December 1, 1999
UPDATE ON RIMADYL
FDA's Center for Veterinary Medicine (CVM) has recently compiled and reviewed adverse drug experience (ADE) reports received for 1998. During this period, the Center received a substantial number of ADE reports for carprofen (trade name Rimadyl®) and consumer inquiries regarding the safety of this product.
CVM has released the "1998 Annual Adverse Drug Experience (ADE) Summary" which includes information about ADEs to all veterinary drugs, including Rimadyl®. This ADE summary is on our Home Page . Copies are also available from CVM's Communications Staff at FDA/Center for Veterinary Medicine, HFV-12, 7500 Standish Place, Rockville, MD 20855, 301-594-1755. FDA also published a descriptive overview of the 1998 ADE reports in the November/December issue of the FDA Veterinarian. This report also is available from the Communications Staff and our Home Page at the above address.
FDA approved Rimadyl® for dogs on October 25, 1996, after a comprehensive review of the product?s safety and efficacy. Rimadyl® is a non-steroidal anti-inflammatory drug (NSAID) indicated for use in relief of pain and inflammation associated with osteoarthritis in dogs. NSAIDs are commonly used in human medicine for relief of pain and include such drugs as aspirin, ibuprofen, and naproxen. Rimadyl® is one of two NSAID products currently approved for use in dogs. The active ingredient in Rimadyl®, carprofen, is not approved for use in humans. The drug is available by veterinary prescription only. The approved drug sponsor is Pfizer Animal Health of Exton, PA.
Pre-approval studies for Rimadyl® included a clinical trial involving 297 dogs administered either the drug or a placebo for 14 days. Similar adverse clinical signs were observed in both the carprofen and placebo-treated groups. These signs included an increase in vomiting, diarrhea, lethargy, behavioral changes, constipation, and an increase in liver enzymes. Safety studies revealed no remarkable side effects associated with long-term drug administration. Based on the studies submitted to CVM, the risk of Rimadyl® was thought to be negligible.
Of all the ADE reports CVM received in 1998, thirty-nine percent (39%) or 3626 involved Rimadyl®. The number of ADE reports received by CVM for Rimadyl® is considerably more than that received for other animal drugs. For any one ADE report, there is no absolute certainty that the suspected drug caused the effect. The adverse effects in these reports are consistent with those expected for NSAIDs. They typically involve the gastrointestinal system, renal/urinary system, hematopoietic (blood) system, neurological system, and the liver. Approximately 13% of the 1998 Rimadyl® ADE reports for dogs involved death of the dog, either on their own or by means of euthanasia.
In spite of the high standards for safety and effectiveness that exist for FDA approval, not everything is known about a drug when it is first marketed. Due to the limited number of animals and controlled nature of pre-marketing clinical trials, only the most common adverse effects will be observed. Uncommon effects or problems may not be discovered until after the drug has been widely used.
Based on adverse experience reports received since Rimadyl® was marketed, a number of actions have been taken to provide the most current product safety information to veterinarians and dog owners. In 1997, shortly after Rimadyl® was marketed, CVM began receiving ADE reports involving the drug. In May 1997, CVM asked Pfizer to change the adverse reaction section of the label.
CVM also asked Pfizer to send a "Dear Doctor" letter to veterinarians informing them of the adverse effects reported with product use. In August 1997, Pfizer mailed a "Dear Doctor" letter to all veterinarians who had purchased the product. By September 1997, Pfizer had revised Rimadyl® labeling to include an extensive adverse reaction section. The possibility of a fatal outcome was mentioned elsewhere on the label, but death was also added to the adverse reactions section in the spring of 1999. In addition, at CVM?s request, Pfizer developed and distributed an information sheet containing safety information for veterinarians to give to owners at the time Rimadyl® is dispensed.
A number of factors might contribute to the high number of ADE reports received for Rimadyl®:
type of drug -- NSAIDs as a pharmaceutical class are commonly associated with adverse affects on a variety of body systems, particularly the gastrointestinal system. Adverse effects on the kidney and liver have also been documented.
wide use -- Rimadyl® has been administered to 2.5 million dogs over its first two years of marketing. This represents a high level of use for a recently approved drug.
duration of use -- Rimadyl® is intended for daily administration to dogs, possibly on a long-term basis. While Rimadyl®-related adverse effects are reported to occur shortly after drug initiation, long-term use may result in a higher risk for adverse effects. A substantial portion of dogs receive Rimadyl® continuously for more than 30 days.
senior dog use -- Over 85% of Rimadyl® ADE reports involved dogs greater than six years of age. Rimadyl® is intended for use in osteoarthritis, a disease condition more pronounced in older dogs. Older dogs in general may be more susceptible to carprofen-related adverse effects.
marketing of the drug -- Pfizer's direct-to-consumer marketing strategy and professional support encourages the submission of a higher number of ADE reports. For instance, Rimadyl® is one of the few animal drugs that provides a toll-free number on the label for reporting ADE reports to the drug company, which facilitates reporting.
Most of the ADEs reported by owners directly to CVM involved owners of dogs who said they were not aware of the potential adverse effects associated with Rimadyl® use. Adequate communication between the veterinarian and client should result in an awareness of the risk and benefit of drug use and alternate therapies that are available. Additionally, communication should establish the importance of evaluation of the dog prior to Rimadyl® initiation and the necessity of periodic follow-up evaluations if drug use is continued long-term. Animal owners have told CVM that adequate communication is not occurring in many instances.
CVM will continue to evaluate ADE reports received for Rimadyl® compared to the benefits of NSAID therapy. In many dogs, the use of NSAIDs is not an elective therapeutic choice, but the primary therapy available for maintaining an acceptable standard of life due to the long-term debilitating effects of osteoarthritis. As an NSAID with potentially serious side effects, however, the use of Rimadyl® should be carefully considered before being incorporated in any therapeutic plan. Moreover, dog owners should have an active role in making that decision. CVM, along with drug sponsors, is actively pursuing a number of avenues to improve the management of NSAID safety issues in order to minimize the risks and maximize the benefits of using these products in dogs.
Issued by:
FDA, Center for Veterinary Medicine,
Communications Staff, HFV-12
7519 Standish Place, Rockville, MD 20855
Telephone: (240) 276-9300 FAX: (240) 276-9115
Internet Web Site: http://www.fda.gov/cvm
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