A Practical Guide to Companion Animal Prescription Drug Labeling;

1. A Practical Guide to Companion Animal Prescription Drug Labeling; & the Role of the Center for Veterinary Medicine (CVM)

2. Overall Goals • To illustrate the importance of product labeling. • To explain the process of creating a label. • To show how labeling information can be used in the clinical setting. • To increase the understanding of CVM’s role in new animal drug development, specifically focusing on how the knowledge obtained from our thorough review process is expressed in the product labeling.

3. Presentation Overview • FDA/CVM Background Information • New Animal Drug Approval Process • Drugs used in Companion Animal Medicine • Prescription Drug Labeling • Conclusions • Case Studies

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

5. 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.

6. Center for Veterinary Medicine (CVM) CFSAN CVM CDER FDA CDRH NCTR CBER ORA

7. Center for Veterinary Medicine • CVM is a consumer protection organization, fostering public and animal health. • CVM’s authority is derived from the Federal Food, Drug, and Cosmetic Act.

8. Center for Veterinary Medicine • CVM is responsible for ensuring that animal drugs and medicated feeds are safe and effective for their intended uses and that food from treated animals is safe for human consumption. • CVM monitors the use of marketed products through surveillance and compliance programs.

9. New Animal DrugApproval Process • Pharmaceutical companies (drug sponsors) conduct the necessary research to support drug safety and effectiveness. • Data is submitted to CVM and reviewed from a scientific and regulatory perspective. • CVM determines if data demonstrates the drug is safe and effective when used as directed on the label.

10. Drugs Used in Companion Animal Medicine • FDA-approved new animal drugs – pioneer and generic • Extralabel use of approved new animal drugs • Extralabel use of approved human drugs

11. Prescription Drug LabelingTopic Overview • Where does the information in the label come from? • What are some limitations on label information? • Who writes the label? • What’s in a label? • Labels as “living” documents.

12. Where does the information in the Label come from? Animal Safety Effectiveness All Other Information

13. Animal Safety • Target animal safety (TAS) studies – multiple levels of exposure to mimic the potential adverse effects in the general population • Specialized studies or tests: - Collie safety studies - Ocular studies - GI endoscopy • Field safety – effectiveness studies and use studies (open-label)

14. Effectiveness • Field effectiveness studies in the target animal – adequate and well-controlled • Dose confirmation studies • Laboratory studies - Disease models - Target animal • Pharmacokinetic studies

15. All Other Information • Literature • Foreign market experience • Known drug class information • Human drug approvals • Post-approval experience

16. What are some Limitations on Label Information? • Pre-approval studies for veterinary drugs include fewer subjects than those conducted for human drug development. For companion animals: • Pre-approval safetystudies are almost exclusively performed in young, healthy animals. • Pre-approval effectiveness studies are generally performed in healthy, client-owned animals.

17. Who Writes the Label? • Labeling language is a collaboration between the drug sponsor and CVM to present fair and balanced information.

18. What’s in a Label? Main Labeling Components: • Package Insert - Written for veterinarians • Useful information for daily practice • Client Information Sheet - Written for owners • Accompany certain new animal drugs • Should be dispensed with each prescription • Bottle/Vial/Outer Box Labeling

19. Example Package Insert (Suggested Major Headings) • Indications • Dosage & Administration • Contraindications • Warnings • Precautions • Adverse Reactions • Clinical Pharmacology • Effectiveness • Animal Safety

20. Example Package Insert • Indications: - Lists the specific disease(s) or condition(s) for which the drug product is approved • Dosage & Administration: • Recommended dose (dose studied in pre-approval) • Duration of treatment & treatment interval • Modifications for special populations

21. Example Package Insert • Contraindication: • Risk of using the drug product outweighs any possible benefit • Usually a proven hazard

22. Example Package Insert • Warnings: - Includes user safety, human food safety, animal safety & environmental safety - May include warnings related to extralabel use • Boxed warnings – potential risk of death or serious injury

23. Example Package Insert • Precautions: • Information that does not warrant a warning or contraindication statement, but needs to be communicated for the safe and effective use of the drug • Tests recommended prior to use • Examples: drug interactions, statements regarding subgroups in which the drug has not been tested

24. Client Information Sheets • Written for pet owners • Contain important information regarding what pet owners should expect when using drugs, and what side effects to look for

25. Labels as “Living” Documents • Labeling language updated based on post-marketing experience, including Adverse Drug Experiences (ADEs) • Sponsor-initiated updates, including manufacturing changes, new tablet sizes, etc.

26. Adverse Drug Experiences (ADEs) • ADEs are voluntarily reported by veterinarians, pet owners, and others to the pharmaceutical company or CVM. • Companies are required to report all ADEs to CVM.

27. Conclusions • Labels are important “living” documents that contain useful information for daily practice. • Read and use product labels regularly. • Report ADE’s to sponsors and/or CVM.

28. Case Studies The following case studies are not intended to guide or dictate the practice of veterinary medicine. They are simply meant as examples of the information that can be found on the labeling of FDA-approved animal drugs, and how that information can be used on a daily basis.

29. Case Scenario #1 – Buddy

30. Case Scenario #1- Questions 1. Do you need any other history before deciding to prescribe firocoxib? 2. Should you perform any other exams/evaluations before prescribing firocoxib? 3. What toxicities are associated with NSAIDs? 4. What clinical signs warrant the discontinuation of firocoxib? 5. Can you use this drug in pregnant horses? Foals? 6. What was the highest dose of firocoxib tested in the studies performed to support approval? 7. At what dose is firocoxib approved? 8. What should you give to the owner in addition to the tubes of EQUIOXX paste?

31. Case Scenario #2 – Shelby

32. Case Scenario #2 - Questions 1. What is the mechanism of action? 2. What is the dose and route? 3. What are the known side effects? 4. What are the contraindications for use? What are the precautions for use? 5. What, if any, medications are allowed concurrently? Not allowed concurrently? 6. What should be done if a dog vomits after administration? 7. Is there a maximum duration of administration? 8. What should be done in an acute overdose situation?

33. Case Scenario #3 – Guzzles

34. Case Scenario #3 - Questions 1. What is the chemical name of the drug? 2. How do you know that the VETORYL you have just taken off the clinic shelf has been FDA approved? 3. Your clinic carries two sizes of VETORYL. Which bottle will you select? 4. Which area of the dosing table will you focus on in order to calculate the starting dose? 5. Where will you look to check for follow-up instructions and testing? 6. The owner is really anxious to eliminate the excessive water drinking, urination, and food thievery. Is there a place on the label that gives a guideline for when she can expect to see improvement?

35. Case Scenario #3 – Questions(continued) 7. The owner is very concerned about side effects on “Guzzles” from this medication. Where would you look on the label to give her this information? 8. The owner wants to know if there are any special storage instructions for this medication. Where can you find this information to let her know? 9. There are small children in the house, and Mrs. Jones is always worried about what they will get into (boys will be boys)…She is also excited to tell you that she is pregnant again! What can you tell her about precautions for humans? 10. Does the medication need to be given with food? If Guzzles decides she doesn’t want to take the pill, can Mrs. Jones mix the powder from the capsules into the food? 11. Mrs. Jones wants to know if she can still give Heartgard Plus and Frontline Plus.

36. Case Scenario #4 – Rascal

37. Case Scenario #4 - Questions 1. Which antibiotic would you prescribe, and why? 2. What dose would you choose? 3. What possible adverse effects would you warn the owner to watch for, based on your choice of treatment? 4. The owner is worried he’ll act “funny” again, and asks if it’s okay for her to give him some OTC Pepcid to prevent any upset stomach. What is your response?

38. Questions?

39. Online Resources • Center for Veterinary Medicine (CVM): http://www.fda.gov/AnimalVeterinary/default.htm • How to report an ADE: http://www.fda.gov/AnimalVeterinary/SafetyHealth/ReportaProblem/ucm055305.htm • Currently approved labels for companion animal NSAIDs: http://www.fda.gov/AnimalVeterinary/Products/ApprovedAnimalDrugProducts/DrugLabels/ucm050105.htm