What with the national epidemic of opioid addiction and tighter federal quotas on the narcotics, rumors are flying that veterinarians, who have had difficulty for more than a year obtaining the painkilling drugs, are being deliberately cut out of the loop.

And they are — but not for the reasons some suspect.

Pfizer, a leading manufacturer of injectable opioids, decided to suspend sales and delivery of the drugs to veterinary customers while it grapples with a supply shortage caused by multiple manufacturing problems.

“We value all customers and understand the importance of these medications, and regret the current need to prioritize shipments to hospital and surgical trading partners,” Pfizer spokesperson Steven Danehy said by email.

Danehy said the company does not anticipate fully recovering from the shortage until the second quarter of 2019. It will resume selling to the veterinary market then.

Pfizer halted veterinary sales and shipments during the second quarter of 2018 — Danehy did not have a precise date — but the shortage dates to June 2017, when Pfizer began upgrading a manufacturing plant in McPherson, Kansas, resulting in reduced output, according to the company.

Veterinarians and other health professionals started feeling the effects soon after. In January, the Veterinary Information Network, an online community for the profession, held a Rounds, or webinar, on strategies for coping with opioid shortages.

Following Pfizer’s manufacturing slowdown, a third-party supplier of a syringe component developed a problem with the component, leading Pfizer to place a hold on affected products and temporarily stop production, the company said.

Speculation rises

The ongoing shortage spurred speculation about causes. Publicity about rampant cases of abuse involving opioids, which are regulated by the federal government as Schedule II controlled substances, led many to suspect the U.S. Drug Enforcement Agency was involved.

Dr. Adrian Kreeger, a veterinarian in North Carolina, heard by email from an animal-health-supplies distributing company that veterinarians might lose access to opioids altogether. He said he called the distributor for details and was told the DEA was considering restricting veterinary access “because none of the Schedule II [drugs] are labeled for veterinary use ... [so] they’re not considered legitimate uses of the drug.”

Contacted by the VIN News Service, the distributor’s employee, asking not to be identified, admitted that the statement about DEA limiting veterinary access was conjecture.

A DEA spokesperson said the agency is contemplating no such thing.

“Not only is this something DEA isn’t considering, it is not our concern,” Wade Sparks, a special agent and staff coordinator in the DEA Office of National Media Affairs, said by email. “Our concern is simply the diversion of Schedule II opioids from the legitimate market.”

Sparks continued: “DEA does not regulate the practice of medicine (for animals or humans), and if a doctor or veterinarian decides to prescribe a medication ‘off label’ or for a use other than the one typically indicated, then that would be up to the determination of the prescriber in his or her best judgment, and up to the people who do regulate the practice of medicine.”

Dr. Rachael Carpenter, a VIN consultant in anesthesia and analgesia and a clinical instructor at the Virginia-Maryland College of Veterinary Medicine, said she and most other veterinarians doing anesthesia in a specialty setting use a variety of Schedule II opioids, including morphine, hydromorphone, methadone, meperidine, alfentanil and remifentanil. All are labeled for human use and used off-label, or “extra-label,” in veterinary patients.

Extra-label drug use in veterinary medicine is a standard practice authorized by law. Under the Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA), veterinarians with a valid veterinarian-client-patient relationship may use drugs not specifically labeled for animals “when the health of an animal is threatened, or suffering or death may result from failure to treat,” according to the U.S. Food and Drug Administration, which enforces AMDUCA.

Lack of access to Schedule II opioids that aren’t labeled for veterinary use would “make it impossible for veterinarians to perform major surgeries humanely,” Carpenter said.

The FDA sometimes restricts extra-label use of particular drugs. The current list of restricted drugs apply only to species chiefly raised for food.

An FDA spokesperson said the agency “has no plans to restrict veterinary extra-label use of Schedule II opioids.”

“We recognize that opioids and other pain medications have a legitimate role in treating pain in animals, although we do encourage consideration of the use of non-opioid alternatives, when appropriate, to control pain,” said Siobhan Delancey, senior adviser for strategic initiatives in the FDA Center for Veterinary Medicine.

According to the FDA and Pfizer, the shortage of injectable opioids stems from multiple manufacturing issues, which are separate from the national opioid crisis. The epidemic of opioid overdose generally involves prescription pain pills; heroin, which is not used in medicine; and fentanyl. Fentanyl is an injectable opioid, but according to the U.S. Centers for Disease Control and Prevention, “most recent cases of fentanyl-related harm, overdose, and death in the U.S. are linked to illegally made fentanyl.”

The DEA substantially reduced manufacturing quotas for Schedule II opiates and opioid medications for 2017 and cut them further for 2018. Sparks, the agency spokesperson, said reduced quotas alone should not constrain legitimate medical uses because the quotas are based upon the amount needed for legitimate medical uses, including veterinary use.

Other companies enlisted to help ease shortage

In a statement posted June 19 about the shortage of injectable opioid analgesics, the FDA said it has enlisted other manufacturers — namely, Akorn Pharmaceuticals, Fresenius Kabi USA and West-Ward Pharmaceuticals — to increase their production.

Contacted by VIN News, Fresenius Kabi spokesperson Geoffrey Fenton said the company is not restricting sales to the veterinary market, although it does not sell medicines direct to practitioners.

“All of our controlled medicines are sold through about a half-dozen distributors (including the big three CAH, ABC and McKesson) with which we have controlled distribution contracts,” Fenton said by email. “... The wholesalers/distributors would manage the allocation to the end customers.”

The “big three” distributors Fenton cited are Cardinal Health Inc., AmerisourceBergen Corp. and McKesson Corp.

Akorn Pharmaceuticals and West-Ward Pharmaceuticals (which now goes by the name Hikma) did not respond to messages asking whether they are selling or willing to sell to the veterinary market.

Kreeger, the veterinarian in North Carolina, wondered whether it is legal for drug manufacturers to deny sales to particular sectors. “Is that not restraint of trade?” he asked.

Apparently not. According to the FDA, drug manufacturers may determine how they distribute their products. A Federal Trade Commission guide to antitrust laws states that while it is illegal for competing companies to collectively agree to impose a restraint, it is lawful for a company to make a unilateral decision to do so.

Kreeger said ordering Schedule II drugs is never simple or fast — practitioners must fill out a DEA form and physically (not electronically) mail copies to the distributor. Normal turnaround time is about two weeks, he said.

The last time he placed an order for an opioid, hydromorphone, was Feb. 24. Kreeger said that more than four months later, the distributor finally told him it could not fill the order due to having no supply.

So far, he is managing on his existing stock. As a solo practitioner, Kreeger said he doesn’t do a lot of surgery, “and thankfully, most of the surgeries we’ve done recently have been on smaller patients, so we’re using a smaller volume” of product.

Should he run out, Kreeger said he’ll have to modify his protocol, using drugs that may not control patients’ pain as well.

The website Veterinary Anesthesia & Analgesia Support Group provides extensive information about the opioid shortage and ways for practitioners to manage.

Updates:

On Aug. 15, the FDA posted a statement about veterinary prescribing of opioids and a "what veterinarians need to know" guide about the opioid epidemic.

On Dec. 13, the FDA announced that it "met with Pfizer to raise awareness about the veterinary community’s need for injectable opioids and discuss how a limited supply of product imported from other countries could be made available for use in the U.S. veterinary market." As a result, limited quantities of imported hydromorphone hydrochloride injection, USP, in 2 mg/ml strength, 1 ml volume ampules, are now available for pain management in animals. In addition, the FDA said, Pfizer has made morphine sulfate injection, USP, in vials and ampules, available to the U.S. veterinary market, as well.