You might call it a made-for-TV drug. Approved for human use in the U.S.
but not marketed that way, an arthritis medicine called
Rimadyl
languished for
nearly 10 years in developmental limbo, then emerged in a surprising new form.
Instead of a human drug, it was now a drug for arthritic dogs. And it became a
hit. With the aid of slick commercials featuring once-lame dogs bounding
happily about, Rimadyl changed the way veterinarians treated dogs. Clients
would walk in and say, 'What about this Rimadyl?' " says George
Siemering, who practices in Springfield, VA.
Today, those TV spots are gone. The reason has to do with dogs like
Montana. A six-year-old Siberian husky with stiff back legs, Montana hobbled
out of a vet's office in Brooklyn, N.Y., six months ago accompanied by his
human, Angela Giglio, and a supply of Rimadyl pills. At first, the drug
appeared to work. But then Montana lost his appetite. He went limp, wobbling
instead of walking. Finally he didn't walk at all. He ate leaves, vomited and
had seizures and, eventually was put to sleep. An autopsy showed the sort of
liver damage associated with a bad drug reaction. Pet drugs are big business;
an estimated $3 billion world-wide and Rimadyl is one of the bestsellers. It
has been given to more than four million dogs in the U.S. and more abroad,
brought Pfizer Inc. tens of millions of dollars in sales, and pleased many
veterinarians and dog owners.
But the drug has also stirred a controversy, with
other pet owners complaining that nobody warned them of its risks. Montana's
owner, Ms. Giglio, is among them. After she informed Pfizer and the Food and
Drug Administration of her relatively youthful dog's death, Pfizer offered her
$440 "as a gesture of good will" and to cover part of the medical costs.
Insulted by the offer and a stipulation that she agree to tell no one about the
payment except her tax preparers. She refused to sign and didn't take the money.
"There's just no way in my conscience or heart I can release them from blame,"
she says.
After reports of bad reactions and deaths started streaming in to the FDA,
the agency suggested that Pfizer mention "death" as a possible side effect in a
warning letter to vets, on labels and in TV ads. Pfizer eventually did use the
word with vets and on labels, but when given an ultimatum about the commercials
mention "death" in the audio or end the ads -- Pfizer chose to drop
them. Pfizer's director of animal-products technical services, Edward W.
Kanara, says that when reports started coming in, "we acted extremely promptly
based on the information we had." Pfizer points out that reported adverse
events involve less than 1% of treated dogs.
Since Rimadyl's 1997 launch, the
FDA has received reports of about 1,000 dogs that died or were put to sleep and
7,000 more that had bad reactions after taking the drug, records and official
estimates indicate. The FDA says such events are significantly underreported.
While the numbers include cases "possibly" related to Rimadyl, it is hard to be
sure. Many dogs given the arthritis drug are older, and few are autopsied after
they die. Pfizer says it analyzed cases of Rimadyl-treated dogs that died in
1998 and found a link to Rimadyl to be "likely" in 12% of cases and "not likely"
in 22%; it says there was too little information for a judgment about the
others.
Rimadyl Still Approved
Despite these problems, the FDA says Rimadyl deserves to be on the market,
provided vets take the proper precautions. These
include advising-dog owners what bad reactions to watch for and periodically
doing liver-function or other lab tests. Within a few weeks, Pfizer will begin
affixing a safety sheet directly to packages of Rimadyl pills. It is the first
time either FDA officials or Pfizer can recall such a step being taken in the
world of animal drugs. Rimadyl, generically carprofen, is an anti-inflammatory
medicine. Developer Roche Laboratories expected to market it for people in 1988
and received FDA approval, but shelved the plan after concluding the market for
such drugs was too crowded. In addition, some outside experts expressed
concerns; a commentary in a pharmaceutical journal noted unusual liver-function
readings in 14% to 20% of test subjects and opined that "until additional data
on carprofen are available, older compounds should probably be tried
initially." The idea of switching the product to the animal-drug track soon
arose. A couple of corporate transactions later, it ended up in the hands of
Pfizer's animal-drug unit.
There, it was treated to the kind of sophisticated marketing Pfizer does
well. A survey of 885 dog owners was done. Besides shedding light on favorite
dog names (Jake, Ginger, Lady), the poll revealed that one-fifth of dog owners
would be willing to spend "whatever it took" to buy an aging dog an extra year
or two of life. No fewer than 53% agreed that "my dog is a better companion
than other members of my family." The FDA requires safety and efficacy testing
for animal drugs just as for human ones, but animal-drug tests are smaller.
Pfizer says about 500 dogs got Rimadyl in various trials, which is no more than
a fifth of the number of subjects in comparable human-drug trials. Some dogs
showed unusual liver-function readings and one young beagle on a high dose died,
but for the most part, the FDA and Pfizer didn't find side effects alarming.
The drug was approved for an early-1997 launch. That same year, the FDA made it
easier to market drugs directly to consumers on TV. Soon, Pfizer was running
commercials in which a once stiff yellow Labrador retriever named Lady bounded
over a fallen tree as she fetched tennis balls beside a lake. In another ad, a
dog leapt through a window and slid down a banister. There were also full-page
magazine ads and a public-relations campaign, whose results, the PR firm later
said, included 1,785 print stories, 856 radio reports and 245 TV news reports
"generating 25.5 million positive impressions on the product."
Early on, vets were floored by the drug's effects. "The results in some cases
have been pretty darn close to miraculous," says David Whitten of the Hilldale
Veterinary Hospital in Southfield, Mich. "I'm using this drug on my own dog.
It has been effective but as with all medications, side effects are certainly a problem."
The First Complaints
Indeed, within months of the launch, vets at Colorado State University in Fort
Collins noticed troubling reactions. Labrador retrievers seemed particularly
affected. Since the safety studies for Rimadyl had emphasized testing on young
beagles, Pfizer went back to conduct another, small test just on Labs; it says
that test showed no particular problem. Bill Keller, an FDA veterinary-medicine
official, notes that "any time you take a product from the investigation and put
it into actual practice, you're going to see things you didn't expect." But
reports about Rimadyl came in by the hundreds. The FDA had received just over
3,000 animal-drug bad-reaction reports in 1996, the year before Rimadyl's
launch; in 1998, the drug's first full year, Rimadyl alone produced more than
that many. They swamped the FDA's tiny Center for Veterinary Medicine in
Rockville, Md. Pfizer was scrambling as well. "Basically, their response," says
Dr. Keller, "was 'Tell us what you want us to do. We love the fact that it's
selling so well, but we don't know what to do with all these adverse reactions."
The FDA and Pfizer discussed a "Dear Doctor" letter to be sent to vets. FDA
records show the agency found parts of an early Pfizer draft "unacceptable as
they are promotional in tone... ." It was revised. The records also show Pfizer
disagreed with the FDA's suggestion that the letter cite "death" as a possible
side effect. To get the letter out, the FDA told Pfizer it was "agreeing to
your exclusion of the 'death' syndrome from the letter at this time. However,
we will revisit the 'death' syndrome issue and other potential side effects for
possible inclusion in labeling at a later date." So the term didn't appear in
the first warning Pfizer sent, in mid-1997.
Clear benefitss
Meanwhile, dog owners were asking for Rimadyl. "It was their advertising that
sold me on the drug," says Michelle Walsh, a Phoenix woman who says her
miniature schnauzer was given it and later died. Not that vets needed much
convincing. They saw clear benefits from the drug. On top of that, they could
get points from Pfizer for each Rimadyl purchase they made; points were
redeemable for PaImPilots, Zip drives for PCs and other equipment.
Although Pfizer's letter told vets to explain to owners the signs of a bad
reaction to Rimadyl, such as vomiting, lethargy or diarrhea, it is evident that
a great many didn't. The FDA's Dr. Keller says, "There are a lot of
veterinarians who don't think they need to take the time, or who forget, or for
whatever reason are not providing animal owners with this information."
Donna Allen, whose chow-mix, Maggie, started on Rimadyl last summer, says,
"All my vet did was give me this little bag of pills, with no information."
She says Maggie "didn't want to take it, but I made her." After four weeks,
Maggie began to vomit violently, Ms. Allen says. The dog vanished from their
home outside Birmingham, Ala., and later was found lying in a ditch. Ms. Allen
loaded her into a truck and sped 35 miles to a veterinary clinic, but the
five-year-old dog died. Her vet wouldn't implicate Rimadyl in the death until
Ms. Allen urged him to send the dog's internal organs to the University of
Illinois vet school, where an examination showed liver toxicity. Maggie was
buried under a marker adorned with the figure of an angel. And Ms. Allen took
to the streets, delivering a letter to all the vets in the area urging them to
"understand that Rimadyl helps certain dogs, but it is poison to other dogs."
The "D" Word
As the complaints poured in, the FDA told Pfizer it would have to revisit the
label issue. Pfizer had referred to "fatal outcomes" on the label as a possible
effect of the drug class to which
Rimadyl
belonged, but not
specifically of this
drug. Now the agency asked that Pfizer cite "death" prominently as a possible
side effect of the drug. Describing the back and forth with Pfizer, the FDA's
Dr. Keller says, "They did it. They weren't enthusiastic about it, but they
have always been cooperative. And that's part of the nature of the game we play
with industry." But the FDA also wanted the word "death" in the audio of
commercials. Pfizer indicated this "would be devastating to the product," FDA
minutes of a February 1999 meeting show. A company spokesman says that "putting
'death' on a 30-second commercial and in proper context was something we didn't
think was possible." Rather than do so, it eventually pulled the commercials.
Pfizer says it now will do traditional marketing to vets, making sure they
know the proper way to use the drug. Another "Dear Doctor" letter will soon go
out, and the company will start attaching a safety sheet to pill packages.
Pfizer acknowledges it has a perception problem with some dog owners; a
consumer group, for instance, has mounted a campaign dubbed BARKS, for Be Aware
of Rimadyl's Known Side-effects. The company is contacting dog owners who have
told their stories on the Internet, and it is offering to pay medical and
diagnostic expenses for some dogs who may have been harmed by Rimadyl.
But Pfizer stands firmly behind the value of the drug, of which it says sales
have continued to grow. Most vets also remain strongly behind Rimadyl. Owners,
too, generally say they think the drug is important -- they just want to know
the risks. Atlantan Roger Williams gave his mixed-breed terrier, William,
Rimadyl for more than a year and believes it contributed to the dog's death.
"But if I had to do it all over, I would give my dog Rimadyl again," he says.
"The difference is I would have known what to expect. Without Rimadyl, William
was miserable. And what's the point of living another three years if you're
miserable?"
