Animal & Veterinary
FDA/CVM 1999 ADVERSE DRUG EVENT REPORTS – A DESCRIPTIVE OVERVIEW
FDA Veterinarian Newsletter May/June 2001 Volume XVI, No III
by Neal Bataller, ME, D.V.M.
This article presents a descriptive overview of the 9,731 post-market adverse drug event (ADE) reports received by the U.S. Food and Drug Administration, Center for Veterinary Medicine (FDA/CVM) during calendar year 1999. An ADE report consists of either an undesired side effect, or the lack of a desired effect associated with drugs administered to animals. Reports may also involve product defects and potential harm posed to persons administering or using animal drugs.
In previous years, a summary of these ADE reports was included as an insert in the FDA Veterinarian. This summary was not included in the newsletter this year because of its length. However, copies of the 1999 Veterinary Adverse Drug Experience Summary may be obtained from CVM’s Internet Home Page or by calling or writing the FDA Veterinarian.
The primary purpose for maintaining the FDA/CVM database is for providing an early warning or signaling system for adverse effects not detected during premarket testing of FDA-approved animal drugs and for monitoring the performance of drugs not approved for use in animals. The FDA/CVM ADE reporting system depends upon the detection of an adverse clinical event by veterinarians and animal owners, the attribution of the clinical event to the use of a particular drug ("suspect" drug), and the reporting of the ADE either to the manufacturer of the suspected drug or directly to FDA. Data from these ADE reports are reviewed, coded and entered into the computerized FDA/CVM ADE database.
The reporting of ADEs by veterinarians and animal owners is voluntary. They may send their reports directly to the FDA/CVM ("Direct" reports), to the drug manufacturer ("Manufacturer" reports), or both. The drug manufacturers of FDA-approved animal drugs are required by law and regulation to submit to the FDA post-market ADE reports received by any means from veterinarians and animal owners.
It is important to remember certain caveats when using data from the FDA/CVM ADE database:
- For any given ADE report, there is no certainty that the suspect drug caused the ADE. This is because veterinarians and animal owners are encouraged to report all suspected ADEs, not just those that are already known to be caused by the drug. The adverse event may have been related primarily to an underlying disease for which the drug was given, to other concomitant drugs, or may have occurred by chance at the same time the suspect drug was administered.
- Accumulated ADE reports should not be used to calculate incidence rates or estimates of drug risk.
- Many factors affect the volume of reports received for any one drug product. Factors might include (1) the nature of the drugs; (2) the diseases being treated; (3) the type and health of the patient involved; (4) the motivations and expectations of consumers; (5) the extent of product marketing; and (6) the vigilance of the drug company in receiving and submitting reports of adverse drug experiences. In consideration of these many factors, the summarized information should NOT be used to make product comparisons or to commercially promote certain products.
In this article, various kinds of data and information are presented for the ADE reports computerized into the FDA/CVM ADE database during the calendar year 1999. Due to rounding, the percentages in tables may not total to 100 percent.
II. Report Submission Information
Table 1 shows the number of reports received for the last eight full calendar years. The numbers only include original reports involving animal injury and product ineffectiveness; follow-up reports are not included. Product defects are additionally included for 1999 but are not included in the figures for previous years. In general, the annual number of reports has increased in recent years, although much of the increase in the latter years is attributable to a few newly approved animal drugs. Reporting levels for the last two years are similar.
While ADE reports are submitted to CVM from a variety of sources, the sponsors of FDA-approved animal drugs submit the bulk of reports (Table 2). As mentioned above, drug sponsors are required by law and regulation to submit all reports involving animal injury, product ineffectiveness, and product defects. Drug manufacturers of human drugs and unapproved animal drugs are not required to submit any ADE reports to CVM, so very few ADE reports are submitted to CVM for these types of drug products.
The USP Practitioner Reporting Network is a "third-party", independent reporting service. Only selected USP ADE reports are entered into the FDA/CVM ADE database. Selected reports include reports involving unapproved animal drugs and human drugs, and where the identity of the reporter is withheld from the sponsor. For the remaining USP reports, the sponsor is expected to investigate the adverse event and officially submit their findings directly to CVM.
III. Animal Zoographic Information
Table 3 lists the species that are most represented in ADE reports. The majority of reports involve companion animals and cattle. Few reports are received that involve poultry; chicken and turkeys did not make the 1999 Top-10 list. The average number of animals adversely affected in each report is more reflective of the animal management and health care associated with each species, and with the type of complaint.
IV. Suspect Drug Information
The remaining tables (4 through 8) in this article only involve reports that the Center has determined to be at least "possibly" drug-related. A number of different factors are considered in determining this classification. Tables 4 through 6 describe the drugs involved in these reports with the data organized by (1) general drug class; (2) active ingredient(s); and (3) product tradename.
V. Drug Usage Information
Table 7 lists the route of drug administration most commonly represented in ADE reports. Note that the "oral" category generally represents tablets, capsules, powders and pastes while the medicated feed category involves the consumption of animal feeds containing drugs.
VI. Adverse Event Information
Table 8 lists the most common complaints contained in ADE reports considered as at least "possibly" drug-related. Again, care should be taken in interpreting this ranking since many factors affect whether a veterinarian or animal owner is motivated to actually report an adverse drug experience. The seriousness of an adverse event may affect the likelihood of reporting regardless of whether other non-drug-related factors could also have accounted for the adverse event.
Dr. Bataller is a Biologist in CVM’s Division of Surveillance.
[All tables follow narrative in "Rich Text File" exported from PageMaker.]
Table 1. ADE Reports by Year
Table 2. 1999 ADE Reports Ranked by Source (n=9,731)
Source Number %
Drug Company 9,627 98.9
USP Practitioner Reporting
Network 59 0.6
Mail, Direct to FDA 43 0.4
Telephone, Direct to FDA 2 <0.1
Table 3. 1999 ADE Reports Ranked by Top-10 Species, Plus Average Number of Animals Adversely Affected per Report (n=9,731)
Species Number % Avg #/Rpt
Dog 6,502 66.8 1.1
Cat 865 8.9 1.5
Cattle 728 7.5 98.9
Horse 412 4.2 1.6
Human 293 3.0 0.4
Pig 55 0.6 1,198.4
Goat 16 0.2 6.8
Sheep 9 <0.1 7.0
Rabbit 7 <0.1 1.4
Deer 5 <0.1 6.8
1999 "Possible" ADE Reports Ranked by Top-10 Classes of Suspect Drugs (n=7,619)
Class Number %
Analgesic, Nonsteroidal 3,116 40.9
Antinematodal 815 10.7
Prevention 716 9.4
CNS, General 680 8.9
Antimicrobials, Penicillins 258 3.4
Anesthetics, General 248 3.3
Fluoroquinolones 194 2.5
CNS Sedatives/Hypnotics 183 2.4
Anti-ectoparasites, Systemic 145 1.9
CNS, Tranquilizers 137 1.8
Table 5. 1999 "Possible" ADE Reports Ranked by Top-10 Active Ingredients of Suspect Drugs (n=7,619)
Active Ingredient(s) Number %
Carprofen 2,541 33.4
Seligiline 675 8.9
Etodolac 492 6.5
Moxidectin 432 5.7
Milbemycin, Lufenuron 183 2.4
Selamectin 178 2.3
Doramectin 166 2.2
Medetomidine 163 2.1
Amoxicillin 150 2.0
Enrofloxacin 144 1.9
Table 6. 1999 "Possible" ADE Reports Ranked by Top-10 Tradenames of Suspect Products (n=7,619)
Tradename Number %
Rimadyl® 2,541 33.4
Anipryl® 675 8.9
EtogesicTM 492 6.5
QuestTM 312 4.1
SentinelTM 183 2.4
RevolutionTM 178 2.3
Domitor® 163 2.1
Immiticide® 150 2.0
Posilac® 123 1.6
Cydectin® 118 1.5
Table 7. 1999 "Possible" ADE Reports Ranked by Top-10 Routes of Drug Administration (n=7,619)
Route Number %
Oral 4,895 64.2
Not Applied, Product Defect 813 10.7
Intramuscular 555 7.3
Subcutaneous 364 4.8
Topical 358 4.7
Intravenous 203 2.7
Unknown Route 160 2.1
Intramammary 85 1.1
Otic 84 1.1
Medicated Feed 39 0.5
Table 8. 1999 "Possible" ADE Reports Ranked by Top-10 Adverse Clinical Manifestations (n=7,619)
Adverse Effect Number %
Vomiting 1,146 15.0
Anorexia 944 12.4
Depression/Lethargy 910 11.9
Product Ineffectiveness 692 9.1
Increased SGPT/ALT 684 9.0
Increased Alkaline Phosphatase 683 9.0
Death 587 7.7
Diarrhea 485 6.4
Ataxia 382 5.0
Increased Total Bilirubin 370 4.9