Key takeaways
Extra-label use of cephalosporins is permitted in specific cases, such as when there is not an approved therapy for a pathogen not on the label, or if an approved therapy has failed, and the veterinarian believes cephalosporin use is justified. However, use of cephalosporins for disease prevention is strictly prohibited.
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Record-keeping is not only important for cephalosporins, but for all medications and vaccines. Animal identification, tracking and record keeping are essential for the FDA and in cases of residue violation investigations.
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A valid VCPR is perhaps the most important initial requirement for any prescription and/or extra-label use of medications, cephalosporin or otherwise.
Q: Cephalosporins have been key to successful management of respiratory disease in swine. However, they are also medically important antimicrobials in human medicine, and FDA has understandably set limits on their use. Are there any issues you’re aware of regarding compliance with cephalosporin use throughout the pork industry?
JH: Swine producers and veterinarians have done a great job adhering to the rules regarding cephalosporin use in food animals. We do get questions from time to time, however, when certain situations lead to uncertainty about compliance, especially regarding extra-label use.1
Q: Are there any situations when extra-label use of a cephalosporin is permitted?
JH: If you have a group of pigs with an illness due to a pathogen that’s not on the label and for which there’s no approved therapy, using a cephalosporin may be justified. Another instance would be if an approved therapy has failed and it’s the veterinarian’s professional opinion that a cephalosporin may be effective. In either case, the cephalosporin needs to be used according to the product label for dosage, frequency, duration and route of administration.
Q: Let’s say a group of young pigs is unthrifty but doesn’t have respiratory signs. If it can be documented in sacrificed pigs that Streptococcus suis is present, can they be treated with a cephalosporin?
JH: Yes, they can, as long as the veterinarian believes their poor health is likely due to S. suis.
Q: Is extra-label use of a cephalosporin permissible for disease prevention?
JH: Never. According to the FDA, prevention entails treating a group of animals without clinical signs of disease or in a situation where disease is likely to occur without medication. This practice is strongly discouraged.
Q: The labels for Naxcel® (ceftiofur sodium) and Excenel® RTU EZ (ceftiofur hydrochloride) say swine “should be treated for a total of 3 consecutive days.” Are there circumstances on farm that may warrant adjusting that exact protocol?
JH: Veterinarians and producers should make every effort to be good antibiotic stewards and follow the recommendations on the product’s label. Those directions for use were deemed by FDA to be most safe and effective after reviewing large pivotal studies with the product. Using those antibiotics at any dose or frequency greater than what’s recommended would be considered extra-label and, as such, would not be allowed under the current regulation. Overmedicating also would lead to higher costs and potentially violative residues. For those reasons, exceeding the dose or treatment frequency indicated on the label rarely occurs.
Q: Let’s look at the other scenario. On the farm, an unexpected labor shortage or significant weather events could potentially stand in the way of treating pigs for 3 consecutive days. What are the veterinarian’s options in those situations?
JH: Every effort should be made to follow the dose and dosing duration provided on the label. However, when those unforeseen, real-world circumstances do arise, it comes down to the attending veterinarian’s judgement to modify treatment from the product label. For example, how did the pigs respond to the initial treatments? Are they doing better from a health and welfare standpoint? In the end, FDA defers to the veterinarian’s expertise, records and clinical observations to ensure that every effort was made to provide good care and use the products in a safe, judicious and efficacious manner.
Q: Are there other treatment options to ensure administration compliance?
JH: Yes. Veterinarians and producers also could consider using sustained-release antimicrobials such as Draxxin® 25 (tulathromycin) or Excede® for Swine (ceftiofur crystalline free acid), which require only one dose. The tradeoff with those products is the longer withdrawal period — 5 days for Draxxin® 25 and 14 days for Excede® for Swine, versus 4 days for Naxcel® and 4 days for Excenel® RTU EZ.
Q: One of the indications for Naxcel®, Excede® for Swine (ceftiofur crystalline free acid) and Excenel® RTU EZ is for control of respiratory disease associated with certain pathogens. FDA’s definition of control is a “drug administered to a group of animals when a proportion of the animals in the group exhibit clinical signs of disease.” Is there a minimum number of animals that have to show clinical signs before the group can be treated with a cephalosporin?
JH: If you use FDA criteria for experimental field trials as a guide — specifically, Guidance for Industry 1782— at least 15% of the group should be exhibiting signs of disease before treatment. This is a starting point, however. In the field, if a group of animals has a history of a disease that has been documented in medical records and a few start breaking with signs of the same disease, treatment may be justified. Once again, it comes down to the attending veterinarian’s judgment.
Q: How important is laboratory evidence of infection for justifying extra-label use of a cephalosporin?
JH: Veterinarians are allowed to practice veterinary medicine. If they see pigs coughing and breathing hard, they can recommend a cephalosporin if they believe the problem is due to one of the pathogens on the label. Laboratory testing is not required. However, if the disease gets more severe and pigs are dying, it would be prudent to conduct post-mortems and send samples for testing. Again, this isn’t required, but it’s good practice.
Q: If young pigs on a farm don’t have signs of respiratory disease but they have joint issues and associated lameness — a condition that can be caused by S. suis — can they be treated with a cephalosporin?
JH: This is a good example of an infectious disease that is not on the label but where extra-label use may occur. The cephalosporin must still be prescribed by the veterinarian according to the label at the approved dose, route of administration, frequency and duration of administration.
Q: Is it OK to reconstitute Naxcel® to a desired potency for lesser injection volume?
JH: Reconstitution with different volumes of sterile water is acceptable as long as the total milligrams an animal receives is according to the label — 3 to 5 mg/kg.
Q: What documentation is acceptable to FDA regarding the use of a cephalosporin?
JH: When a group of pigs is treated with a cephalosporin, don’t rely on anyone’s memory. Write it down, date it and sign it. A document that’s handwritten, dated and signed is golden. The records should include the estimated number of pigs in the facility, the disease and the dosage received, which of course must comply with the label. There should also be an estimate of the total number of pigs treated. I say “estimate” because it’s often not possible to get a completely accurate head count with a large group of pigs. The FDA puts a high value on handwritten, hard copies of medical records.
Q: If there’s a residue violation with a cephalosporin, will handwritten records adequately document compliance for the prescribing veterinarian?
JH: Yes, assuming the cephalosporin was prescribed appropriately. Veterinarians also have the responsibility of ensuring that producers observe required withdrawal periods. I’m aware of several residue-violation cases where veterinarians who prescribed a cephalosporin had accurate treatment records demonstrating compliance with the label and that accounted for the necessary withdrawal time. FDA found the veterinarians did nothing wrong.
Q: What records should be kept when the veterinarian can’t get to the farm and provides a prescription over the phone?
JH: First, there should be a veterinarian-client-patient relationship, as defined by FDA. The swine facility should keep a record of exactly what was prescribed for which animals and when. But veterinarians should make note in their own dated records about who contacted them and what was prescribed. FDA understands that veterinarians can’t always get to a farm, but it may check to see if records from the facility and the veterinarian match.
Q: Are there any common mistakes you see regarding the use of cephalosporins in swine?
JH: It doesn’t happen often, and I know of this happening with different types of drugs, not just cephalosporins, but there are cases where farm workers weren’t clear on the instructions or simply grabbed the wrong bottle. To me, this underscores the need for producers to carefully select the employees they permit to administer any medications, not just cephalosporins, and to provide careful training.
Learn More
Contact your Zoetis representative to learn more.
John W. Hallberg, DVM, PhD – Sr. Director, VMRD Global Regulatory Affairs,
John W. Hallberg, DVM, PhD, serves as the Sr. U.S. Director of Regulatory Affairs at Zoetis, where he leads efforts to secure FDA approvals for new livestock products. He holds a Bachelor of Science in Animal Science, a Master of Science in Meat Science, a Doctor of Veterinary Medicine, and a Doctor of Philosophy in Meat Science — all from Iowa State University. With a career spanning veterinary practice, clinical research, and regulatory affairs…more
