Opioids in veterinary medicine: Just say “no” (sometimes)

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Cat with dental pain? The answer is opioids. Dog with arthritis pain? Administer opioids. Cocktail for surgery? Opioids. Postoperative soreness? Again, opioids.

Opioids answer lots of therapeutic questions for animals and people alike. They are the brawniest drug class for managing acute pain, and they chip away at chronic discomfort too. But opioids are, so to speak, a double-beveled needle.

According to the Centers for Disease Control and Prevention (CDC), more than 81,000 human drug overdoses occurred during the 1-year period ending in May 2020—the highest annual number of such deaths ever reported—and the overdose rate was accelerated during the pandemic months.¹ Although the killing compounds that drove this jump were primarily synthetic opioids, such as fentanyl, one-third of all overdoses occurred using prescribed medications. In fact, prescription drug overdose is now the leading cause of accidental death in people under 50.²

Where do veterinarians come in? We extensively use opioids and other controlled substances that vary in danger and hooking capacity, from the Schedule IIs, such as hydrocodone, to the IIIs, which include buprenorphine and ketamine, to the less addictive but nonetheless sought-after IVs, such as tramadol and alprazolam.

Whose pill is it, anyway?

The heaviest veterinary use of opiates is within the clinic setting³—say, to deliver analgesia for a surgical procedure. Here, drug diversion by hospital workers is an obvious risk. Simon Platt, BVM&S, FRCVS, DACVIM, DECVN, a professor of neurology at the University of Georgia College of Veterinary Medicine, recalls an issue at the college several years ago with disappearing fentanyl patches.

Students were the suspected users and, for this reason, the institution has phased down its use of patches. But there’s no way to control pills once they go out the door with pet owners. “It’s precarious,” Platt says.

Probably the most common opioid that veterinarians dispense—and that gets diverted from pet to human use—is tramadol. Julia M. Block, VMD, who owns Hamilton Veterinary Hospital in Abington, Pennsylvania, recalls an issue she had a few years ago with a client who regularly requested tramadol for her 2 elderly dogs. She wanted it prescribed through her human pharmacy rather than buying it from Block’s hospital.

When the pharmacy later required that these refills be phoned in, Block checked the owner’s record of refill requests and realized things didn’t add up. “There was no way she should have needed more pills unless she was taking them herself,” she recalls. “So we worked in conjunction with the pharmacist, and we contained it.”

A 2018 survey of 189 Colorado veterinarians found that 44% were aware of opioid abuse or misuse by either a client or a hospital staffer, and 13% had discovered that an owner had intentionally injured or sickened a pet, or made it seem compromised, to obtain controlled drugs.⁴

Clients questing after their own narcotic relief will sometimes “vet shop” until they find a clinic willing to send them home with tramadol and other drugs they typically request by name, such as Valium, Xanax, Buprenex, phenobarbital and, increasingly, the unscheduled selective serotonin reuptake inhibitor trazodone.

Few opioids are approved for animals, and only 2 are now marketed: buprenorphine, for use in cats, and butorphanol, for use in cats, dogs, and horses. But the Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA) permits veterinarians extra label use of certain approved human drugs for animals under certain conditions, availing them of a buffet of opioids and other controlled compounds for pain relief in their patients.

But there’s a downside to treating animals with human medications, maintains Block. She believes owners are more likely to pop their pets’ people drugs than those labeled for use in animals only. “One of the ways that we as a veterinary community can control it is to use only veterinary drugs.”

Is pain such a pain?

Some experts, like Emily McCobb, DVM, DACVAA, clinical associate professor at Tufts University Cummings School of Veterinary Medicine, question the rationale behind chronic therapy with this class of drugs. “It’s not a great idea to have any creature on long-term opioids,” she says.

She points to the early 2000s, when the veterinary community paid far less heed to pain in animals. But, she says, the pendulum has swung wildly the other way.

This is a problem because there is some therapeutic value to pain: It makes animals rest and restore. Furthermore, pain is both hard to define and hard to opine on. “Pain is a subjective state,” she says. “And in people, value systems and even religious beliefs come into play.”

But in our society, she adds, there’s a pill for everything. In a recent study at Colorado State University,³ members of the Veterinary Information Network (VIN) were surveyed about their use of opioids in practice. Most (99.7%) of the nearly 700 respondents reported using, dispensing, or prescribing opioids for their patients.

The survey also found the top 3 opioids used in veterinary practice to be (in descending order) buprenorphine, tramadol, and butorphanol. The latter 2, plus hydrocodone, are the opioids that most respondents reported dispensing or prescribing “frequently.” For in-clinic hospital administration, buprenorphine, butorphanol, and hydromorphone are the apex drugs.

Red tape and super sleuthing

The US Drug Enforcement Administration (DEA) creates and oversees the regulations regarding these and other controlled substances. DEA’s statute 21 CFR § 1301.71 states that “all applicants and registrants shall provide effective controls and procedures to guard against theft and diversion of controlled substances.”

Doctors are also governed by state laws as well as their state boards of both veterinary medicine and pharmacy. When the different sets of rules clash, they are bound to comply with the most stringent.

In response to the growing opioid crisis in this country, 14 states and Washington, DC, now direct veterinarians to report to their state prescription drug monitoring program (PDMP) all instances of dispensing or prescribing opioids and other DEA Schedule II-IV substances.

Many states, in further effort to head off drug diversion from pets to human parents, also require—or urge—veterinarians to look up a pet owner’s pharmaceutical purchase history before providing these medications for their pets. In human medicine, this extra measure has made a difference: The CDC reported a 75% drop in doctor shopping in 2012, a year after a law was enacted mandating that human medical prescribers check their state’s PDMP before prescribing opioids.⁵

Some states have gone a step further by imposing limits on drug quantities and treatment durations. New Jersey, for instance, sets a 5-day maximum on initial opioid prescriptions for both pets and people.

For Block, compliance also means meeting extra marks stipulated by the American Animal Hospital Association. Her hospital’s accreditation requires added record-keeping for bottles coming in, bottles on hand, open bottles, and pill numbers for controlled medications.

But whether veterinarians must count and recount pills, audit their clients’ opioid prescription histories, or just look owners in the eye when they say their pets are in pain, the question holds: Is it the veterinarian’s responsibility to sniff out 2-legged drug users?

Not really, Platt says. “Although we might be suspicious about someone,” he says, “we’re not trained to recognize even obvious signs of addiction in people.”

Dwindling supply

If drug abuse and regulatory burdens are not enough to make veterinarians snub opioids, the opioid supply chain started to burn out 3 years back. By late 2018, hydromorphone, oxymorphone, morphine, and fentanyl (injectable and patches) had become scarce.

The DEA responded to the human opioid abuse epidemic by restricting the quantity of opioids a manufacturer may produce. Compounding matters were production snags at Pfizer, the largest manufacturer of opioids in the United States. The company slashed sales to its veterinary customers because of mandatory upgrades to its newly acquired plant in Kansas.

To alleviate shortages, the Food and Drug Administration (FDA) worked with Pfizer to shunt limited quantities of product from the human to the veterinary side and to import hydromorphone from Canada. But they didn’t work quickly enough.

More than 40% of participants in the VIN study³ said they were hindered in delivering pain relief and optimal anesthesia to their patients. Particularly hobbled were specialty practices and university teaching hospitals, which see critical cases needing complex surgical interventions that often cannot be managed safely under gas anesthesia alone.

Alternatives to the rescue

These shortages have nudged the veterinary community out of its opioid comfort zone, spurring creativity among veterinarians in their anesthesia and analgesia protocols. At the same time, the FDA Center for Veterinary Medicine pushed the use of “non-opioid alternatives, when appropriate, to control pain.”

The move toward multimodal approaches has meant bringing in alternative analgesics that can lessen needed quantities of opiates:

• Local and regional blocks using lidocaine or bupivacaine provide preemptive analgesia; the latter can provide analgesia for up to 72 hours.
• Gabapentin, an anticonvulsant with analgesic properties, reduces neuropathic pain by an unknown mechanism, and can be administered a few days before surgery.
• Ketamine can provide analgesia as a constant-rate infusion or as a one-time dose.
• Dexmedetomidine, an ⍺2 agonist, provides some analgesia and prolongs the duration of analgesia when combined with an opioid.
• Amantadine exerts a pain-modifying effect and may reduce chronic neuropathic pain.
• Maropitant is a central-acting antiemetic that blocks substance P, which is involved in pain processing.
• Nonsteroidal anti-inflammatory drugs (NSAIDS) and corticosteroids modulate pain by decreasing inflammation.

Sedatives, nutraceuticals, acetaminophen (dogs only), weight optimization, physical rehabilitation, acupuncture, cold compression, and environmental modifications (eg, soft bedding) can also reduce pain and pain perception, and ultimately shrink opioid dosing.

Many veterinarians have ditched their Schedule II mu agonists such as morphine and fentanyl, opting instead for partial mu agonists and agonist-antagonists such as buprenorphine, butorphanol, and tramadol. At Block’s hospital, some of the more highly regulated drugs have been switched out in favor of milder formulations, such as trazodone and maropitant.

Like most practitioners, Block also uses tramadol, but she questions its efficacy. So does anesthesiologist McCobb. She refers to the Schedule IV opioid, whose low plasma levels diminish soon after administration, as “tramadil” because of its synergistic use with Rimadyl (carprofen, Zoetis); the latter is thought to be the main driver of pain reduction.

For the sake of both safety and simplicity, Block also reduced her inventory of controlled drugs a few years ago from about a dozen to 5 or 6. “We can still control anesthesia beautifully,” she said.

Opioids… here to stay

While practice owners like Block have started to wean their clientele off of compounds that carry abuse potential, one thing is sure: Controlled meds aren’t going anywhere.

But Block joins a chorus of her colleagues in voicing desire for a uniform, nationwide database to address gaps in current state reporting. If DEA license holders have a platform for “talking” to each another, they might be able to sift out instances of drug diversion, and even animal abuse, and boost industry standards for inventory stocking, tracking, and security.

To this end, the FDA has outlined a 6-step plan for veterinarians who stock and administer opioids:

1. Follow all federal rules on prescribing opioids.
2. Follow all state rules on prescribing opioids.
3. Use alternatives to opioids.
4. Educate pet owners on safe storage and disposal of opioids.
5. Know what to do if a pet overdoses on opioids.
6. Have a safety plan and know the signs of opioid abuse.

Where scheduled drugs are concerned, McCobb reminds us to reduce use, reorganize protocols, and remember this: “We really don’t have control over what happens once those medications leave our office.”

Joan Capuzzi, VMD, is a small animal veterinarian and journalist based in the Philadelphia area.

References

1. Overdose deaths accelerating during COVID-19. Press release. Centers for Disease Control and Prevention. December 17, 2020. Accessed January 12, 2021. https://www.cdc.gov/media/releases/2020/p1218-overdose-deaths-covid-19.html
2. Rudd RA, Seth P, David F, Scholl L. Increases in drug and opioid-involved overdose deaths - United States, 2010-2015. MMWR Morb Mortal Wkly Rep. 2016;65(5051):1445-1452. doi: 10.15585/mmwr.mm655051e1.
3. Kogan L, Hellyer P, Rishniw M, Schoenfeld-Tacher R. The US opioid epidemic and its impact on US general practice veterinarians. Front Vet Sci. 2019;6(222):1-6. doi:10.3389/vets.2019.00222.
4. Mason DS, Tenney L, Hellyer PW, Newman LS. Prescription opioid epidemic: do veterinarianshave a dog in the fight? Am J Pub Health. 2018;108(9):1162-1165. doi:10.2105/AJPH.2018.304603.
5. Opioid overdose: State successes. Centers for Disease Control and Prevention. 2017. Accessed January 12, 2021. https://www.cdc.gov/drugoverdose/policy/successes.html