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Extra-Label Drug Use, Compounded Drugs, and Generic Drugs


A new animal drug (NAD) is “any drug intended for use in animals other than man... not recognized... as safe and effective for use under the conditions prescribed, recommended, or suggested in the labeling....” A drug's label includes the label on the product as well as any accompanying material in or on the package. A prescription drug is defined by whether or not adequate directions can be prepared for use of the drug by a layperson. Any drug for which this is possible must be sold as an over-the-counter preparation; any other product is a prescription product.

To use a NAD in a legal manner, the veterinarian must adhere to the specifications noted on the label. Otherwise, the drug is used in an extra-label manner. Extra-label drug use, whether actual or intended, occurs when the drug is used in a manner that is not in accordance with the approved label directions. This includes but is not limited to a different dosage, interval, route, indication, or species.

In 1994, Congress passed the Animal Medicinal Drug Use Clarification Act (AMDUCA), which legalized extra-label drug use by veterinarians as long as specific criteria or restrictions are met. Most restrictions are largely applicable to extra-label drug use in food animals. For nonfood animals, a valid veterinary-client-patient relationship must exist. For food animals, extra-label drug use is permitted only by or under the supervision of veterinarian; is allowed only for FDA animal or human drugs; requires a valid veterinary-client-patient relationship; is allowed only for therapeutic purposes (ie, the animal's health is suffering or threatened) and is not allowed for drugs intended for production use (food animals); applies only to dosage form drugs or drugs administered in water and not drugs administered in feed; is not permitted if it results in violative food residues or any residues that may present a risk to public health; and is not allowed if specifically prohibited by the FDA.

Drugs specifically prohibited in food animals by the FDA as of May 2005 include chloramphenicol, clenbuterol, diethylstilbestrol, dimetridazole, ipronidazole, other nitroimadazoles, furazolidone, nitrofurazone and other nitrofurans, sulfonamide drugs in lactating dairy cattle (except for those specifically approved), fluoroquinolones, and glycopeptides (eg, vancomycin), phenylbutazone in female dairy cattle 20 mo of age or older, and amandatine or neuraminidase inhibitor classes of drugs used to treat influenza A in poultry and ducks.

Use of a compounded drug constitutes extra-label drug use, although a compounded drug is not an approved drug. Conditions under which compounding is legal are specified in the AMDUCA. Compounding includes any manipulation of the drug beyond that stipulated on the label (such as reconstitution of a powdered drug). The guidelines regarding the compounding of pharmaceuticals under the direction of a veterinarian are delineated in Compliance Policy Guideline 7125.40. Conditions under which compounding is not subject to regulatory actions include a legitimate practice (pharmacy or veterinary; includes licensure), operation within the conformity of state law, for pharmacists in response to a prescription, and for veterinarians in response to a valid veterinary-client-patient relationship. Compounds of human drugs and, very occasionally, bulk drugs into appropriate dosage forms may be acceptable in certain circumstances. A legitimate medical need must be identified (eg, health or life of the animal is threatened or suffering may occur). Additionally, there must be no marketed, approved animal or human drug, regardless of whether it is used as labeled or in an extra-label fashion, that may be substituted for the compounded agent. Occasionally, other rare circumstances may be considered.

Pharmacists often can dispense an equivalent, less expensive, nonproprietary (generic) drug without prescriber approval. An exception occurs if a state has a mandatory substitution law or if the brand name product is dispensed along with a “dispensed as written” order. Generics may be pharmaceutically equivalent but may not be therapeutically equivalent. Those tested by the FDA and found to be therapeutically equivalent are listed in Approved Drug Products with Therapeutic Equivalence Evaluations, otherwise known as the “Orange Book.” Generic products not only contain the same active ingredient as the proprietary drug but also meet bioequivalence standards. Substitutions of generic drugs for proprietary drugs are recommended only for those drugs shown to be therapeutically equivalent.

Although the AMDUCA of 1994 legalizes extra-label drug use in the USA, selected states or other countries may have additional or complementary regulatory or legal restrictions. In all instances, it is important to read carefully the label instructions for use of specific drugs.

Last full review/revision March 2012 by Dawn Merton Boothe, DVM, PhD, DACVIM, DACVCP; Philip T. Reeves, BVSc (Hons), PhD, FANZCVS

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