In February 2000, this column discussed the prudent antimicrobial use guidelines developed by the American Association of Bovine Practitioners. Because we believe beef producers and their veterinarians are partners in prudent antimicrobial use, we return to the subject this month using a specific drug group — aminoglycosides — as an example.
This group includes neomycin, gentamicin and several others. Together, they illustrate the issues and points for consideration involved in an extra-label antimicrobial use decision.
The wrong decision could result in a producer being asked — more than a year after the calf left his premises — to pay for a condemned carcass at slaughter. Here are some points to consider:
1. Is there an approved label for the antimicrobial and disease combination you are considering? If a label exists, does it allow for sale “over the counter” or must a valid veterinary-client-patient relationship (VCPR) exist to allow purchase?
If you use the product according to label directions and the label does not contain the legend “Caution: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian,” then a VCPR is not necessary to purchase or use the product.
If the product contains this legend, however, or if you deviate from the label in any manner (different dose regimen, species, disease), then the law requires a valid VCPR. Changes in a dose regimen include any alterations of the amount, route, duration or frequency of administration. Extra-label drug use (ELDU) by a layperson outside of a valid VCPR is illegal.
Aminoglycoside labels in cattle include a neomycin label for oral use — “indicated for the treatment and control of colibacillosis (bacterial enteritis) caused by Escherichia coli susceptible to neomycin sulfate in cattle (excluding veal calves), swine, sheep and goats” (Biosol® liquid, Pharmacia Animal Health). There are no labeled gentamicin products for oral or injectable use in cattle.
2. What decisions must be made by a veterinarian to support extra-label drug use (ELDU)?
The first decision leading to legal ELDU, as described in the Animal Medicinal Drug Use Clarification Act (AMDUCA) Regulations, is that there is no labeled drug for the application in question that is effective as labeled. The veterinarian is then required to first consider changing the regimen of the labeled compound. (The AMDUCA regulations may be viewed at www.fda.gov/cvm/index/amducca/amducafr.htm.)
If this is not an option, then other drugs labeled for use in food animals must next be considered for use. If no food animal drug may be used in an extra-label manner to fulfill the need, then the veterinarian may consider other veterinary and human drugs. That's providing all requirements of the regulations are met.
Compounded products may only be used after it's determined that no veterinary or human approved products may be used as provided by the manufacturer to meet the need. Compounding from drugs that are not approved for veterinary or human use (bulk compounds) is strictly prohibited. Cost is not a valid reason for ELDU.
Let's apply these regulations to the consideration of a gentamicin product (labeled for an indication in horses) for therapy of bovine respiratory disease.
The veterinarian would be expected to justify the conclusion that products such as Micotil® 300 Injection (Elanco), Naxcel® or Excenel® (Pharmacia Animal Health) or Nuflor® (Schering Plough) could not have been used in a label or extra-label manner to effectively treat the condition.
The use of Baytril® 100 Injection (Bayer) may only be considered in a label manner because of a specific prohibition of extra-label use. Thus, use of this drug for calf scours is illegal.
The veterinarian must also have made the decision that no other food animal labeled product (including gentamicin injectable products for other food animal applications) could have been used in an extra-label manner to treat the condition.
3. What are the responsibilities assumed with extra-label drug use?
The veterinarian involved in the VCPR is responsible for determining an exaggerated withdrawal time for meat or milk. This is so that illegal residues don't enter the food chain and animal safety is protected.
In the extra-label gentamicin example described above, the Food Animal Residue Avoidance Databank (FARAD) recommends a slaughter withdrawal time of 18 months due to prolonged residues in the kidneys.
A new test organism is being used to detect residues in tissues such as the kidney. Some work indicates this organism will be more sensitive to the aminoglycosides than the previous test organism.
No tissue tolerance for gentamicin has been developed in cattle. This means that any amount of gentamicin detected in a beef carcass is violative and could result in condemnation of the entire carcass.
Put all of this together, and there is the real potential of getting a call asking for compensation for a condemned carcass at slaughter more than a year after you used gentamicin in an ELDU manner while the calf was in your possession.
The ELDU of neomycin by injection in cattle would also be expected to result in prolonged residues as well as a high chance of kidney toxicity. In fact, neomycin is not used in human medicine because of this potential.
Hopefully, these examples help clarify the regulations and responsibilities involved in extra-label drug use in cattle. Discuss ELDU with your veterinarian.
Gerald Stokka, DVM, MS, is an associate professor and Extension beef veterinarian at Kansas State University in Manhattan. Mike Apley, DVM, PhD, is an assistant professor of beef production medicine at Iowa State University in Ames. This column appears in alternate months.