Veterinarians commonly administer or prescribe drugs in ways unapproved by the Food and Drug Administration’s Center for Veterinary Medicine (CVM) to treat a variety of conditions and diseases. The FDA, the government agency responsible for overseeing drug safety, allows the widespread practice because it does not want to interfere with medical decision-making.

Indeed, drugs used extra-label or “off-label,” have saved the lives of many pets, particularly when there are no alternatives for treatment of severe and chronic illnesses.

Veterinarians can use drugs extra-label when the health of an animal is threatened, or suffering or death may result from failure to treat, according to Linda Grassie, communications director at the FDA. The agency explicitly prohibits drug manufacturers from promoting or recommending the extra-label use of drugs or medical devices. In doing so, the FDA wants to keep companies from skirting requirements to test the safety and efficiency of a drug before it goes to market.

But in practice, what is promotion and widespread discussion of extra-label use of drugs among vets can be unclear.

“Whena pharmaceutical company that is the `sponsor’ of an approved animal drug `instructs’veterinarians in the extra-label use of their products, the legality of such instruction depends on a number of factors,” said Grassie. “In general, FDA does not intend to interfere with bona fide continuing medical education (CME) of veterinary practitioners. However, continuing medical education events are frequently paid for by drug sponsors. The information being provided can easily cross the line between `education’ and `promotion.’ When drug sponsors promote use of their FDA approved products for indications or dosages that are not part of the approval, this tends to violate the Federal Food, Drug, and Cosmetic Act.”

Veterinarians at the Sylvania Veterinary Hospital, on Holland-Sylvania Road, say the extra-label use of Domitor (medetomidine) a potent sedative, was widely discussed at CME seminars held by Pfizer, which manufactures the drug.

Domitor, according to the label, can be used to sedate dogs for short procedures, such as teeth cleaning and minor surgeries not requiring muscle relaxation.

The facility, which provides round the clock care, routinely uses Domitor on dogs after surgery, an extra-label use.

Dr. Robert Esplin and Dr. Ross Mahowald, veterinarians at the hospital, said discussion of the drug’s extra-label use occurred at two seminars funded by the drug giant as part of its DALE (Domitor Antisedan Local Expert) program.

Mahowald was among 400 veterinarians invited by Pfizer to go on an all-expense paid trip to Chicago to attend the seminars, said Esplin, who occasionally appears on Channel 13's "Ask the Expert," segment and "Ask Dr. Bob" on radio station Star 105 FM. Pfizer chooses vets already using the drug at a "high rate" for the DALE program, according to Pfizer.

“We had very limited material on Domitor before I went to the seminar,” Mahowald said. "We discussed how Domitor was used, different methods, and how it is used in different species.”

Agent of Pfizer

Vets in the DALE program sign one year contracts with Pfizer, who expects them to schedule seminars for area veterinarians to discuss the “new uses" of Domitor, Mahowald said. Pfizer pays DALEs for each seminar they hold.

Mahowald called discussion of extra-label use of Domitor at the seminars “a matter of semantics.”

“I believe discussion is the same as recommendation,” said Mahowald. “When I signed the contract, I am acting as a representative of Pfizer and I am able to discuss off-label use with other vets.”

Barry Poole, of the FDA, said drug companies, and their representatives, cannot recommend or promote a drug for any indication unapproved by the FDA, “either in writing or by word of mouth.”

“You can’t recommend off-label,” he said. “That is promoting. That’s what the law says.”

S. Kristina Wahlstrom, DVM, MS, group director, U.S. Companion Animal Veterinary Operations for Pfizer, said the company does not recommend extra-label use of Domitor at DALE seminars.

Pfizer, she agreed, signs DALEs to become "agents" of the drug company upon completion of the seminars, but “they are under the same regulations we are, in that they cannot promote the extra-label use of Domitor.”

DALEs can tell other vets about Domitor's extra-label uses, but only if they are asked, per FDA regulations, she said.

“If someone asks them about an extra-label use, they have to tell the vet that what they're considering doing with the drug is extra-label,” she said. “The DALE can then give the vet the information, if they have it, on the specific extra-label use. DALEs then have to remind the vet again that it is an extra-label use.”

Robert Fauteux, public relations representative at Pfizer, also said Pfizer does not recommend extra-label use of Domitor.

DALEs, as agents of Pfizer, are "obligated to comply with the regulations that govern Pfizer employees," he said.

Veterinarians who attend DALE seminars are paid for their travel, lodging and meals. Additionally, they receive $500 in honoraria to compensate for their time, said Fauteux.

Safety is an issue when drug companies promote the extra-label use of drugs, said Grassie.

“We do not have evidence of the safety and effectiveness of the drug for the unapproved indication,” she said. Extra-label promotion, “may mislead a medical or veterinary practitioner to use a product inappropriately” for an extra-label use.

Domitor, according to its label, is contraindicated in dogs with underlying health conditions, including liver, heart and kidney disease, respiratory disorders, fatigue, dogs that are in shock, or are severely debilitated. Special care is recommended when treating very young animals, debilitated older animals, coughing dogs, or dogs in poor general condition, says the label.

Clinical trials of Domitor, approved by the FDA in 1996, concluded that it is mostly safe and effective so long as it's used "according to the label."

Sylvania Veterinary Hospital, according to Mahowald, routinely uses Domitor on dogs after surgery to keep them sedated and quiet, an extra-label use.

Esplin and Mahowald still support the DALE program. Mahowald's contract with Pfizer expired, though he would not hesitate to hold future seminars on the drug.

"Extra label use allows us the flexibility to include the drug in multiple protocols,” Mahowald said.

Esplin agreed. “I have used it enough that I am comfortable and confident to use it in a lot of scenarios.”

Facts on label

A drug’s label “is the first source of important facts for veterinarians," Dr. Victoria Hampshire, former adverse drug events coordinator in the office of surveillance and compliance in the FDA's Center for Veterinary Medicine, said in a Jan. 15, 2004 article in the Journal of American Veterinary Medical Association (JAVMA).

“The label is the result of considerable scientific regulatory review before CVM approves the drug,” she said.

“Product precautions, contraindications, safety information, and warnings should identify animal patients that are not good candidates for the medication,” she said.

But Wahlstrom leaves it to veterinarians to conduct a risk/benefit assessment of an animal before the drug is used.

The drug industry for years has been under fire for promoting extra-label use of human drugs, which reportedly expands their profit margin.

Promotional activities of drug companies and others are substantially motivated by profit and market expansion, William B. Schultz, former deputy commissioner for policy and drug administration in the U.S. Department of Health and Human Services, said before a Senate committee in 1996.

"If drug companies were allowed to freely promote extra-label uses, there would be no incentive to conduct or fund the necessary scientific research and to present data to FDA to verify the safety and efficacy of those extra-label uses," said Schultz.

The FDA can take a number of enforcement actions against drug companies, ranging from sending a warning letter, to injunctions, and even criminal prosecution, according to Grassie.

The Sylvania Veterinary Hospital promotes Mahowald as a DALE on its website, and touts the “several new ways we will be able to use Domitor."

“We have used this drug for many years," says the website. Mahowald, described as "a local expert" on the use of Domitor, "will be conducting several seminars for other local veterinarians and their staff."

Since becoming a DALE, Mahowald has yet to hold a seminar, but held a lecture for the facility’s staff concerning new uses of the drug.

Two seminars for local vets had been scheduled, he said, but were canceled by Pfizer's area representative.

Pfizer awarded four veterinarians with trips to Hawaii in May, 2004, to attend a national dermatology conference. A veterinarian at Sylvania Veterinary Hospital was among the winners, according to the facility's website.

Features editor Tammy Wilhelm contributed to this report

To comment on this story, email .