RE: NADA 141-053, 141-111, 141-199 -Rimadyl® caplets, chewable tablets, and injectable solution for dogs
Dear Dr. McKenzie:
The U.S. Food and Drug Administration (FDA), Center for Veterinary Medicine (CVM), Division of Surveillance has reviewed your February 20, 2008, Drug Experience Report (DER) concerning Rimadyl® (carprofen) caplets, tablets, and injectable solution, NADAs 141-053, 141-111, and 141-199. This submission includes six meter boards (RIMlO06116). These boards are false or misleading because they make unsubstantiated safety claims and minimize the risk associated with Rimadyl®.
CVM has also reviewed an advertisement that appeared in the May 2008 DVM Newsmagazine (RIM1206128R) that is false or misleading because it makes unsubstantiated safety claims and minimizes these risks associated with Rimadyl®.
Finally, CVM has reviewed your April!l, 2008, DER submission. This submission includes a Duration of Efficacy chart (RIM1207134). This item is false or misleading because it makes unsubstantiated efficacy claims regarding Rimadyl®.
For these reasons, Rimadyl® is misbranded within the meaning of section 502(n) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. 352(n)].
Background: Rimadyl® (carprofen) is a non-steroidal anti-inflammatory drug (NSAID) indicated for the relief of pain and inflammation associated with osteoarthritis and for the control of postoperative pain associated with soft tissue and-orthopedic surgeries in dogs. Rimadyl® is approved for use at a dose of 2 mg/lb of body weight once daily or divided and administered as I mg/lb twice daily.
Unsubstantiated Claims: The meter boards, RIMI006116, state that "Rimadyl (carprofen) has been proven safe at 5.7 times the recommended dose for up to 52 weeks." We are aware that this particular advertisement has been used as recently as June 2008 at the trade show for the forum for the American College of Veterinary Internal Medicine in San Antonio, Texas. The statement is accompanied by a disclaimer, in fine print, indicating that "Pfizer Animal Health does not endorse use higher than the recommended dose of 2 mg/lb/day." The fine print disclaimer goes on to explain, "In a clinical study, at doses as high as 5.7 times the labeled amount for 52 straight weeks, no gross or histologic changes were seen in any treated dogs." This claim implies that Rimadyl® is safe for use at 5.7 times the recommended dose when this has not been demonstrated by substantial evidence of safety. The claim is supported by a citation to Rimadyl Freedom of Information Summary, NADA 141-053, Pfizer Animal Health, Report Nos.. N-29736 and N-30191. This study of healthy animals had a stated purpose ~~to assess the toxicity of [Rimadyl®]," not to prove the safety of Rimadyl® when used at doses greater than those indicated on the label for the relief of pain and inflammation associated with osteoarthritis and for the control of postoperative pain associated with soft tissue and orthopedic surgeries in dogs. The claim is therefore misleading because it contains a representation or suggestion, not approved or permitted for use in the labeling, that Rimadyl® is safer than has been demonstrated by substantial evidence or substantial clinical experience. See 21 C.F.R. 202.1 (e)(6)(i). Not only is this statement misleading, it also sends a dangerous message to veterinarians by suggesting an overdose (> 1 times dose) is safe. Veterinary patients may be injured by being given an unapproved overdose.
The advertisement (RIMI206128R) published in the May 2008 edition of DVM Newsmagazine included the statement, "Proven safe in a 5 year compassionate use study." This advertisement apparently refers to a report entitled "Extended-use studies of carprofen in dogs", a description of which appears in the Rimadyl Freedom of Information Summary, NADA 141-053, Pfizer Animal Health. The stated purpose of this particular study was to "allow for the"continued (compassionate) use of carprofen in dogs previously enrolled in clinical efficacy studies and to survey the safety of repeated use," not to prove the safety of the drug. Therefore, the claim that the drug was "proven safe" in this study is misleading because it contains a representation or suggestion, not approved or permitted for use in the labeling, that Rimadyl® is safer than has been demonstrated by substantial evidence or substantial clinical experience. See 21 C.F.R. 202. 1(e)(6)(i). I
Finally, the Duration of Efficacy chart includes the statement, "Rimadyl® has a quick onset of action with a long duration of efficacy" and presents 'pharmacokinetic data including Tmax of both subcutaneous and oral administration. This data is apparently drawn from a study by Clark, TP, et al.I. However, the Tmax data presented in this study 1 Clark, TP, Chieffo C, Huhn JC, et al. The steady-state pharmacokinetics and bioequivalence of carprofen administered orally and subcutaneously in dogs. 1. Vet. Pharmacology Ther. 2003; 26: 187-192. does not necessarily correlate with clinical analgesic effect because the study does not address analgesic effects of Rimadyl®. Instead, this study addresses the pharmacokinetics and bioequivalence of the different forms of administration of Rimadyl®. A demonstration of analgesic effect would typically require testing the pain threshold of dogs at given time intervals after the administration of the product. Therefore, this claim is misleading because it presents a favorable conclusion from a non clinical study for which clinical significance has not been demonstrated in a way that suggests the conclusion has clinical significance. See 21 C.F.R. 202.1 (e)(6)(vii).
Conclusion and Requested Action: The misleading statements in your advertisements misbrand Rimadyl® within the meaning of section 502(n) of the Act, 21 U.S.C. 352(n). The Center for Veterinary Medicine requests that Pfizer Animal Health immediately cease the dissemination of the Rimadyl® promotional items described above, and any other·materials that may contain similar unsubstantiated promotional claims.
Please submit a written response within thirty (30) days of receipt of this letter describing whether you intend to comply with this request, and listing all violative promotional materials for Rimadyl® the same as or to those described above, and explaining your plan for discontinuing use of such materials.
Please direct your response to me at the Food and Drug Administration, Center for Veterinary Medicine, Division of Surveillance, HFV-210, 7519 Standish Place, Rockville, MD 20855. We remind you that only written communications are official.
The violations discussed in this letter do not necessarily constitute an exhaustive list. It is your responsibility to see that your promotional materials for Rimadyl®, as well as other Pfizer Animal Health products, comply with the requirements of the Act and FDA implementing regulations.
Sincerely yours,
Lynn O. Post, DV M, PhD, D
BVT Director, Division of Surveillance HFV-21O
Center for Veterinary Medicine
The WHY of pets killed by Rimadyl is easy: PROFIT!
Here's HOW it's happened and continues to happen:
The drug companies are probably the most powerful 'lobby' in our country, even having suffient power to place 'caps' on the amount of money a patient is 'allowed' to recover from a drug company today and undoubtedly all operate in the same manner. Pfizer, and the rest of them, are in business to make money; 'profit' is the bottom line.
They make their own drugs;
They 'test' their own drugs;
They provide the FDA and FDA/CVM with their alleged test results in order to get approval of their drugs from the FDA and FDA/CVM in order to put them on the market.
They PAY the FDA and FDA/CVM 'annual user fees' to KEEP their drugs on the market.
There is NO 'independent' testing done; the FDA and FDA/CVM do NOT do any testing, but take the word of the drug companies that their drugs are 'safe' or 'relatively safe' to be used by the public.
The drug companies spend millions of dollars yearly for advertising, which includes 'perks' for the drug company's 'customers': doctors and veterinarians.
These 'perks' range from pens/note pads, clocks, scrub suits, lunches, billing software for computers and the computers as well to fully paid 'seminars' for alleged continuing education which the drug companies provide at very nice places to 'teach' the doctors and veterinarians 'how to grow their practice' very profitably by using/selling/dispensing/prescribing the drugs.
The 'perks' are based on the amount of a specific drug bought; the higher the sales, the more 'expensive' the 'perks' provided.
The 'education' provided to doctors and veterinarian for 'drugs' and their usage is provided 100% by the drug companies.
In addition, the drug companies give monetary 'grants' to teaching hospitals, who often proudly display 'appreciation plaques' on their walls.
Drug companies are now known to PAY 'qualified experts' to provide articles for medical journals by falsifying the information. Merck was recently exposed, see: http://www.thecrimson.com/article.aspx?ref=527563.
The FDA and FDA/CVM use taxpayer funds to operate along with the 'annual user fees' charged to keep drugs on the market [I don't know what the 'percentages are [taxpayers vs. 'annual user fees] but I see an mind-boggling 'conflict of interests' in this.
The FDA and FDA/CVM 'keeps score' of the associated damage/deaths caused by and/or associated with administration of these drugs via ADEs [adverse drug events], IF/WHENthey are reported to the FDA and FDA/CVM.
The FDA and FDA/CVM basically just counts the 'body bags' of reported deaths and side effects and when the reported 'counts' becomes higher then the 'expected count' the FDA and FDA/CVM just say that 'all drugs have risks' and then ASK the drug companies to include the 'known risk information' on the drug companies 'CIS' [client information sheet' that's supposed to be given to the patient/pet by the drug providing doctor/veterinarian. see: http://www.fda.gov/cvm/Documents/PfizerLtr112408.pdf, the most recent 'warning' to Pfizer regarding Rimadyl. Despite the 'stacked deck' I am a strong advocate of pet owners filing their OWN 'ADE' to get their tragedy on the record even nothing will be done about it.
There is NO state or federal law enforcing the providing of 'CIS' to patients/pet owners and NO law that enforces patients/pet owners being even verbally informed of the 'known risks/side effects' of the dispensed/prescribed drugs.
The veterinarians are 'accountable' only to each state's veterinarian board, which is generally made up of fellow veterinarians to deal with any complaints filed with the state by pet owners. The criteria for determining 'veterinarian malpractice' apparently consists of a determination of whether enough veterinarians are doing the same thing for it to be considered 'the standard of care' and therefore 'acceptable' practice within the veterinarian community. Again, despite the 'stacked deck', I am a strong advocate for pet owners filing their own state veterinarian board complaint, even though nothing gets done about it because, again, it gets it 'on the record'.
There have been some pet owners who retained an attorney to file a civil complaint against their veterinarian, but there are horrendous financial obligations involved and the 'case' can go on for years and in the 'end' the courts consider pets to be 'chattel' and only 'worth' their monetary replacement value. One of the fastest growing area of law recently has been 'animal law' because the attorneys get paid by the pet owner by the hour, regardless of the outcome.
Although I don't know this for a fact, but it would not surprise me to eventually learn that the veterinarians 'legal expenses' are provided by and paid for by Pfizer in the case of Rimadyl.
The sole reason veterinarians generally do NOT provide the 'CIS' OR verbally and fully warn pet owners of the known risks is due to it not being good for their business and their 'bottom line is profit', however how much they claim to care about animals.
How many pet owners would knowingly and willingly allow Rimadyl, for example, to be used on their pet IF they knew/understood the deadly risks involved? It would be much kinder to just kill their pet in the beginning and avoid all the 'misery' for the animal!
Veterinarians have also been thoroughly 'coached' by the drug companies to DENY the obvious side effects and additionally 'lay the blame/cause' to the pet owner with tales of the 'diagnosis' being the dog's age, the dog's breed, preexisting previously undiagnosed diseases, etc.,ad nauseam, but NEVER telling the full truth about the known information about Rimadyl.
While knowing/understanding what has happened and who the 'guilty parties' are, nothing is going to bring your beloved pet back; BUT here are some proactive things to consider:
Hundreds of dogs suffered and many were killed in tests for canine
“lifestyle” drug
2
nd February 2009
The British Union for the Abolition of Vivisection (BUAV)
and the Irish Anti-
Vivisection Society (IAVS)
have exposed the plight of almost 300 dogs to test the effects of dirlotapide (Slentrol®), a drug recently marketed to manage canine obesity.
In the experiments carried out by drug company Pfizer, hundreds of dogs suffered and at least 73 were killed. Most of the experiments took place in the USA. One experiment, carried out by Pfizer UK (based in Sandwich, Kent), involved Labrador retrievers and took place in Ireland.
The studies, published in recent scientific literature, revealed that 114 Labradors retrievers and 175 beagles were given dirlotapide. Some of the experiments continued every day for up to a year and many of the dogs were housed individually, with no mention of exercise or social interaction. In at least one test, the drug was given by gavage (the forcing of a tube down the throat or through the nose into the stomach).
Some dogs were also subjected to invasive abdominal surgery to implant tubes. In most of the experiments, some dogs experienced diarrhoea and vomiting.
The source and fate of many of the dogs was not mentioned. In the experiment published by Pfizer, UK, 114 Labrador retrievers were dosed every day with the drug for up to 52 weeks.* It was not revealed where the dogs came from, how they came to be overweight or obese at the start of the experiment, or what happened to them when the experiment was over.
It was noted by the researchers that once the drug is discontinued, there would be rebound weight gain unless an appropriate diet and exercise regimen is instituted. It should be obvious, therefore, that the latter could have resulted in the same weight loss caused by the drug.
Chief Executive of the BUAV, Michelle Thew
, says “Pet owners everywhere will be shocked to learn that hundreds of dogs, such as beagles and Labrador retrievers, suffered and many were killed just to study the effects of an unnecessary drug. Pfizer's stated commitment to the health and wellness of pets has to be called into question here. In these experiments, dogs who could otherwise be members of a loving family, were treated as disposable research tools. At the end of the day the answer to helping overweight pets is a restricted diet and regular exercise - everyone knows that.”
IAVS Spokesperson, Yvonne Smalley,
says "Animal experiments in Ireland are governed by the Cruelty to Animal Act 1876, as amended by EU Regulations 2002 & 2005. Licences are granted subject to the experiment being essential and the objective can not be achieved by the use of alternative techniques. The scientific value of the outcome must be deemed to outweigh the suffering to the animals involved (e.g. licences are not granted to conduct cosmetics testing in Ireland). On this basis, the IAVS believes this work should not have been licensed. We call on the Department of Health to suspend any current licence for ongoing or similar experiments immediately, pending a full investigation into the use of these dogs, the conditions in which they are held and what is happening to the surviving dogs today."
Veterinary Consultant to the BUAV
, Dr Nedim Buyukmihci, says “In my professional opinion, the published literature fails to demonstrate a medical benefit for Slentrol that cannot be achieved through other safer and more sustainable means such as good pet nutrition and regular exercise. To cause dogs to suffer or to kill them to produce a drug that is nothing more than for convenience is morally unacceptable.”
NOTES TO EDITORS
*Gossellin, J.; Peachey, S.; Sherington, J., Rowan, T.G. and Sunderland, S.J. Evaluation of dirlotapide for sustained weight loss in overweight Labrador retrievers.
Journal of Veterinary Pharmacology and Therapeutics 2007;30;55-65.
The Chief Executive of the BUAV, Michelle Thew, is available for interview.
The BUAV has been campaigning for over 100 years to achieve a world where nobody wants or believes we need to experiment on animals. We are committed to achieving our aims through reliable and reasoned evidence-based debate. We are proudly non-violent and respect the quality of life for all – animals and people.
For more information contact: Carla Owen +44 (0)20 7619 6965/Out of
bravenet.com