Extra label use, know the rules

With the constant infusion of new products to the human and veterinary market, it becomes a daunting task to keep up with veterinary pharmacology and vaccine technology.

And although all veterinarians have the responsibility of safe and prudent drug use in animals, food animal veterinarians have the added responsibility of residue avoidance. Most food animal practitioners are aware of the Animal Medicinal Drug Use Clarification Act (AMDUCA), but understanding what is actually allowed and what is not allowed can be difficult.

This article will discuss the sometimes confusing rules and regulations of prudent drug use in food animals and provide resources that food animal veterinarians can use to find information.

What's legal?

AMDUCA allows for extra-label drug use in food animals. But what is extra-label use? It is using a drug:

1) in a food animal species that is not on the label,

2) for an indication that is not on the label,

3) at a dose level, frequency or duration that is not on the label,

4) by a route of administration that is not on the label,

5) in a class of food animal that is not on the label.

So, using a drug in a goat that is only labeled for cattle is extra-label use. Using a drug in a dairy cow that is only labeled for beef cattle is extra-label use. Using a drug in a lactating dairy cow that is only labeled for non-lactating cows is extra-label use.

There are constraints associated with extra-label drug use under AMDUCA. Two of the most important are that extra-label use must be by or on the order of a veterinarian within the context of a veterinarian-client-patient relationship (VCPR), and that extra-label use must not result in violative residues in food-producing animals.

For example, producers are not allowed to increase a dose of a drug, even if it is an over-the-counter product. Only a licensed veterinarian can do that. And veterinarians must have a valid VCPR even to prescribe drugs on label. For example, advising an unknown producer to give a dose of penicillin that is higher than the label indicates is not permitted, even though this is an over-the-counter drug.

If a drug is prescribed in an extra-label manner, a withdrawal time must be established that prevents violative residues. Some resources to help establish proper meat and milk withdrawal times are the drug manufacturer for the particular product and the Food Animal Residue Avoidance Databank (FARAD) at www.farad.org

Other constraints to extra-label drug use in food animals include: the drug must not be on the prohibited list (see the next section); and there must not be any drug(s) labeled for use in food animals that has the needed ingredient, in the proper dosage form, is labeled for the indication and is clinically effective.

Knowing when a human-approved drug can be used in a food animal is a common dilemma. AMDUCA states that extra-label use of human-approved drugs is not permitted if a drug approved for food animals exists that can be used in an extra-label manner. So, for instance, if a cephalosporin is indicated for a condition in a food animal, like neonatal septicemia in a calf, the veterinarian must use ceftiofur because it is labeled for food animals, even though not for neonatal septicemia. If in this case culture results indicate there are no food animal drugs that would be appropriate, then another veterinary or human drug would be permitted for use.

What's Illegal?

Practitioners have to remember that even under AMDUCA, which allows for extra-label drug use, some drugs are absolutely off limits for use in food producing animals. A list of drugs specifically prohibited from extra-label use as well as other pertinent information can be found at the Food and Drug Administration Center for Veterinary Medicine (FDA/CVM) Web site www.fda.gov/cvm/. Most of the drugs on the prohibited list are not approved for food animals. Some do have a food animal approval but can only be used according to the label.

Drugs can be added to this list at any time, and it behooves all food animal practitioners to constantly monitor regulatory announcements for changes to drug-use rules and regulations. Newsletters and publications from organizations such as the American Veterinary Medical Association (AVMA), American Association of Bovine Practitioners (AABP), American Association of Small Ruminant Practitioners (AASRP) and American Association of Swine Veterinarians (AASV), to name a few, will alert practitioners to these changes.

In the field

Here are a few common situations that food animal practitioners deal with in relation to drugs prohibited for extra-label use. The first situation is the extra-label use of fluoroquinolones. Currently, there are fluoroquinolone products labeled for use in beef cattle for respiratory disease. This is the only approved use, and any other use is prohibited. That includes another class of bovine, another food animal species or another indication. So, for example, use of fluoroquinolones to treat dairy cattle with respiratory disease, small ruminants with respiratory disease or calf diarrhea is prohibited.

The second scenario is use of a prohibited drug in a food animal species that is more of a pet. In the eyes of the FDA/CVM, pet food animals do not exist. So extra-label use of prohibited drugs in the pot-bellied pig that lives in the house, as well as a pet goat or steer, etc., even if the owner guarantees it will never enter the food chain. Food animal practitioners are usually alert to this issue.

However, our colleagues who have companion animal practices may not be. And as many of them have food animal companions presented to them, we must make them aware of these legalities.

Case in point

A common situation food animal practitioners face in relation to the constraints of extra-label use under AMDUCA is the need for a non-steroidal anti-inflammatory drug for endotoxemia in a beef animal. Flunixin meglumine is approved for use in cattle for endotoxemia and is highly effective. Phenylbutazone is not prohibited for use in beef animals, but it has no label approval for any indication in food animals. So even if phenylbutazone is deemed equally effective for the endotoxemia and is most likely cheaper, it is not permitted for use in this situation.

If however, a case of chronic osteoarthritis presents in a beef animal, and the veterinarian considers phenylbutazone to be superior to flunixin meglumine therapeutically, it can be selected as long as adequate withdrawal times are established. Because of the very long half-life of phenylbutazone in cattle, one dose of phenylbutazone can lead to violative residues for months. So, it is an acceptable choice for a valuable breeding animal that's value is not in its carcass. It is not an acceptable choice in a feeder or veal calf that will go to slaughter.

So for any extra-label use, it is imperative to know what the withdrawal time should be, and any other pertinent pharmacological information before administering a drug. Phenylbutazone is also prohibited for extra-label use in female dairy cattle 20 months of age and older, so it cannot be used in this class of animal for any reason.

Compounded and counterfeit drugs

A complete discussion of compounded and counterfeit drugs is beyond the scope of this article. However, practitioners should be aware that except for a few specific antidotes, the use of compounded drugs in food animals is prohibited.

Practitioners should be on the lookout for compounded and counterfeit drugs on farms. If a drug is offered at a very discounted price from an unknown distributor, and if it is unsolicited, it should be suspected to be a compounded or counterfeit drug.

Drugs approved by the FDA will have either an NADA (original) or ANADA (generic) number. Counterfeit products may have labels almost identical to legitimate labels, including NADA or ANADA numbers and can be very difficult to spot. When in doubt, call the drug manufacturing company or the FDA/CVM.

Dr. Navarre works as an extension veterinarian with Louisiana State University's Department of Veterinary Science.