History of Rimadyl by Jane Sinclair (posted on doghealth2 11/4/2000)

To those of you who are new to the list, you may not be aware of where Carprofen (Rimadyl) came from. Here's a history of this old drug, now the darling of the vets and considered some kind of safe new wonder drug for dogs.

Years ago Hoffman La Roche (a Swiss company) set out to find a cure for arthritis and came up with Carprofen which they called Imadyl. But early tests showed that the drug performed no better than those of dozens of competitors. Roche was stymied. Imadyl lacked what drug companies call a USP, a unique selling proposition. So back to the labs went Imadyl to find something "unique". When new tests showed that Imadyl might spare users the ulcers that sometimes occur in users taking the existing drugs, only then did Imadyl get a big launch that made it a big hope for Roche in 1983. This is the origin of the current slogan vets use today - "safer than Aspirin". However, Imadyl never became a block buster drug, and some years later Roche withdrew it from the European human market for commercial reasons. Carprofen ended up in Roche's Animal Health.
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SmithKline Beecham bought Roche's Animal Health in 1993 and then decided to concentrate on human drugs. So, sold their Animal Health to Pfizer in 1995. Pfizer had been in drugs for feed animals and now got into drugs for companion animals. By October 1996, Pfizer had gotten Carprofen through the FDA/CVM approval process and in January 1997 the new wonder drug for dogs was launched. Pfizer had rights to the molecule in all but the countries where it was called Zenecarp (UK, Ireland, Australia, and New Zealand). In April 1999, Pfizer acquired Carprofen in the Zenecarp countries, changed the name to Rimadyl, and now owned the drug world wide.

Some drug company got Carprofen approved for humans in the US in 1987, maybe Roche, but it never made it to market.

Pfizer's US ad campaign for Rimadyl for dogs was Pfizer's most successful before Viagra. The Rimadyl campaign created a craze for the drug. In September 1997 my vet switched my little dog from Aspirin to Rimadyl and, in ignorance, I put my Misty through months of Hell. My dog suffered terribly before I found out about the harm I was doing to her, and then we had to put her to sleep to stop her misery. Misty's Rimadyl experience changed my life. Since her death, I have worked with other BARKS people to inform unknowing dog owners about this potentially dangerous drug. Pfizer and its reps continue to play the statistics game with vets and most of the vets are still in love with the drug. In spite of FDA actions and cautions, dogs are still getting sick or dying and dog owners are still not being informed.

So the final history of Imadyl/Rimadyl has yet to be written.

Jane S
For Misty and all the Rimadyl dogs

Bob Sinclair's address to the 'April 28, 1999, FDA Stateholders' meeting' (copied from transcript, pages 85-94)

MR. SINCLAIR: "Good afternoon. My name is Bob Sinclair. My wife, Jane, and I are from West Bloomfield, Michigan. We are here with our colleague, Jean Townsend from John's Island, South Carolina. We'd like to thank the CVM for the opportunity to attend this meeting and offer some views.

As consumers and dog owners, we feel strongly that the communication efforts of the FDA can be improved so that users of animal health products can have better access to understandable and timely information. The quality of life of the hundred million-plus American companion animals and their owners and households will benefit when the agency treats information about animal health products the way it treats information about human health products.

Question 2 in the March 22nd Federal Register notice, let me offer two comments. First, FDA can improve the timeliness of publishing adverse drug experience reports, particularly when new drugs are introduced in the market. Delays in the exchange of information between the FDA and consumers can have serious implications for the companion animals that they care for.

Many manufacturers are required to submit ADAA reports to the Agency. Availability of evaluations of these reports to the general public, in our view, should not await preparation and subsequent publication of annual summaries.

An example, Pfizer introduced Rimidil Purprophen for dogs in January 1997. Clearly ADE reports were received during the '97 calendar year, but the '97 FDA summary of ADE reports on veterinary drugs was not published until October 29, 1998. Dog owners were denied access to this important information for an unacceptably long period of time, in our view. For months during which the volume of ADE reports about Rimidil was building, owners were purchasing and administering the drug to their pets with little knowledge about adverse effects. Dear Doctor letters may be issued, and they were, and label changes may occur, and they did, but there is no assurance that balanced risk/benefit information is available to consumers. Lack of information about Rimidil's potentially toxic side effects seriously affected the quality of life of our toy poodle, Misty, and caused the death of Jean Townsend's chocolate lab, George.

We detailed Misty's story in reports submitted last October, and in February Georgia's necropsy report was sent to Pfizer and to the FDA/CVM.

Second, various means can be employed to disseminate balanced information about animal health products to consumers. Internet web site updates plus post read line bulletins to veterinary facilities and other communication techniques come to mind.

In view of the time, I'm going to edit this on the fly and go right on to the next point.

Question 3 in the notice asks, "What actions do you propose for educating the public about the concept of balancing risks against benefits in public health decision-making?" We have several responses to this question.

Direct to consumer so-called DTC advertising posts, we believe FDA can re-institute its earlier policy requiring that DTC advertising of human and animal prescription drugs in all media include a brief summary -- quote, "a brief summary" -- of hazards and contraindications.

After broadcast advertising restrictions were eased on August 8th, 1997, it became apparent that procedures are not in place to assure that balanced information is, in fact, delivered in all media.

Unbalanced TV commercials encourage animal owners to unknowingly demand drugs like Rimidil that may cause their pets to suffer lethal or sublethal side effects. Coupled with unavailability of label information or patient information leaflets, animal owners hoping to help their pets cannot evaluate the risks versus the benefits and make informed decisions.

We suggest a new regulation. We suggest that FDA can initiate rule-making towards a federal regulation requiring that consumer information prepared and supplied by the manufacturer must absolutely be delivered to animal owners when prescription drugs are purchased.

Drugs suppliers and veterinary practitioners who fail to provide such information to animal owners would be held in violation of this regulation. And obviously means to monitor compliance and enforce the proposed regulation would be required.

Blister pack and tube packaging include inserts that do provide information, but many animal prescription drugs are dispensed in small vet-supplied containers without either label information or PILs, containing balanced risk/benefit information. Typically these containers indicate the name of the drug, the dosage and the condition for which it was prescribed. Animal owners are not assured receipt of accurate guidelines advising that their animals should be carefully and objectively monitored.

We -- Jean and I -- we never received such guidance about Rimidil. The only information that was provided verbally to us was that Rimidil is, quote, "safer than aspirin and has less GI effects." Something clearly is wrong in the risk/benefits communication process between the manufacturer/distributor, the veterinarian, and the consumer/owner of the animal receiving the drug.

A veterinary drug database. Many users don't understand possible risks without personally conducting exhaustive research which they may or may not be able to pursue. Information about new human drugs is readily accessible by consumers from the FDA home page, a database of veterinary prescription drug information that can be accessed from the CVM home page we recommend should be created. The FOI summaries don't answer the need. Consumers cannot readily access information about a new animal drugs like Etogesic as they can about a new human drug like Celobrex (phonetics).

U.S. approval status reports. We believe the FDA can do a better job of informing the public about the U.S. approval status of drugs approved and being used successfully in other countries. Cartofovet, penicillin polysulfate sodium (phonetics), for example, has been available in Australia, New Zealand, Canada, the United Kingdom and Ireland for years. This therapy for osteoarthritis in dogs is not available in the United States, and we do not know how to determine its status.

We think the public needs to know. We think the CVM could explain its position on fighting this promotional advertising works advising material to the American public.

Here are four copies -- or copies of four letters from the Agency to Pfizer dated April 4, October 8, December 19 and December 21, 1998. Each of these letters discussed fair balance and advised that Pfizer was found in violation of the FFDC act and applicable regulations. The public, we believe, deserves to know the results of these actions. Pfizer has claimed Rimidil is safer than aspirin. This is a bogus claim.

And I'll skip. I'm getting signs telling me to stop talking. So I'll again edit further on the fly.

The claim that Rimidil is safer than aspirin is wrong. That was documented in the October '98 summary of '97 ADE reports highlighted in the January-February issue of the FDA Veterinarian and discussed in articles appearing in recent issues of APC Veterinary News and Dog World.

The Pfizer commercials continue. The golden retriever is still jumping over garbage cans, leaping to the second floor and sliding down banisters. We think that and merchandising materials, toy dogs, desk pads, calendars, lack fair balance of risk/benefit information.

We'd also like to know why -- we'd like CVM to comment on why the U.S. Dosage for Rimidil after one week is twice that in Australia, the United Kingdom and Europe where adverse experiences seem to be less than in this national market.

Let me close by describing a personal experience that occurred in March at a specialty show the day before the Detroit Dog Show. A lady that we met brought her six-year-old dog for obedience trials and a beautiful fourteen-year-old along for the ride. In conversation, the owner said that her vet had just put the older dog on Rimidil. We asked why. Her answer? "Oh, no symptoms. She just slowing down a little and the vet said Rimidil is very popular now."

Jean, Jane and I are here in part seeking closure and for those who record the remote, statistically insignificant judgment, I say that for Misty and George and many others, it was a hundred percent. As you people in CVM well know, the premarket testing rarely indicates the full range of problems. Our plea is simply one for better communications, improvements in the exchange of information about animal drugs. The so-called action plan for the provision of useful prescription medicine information approved for human drugs by Secretary Shalala January 13, '97, we recommend be adopted for animal drugs.

What we miss today is the guarantee that information about the drugs we give to our animals is timely, accurate, up-to-date, unbiased, specific, and comprehensive and is presented in an understandable and legible format and is useful.

Thank you very much for your time."

 

June 24, 1999 Pfizer Meeting by Jane Sinclair (posted on doghealth2 6/25/1999)

The following individuals met June 24, 1999 at an American Airlines Admirals Club conference room at the Detroit Metro Airport:

Jean Townsend, Johns Island, SC
Dr. Mary Wall, DVM, Johns Island, SC
Jane and Bob Sinclair, West Bloomfield, MI
Dr. Edward W. Kanara, Director, Technical Services, Companion Animal Division, Pfizer, Inc., Exton, PA.
Laura Devlin, Vice President, Public Affairs, Animal Health Group, Pfizer, Inc., New York, NY.

Dr. Kanara attended the April 28 FDA-CVM Stakeholders Meeting at Overland Park, Kansas. He said that Pfizer agrees with a number of the points/proposals made in our April 28 presentation, and that he and Laura Devlin wanted to discuss current Pfizer activities that relate to those comments. He proposed the meeting during the week of June 7 and his office made all arrangements.

Dr. Kanara opened the meeting by restating what he hoped we could accomplish...

- by sharing information relative to current Pfizer communications initiatives
- by sharing information on programs Pfizer currently has under development,
and
- by seeking Townsend's, Wall's, and the Sinclair's input on these and future Pfizer progam ideas.

The attendees agreed early in the meeting that societal trends in recent years require that pharmaceutical manufacturers/distributors upgrade their promotional materials and improve their communications practices.

- Human and pet populations have grown.
- Companion animals have become more important in the lives of their owners.
- The variety and volume of animal drugs has increased.
- Direct-to-consumer advertising of drugs has expanded dramatically since DTC advertising restrictions were eased by the FDA in August 1997.

Dr. Kanara stated several times that "whatever we do we must keep (the interest of) the pet in the center." He and Laura Devlin advised that they are meeting with a variety of people around the country, eliciting input on how Pfizer can improve its communications with vets and pet owners.

Laura Devlin distributed copies of six (6) new Pfizer print documents:

- Three single-page Consumer Information Pages: "Important Information About" Anipryl, Primor, and Clavamox
- An advance proof print of a new Rimadyl Consumer Information Page
- An advance proof print of a new Rimadyl Technical Bulletin
- An advance proof print of a new "Advertorial"

The Anipryl, Primor, and Clavamox pieces contains Pfizer's answers to the questions "What Is (the drug)?", "How Safe Is (the drug)?", "What Kind of Results Can I Expect?", and brief "How To Give This Medication" instructions. Each piece also contains highlighted boxes: "Treatment Success Is Largely Up To You!", followed by simple instructions and the statement "No handout can take the place of discussion between you and your veterinarian. If you have questions or need more information, contact your veterinarian." The Townsend-Wall-Sinclair team reacted positively to these handouts.

We recommended change to the new Rimadyl Consumer Information Page: Do not use the percentages indicating rarity. They mean nothing to the consumer and encourage the game of "Rimadyl Roulette". Change the language "If you see behavior changes, call the vet" to "If you see behavior changes, stop the drug and then call the vet".

The new Rimadyl Technical Bulletin is based on information acquired after two years of Rimadyl use. We were told that this document would be mailed to veterinary establishments and that Pfizer's sales representative would also have it to distribute.

We recommended specific changes and strongly objected to Pfizer's continuing use of such expressions "proven safe" and "rare" that appeared repeatedly in the original 1997 Rimadyl promotional materials. We contend that such language invites vets to play the game of "Rimadyl Roulette".

Dr. Wall added that the requirement to conduct baseline laboratory tests before administering the drug should be added, and that the need to periodically reevaluate patients should be clearly stated in this new Rimadyl document.

Dosing
We asked why a comment about individualized dosing is not included and were told that legally Pfizer cannot deviate in print from the FDA approved label dosing. Dr. Kanara said that he could have a vet-to-vet discussion of dosing.
We also raised the question of accurate dosing of small dogs given the fact that the smallest Rimadyl caplet is 25 mg and is scored for half-caplet dosing. The half caplet must be cut further for a dog weighing less than 12.5 pounds. The problem may be more difficult with the new chewable tablets.
Interestingly, Fort Dodge's EtoGesic Package Insert states: "Due to tablet sizes and scoring, dogs weighing less than 5 kg (11 lb) cannot be accurately dosed".

Laura Devlin noted our inputs and said that 1) Pfizer will seriously consider the suggested changes, but 2) it will probably not be possible to incorporate changes in the initial printing of the document. She said, "I think it's already at the printers."

The new "Advertorial" is a discussion of how consumers should view animal drugs in general and work closely with their veterinarians. The Townsend-Wall-Sinclair team said "Excellent!", and suggested that Pfizer has the opportunity to assume a leadership role. We recommended that a TV version of this "Advertorial" be developed and broadcast regularly on American network and major cable channels.

We said that Rimadyl needs a new image. The perception that the drug is serious medicine and not to be taken lightly needs to be projected. We stated emphatically that the "Flying Golden" image has to go. We showed the Rimadyl ad in the May 17, 1999 issue of People magazine as an example of Pfizer's continuing use of the "Flying Golden" image.

Brain-storming occured on specific means to...

- assure that animal owners are well informed when they administer potentially harmful drugs to their pets,
- assure that animal owners carefully monitor their pets for possible adverse reactions,
- promote better vet-client communications, and
- facilitate baseline tests before non-steroidals are prescribed.

The Townsend-Wall-Sinclair team suggested that...

- Pfizer can supply packaging materials with every order of potentially harmful animal drugs: Graphically attractive client delivery bags that would contain appropriate instructions and pre-labeled caplet/tablet containers.
Information printed on the container labels would be in front of the animal owner each time the drug is administered, finessing problems that may arise after package inserts are lost, discarded, or ignored. Pfizer could supply these materials free to vets. It was noted and agreed that many pet owners never see the current label information, are told nothing about the drugs they purchase from their vets, and are not advised to carefully monitor for behavioral changes.

- A check-off chart, similar to the "Senior Dog Behavior History Form" now provided to users of Anipryl, can be included in the delivery bags to assist pet owner monitoring for behavioral changes and to assist collection of
information that can be important to vets and to Pfizer.

- A first step Pfizer could take in this approach would be to print and distribute bright-colored stickers that can be applied to containers that vets now use when dispensing drugs.

- A project can be undertaken to establish "24-Hour Pfizer-Help" 800 telephone line service. The 800 number can be printed on the container label, on refrigerator magnets and other promotional materials, and technical service
can be made directly available to any animal owner or veterinarian in need of qualified guidance about the drug.

- Dr. Wall said that Pfizer should require pre-screening laboratory work and pay for it.

All inputs provided via e-mail from various subscribers to the doghealth2 list were delivered to Dr. Kanara.

We advised Dr. Kanara and Laura Devlin that in response to our May 6, 1999 Freedom Of Information Request to the FDA, on June 23 we received copies of 2,724 Rimadyl ADE Reports from the FDA-CVM FOI Staff covering the period February 20, 1997 through November 14, 1998. The 1998 rate exceeds the 1997 rate, and application of the 1998 rate to the months to date suggests that approximately 3800 Rimadyl ADEs have been submitted since the drug was introduced in January 1997. Using the common estimate that only 10-15% of all ADEs are reported, it can be inferred that somewhere between 25,200 and 37,800 adverse drug experiences with Rimadyl have occurred. Using the same methodology, extrapolation of the 195 deaths reported in the October 29, 1998 FDA Summary of 1997 Adverse Drug Experience Reports on Rimadyl suggests that approximately 600 deaths may have occurred since the drug was introduced.

We stated that while estimated frequencies of ADE Reports may be characterized by Pfizer as "rare" and by Pfizer researchers as "statistically insignificant", the numbers of adverse experiences in animals treated with Rimadyl are large, and hardly "rare" or "insignificant" to those who have suffered.

Dr. Kanara concluded the meeting by stating that Pfizer is trying to develop ways to "change vets habits" by working with the American Veterinary Medical Association and "other groups in the profession ... symposia, working with veterinary schools to influence the mind-set of vet students", etc. He said that the focus of the veterinary community has been on setting up veterinary practices and maintaining good business practice, and that we are now moving into a new era.

We thanked Dr. Kanara and Laura Devlin for inviting us to meet with them.

Our over-all impression is that such discussions may yield positive benefits in the long run. In the near term, veterinarian-client communications problems continue, and the growing number of Rimadyl Adverse Drug Experiences is a major concern. We, like Jean, are cautiously optimistic. We will see what happens.

Jane and Bob Sinclair
June 25, 1999