1. Canine NSAIDs and Client Education
An FDA Perspective
Dr. Amy Omer, Dr. Barbara Leotta, and Dr. Michele Sharkey
Center for Veterinary Medicine

2. The Food and Drug Administration
The Food and Drug Administration (FDA) is a federal agency within the Department of Health and Human Services.

3. FDA FDA is responsible for ensuring that:
foods are safe, wholesome and sanitary
human and veterinary drugs, biological products, and medical devices are safe and effective
cosmetics are safe
electronic products that emit radiation are safe
products are honestly, accurately and informatively represented to the public.

4. Who are we?

5. CVM
FDA’s Center for Veterinary Medicine (CVM) is a consumer protection organization.
We foster public and animal health by approving safe and effective products for animals and by enforcing other applicable provisions of the Federal Food, Drug, and Cosmetic Act and other authorities.

6. What We Do
The Center for Veterinary Medicine is responsible for animal drug approval as well as post-approval monitoring of marketed animal drugs to assure continuing safety and effectiveness.

7. How are veterinary drugs approved?
Pharmaceutical companies decide, based on marketability, need, economics, etc., to pursue development of a drug.
CVM does not propose products or label indications.

8. How are veterinary drugs approved?
Pharmaceutical companies conduct the necessary research to support drug safety and effectiveness.
Data is submitted to CVM and scientifically reviewed.
CVM determines if data demonstrates the drug is safe and effective when used as directed on the label.

9. How are veterinary drugs approved?
Pre-approval studies for veterinary drugs generally include fewer subjects than those conducted for human drug development.

10. How are veterinary drugs approved?
For companion animals:
Pre-approval safety studies are almost exclusively performed in young, healthy animals (generally 32 animals).
Pre-approval effectiveness studies are generally performed in healthy, client-owned animals.

11. How are veterinary drugs approved?
“Pre-testing by the manufacturer and review of the data by the government does not guarantee absolute safety and effectiveness of approved veterinary drugs due to the inherent limitations imposed by testing the product on a limited population of animals.”
-CVM’s Adverse Drug Experience Reporting Webpage

12. What are NSAIDs?
Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce prostaglandins throughout the body by inhibiting the enzyme cyclooxygenase (COX).
Cyclooxygenase catalyzes the formation of prostaglandins from arachidonic acid.

13. Kurie, J. M. et al. Clin Cancer Res 2001;7:2608-26

14. How NSAIDs Work Prostaglandins have several important functions:
promote inflammation, pain, and fever
support the function of platelets
protect the lining of the stomach from the damaging effects of acid
play a role in renal homeostasis

15. What NSAIDs Do
As a consequence, ongoing inflammation, pain, and fever are reduced.
BUT …..
There is a risk of gastrointestinal bleeding, ulcers, perforations, and in rare cases kidney damage and liver problems.

16. Why talk about NSAIDs? NSAIDs:
are the most commonly prescribed veterinary analgesics.
account for the largest amount of Adverse Drug Events (ADEs) reported to CVM.
Newer human NSAIDs (COX-2 selective) have been shown to be safer on the GI system; NOT the case in veterinary medicine*.
* Based on CVM ADE database.

17. Approved NSAIDs
To date, NSAIDs for use in dogs have been approved for two indications:
Osteoarthritis
Postoperative pain (ortho &/or soft tissue)

18. Approved NSAIDs
Consider the risk factors commonly associated with these two populations of patients:
Osteoarthritis→ geriatric population → underlying concomitant diseases (hepatic/renal disease)
Postoperative → hydration status → potential for compromised renal function

19. Approved NSAIDs Veterinary NSAIDs approved for use in dogs:
ETOGESIC (etodolac)
RIMADYL (carprofen)
METACAM (meloxicam)
DERAMAXX (deracoxib)
PREVICOX (firocoxib)
ZUBRIN (tepoxalin)
NOVOX (carprofen)
VETPROFEN (carprofen)

20. Recently Approved Veterinary NSAIDs

21. Approved NSAIDs
In the United States, there are no veterinary NSAIDs approved for oral use in cats.
Cats have a reduced ability to metabolize NSAIDs compared to other species.

22. NSAIDs: Benefits
The approved NSAIDs provide a tremendous amount of good to our canine patients.
NSAIDs offer pain relief and improved quality of life to many dogs.
NSAIDs contribute to the effective management of postoperative pain.

23. NSAIDs: Risks Risks are associated with the use of any drug.
All veterinary NSAIDs have inherent risks.
CVM strives to promote the safe and effective use of NSAIDs by painstakingly crafting drug labels, including Client Information Sheets (CISs).
CISs are intended to be dispensed to clients with each NSAID prescription.

24. NSAIDs: Signs of Toxicity
As a class, NSAIDs are associated with gastrointestinal, renal and hepatic toxicity.
The four most commonly reported adverse events are vomiting, anorexia, depression, and diarrhea.
Others include: gastric ulceration, intestinal ulceration, renal failure, hepatic failure, and death.

25. Adverse Drug Events (ADEs)
Adverse drug experience is any adverse event associated with the use of a new animal drug, whether or not considered to be drug related, and whether or not the new animal drug was used in accordance with the approved labeling CFR 514.3

26. Adverse Drug Events (ADEs)
ADEs are voluntarily reported by veterinarians, pet owners, and others to the drug company and/or CVM.
Companies are required to report all ADEs to CVM.
ADEs are stored in CVM's database and analyzed by clinical veterinarians.

27. Why You? Technicians often prepare drug prescriptions.
Even when clients have heard the benefits and risks of NSAIDs from the veterinarian, hearing it again from you will increase their understanding.

28. What You Can Do
Technicians can ensure that the Client Information Sheets are included with each NSAID prescription.
Technicians are often in charge of ordering. Technicians can request CISs from the drug representative or distributor.

29. What You Need To Know
Many ADEs may be prevented or treated successfully through better understanding of these drugs and good client communication.
Educate Yourself…on the safe use of NSAIDs, the benefits/risks, and the potential ADEs.
Educate Your Clients…so they can recognize potential ADEs, stop using the drug, and seek immediate veterinary care.
Report ADEs associated with any drug.

30. Educate Yourself
Labels – Package Inserts contain important information, including:
Indications & Usage
Dosage & Administration
Contraindications
Warnings
Precautions
Adverse Reactions
Post Approval Experience

31. Educate Yourself
Extralabel Use (ELU) –veterinarians may prescribe certain approved animal drugs, including NSAIDs, for use in animals that is not in accordance with the approved label directions, in the context of a veterinarian-client-patient relationship. -The Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA)
ELU has not been tested and clients should be informed of ELU.

32. Educate Your Clients Communication is Key!
Written Communication
Labels – Client Information Sheets:
are part of labeling for FDA-approved oral NSAIDs.
provide information written specifically for pet owners.
should be provided by pharmaceutical companies with your drug order.
should be sent home with each NSAID prescription to provide an easy reference for clients after they leave your clinic.

33. Educate Your Clients Communication is Key!
Verbal Communication
Face-to-Face conversations with your clients can reinforce the information provided to them by the veterinarian, and included in the Client Information Sheet.
Explain the potential benefits and risks.
Describe the signs of possible adverse reactions to the drug.
Tell your clients what to do if they notice any of these signs – STOP THE DRUG and CONTACT THEIR VETERINARIAN.

34. REPORT Options: Report any ADEs to the pharmaceutical company.
Toll-free number on the label.
Report any ADEs directly to the Center for Veterinary Medicine if necessary.
1-888-FDA-VETS

36. 5 Take Home Points Benefits/Risks are associated with any drug.
Know the signs of NSAID toxicity so you can educate your clients. Client communication is key.
Provide CIS with each NSAID prescription.
Problems: Stop the drug & Call your Veterinarian.
Report ADEs.

37. Further Information Center for Veterinary Medicine (CVM) Website:
Veterinary NSAID specific information:
Free NSAIDs Brochure:
# 503R: Keeping Your Best Friend Active, Safe, and Pain Free
Current Labels:
May 2008