884 Vet Med Today: FARAD Digest JAVMA, Vol 226, No. 6, March 15, 2005 B ecause of restrictions on compounding and a limit- ed number of approved veterinary products, there are few antidotes available for treatment of food ani- mals with toxicoses. 1 Because there is little economic incentive for pharmaceutical companies to pursue antidote approval for a limited market, it is unlikely that this situation will change in the near future. In most instances, practitioners seeking to treat food ani- mals for toxicoses are compelled to either use products in an extralabel manner or to compound antidotes from bulk sources. There are relatively few data from which scientifically based withdrawal intervals (WDIs) may be developed for the protection of human health. This Food Animal Residue Avoidance Databank (FARAD) Digest provides a summary of reg- ulatory and scientific information regarding the most commonly recommended antidotes used in food ani- mals. None of the drugs covered in this digest have been approved by the FDA Center for Veterinary Medicine (FDA/CVM) as New Animal Drugs. The information on residues presented in this digest is for the antidotes, not for the toxicants. When an antidote must be used to treat a food animal for a toxicosis, a WDI to ensure depletion of the toxicant is also required, and it may be longer than the WDI for the antidote. FARAD can provide WDI recommenda- tions for a wide range of toxicants; however, these rec- ommendations must be made on a case-by-case basis because of differences in exposure route, dose, and duration. Unapproved Veterinary Antidotes Marketed with Veterinary Labels The FDA/CVM has applied regulatory discretion and does not prohibit the commercial manufacture and marketing of several veterinary antidotes. These prod- ucts do not have New Animal Drug Approval (NADA) numbers and have not been formally approved by the FDA/CVM. These products are manufactured under Good Manufacturing Practices, and their labels are reviewed and on file with the FDA/CVM. They may be used as antidotes in food animals, although higher dosages or more prolonged treatment than that indi- cated on the labels may be necessary. Animal Medicinal Drug Use Clarification Act requirements do not apply to these drugs because they are not approved drugs; however, veterinarians are strongly encouraged to fol- low AMDUCA requirements when using these drugs. 2 Veterinarians who must use these drugs as antidotes in any food animal species not covered herein should call FARAD for WDI recommendations. Atropine sulfate—Large animal atropine formula- tions containing 15 mg of atropine/mL are marketed for treatment for organophosphate toxicosis in cattle, sheep, and horses. Human atropine formulations are also approved and marketed. Published recommenda- tions for treatment for cholinesterase inhibitor toxico- sis range from 0.1 to 0.5 mg/kg (0.045 to 0.23 mg/lb) and are consistent with product label recommenda- tions that indicate that approximately one fourth of the dose should be given IV with the remainder given IM or SC. Treatment may be adjusted and repeated as nec- essary every 4 to 6 hours. Practitioners are cautioned that these dosages far exceed those recommended for atropine as an adjunct to surgery. Exceeding the rec- ommended dosage for treatment should be avoided because of the potential for atropine toxicosis. In the United Kingdom, atropine is approved for single-dose use in cattle, sheep, and pigs SC, IM, or IV, with a 3-day milk and 14-day meat withdrawal time (WDT). When atropine is used as an antidote at multiple doses up to 0.2 mg/kg (0.09 mg/lb), a 6-day milk and 28-day meat WDI is recommended. Tissue residue depletion studies in food animals are not available, although results of kinetic studies in pigs and sheep indicate a short ter- minal elimination half-life of 1 to 3 hours. Results of radiolabeling studies in mice confirm that there is no appreciable long-term incorporation of atropine or its metabolites into body tissues, suggesting that the United Kingdom’s 6-day milk and 28-day slaughter WDTs are appropriately conservative. Practitioners are reminded, however, that depletion of organophosphate residues must be considered when making withdrawal recommendations. Epinephrine—In the body, epinephrine is a natu- rally occurring compound and when administered it is rapidly inactivated by metabolism after injection. FARAD Digest From Food Animal Residue Avoidance Databank (FARAD), Department of Environmental Toxicology, College of Agricultural and Environmental Sciences, University of California, Davis, CA 95616 (Haskell, Payne, Craigmill); FARAD, Center for Chemical Toxicology Research and Pharmacokinetics, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606 (Riviere); and FARAD, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610-0136 (Webb). Address correspondence to Dr. Haskell. Antidotes in food animal practice Scott R. R. Haskell, DVM, MPVM; Michael Payne, DVM, PhD; Alistair Webb, BVSc, PhD, DACVA; Jim Riviere, DVM, PhD; Arthur L. Craigmill, PhD