Extralabel Use Background
Under the provisions of Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA) and 21 CFR 530, the FDA recognizes the professional judgment of veterinarians, and permits the extralabel use of drugs by veterinarians under certain conditions. Among other things, in food-producing animals, extralabel uses of antimicrobials must:
- Occur under a valid veterinarian-client-patient relationship (VCPR),
- Not be administered via feed,
- Not result in a residue that may present a risk to public health.
Also under the AMDUCA provisions, FDA has the right to prohibit extralabel uses of certain drugs in food animals if the extralabel use of the drug or class of drugs presents a risk to human health, including antimicrobial resistance.
Two notable classes of antimicrobial drugs that are approved for use in the U.S. in food-producing animals have an extralabel use prohibition: fluoroquinolones and cephalosporins.
Fluoroquinolones are broad-spectrum antimicrobials and are an important class of drugs to both human and animal health. Examples of fluoroquinolones used in human medicine include ciprofloxacin, levofloxacin and moxifloxacin. Two fluoroquinolone drugs are approved for use in food-producing animals in the U.S.: danofloxacin and enrofloxacin.
Danofloxacin is currently approved to:
- Treat respiratory disease in cattle,
- Control respiratory disease in cattle at high-risk of developing disease.
Enrofloxacin is currently approved to:
- Treat respiratory disease in cattle,
- Control respiratory disease in cattle at high-risk of developing disease,
- Treat and control of respiratory disease in swine.
Enrofloxacin is currently conditionally approved to:
- Treat respiratory clinical anaplasmosis in specific classes of cattle.
Danofloxacin and enrofloxacin are only available as an injectable drugs administered under a prescription from a veterinarian. Use of a fluoroquinolone in a food-producing animal that is not in accordance with the label is illegal.
In the May 22, 1997 Federal Register, The Food and Drug Administration (FDA) issued an order prohibiting the extralabel use of fluoroquinolones and glycopeptides (no glycopeptides have been or are currently approved for use in food-producing animals in the U.S.). The Agency issued this order because it believes that some extralabel uses of fluoroquinolones and glycopeptides in food-producing animals are capable of increasing the level of drug resistant zoonotic pathogens (pathogens that are infective to humans) in treated animals at the time of slaughter.
In the 1997 order, FDA determined that some extralabel uses of fluoroquinolone and glycopeptide drugs in food-producing animals likely will cause an adverse event, which constitutes a finding under the AMDUCA that extralabel use of these drugs in food animals presents a risk to the public health. Therefore, the Agency issued the order of prohibition.
Currently, no fluoroquinolones are approved for use in poultry in the U.S. Due to the extralabel use prohibition in place for fluoroquinolones, use in poultry is currently illegal in the U.S.
Cephalosporins are widely used antimicrobial agents in human and veterinary medicine. They were introduced into human clinical use in 1964 and include numerous drugs approved for use in humans. There are two cephalosporins currently approved for use in food-producing animals: cephapirin and ceftiofur.
Injectable ceftiofur products are approved for the treatment and control of certain diseases, including:
- the treatment of respiratory disease in cattle, swine, sheep, and goats;
- the treatment of acute bovine interdigital necrobacillosis (foot rot) and acute bovine metritis;
- the control of bovine respiratory disease; and
- the control of early mortality associated with Escherichia coli infections in day-old chicks and poults.
In addition, ceftiofur is approved as an intramammary infusion for the treatment of clinical mastitis in lactating dairy cattle and the treatment of subclinical mastitis in dairy cattle at the time of dry off.
Cephapirin is only approved as an intramammary infusion for the treatment of lactating cows having bovine mastitis.
FDA’s Center for Veterinary Medicine is issued an order in 2012 that prohibited the extralabel use of cephalosporin drugs (not including cephapirin) in cattle, swine, chickens, and turkeys. Specifically, the prohibited uses include:
- Using cephalosporin drugs at unapproved dose levels, frequencies, durations, or routes of administration;
- Using cephalosporin drugs in cattle, swine, chickens or turkeys that are not approved for use in that species (e.g., cephalosporin drugs intended for humans or companion animals);
- Using cephalosporin drugs for disease prevention.
The following exceptions to the prohibition apply:
- Extralabel use of approved cephapirin products in food-producing animals;
- Use to treat or control an extralabel disease indication, as long as this use adheres to a labeled dosage regimen (i.e., dose, route, frequency, and duration of administration) approved for that particular species and production class; and
- Extralabel use in food-producing minor species, such as ducks or rabbits.
- Drugs prohibited for extralabel use in animals (21 CFR Part 530.41)
- Animal Drugs @ FDA
- Final Rule: Extralabel Animal Drug Use; Fluoroquinolones and Glycopeptides; Order of Prohibition (FR Doc No: 97-13677)
- Cephalosporin Order of Prohibition Questions and Answers
- Final Rule: New Animal Drugs; Cephalosporin Drugs; Extralabel Animal Drug Use; Order of Prohibition (FR Doc No: 2012-35)
- Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA)
- Withdrawal of Enrofloxacin for Poultry