Veterinary Pharmacy

56
Veterinary Pharmacy


Gigi Davidson and Mark G. Papich


Introduction


A pharmacist’s responsibility for providing patients with high-quality pharmaceutical care extends beyond the human species. Although colleges of pharmacy and licensing boards have focused almost exclusively on human pharmacotherapy, society expects an equally competent quality of pharmaceutical care and products to be provided for nonhuman family members. Veterinarians are trained to provide quality care and products for animal patients, but few pharmacists receive training in pharmacy school about veterinary medicine. Pharmacists may be asked more frequently to dispense medications for animals in their day-to-day practice and they must familiarize themselves with veterinary pharmacotherapy and develop a clinically and legally sound algorithm for processing veterinary prescriptions. Pharmacists who dispense medications for animals have an obligation to become familiar with important species differences with respect to pharmacotherapy and susceptibility to drug adverse reactions (Table 56.1). Because this process is very slowly evolving in the pharmacy profession, veterinarians should be well versed in pharmacy issues related to veterinary medical therapy. Although several of these issues have been introduced or discussed in other chapters of this book, this chapter describes a variety of pharmacy-related topics of which all veterinarians should be aware.


Table 56.1 Information for pharmacists: excipients in medications or human drugs that may be harmful to pets

































































































































Drug/excipient/food Species affected Toxicity Reference
Acetaminophen Dogs, cats Hepatotoxicity (dogs) and red blood cell oxidative injury (cats) Campbell and Chapman, 2000, p. 31, 205
Alcohols Dogs, cats birds Central nervous system toxicity Osweiler et al.,1976, p. 388
Avocado Birds Pulmonary congestion, nonsuppurative inflammation of the liver, kidney, pancreas, skin, and proventriculus LaBonde, 2006
Benzocaine Cats Red blood cell oxidative injury, hemolytic anemia Harvey, 2006
Chamomile Cats Emesis, diarrhea, depression, lethargy, epistaxis            
Chocolate Dogs, birds Cardiovascular and central nervous system stimulation Campbell and Chapman, 2000, p. 106
Estrogen Dogs Bone marrow suppression Campbell and Chapman, 2000, p. 245
Ethyl glycols (diethylene glycol, ethylene glycol) Dogs, cats Central nervous system toxicity, nephrotoxicity Campbell and Chapman, 2000, p. 22, 127
Fat, fatty foods Dogs Increased risk of pancreatitis            
Garlic/onions Dogs, cats Hemolytic anemia Warman, 2007
Grapes/raisins Dogs Renal toxicity Warman, 2007
Macadamia nuts Dogs Neurotoxicity Warman, 2007
Macrolide antibiotics, oral route Horses, rabbits Diarrhea, enteritis, colic Papich, 2003
Methylene blue Cats Red blood cell oxidative injury, hemolytic anemia Harvey, 2006
Nonsteroidal antiinflammatory agents for humans (naproxen, ibuprofen) Dogs, cats Gastrointestinal ulceration and perforation, nephrotoxicity Campbell and Chapman, 2000, p. 148, 192
Pennyroyal Cats Hepatotoxicity Wismer, 2007
Permethrin Cats Neuromuscular and central nervous system toxicity Campbell and Chapman, 2000, p. 238
Phenazopyridine Cats Hepatotoxicity and red blood cell oxidative injury Harvey, 2006
Phosphate enemas Cats Profound hypocalcemia Wismer, 2017
Pseudoephedrine Dogs, cats Cardiovascular and central nervous system stimulation Plumlee, 2004a
Raw yeast dough Dogs Alcohol poisoning, gastrointestinal dilatation and volvulus Warman, 2007
Salt Dogs, cats Hypernatremia, central nervous system toxicity Campbell and Chapman, 2000, p. 42
Tobacco products Dogs, cats Muscle weakness, twitching, depression, tachycardia, shallow respiration, collapse, coma, and cardiac arrest Plumlee, 2004b
Xylitol Dogs, birds Profound hypoglycemia and hepatocellular necrosis Wismer, 2006

Regulatory Discretion for Extralabel Use


Advances in medical knowledge occur at a much faster rate than do drug product approvals. Since it is impossible for a drug company to test marketed drugs in all species at all doses and for all indications, it is difficult for veterinarians to adhere to the strict limitations of approved drug labels. Passage of the Animal Drug Amendment in 1968 significantly restricted use of drugs in animals to use only in those species for which the product was labeled with strict adherence to the labeled indication, dose, route of administration, and duration of therapy. Any use of a human-labeled drug in animals, for example, was considered illegal under the 1968 Amendment. Pursuant to enactment of this legislation, veterinarians were forced to break the law most of the time when using drugs in their patients. Physicians, on the other hand, were still allowed to use any drug at any dose for any indication in human patients.


Realizing the impracticality of strict interpretation of this law for veterinarians, the Food and Drug Administration published compliance policy guidelines (CPGs) in 1993 to show veterinarians the boundaries for regulatory discretion by FDA inspectors. Four main CPGs provided the boundaries for drug use by veterinarians: Extralabel Drug Use, Human Label Drug Use, Use of Drugs in Food Producing Animals, and Compounding for Animals (see www.fda.gov for summaries of these CPGs); however, the CPG for Compounding for Animals was rescinded in May 2015 and replaced with Guidance For Industry #230, Use of Bulk Drug Substances in Compounding For Animals. Chapter 55 of this book provides a background on the drug approval process by regulatory authorities and a summary of the legal control of veterinary drugs.


Need for Legal Extralabel use — AMDUCA


Although these CPGs provided veterinarians with a higher comfort level for using drugs in animal patients, extralabel use of drugs in animals was still illegal. The law did not change; CPGs only informed veterinarians of occasions when FDA inspectors would exercise regulatory discretion with respect to interpreting and enforcing extralabel drug use. In 1993, veterinarians, increasingly frustrated by being forced to break the law, demanded the same legal right physicians had in treating their patients. On October 22, 1994, the Animal Medicinal Drug Use Clarification Act (AMDUCA) was passed allowing veterinarians to legally use drugs extralabel under certain circumstances. AMDUCA went into effect December 9, 1996. Concurrently, Congress passed the Animal Drug Availability Act, significantly expediting the process by which FDA approved products intended for use in animals. Passage of both laws was intended to significantly improve the ability of veterinarians to best treat nonfood-producing animal patients.


Animal Medicinal Drug Use Clarification Act


On October 22, 1996, the Animal Medicinal Drug Use Clarification Act of 1994 was enacted into law, allowing veterinarians to prescribe extralabel use of veterinary and human drugs for animals under specific circumstances and also codified compounding for animal patients provided the starting ingredients were FDA-approved drug products. The key extralabel provisions of the Animal Medicinal Drug Use Clarification Act are provided in Table 56.2. (A copy of the AMDUCA Extra Label Drug Use Guidelines Brochure is available in the February 15, 1998, issue of the Journal of the American Veterinary Medical Association (JAVMA) or may be obtained from the AVMA website: www.avma.org.) Some drugs are strictly prohibited from administration to food animals because a safe level of residue in food products cannot be identified (Table 56.3). Additional provisions of the AMDUCA legislation require proper dispensing and labeling of prescribed drugs for animals (Tables 56.4 and 56.5).


Table 56.2 Requirements for extralabel drug use (ELDU) in animals







  • ELDU is permitted only by or under the supervision of a veterinarian.
  • ELDU is allowed only for FDA-approved animal and human drugs.
  • A valid veterinarian/client/patient relationship is a prerequisite for all ELDU.
  • ELDU is for therapeutic purposes only (animal’s health is suffering or threatened), not for production use.
  • Rules apply to dosage for drugs and drugs administered in water. ELDU in feed is prohibited.
  • ELDU is not permitted if it results in a violative food residue, or any residue that may present a risk to public health. FDA prohibition of a specific ELDU precludes such use (Table 56.3 ).

Table 56.3 Drugs prohibited for extralabel use in food animals







  • Chloramphenicol
  • Clenbuterol
  • Diethylstilbestrol (DES)
  • Dimetridazole
  • Ipronidazole
  • Other Nitroimidazoles
  • Furazolidone (except for approved topical use)
  • Nitrofurazone (except for approved topical use)
  • Sulfonamide drugs in lactating dairy cows (except approved use of sulfadimethoxine, sulfabromomethazine, and sulfaethoxypyridazine)
  • Fluoroquinolones
  • Glycopeptides (example: vancomycin)
  • Phenylbutazone for female dairy cattle over 20 months of age

Table 56.4 Record requirements for drugs dispensed for animals







  • Identify the animals, either as individuals or a group
  • Animal species treated
  • Numbers of animals treated
  • Condition being treated
  • The established name of the drug and active ingredient
  • Dosage prescribed or used
  • Duration of treatment
  • Specified withdrawal, withholding, or discard time(s), if applicable, for meat, milk, eggs, or animal-derived food
  • Keep records for 2 years
  • FDA may have access to these records to estimate risk to public health

Table 56.5 Label requirements for drugs prescribed for animals













Name and address of the prescribing veterinarian
Established name of the drug
Any specified directions for use including the class/species or identification of the animal or herd, flock, pen, lot, or other group; the dosage frequency and route of administration; and the duration of therapy
Any cautionary statements
Your specified withdrawal, withholding, or discard time for meat, milk, eggs, or any other food

Classification of Drugs


Drug


A chemical can be considered a drug if it meets one of the following criteria: (Chapter 5 of this book covers special considerations on pharmaceutics.)



  1. It is an article recognized in one of the official compendia, i.e., the United States Pharmacopoeia/National Formulary or the official Homeopathic Pharmacopoeia of the United States or their supplements.
  2. It is an article intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals.
  3. It is an article other than food intended to affect the structure or any function of the body of man or other animals.
  4. It is an article that is intended to be used as a component of an item falling into one of the three categories above.

This definition does not differentiate between prescription drugs and nonprescription drugs, nor does it distinguish legal or lawful drugs from illicit ones. Because of this broad definition, any substance that is used to treat an animal can be ultimately considered to be a drug and can be regulated and actionable as such.


Legend (“Prescription”) Drugs


Prescription drugs are limited to dispensing by or upon the order of a licensed prescriber (“prescription”) because they are habit forming, are toxic, or have potential for harm. These drug labels contain the following warnings identifying them as legend drugs:



  • Veterinary Legend: “Caution: Federal law restricts this drug to use by or on the order of a licensed veteri-narian.”
  • Human Legend: “Rx only.”

Legend (prescription) drugs cannot be dispensed without a prescription and may only be prescribed and dispensed within the confines of a valid veterinarian–client–patient relationship (VCPR) (Table 56.6). Because of the requirement of a valid VCPR, if a veterinarian has not examined the animal, he/she cannot prescribe legend drugs for use in that animal. Likewise, a veterinarian cannot “fill a prescription” for an animal unless he/she has a valid VCPR with that animal. Veterinarians filling prescriptions for other veterinarians are considered to be practicing “pharmacy” and are subsequently subject to action by state pharmacy regulatory boards.


Table 56.6 A valid veterinarian–client–patient relationship (VCPR)







  • The veterinarian has assumed the responsibility of making medical judgments regarding the health of the animal(s) and the need for medical treatment, and the client (owner or other caretaker) has agreed to follow the instructions of the veterinarian.
  • There is sufficient knowledge of the animal(s) by the veterinarian to initiate at least a general or preliminary diagnosis of the medical condition of the animal(s). This means that the veterinarian has recently seen and is personally acquainted with the keeping and care of the animal(s) by virtue of an examination of the animal(s), and/or by medically appropriate and timely visits to the premises where the animal(s) are kept.
  • The practicing veterinarian is readily available for follow-up in case of adverse reactions or failure of the regimen of therapy.

Over-The-Counter (“Nonprescription”) Drugs


Over-the-counter (OTC) drugs are also considered “nonprescription” drugs. These are familiar to veterinarians and pet owners because they are available for human use in retail outlets such as pharmacies, markets, and grocery stores. Such OTC products can also be found for animals in the same retail outlets as for humans as well as in pet and feed stores. These drugs have been recognized by experts as safe and effective and bear extensive labeling that renders them safe for use by laypersons and are sold “over the counter,” without a prescription.


All OTC products must be used precisely as labeled just as legend drugs. Use outside of these specifications constitutes extralabel use and the aforementioned guidelines should govern this use. Pharmacists must not make recommendations for use of human OTC drugs in animals unless so directed by a veterinarian. Veterinarians should avoid repackaging OTC medications for dispensing because reproducing the required labeling that is comprehensive enough for safe use by a layperson is difficult and dangerous.


VFD Drugs


A separate and unique category of drugs are those that fall under the Veterinary Feed Directive (VFD). A “VFD drug” is a drug intended for use in or on animal feed, which is limited to use under the professional supervision of a licensed veterinarian. A VFD drug is not a prescription drug, but is a written (nonverbal) statement issued by a licensed veterinarian in the course of the veterinarian’s professional practice that authorizes the use of a VFD drug or combination VFD drug in or on an animal feed. Because there are new regulations that pertain to the VFD taking effect on January 1, 2017, this topic is discussed in more detail in Chapter 55 and 59 in the regulatory section of this book.


Controlled Substances


Controlled substances (“narcotics”) are defined and monitored by the Drug Enforcement Authority (under jurisdiction of the Controlled Substances Act of 1970) and are divided into five schedules according to potential for abuse. An example of the schedules used for opiate drugs is provided in Chapter 13. Other controlled drugs are anesthetics and sedatives listed in Chapters 12 and 14. These drugs are strictly controlled by federal and state law and specific requirements for administering, dispensing, and prescribing are addressed in Section Prescribing Controlled Substances. Individual states are allowed to have more strict requirements than the federal (DEA) scheduling.


Compounded Drugs


Compounded drugs are mixtures of approved dosage forms or drugs formulated from bulk chemicals that are not approved by FDA for use as drugs in the United States. Veterinarians may compound items for their own use or write prescriptions for their patients for some of these active pharmaceutical ingredients to be used in preparing compounds by licensed pharmacists. These active pharmaceutical ingredients (e.g., potassium bromide, cisapride, diethylstilbestrol) are considered as drugs when used for therapeutic purposes and are recognized by FDA to be essential in the treatment of some companion, nonfood animals. As many of these drugs have been withdrawn from the market because of human safety hazards, the FDA has published a “negative” list (Drugs Withdrawn for Safety or Efficacy Reasons) for human compounding describing the drugs that are either prohibited for use in humans or are restricted to small dosages. Note that some of the drugs (e.g., cisapride and diethylstilbestrol) may still be compounded for nonfood animals such as companion animal pets but never for food animals or humans.


Current Status of Compounded Veterinary Drugs


Drug compounding has always been an important component of veterinary medicine. Historically, veterinarians have prepared concoctions, mixtures, and remedies for their patients because there were few approved formulations on the market for animals. Now, there are more available drugs for animals, and pharmaceutical science has provided for a better understanding of the factors contributing to poor drug bioavailability, instability, and physical incompatibility. Over the last several years, questions concerning the practice of compounding have been raised, particularly with respect to stability, purity, and strength when the original dosage form of the drug is altered. (Note that the term “potency” used in some publications has been replaced by “strength” in this chapter because it is a more accurate term. Potency is used to describe the biological activity of a medication in a patient, and is not a measure of drug concentration.)


Compounding is the alteration of the original drug dosage form for the purposes of ease of administration or because the original dosage form is unsuitable for the purpose intended. According to the United States Pharmacopeia (USP), compounding involves the preparation, mixing, assembling, packaging, and labeling of a drug or device in accordance with a licensed practitioner’s prescription. The USP chapter on pharmacy compounding (Chapter <795>: Pharmaceutical Compounding—Nonsterile Preparations) states that “compounding is an integral part of pharmacy practice and is essential to the provision of health care” (USP-NF, 2015a).


Compounding does not include the preparation of a drug by reconstitution or mixing that is according to the manufacturer’s instructions on an approved human or veterinary drug product.

Related posts:

  1. Anticonvulsant Drugs
  2. Tetracycline Antibiotics
  3. Drugs Affecting Animal Behavior
  4. Neuromuscular Blocking Agents

Stay updated, free articles. Join our Telegram channel
Tags:
Feb 8, 2018 | Posted by in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on Veterinary Pharmacy

Full access? Get Clinical Tree
Get Clinical Tree app for offline access