Extralabel, legal, and illegal drug use in food animals (Proceedings)

Antibiotic selection is generally based on a range factors including tentative diagnosis, culture and sensitivity data, pharmacokinetic constraints, economics, and legality. Many diagnoses are predominated by a single pathogen with well described, efficacious treatment protocols that may be used for antibiotic selection. When culture data is available the known behavior of the etiologic agent may be used to select a potentially efficacious antibiotic. The availability of sensitivity data may also point to potentially efficacious antibiotics. While this selection method seems fool proof there are limitations. The time lag involved for the necessary data may hinder prompt treatment of the patient. In addition in vivo and in vitro results may differ in the ability of an antimicrobial to kill a pathogen. Knowledge of the pharmacology and pharmacokinetics of the antimicrobial of choice is also important. The ability of the drug to penetrate into the target tissues and the activity of the drug in the host environment may limit efficacy even if the face of a susceptible pathogen. The persistence of therapeutic concentrations must also be considered as frequent dosing in some settings may lead to poor administration compliance. Economics of drug administration are often ignored or underestimated. It is possible for the most inexpensive antibiotics to have the highest treatment costs when labor associated with dosing intervals and meat and milk withholding times are factored in to the total cost.

In order for drugs to be approved by the FDA manufacturers must demonstrate that the drug is safe and efficacious for its intended purpose in its intended species. Any variation from the label including dosage, dosing interval, or disease treated is considered extra label use. In general physicians and veterinarians have the ability to use drugs in an extra label fashion. However, restrictions to that use are imposed when prescribing products to food producing animals. In addition some products are banned from use in food producing animals regardless of the veterinarian's judgment. The most obvious benefit of regulating drug use in food producing animals is to limit potential contamination of the food supply. Regulation also serves to limit the development of antimicrobial resistance to drugs that may have a use in human medicine and to limit the potential for meat and milk residues of drugs that may harm humans ingesting tainted products.

In addition to federally mandated bans, national organizations such as the American Association of Bovine Practitioners and the American Veterinary Medical Association will occasionally recommend a voluntary moratorium on the use of specific drugs in food producing animals. The use of aminoglycosides in food producing animals currently falls in this category.

Requirements for extralabel drug use

• Permitted only under the supervision of a veterinarian

• For FDA approved human and animal drugs

• Valid veterinarian/client/patient relationship

• Therapeutic use only

• Rules apply to dosage form drugs administered in water

• Prohibited in feed

• Prohibited if it results in violative food residue

• FDA prohibition of a specific extralabel drug use precludes use

Medical record requirements

• Identify animal or group of animals

• Species identification

• Number of animals treated

• Conditions being treated

• Established name of the drug and active ingredient

• Dosage prescribed or used

• Duration of treatment

• Specified withdrawal, withholding, or dicard time for meat, milk, eggs, or animal derived food

• Keep records for 2 years

• FDA may have access to records to estimate public health risk

Drug label requirements

• Name and address of the prescribing veterinarian

• Established name of the drug

• Directions for use including species or identification of the animal or herd, flock pen, lot, or other group; dosage frequency; route of administration; and the duration of therapy

• Cautionary statements

• Specified withdrawal, withholding, or discard time for meat, milk, eggs, or any other food

Drugs prohibited for extralabel use

• Chloramphenicol

• Clenbuterol

• Diethylstilbesterol

• Dimetridazole

• Ipronidazole

• Other nitroimidazoles

• Furizolidone, nitrofurazone, and other nitrofurans

• Sulfonamides in lactating dairy cattle (except approved use of sulfadimethoxine, sulfabromomethazine, and sulfaethoxypyridazine)

• Flouriquinilones

• Glycopeptides

• Phenylbutazone in female dairy cattle 20 months of age and older

• Adamantane and neuraminidase inhibitor classes of drugs approved for use in treating influenza A are prohibited for use in chickens, turkeys, and ducks

Suggested reading/websites with reliable and useful information

Animal Medicinal Drug Use Clarification Act Brochure and Extralabel drug use algorithm http://www.avma.org/reference/amduca/amduca1.asp

United States Food and Drug Administration Animal and Veterinary Webpage. http://www.fda.gov/AnimalVeterinary/default.htm