How NSAIDs Deliver Big Rewards, but Also Some Risk

And why you need to make it a point to explain how NSAIDs work with your clients.

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To pain specialist Alicia M. Karas, nonsteroidal anti-inflammatory drugs are an incredible tool for managing pain in companion animals but a potential pharmaceutical quagmire that requires veterinarians to tread cautiously.

“They are a godsend,” said Karas, DVM, MS, Dipl. ACVAA, an assistant professor of anesthesia and pain medicine at the Tufts University Cummings School of Veterinary Medicine. “These specific NSAIDs that have been made for dogs and cats have really revolutionized animal comfort.

“At the same time, they are capable of causing adverse effects, and those adverse affects can sometimes be very serious,” Dr. Karas added. “Practitioners often have a healthy awareness of the fact that they should be careful, but if there’s one thing that I’ve found from my interactions with clients, it’s that the clients do not understand the medications we are giving them at all.”

Veterinarians cannot emphasize enough to pet owners about the way NSAIDs are to be used. Printed information as well as verbal discussions when a nonsteroidal is first prescribed and later refilled are paramount.

“[Clients] will not realize they can’t give another nonsteroidal like aspirin,” she said. “They will not report what they are giving when they go to the emergency room, and they will double the dose because ‘If some is good, more is better.’

“I always think you should give them a test: ‘What do you do if your dog has vomiting, diarrhea, black tarry stool or lethargy while on this drug?’ And the answer is, ‘Stop it.’”

NSAIDs and Chronic Pain 

An interesting and somewhat recent finding about NSAIDs, particularly for chronic pain patients, is that longer-term use might be a better approach, said B. Duncan X. Lascelles, BVsc, Ph.D., CertVA, Dipl. ACVS

“That doesn’t necessarily mean lifetime use,” said Dr. Lascelles, a professor of surgery and pain management at the North Carolina State University College of Veterinary Medicine. “It just means a longer-term use to, in particular, help reset the central nervous system.

“Whenever there’s pain,” he said, “the central nervous system gets fired up, becomes hypersensitive, and the current thinking is that a longer course of nonsteroidals [over several months] can help reset the system.

“We have some clinical evidence this is the case, but solid evidence to show the NSAIDs can reset the system is currently lacking.”

A human study published this year in the Journal of Pain demonstrated that the COX-2 inhibitor etoricoxib given daily for one month significantly modulated the peripheral/central sensitization and temporal summation in patients with painful knee osteoarthritis.1 

“In many respects, we are neck and neck with the human field on the thinking about how best to use nonsteroidals,” Lascelles said. “I can say that because of the studies in veterinary medicine and human medicine that have looked at the benefits of longer-term use, and we’re both thinking along the same lines.”

NSAIDs and Cats 

The U.S. Food and Drug Administration has approved two NSAIDs for use in cats: robenacoxib (Onsior), both oral and injectable, and meloxicam (Metacam), as a single injectable dose. But the topic of using NSAIDs to treat chronic pain in cats is complicated.

“As a rule, veterinarians in the United States really are at a loss for what to use for chronic pain in cats,” Karas said. “Despite what I’m presenting to veterinary students, they come out of fourth year thinking you can’t use nonsteroidals chronically in cats. And that’s what most veterinarians think. They think that because of the black-box warning on Metacam.

“Almost everything on your shelf that you prescribe for cats is off-label. Using Metacam chronically in cats is off-label, but it doesn’t mean it’s illegal.”

Karas pointed out that Meta-cam is not approved for chronic use in U.S. cats but is permitted in Europe and Canada. As with many other drugs used off-label, veterinarians must weigh the benefits versus the risks.

“Pain is a disease just like cancer and infection,” Karas said. “There are times when we’re going to take the risk because it means a better quality of life and a longer life in a lot of cases.

“If you’re saying, ‘I can’t use it because it’s not approved by the FDA,’ then you have to pretty much wipe off many of the bottles of pills and injections on your shelf because they are not approved for use in cats.”

Robenacoxib can be very effective for cats suffering from chronic osteoarthritis pain, but some veterinarians are hesitant to use it if the patient has concurrent kidney disease. However, a recent study Lascelles was involved with found that robenacoxib was well-tolerated when given daily for one month to osteoarthritic cats, even if the animals showed evidence of chronic kidney disease.

“The concern is using nonsteroidals and making chronic kidney disease worse or progress more quickly,” Lascelles said. “Many veterinarians will not use nonsteroidals in a cat with chronic kidney disease. Other veterinarians will, hopefully doing it cautiously, recognizing that you can use nonsteroidals long-term in cats with chronic kidney disease and that the chronic kidney disease does not necessarily get worse.

“The most important aspect is to carefully select the patient in which to use NSAIDs.”

Managing Side Effects 

When veterinarians have a patient that does not tolerate one NSAID, they might wonder about trying a different one.

“I have had patients who could not tolerate carprofen [due to stomach upset] who did just fine on meloxicam, and vice versa,” said Robin Downing, DVM, Dipl. AAPM, Dipl. ACVSMR.

“That said, if I have a patient who experiences any adverse event with two NSAIDs, then I choose not to offer a third,” Dr. Downing added. “Odds are pretty good at that point that I have a patient who simply cannot tolerate this class of medication.”

Although rotating different NSAIDs over time can be fairly routine in human medicine, Downing doesn’t recommend the practice in veterinary medicine.

“There is really no compelling evidence to suggest that this is useful, and no controlled studies to suggest it should be or needs to be done,” said Downing, the hospital director at Windsor Veterinary Clinic and the Downing Center for Animal Pain Management in Windsor, Colo.

A study published in the Veterinary Journal found low rates of reported adverse NSAID events in British animals.

“They also did a really sophisticated analysis of how the drugs that had been on the market for longer probably had a reduction in the reporting of adverse events and that one of the problems with knowing about the safety of these drugs is that practitioners do not take the time to report the adverse effects to the drug companies,” Karas said. “We should be doing that. And I’m guilty.”

NSAIDs Are Not Enough 

Veterinarians need to understand that chronic maladaptive pain, in order to be addressed effectively, requires a multimodal approach, Downing said.

“Multimodal pain management does not mean having three NSAIDs on the shelf in the pharmacy,” she said. “[It] means carefully assessing each individual patient and targeting the various sources of their pain with appropriate tools.”

Downing routinely sees referral patients that present with pain palpation scores of 7 to 8 out of 10 despite NSAID use for months or even years.

“These are patients who suffer needlessly,” Downing said. “It is not the owner’s job to tell us their pet is [in pain]; it is our medical and moral obligation to inform them when their pets suffer pain.

“It is not about a particular NSAID ‘no longer working.’ It is simply the fact that a NSAID alone is not sufficient as a single agent.”

References

  1. Arendt-Nielsen L, Egsgaard LL, Petersen KK. “Evidence for a Central Mode of Action for Etoricoxib (COX-2 Inhibitor) in Patients With Painful Knee Osteoarthritis.” Pain. March 22, 2016.
  2. King JN, King S, Budsberg SC, Lascelles BD, Bienhoff SE, Roycroft LM, Roberts ES. “Clinical Safety of Robenacoxib in Feline Osteoarthritis: Results of a Randomized, Blinded, Placebo Controlled Clinical Trial.” J Feline Med Surg. June 9, 2015.
  3. Hunt JR, Dean RS, Davis GND, Murrell JC. “An Analysis of the Relative Frequencies of Reported Adverse Events Associated With NSAID Administration in Dogs and Cats in the United Kingdom.” The Veterinary Journal. Volume 206, Issue 2, November 2015.

Originally published in the August 2016 issue of Veterinary Practice News. Did you enjoy this article? Then subscribe today! 

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