most now have only three or four days' worth of many medicines.
In the absence of any central warning system, institutions are improvising ways to address the problem.
"Rationing is a strong word," Dr. Tyler said, "but that's in essence what we're doing." Getting the word out as early as possible to physicians and to pharmacy and therapeutics committees allows them to develop criteria for who will get limited drug supplies and what substitutes will be used.
At the University of Utah, for instance, tetanus diptheria vaccine is now reserved exclusively for trauma patients, while dexamethasone is available to neurologists but not to sports medicine physicians.
Denver hospitalist Dr. Lepkowski gets monthly e-mails on shortages from the staff pharmacists at Exempla St. Joseph's Hospital, where she works. Physicians use that heads-up to plan for shortages and seek out suitable alternatives.
Melvyn L. Sterling, FACP, the College's Governor for the Southern California Region II Chapter and pharmacy and therapeutics committee chair of St. Joseph Hospital in Orange, Calif., said that as physicians and pharmacists become aware of impending shortages, the hospital takes steps to stockpile a drug—a practice that adds greatly to pharmacy costs. The hospital also tries to obtain supplies from alternative sources, including suppliers it doesn't normally deal with or other pharmacies that may not have as great a need for a drug.
The FDA is also getting more involved. Mark J. Goldberger, ACP-ASIM Member, acting director of the office of drug evaluation and drug shortage coordinator for the Center of Drug Evaluation and Research (CDER), explained that the FDA is trying to help drug companies address shortages by rapidly qualifying a new raw material source, for instance, or approving new production facilities.
But while FDA officials try to work with manufacturers to prevent shortages, regulatory—if not statutory—changes would be needed to require drug companies to notify the agency in advance about decisions to discontinue products. The FDA currently has no authority over drug makers' production schedules, even if those schedules affect the nation's drug supply.
Nor has a groundswell of demand arisen for legislation to expand the government's role in the supply chain. "There has certainly been concern in the last year about the range and impact of shortages," Dr. Goldberger said. "But it hasn't yet gotten to the point of substantial discussion of changes that might be necessary to improve the situation." In any event, Dr. Goldberger continued, momentum among policy makers on the drug shortage issue may have been overtaken by concerns about biological attacks.
But David R. Witmer, PhD, ASHP's director of professional practice and scientific affairs, takes a different view. "If anything, recent events are highlighting problems in the national supply chain and demonstrating the public's angst about drug availability," he said. "The discussions about ciprofloxacin and vaccines prove that drugs are critical to national security—and that the drug supply is an issue that needs national attention."
At press time, the country was not experiencing any "shortage" of flu vaccine. According to the CDC, manufacturers are delivering 84 million vaccine doses this year, up from about 75 million last year.
The problem is that many public officials this fall are urging healthy adults—who would normally not get immunized—to get vaccinated against influenza. Reducing the number of flu cases, some officials argue, would cut down on the number of early flu cases that might be mistaken for inhalational anthrax.
But infectious disease experts claim that is bad advice. They say that 60 million Americans (including elderly and pregnant patients, as well as those with chronic heart and lung conditions and compromised immune systems) are considered to be at high risk for influenza. If there is a run on flu vaccines by healthy patients, those at high risk may not get vaccinated, and the number of flu deaths in this country—which already hits 20,000 annually—may climb even higher.
Even if no shortage develops, flu vaccine shipments have been delayed because of production problems that wreaked havoc in the flu vaccine supply last year. Across the country, physicians are giving this year's deliveries mixed reviews. Physicians in Georgia, for instance, received their shipments on time—although Glenn Carter, FACP, an internist in Hinesville, Ga., said in mid-October that he was already vaccinating patients in his office, while his county health department had not received its allotment.
Yul D. Ejnes, FACP, an internist in Cranston, R.I., and Governor for the College's Rhode Island Chapter, said that his practice was getting timely shipments and that prices had gone up "only slightly." He added, however, that his group's shipment may run smoother because his practice buys vaccine directly from the manufacturer through a large purchasing group of 50 physicians.
Not everyone has been so fortunate. Former College Regent Cyril "Kim" Hetsko, FACP, an internist with Dean Medical Center in Madison, Wis., said that while the center usually gets its full shipment by early September, the vaccine had arrived "only in trickles" by mid-October.
Joseph Y. Bordelon Jr., FACP, an internist in Opelousas, La., said he is worried that his usual 1,000 doses will be delivered this year in two 500-count batches. He must administer the first 500 doses before he can get the second shipment. And because he won't be able to return unused doses for a refund—a new policy designed to discourage people from ordering doses of the vaccine they don't need—he is concerned that patients may get vaccinated elsewhere if the second half of his order gets delayed. That will leave him holding outdated vaccines he can't return.
And in San Diego, College Regent Paul E. Speckart, FACP, said that his group may not offer vaccinations at all this year. As of mid-October, when the four-physician group should have been vaccinating patients, the vaccine was not yet available. In addition, the best price being quoted by suppliers was $110 for a vial good for 10 injections. (Last year, that same vial cost $50.) According to Dr. Speckart, manufacturers this year are asking 50% more for the same product, while suppliers are slapping on a 100% mark-up.
"This year's price is double what Medicare will reimburse us for the injections," Dr. Speckart said. Administering the vaccine at that price, he claimed, would cost the group "tens of thousands of dollars."
Unless the price comes down, each physician in the group would basically have to forego one month's salary to absorb the costs of immunizing patients. Instead, Dr. Speckart said, his group will probably forego buying the vaccine—and will tell patients they'll have to get it elsewhere.
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