Ronda Archangelo never knew until it was too late, that the medicine her veterinarian prescribed for her dog’s seizure disorder, would poison and kill her dog Mimi. She didn’t know that with every dose, she was slowly poisoning her dog with the very drug that was supposed to make her dog better. It wasn’t until her dog died that Ronda found out that the medicine she had been giving Mimi was made with xylitol – an artificial sweetener deadly to dogs.
THE BLACK HOLE
Every year millions of dogs are prescribed human drugs by veterinarians – drugs that might contain the lethal sweetener xylitol. Drug companies do not make public the volume of human drugs prescribed by veterinarians. Nor is it known how often human medicines containing xylitol are prescribed to treat illness in dogs or what the consequences are.
No one knows the number of dogs who become ill or die from drugs that are made with the deadly sweetener. Veterinarians may not be aware that the drugs they prescribe to their patients contain xylitol, and pet parents may never know that xylitol was the reason for their dog’s worsening symptoms or death. And veterinarians are not required to report adverse events of drugs used to treat their patients. Pharmacists ignorant of the fact that some medicines contain xylitol continue to fill the deadly prescriptions. Pharmacists are not required to report errors, errors, pharmacy chains say, are regrettable but rare; but decline to provide data about mistakes. Drug companies are under no requirement to report adverse events in animals prescribed human drugs.
Therefore, it’s impossible to say, with any certainty, just how many cases there are. There are no freely accessible databases for medication errors or adverse events involving human drug use in animals, and even if there were, it would not represent the scope of the problem.
The U.S. Food and Drug Administration (FDA) explains how the agency finds out about problems. An FDA spokeswoman said,
“…sponsors of approved human and animal drugs are required to report adverse events to the agency. In the case of reports involving human products used in animals, they may either be submitted to the Center for Drug Evaluation and Research (CDER), which refers reports involving animals to CVM; or they may come directly to CVM. In the case of veterinarians and pet owners, reporting is voluntary and generally comes directly to CVM.”
THE VETERINARIAN’S ROLE
Ronda had been prescribed an oral solution of gabapentin for Mimi’s seizures by her veterinarian to make it easier for her to administer the drug to her dog. But Mimi didn’t get better. Instead, her health declined, and her seizures became more frequent. And the more seizures Mimi had, the more gabapentin her veterinarian prescribed.
Yet, something struck Ronda as odd with the rapid decline of Mimi’s health immediately after her dose of gabapentin was increased. So she began searching on the internet for answers. And that’s where she found it. The oral solution of gabapentin that she had been giving Mimi was sweetened with xylitol.
Using human drugs in animals is a common practice among veterinarians (under certain conditions, it is legal to use FDA-approved human drugs to treat animals in an extra-label manner). Still, some veterinarians may not be aware that human medications can be sweetened with xylitol. And a drugmaker can change inactive ingredients such as sweeteners without notice, and drugs that were once sweetened with natural sugars can be replaced with xylitol.
While veterinarians are obligated to explicitly communicate with the pharmacy that a prescription cannot contain xylitol, mistakes happen. What Mimi’s vet didn’t realize is that xylitol is frequently used to increase palatability in human medicines, particularly those that are in a liquid or chewable form.
Mimi’s veterinarian should have been aware of her obligation to the State Board of Veterinary Medicine and applicable federal regulations, including FDA’s Extralabel Drug Use Rules (21 CFR 530), but she wasn’t. The rule states in part that,
“Any human or animal drug prescribed and dispensed for extralabel use by a veterinarian or dispensed by a pharmacist on the order of a veterinarian shall bear or be accompanied by labeling information adequate to assure the safe and proper use of the product.”
THE DRUGMAKER’S ROLE
With alarming frequency, medications that were once formulated with simple sugars are now formulated with xylitol. As more and more foods are increasingly being formulated with xylitol, so are medications. Drugmakers that formulate drugs intended for humans are not required to exclude xylitol. When drugs are submitted for review and approval by the FDA, there is no requirement to omit xylitol in their formulas for drugs intended for humans.
An FDA spokeswoman said, however, that some gabapentin oral solutions for human use contain no xylitol; and some contain amounts lower than those known to be toxic to dogs.
“However, there may be instances in which the dog’s condition or liver function status may be poor enough that the veterinarian may want to avoid even the possibility of xylitol exposure. Veterinary drug formularies include the information that human gabapentin products can contain xylitol (Plumbs and Saunders both do).”
Drug companies are under no legal requirement to warn veterinarians or pet owners about human drugs that may have an adverse effect on an animal. Complicating matters are that unlike foods, which are required to list all ingredients, drug companies are not required to list inactive ingredients (also known as excipients or inactive ingredients) such as xylitol.
However, Pfizer, one of the companies that manufacturers gabapentin, does list xylitol as an excipient in its patient insert – a document typically given to patients upon receipt of a prescription. And Acella, the drugmaker that manufactured the gabapentin that was given to Mimi, also lists xylitol as an excipient in its oral formula. However, Ronda’s pharmacist failed to provide her with one.
Because drug companies do not list the amount of xylitol in a drug’s formula, it is left to the pharmacist to contact the manufacturer to find out whether the drug contains xylitol and, if so, in what quantity.
THE PHARMACIST’S ROLE
Unfortunately, pharmaceutical care provided by pharmacies to non-human species may not be as safe as pet owners would like. As more consumers are having their veterinary prescriptions filled online or at a local pharmacy, and not by the treating veterinarian, pharmacists are playing an increasing role in the health care of animal patients. Given this emerging role, pharmacists must contact veterinarians directly with any concerns about the patient’s prescription.
The burden of care has fallen to pharmacists who, because of overwork and increasing pressure from corporate, are making mistakes. A lethal combination of ignorance and fatigue are causing pharmacists to make mistakes. In an explosive piece by the New York Times, the article describes an industry in chaos:
“…pharmacists at companies like CVS, Rite Aid, and Walgreens described understaffed and chaotic workplaces where they said it had become difficult to perform their jobs safely, putting the public at risk of medication errors.
They struggle to fill prescriptions, give flu shots, tend the drive-through, answer phones, work the register, counsel patients and call doctors and insurance companies, they said — all the while racing to meet corporate performance metrics that they characterized as unreasonable and unsafe in an industry squeezed to do more with less.”
Tragically, Mimi’s pharmacy was unaware that under the National Association of Boards of Pharmacy Model State Pharmacy Act requires pharmacies that dispense veterinary drugs to have at least one current reference on veterinary medicines, such as Plumb’s Veterinary Drug Handbook, to reduce the risk for error when pharmacies fill prescriptions intended for animals. Had Ronda’s pharmacy had Plumb’s Veterinary Drug Handbook on hand, they would have seen this warning regarding gabapentin:
NOTE! The oral liquid manufactured for humans may contain the sweetener xylitol; xylitol is toxic to dogs and should not be used in this species.
Unless pharmacists are aware that certain additives in human drug formulations are lethal, disastrous consequences, like the one that happened to Mimi, will continue.
As explained in How Chaos at Chain Pharmacies Is Putting Patients at Risk, an investigation by the New York Times,
“A majority of state boards of pharmacy do not require pharmacies to report errors, let alone conduct thorough investigations when they occur. Most investigations focus on pharmacists, not the conditions in their workplaces.”
Yet, when Ronda’s husband reported the error and Mimi’s death to the Deleware State Department Board of Pharmacy, the director of the board, Sarah H. Siok, expressed deep concern and a promise to help. Although she is aware of the danger gabapentin liquid (with the xylitol ingredient) can be for pets, she says that
“Unfortunately, I don’t think it is common across the board that all pharmacists are aware of the lethal effects this can have, and believe an error such as this could happen again if proper awareness and education are not provided.”
THE DRUG REGULATOR’S ROLE
The FDA that regulates both human and animal drugs are tied to the separate status a drug has: it is either a human drug or an animal drug. Regulators struggle with the problem of straddling the divide between drugs formulated for humans and ones that are given off label or extra-label to treat animal illnesses.
The FDA cannot require a drug company that makes human drugs to notify the agency or the public if a drug has shown to have adverse consequences in animals. The most the agency can do is educate the public, to urge consumers to take care to keep medications out of the reach of their pets.
In a recent FDA update on the dangers of xylitol, Paws Off Xylitol; It’s Dangerous for Dogs, the notice failed to address the risks associated with human medicines formulated using xylitol.
In a separate issue, the FDA issued a warning recently regarding the risk of central nervous system depression in patients prescribed gabapentin alone or in combination with opioids.
In the warning, it was noted that the same risks could be applied to the use of the drug in animals as well, saying,
“the published animal studies suggest that gabapentinoids have an independent dose-dependent depressive effect on respiration and can augment the respiratory depression caused by opioids.”
The tragedy of Mimi’s death was that it shouldn’t have happened. The agonizing heartbreak Robin still suffers is the knowledge that with every dose of gabapentin she gave her beloved dog Mimi, she was inadvertently poisoning her beloved dog little by little.
The catastrophe is Mimi’s death could have been avoided had her veterinarian taken more care, had her pharmacist been aware that human medicines can contain xylitol, had the government issued a warning, had Robin known that the medication she was giving Mimi could kill her – Mimi would still be alive today.
Because drug companies that make human drugs intended for humans that contain xylitol are not legally required to inform pet parents of the public of the risk they pose to dogs. It is incumbent upon the FDA to warn pet parents, veterinarians, and pharmacists about the danger of prescribing human medications that contain xylitol to dogs.
Since Ronda reported the event, to the FDA, the agency has decided to update their xylitol warning page to include the danger of medications that could consist of xylitol. An FDA spokeswoman told me,
“We are also looking at ways to add information about “hidden” xylitol to our recent communication and video, Xylitol and Dogs, A Deadly Combination.“
Adding, “I will let you know when our video and Consumer Update are updated with additional information about the potential presence of xylitol in human oral medications.”
STEPS TO PROTECT YOUR PET FROM MEDICATION ERRORS
Before you give your pet a human medicine, ask your veterinarian if it could be formulated with xylitol. Don’t assume, as Ronda did, that your veterinarian knows whether it is.
Likewise, don’t assume your pharmacist is aware of the medication is intended for a pet and that the drug should not include xylitol. Ask to speak with your pharmacist, especially when the prescription involves a medication that is for your pet. Don’t allow them to rely on their memory or a veterinary drug manual for reference to ascertain a drug’s safety because inert ingredients can change without notice. Make sure your prescription includes a patient insert or patient information sheet, one that should be included with your prescription and read carefully to determine if the inert ingredient listed contain xylitol. Take particular care if your prescription is being filled online.
Inquire of the drug manufacturer if their formula contains xylitol, and if so, in what quantity.
WHO TO CONTACT IF YOU SUSPECT YOUR PET HAS BEEN POISONED
If you suspect that your pet has eaten a xylitol-containing product, please contact your veterinarian, the National Pet Poison Helpline at 800-213-6680 ($59 per incident fee), or the ASPCA’s Animal Poison Control Center at 888-426-4435 (a $65 consultation fee may apply). For owners who cannot afford to call the animal poison control centers, the National Capital Poison Center may be able to help and can be reached at 800-222-1222.
HOW TO REPORT AN ADVERSE DRUG EVENT
For an FDA-approved product, you should report the adverse drug experience to the manufacturer of the drug and the FDA. The drug company responsible for the approved product(s) is required to submit reports of adverse drug experiences and product defects to the FDA.
The FDA suggests,
“When you call the drug company, you can tell them that you wish to report an adverse drug experience or product defect and ask to speak to a technical services veterinarian. The technical services veterinarian will likely ask you a series of questions about the event, will complete an adverse drug experience reporting form and will forward the report to the FDA’s Center for Veterinary Medicine (CVM). The technical services veterinarian may also contact the veterinarian who treated your pet to obtain more information about the adverse drug experience.”
You should also make a report to the FDA by submitting a FORM FDA 1932a, “Veterinary Adverse Experience, Lack of Effectiveness or Product Defect Report.” You can use this form to report adverse drug experiences for any animal drug (approved or not approved by the FDA) or animal device. Unapproved animal drugs include compounded drug products. To do so, download/open the fillable 1932a electronic form.
An FDA spokeswoman explained,
“In the case of reports involving human drugs used in animals, they may either be submitted to the Center for Drug Evaluation and Research (CDER), which refers to reports involving animals to CVM.”
THE IMPORTANCE OF REPORTING ADVERSE DRUG EVENTS
The FDA relies on voluntary reporting by veterinarians and pet parents about adverse drug events to help the Centers for Veterinary Medicine (CVM) determine the frequency and severity of medication errors in animals.
The information collected about these kinds of events helps CVM develop education outreach programs to prevent medication errors in animals. Your report may be the critical action that prompts a modification in the way human drugs are dispensed to animals.
Once the agency learned of Ronda’s report to the FDA, the agency told me,
“Reports like these add to our understanding about the use of FDA-approved human drugs in veterinary medicine.”
More information and instructions on how to report an adverse drug event can be found on CVM’s Web site at: How to Report Animal Drug Side Effects and Product Problems.
If you have a question about adverse event reporting, contact CVM by email at AskCVM@fda.hhs.gov, by phone at 1-888-FDA-VETS (1-888-332-8387)
REPORT TO YOUR STATE BOARD OF PHARMACY
National Association of Boards of Pharmacy (NABP) member boards of pharmacy are grouped into eight districts that include all 50 United States, the District of Columbia, Guam, Puerto Rico, the Virgin Islands, Bahamas, and all 10 Canadian provinces. You are encouraged to report problems with a pharmacy to your State’s Board of Pharmacy located on NABP’s website.
FOR MORE INFORMATION ON XYLITOL
MORE INFORMATION ON DRUG USE IN ANIMALS
MORE INFORMATION ON GABAPENTIN
MORE INFORMATION ON MEDICATION ERRORS
p style=”text-align: justify;”>Veterinary Medication Errors; FDA
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