Officials at at least one U.S. hospital admit they've discarded the scarce cancer drug doxorubicin in order to comply with strict regulations for storage and sterility.
Mounting shortages of crucial drugs are creating a new dilemma for the nation’s hospital pharmacists, who say they find themselves caught between breaking government rules for storage and safety -- or throwing away vital and lifesaving medications.
At one hospital in Florida, officials acknowledge they’ve discarded the scarce cancer drug doxorubicin, even as patients nationwide clamor for treatment.
“I’d never want to take a chance with not following the rules,” said Alan K. Knudsen, director of pharmacy legal services for Shands HealthCare at the University of Florida in Gainesville. “I wish I didn't have to throw it out."
Others, however, admit they’re bucking regulations imposed by federal agencies, including the Centers for Medicare & Medicaid Services, in the interest of patient care, as long as they have strong scientific evidence that the drugs are still safe.
"With the medications in very high need, we are using it," said Thomas Burnakis, coordinator of pharmacy clinical services at Baptist Medical Center in Jacksonville, Fla. It would gall him, for instance, to toss midazolam, a widely-used anesthetic known as Versed that has been in short supply for months, simply because it exceeded arbitrary storage limits.
“I am not throwing out the rest of that Versed,” he said.
And in the eyes of some patient care experts, he shouldn’t have to.
Organizations such as the Institute for Safe Medication Practices and the American Society of Health-System Pharmacists are raising questions about federal rules they believe exacerbate a crisis that saw 267 drugs in shortage last year, up from 211 the year before, the most in U.S. history.
“It’s really a major issue,” said ISMP president Michael R. Cohen. “It’s a waste of money and it’s a waste of drugs in short supply.”
Most drugs, including those in shortage, have specific requirements for handling that limit how long and in what manner they are stored or how quickly they must be used after they're opened, industry experts say. Some must be refrigerated; others must be used within 24 hours after opening, or even immediately.
Those requirements should be listed in the official prescribing information package inserts that are approved by the federal Food and Drug Administration when a drug is cleared. But the directions may be incomplete or outdated. It can be costly and time-consuming to seek new FDA label approval, so updated science often doesn't make it into the inserts.
ISMP officials contend that pharmacists are hamstrung by Medicare regulations that require them to follow only the manufacturers’ package instructions for storage and use of medication, even when it's not current -- and even when there’s valid new scientific information available.
For instance, take the widely-used neuro-muscular blocker succinylcholine, which has been in shortage off and on for more than a year.
"The manufacturer says it's good for two weeks outside the refrigerator, but the literature says it would be good for three weeks or a month," said Allen Vaida, executive vice president for the ISMP. "That period makes a big difference when you're talking about a drug shortage."
According to CMS interpretive guidelines for the agency's standard 482.25, “drugs and biologicals are stored in accordance with manufacturers’ directions and State and Federal Requirements.”
But a recent analysis conducted at Cedars-Sinai Medical Center in Los Angeles confirmed that directions for many of the drugs in shortage are flawed or lacking. Of 50 random drugs on the national shortage list, a third lacked basic information about compatibility with diluents and half lacked information about stability, storage and expiration dates after dilution, according to an ISMP report.
When pharmacists ask the manufacturers directly, the answers still may remain unclear, ISMP officials said. In that case, pharmacists often turn to recent studies or other accepted industry documents for guidance -- or they face trashing drugs based on falsely cautious parameters.
It's not clear what volume of drugs in shortage is being discarded. Officials with federal agencies including CMS and the Environmental Protection Agency say they don't keep those figures. Individual hospitals say they have no incentive to track them.
ISMP officials have launched a survey of the agency's members to determine the extent of the problem and to decide whether the group should petition CMS to relax the rule. Results are expected this month.
Dr. Patrick Conway, chief medical officer for CMS, says that the agency is willing to talk to ISMP about alternatives.
“The concern is that we don’t currently have another standard to apply,” Conway said. “The manufacturers’ label is a Food and Drug Administration-approved label.”
Hospitals found to violate storage and stability rules could face CMS fines or other sanctions.
Even when there are trusted regulations, such as the pharmaceutical compounding directions issued by the U.S. Pharmacopeia -- known as USP 797 -- being forced to toss limited drugs can put pharmacists in a quandary, said Bona Benjamin, ASHP’s director of medication-use quality improvement.
“In these situations, clinicians are likely to question whether there’s greater benefit or risk to the patient if medications that are scarce must be discarded,” she said, adding that ASHP officials support 797's science-based rules.
Other experts say they know some pharmacists are side-stepping requirements from the USP, the nonprofit organization that sets standards for drug safety and sterility, in order to conserve medications already in short supply.
“If I know I’ve got 10 single-dose vials to last me through the week, and 30 procedures, I have to make those 10 vials last,” said Gigi Davidson, a veterinary pharmacist at North Carolina State University who heads pharmacy compounding for the USP council of experts. “I am clearly stepping away from the standard when I make those choices.”
Pharmacists are repackaging drugs into smaller units, stretching the medications to serve more patients, even when the USP 797 rules warn that there's more risk of problems such as contamination and infection. The important thing is to make sure proper aseptic technique and procedures are followed, Davidson said.
“It makes me nervous, but it’s something I do with eyes wide open,” she added.
While the dilemma for the pharmacists is acute, some cancer patients believe there should be no question at all. Maggie Heim, 58, of Hermosa Beach, Calif., is a lawyer who was diagnosed in 2009 with stage 3 ovarian cancer.
She was prescribed the cancer drug Doxil, which has been in short supply since last year, particularly after a troubled contract manufacturer, Ben Venue Laboratories Inc., suspended operations last fall. She was placed on the Doxil waiting list arranged by Janssen Products LP, the Johnson & Johnson subsidiary that owns the drug's patent. She never received the medication, though, and had to be treated with a different protocol.
During her treatment, several other medications used to treat ovarian cancer were added to the drug shortage list.
“Give that I am fighting for my life, I would be very upset if I found out that a pharmacist was required to throw out a drug I needed that is in shortage,” said Heim, adding: “How could a pharmacist pour it down the drain when it is so needed to keep people alive?”
Some pharmacists refuse to take the risk. At Shands HealthCare, Knudsen, the pharmacy legal director, says rules are rules, even when drugs are in short supply. His hospital has been able to transfer doxorubicin patients safely to other drugs, he said.
"The Florida Board of Pharmacy and USP 797 rules were created to protect patients," Knudsen said. "Selectively choosing which rules to follow, particularly when alternatives to doxorubicin exist, seems risky."
Davidson agrees that standards should not be relaxed to accommodate the crisis of the moment.
"If it’s not drug shortages, it’s going to be something else,” she said.
At the same time, she understands the Catch-22 faced by a pharmacist who knows the drugs he discards could save someone’s life.
“Then I have to do some soul-searching,” she said. “Am I afraid of harming the patient, and that’s why I throw it away? Or am I afraid of regulatory authority?”
If it’s the latter, the pharmacist should seek guidance from the state board of pharmacy before tossing the medication, she said.
As far as experts can say, no hospital has yet faced sanctions for failing to discard drugs during the current shortages. “If someone comes in and surveys, there probably would be hell to pay,” said Burnakis, the Baptist Medical Center pharmacist.
But any sanctions, even in the case of patient harm, would have to be tempered with the reality of trying to salvage life-saving drugs in the midst of a crisis, Davidson said.
"If I were sitting on the jury and someone had to choose to stray from 797 to provide a needed drug to serve a child with cancer, I know exactly how as a juror I would vote."
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