Chapter 10: Regulatory Points to Consider

Web Chapter 10

Treatment of Animal Toxicoses

Regulatory Points to Consider

Veterinarians in both small and large animal practices are frequently called on to treat known or suspected animal toxicosis. A definitive diagnosis is not always established at the time of clinical presentation because many of these cases pose diagnostic or therapeutic challenges. Yet an early diagnosis and specific treatment are often keys to successful outcomes. In these efforts, veterinarians should avail themselves of diagnostic and treatment information from a variety of sources (see Web Chapter 9).

When a toxicosis is suspected, obtaining a detailed clinical history is of prime importance, particularly to determine if the administration of a specific antidote is indicated. The prognosis for any animal may vary considerably depending on the toxin, exposure dose, length of time between exposure and treatment, and availability of drugs to treat the patient. Treatment generally requires stabilization of vital signs, institution of supportive care, decontamination to prevent further toxin absorption, administration of compounds to enhance the elimination of absorbed toxins, or a combination.

This chapter is not intended to describe the diagnosis or treatment of animal toxicosis. The reader is directed to other chapters in this section and the references in this chapter for such information. Rather, the focus of this chapter is on the regulatory status of drugs used to treat animals with toxicoses because virtually all these drugs are not approved for that use by the Food and Drug Administration (FDA). Accordingly, regulations guiding extralabel drug use may be of interest to practitioners.

This chapter considers the prevalence of toxicoses briefly, then follows with a discussion of drugs that are commonly used to treat these toxicoses. The discussion is framed by the drugs’ regulatory status: approved use, extralabel use (ELU), and unapproved use. It is hoped that this information will benefit practicing veterinarians as a reminder of the regulatory status of drugs used in these emergency situations.

Drugs Used to Treat Animal Toxicoses

The prevalence of toxicoses in dogs and cats is reasonably well known (see Chapters 20 and 21). Consequently, the majority of drugs needed to treat toxicoses in companion animals are known and indirectly provide information for stocking emergency drugs in practices and emergency/critical care centers. Prevalence data of animal toxicoses also may be useful to pharmaceutical companies when considering which therapies to develop and what types and amounts of drug inventories may be needed for treating animal toxicoses. This chapter includes information on the treatment of both companion animal toxicoses and food animal toxicoses because the authors anticipate that some readers work in a mixed animal practice. The use of extralabel drugs and compounding drug considerations are particularly pertinent when treating food animals.

The Federal Food, Drug, and Cosmetic Act (FFDCA) (Section 201 [21 U.S.C. 321(g) (1)]) defines a drug as*:

General Treatment

General treatment is normally given irrespective of the toxin, unless there is a preexisting contraindication. General treatment is often intended to induce emesis, reduce absorption, or enhance elimination of toxins. Emetics commonly used in dogs or cats include apomorphine, xylazine, salt, syrup of ipecac, and hydrogen peroxide (see references). Activated charcoal is often used orally to reduce further absorption of toxins from the gastrointestinal tract, whereas soap and water are often used dermally to remove a toxin from the skin or reduce toxin absorption through the skin. Mineral oil, sodium sulfate, and other laxatives are often used to enhance elimination of toxins still present in the gastrointestinal tract. Gastric lavage may be used to enhance removal of toxins still present in the stomach.

Specific Treatment

A few drugs are indicated when a specific toxin is known or suspected. These specific treatment agents are often called antidotes. (The definition of antidote used in this article is not as defined by the FDA but rather as presented in different veterinary texts). An antidote is a substance that can counteract the activity or effect of a known or suspected poison.

Antidotes may be classified according to their mechanism of action: chemical or pharmacologic. Chemical antidotes interact specifically with a toxicant or neutralize a toxicant. For example, chelators combine with elements (especially heavy metals) to form complexes that can then be eliminated (as with molybdenum and sulfate for copper toxicity and calcium ethylenediaminetetraacetic acid [EDTA] for lead toxicity). Pharmacologic antidotes may neutralize or antagonize the metabolic or physiologic effects of a toxicant, for example (1) preventing formation of toxic metabolites as with 4-methylpyrazole for ethylene glycol toxicity; (2) competing with a toxicant’s action at a receptor site as with naloxone for opioid toxicity; (3) facilitating more rapid or complete urinary elimination of a toxicant by alkalizing the urine with sodium bicarbonate (to eliminate salicylate, phenobarbital, and 2,4-D), (4) facilitating elimination by acidifying the urine with ammonium chloride (to eliminate amphetamine, phencyclidine, and strychnine); (5) blocking receptors responsible for the toxic effect as with atropine for organophosphate toxicity; or (6) aiding in the restoration of normal detoxification mechanisms as with N-acetylcysteine for acetaminophen toxicity). In addition, specific antidotes may act directly on the toxin as in the case of antitoxins.

Animal Drugs That Are Biologics

Some drugs used to treat toxicoses are not approved by the FDA under the FFDCA but are licensed by the U.S. Department of Agriculture (USDA) under the Virus-Serum-Toxin Act (VSTA). The VSTA is implemented by the Center for Veterinary Biologics of the USDA Animal and Plant Health Inspection Service. Examples of such products include antivenins and antitoxins. Animal drugs produced and distributed in full conformance with VSTA have a USDA code rather than an FDA-assigned New Animal Drug Application [NADA] or Abbreviated New Animal Drug Application [ANADA] number. Examples include botulinum antitoxin (USDA Code 6400), tetanus antitoxin (USDA Code 6302.00 & 6302.01), and Crotalidae antivenin (USDA Code 6101.00). Antivenins for animals that are licensed as biologics by the USDA are a unique form of legally marketed animal drugs.* More information about the USDA Center for Veterinary Biologics and a listing of licensed veterinary biologics are available at

Drugs Approved to Treat Toxicoses

The limited availability of drugs approved to treat toxicoses is a long-standing problem in veterinary medicine. The drugs listed in Web Table 10-1 are approved by the FDA for use in animals for treatment of toxicoses. Use of these drugs, as indicated on labels, does not give rise to the extralabel drug use issues (discussed later in this chapter). Other than the approved uses of the seven drugs listed in Web Table 10-1, any drug used to treat animal toxicoses is likely done so in an extralabel, or an unapproved, manner. Consequently, review of extralabel drug use regulations may be of value to practicing veterinarians (see Web Table 10-1).

Extralabel Drug Use in Treating Animal Toxicoses

The Animal Medicinal Drug Use Clarification Act (AMDUCA) of 1994 (Pub. L. 103-396) allows veterinarians to legally administer or prescribe any drug approved for use in humans or animals in an extralabel manner (“Extralabel Drug Use in Animals; Final Rule,” published in the Federal Register 61[217]:57732-46, 1996). AMDUCA and the regulations that implement it, however, require that such ELUs conform with several conditions and comply with several limitations (described later in this chapter). Because of the need to avoid potentially harmful tissue residues in food derived from food-producing animals, there are additional conditions and limitations that apply when food animals are treated with a drug in an extralabel manner. (See the Veterinary Clinics of North America Food Animal Practice, p. 481 for a more detailed discussion of the food animal requirements.)

Extralabel Drug Use: Definition

ELU is defined in 21 CFR § 530.3 as actual use or intended use of a drug in an animal in a manner that is not in accordance with the approved labeling. This includes, but is not limited to, use in species not listed in the labeling; use for indications (disease or other conditions) not listed in the labeling; use at dosage levels, frequencies, or routes of administration other than those stated in the labeling; and deviation from the labeled withdrawal time based on these different uses. According to 21 CFR § 530.2, extralabel drug use is limited to treatment modalities when the health of an animal is threatened or suffering or death may result from failure to treat.

When considering an ELU of an approved drug, veterinarians are encouraged to keep in mind that ELUs are permitted only for such therapeutic uses. In the authors’ view, treating animals with a toxicosis are cases in which the health of the animals is threatened or suffering or death may result from a failure to treat the animals. Consequently, treatment of animals with a toxicosis often meets the purpose of the regulation implementing the ELU statute. Only veterinarians may authorize or prescribe ELU. Laypersons may administer an approved animal or human drug in an extralabel manner only under the supervision of a licensed veterinarian.

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Jul 18, 2016 | Posted by in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on Chapter 10: Regulatory Points to Consider
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