The Top 10 Things You Should Know Before Filling Veterinary Prescriptions

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The Top 10 Things You Should Know Before Filling Veterinary Prescriptions Gigi Davidson, BSPharm, Dipl.ICVP NC State University College of Veterinary Medicine

Disclosure Gigi Davidson declare(s) no conflicts of interest, real or apparent, and no financial interests in any company, product, or service mentioned in this program, including grants, employment, gifts, stock holdings, and honoraria.

Objectives Identify Identify information resources most useful to community pharmacists when filling prescriptions for animal patients Recognize Recognize the overarching principles of veterinary drug laws and regulations Describe Describe the impact of species-specific vital signs, metabolic capacity, gastrointestinal physiology, and dietary habit on drug disposition in animals Review Review the most common veterinary-only drugs List List most common dispensing errors for veterinary prescriptions

#1 Veterinary Information Resources

Plumb s Veterinary Drugs (electronic) www.plumbsveterinarydrugs.com One Stop Veterinary Drug Information Desktop, smartphone, tablet versions available Veterinary Medication Guides (client education) Plumb s Veterinary Drug Handbook (print) Donald C. Plumb Wiley-Blackwell January 2015 (8th edition) Desk-size and pocket-size formats available 9 th Ed. 2018

Veterinary PDR Equivalent Compendium of Veterinary Products https://bayerall.naccvp.com/?u=bayer&p=dvm Free with online registration US and Canadian versions Over 6010 product package inserts Charts Anthelmintics and Parasiticides Biologicals (vaccines) Withdrawal times Phone app CVP Vet

The Merck Veterinary Manual (print) Merck & Co., Inc. July 2016 (11th edition) Disease State Management The Merck Veterinary Manual (electronic) www.merckvetmanual.com Free Updated continuously

Today s Veterinary Practice (electronic) Today s Veterinary Practice http://todaysveterinarypractice.navc.com/ Free with registration Current topics Clinical resources Disease state management Today s Veterinary Practice (print)

#2 Understand Veterinary Abbreviations

What Does This Mean??

mg/kg What is the dose? Veterinary dosing is commonly allometric and not empiric mg/lb mg/m 2 Species Specific formulas Chemotherapy Do not misinterpret empiric dosing as allometric dosing amlodipine: 0.625 mg/cat not 0.625mg/kg atenolol 6.25 mg/cat not 6.25mg/kg

Check in: Translate the Script

#3 Understand Veterinary Drug Law

Overarching Principle: Animals are food for humans. Intended Use In the US, the only species that cannot be consumed as food are: Food animal or pet? Always assume food! Humans Endangered list species Horses (intermittently) Human dietary preferences determine if an animal or their byproducts are food Cattle, chickens Meat, milk, eggs Buffalo, ostrich Meat, milk, eggs Rattlesnakes

Which are most likely food animals?

Humans Eat Animals: Consequence #1: Withdrawal Times WDT: the length of time after the last dose during which an animal or its byproducts may not be consumed as food Must be supplied by veterinarian on prescription Examples: Do not sell for slaughter for 5 days after last dose. Discard milk for 36 hours after last dose. Discard eggs for 14 days after last dose.

Humans eat animals: Consequence #2: OTCs must be used as labeled FDA approves veterinary OTC s: For target species For approved indication(s) At approved dose By approved route For approved duration Extralabel use of veterinary OTC must be directed by veterinarian Pharmacists may NOT recommend use of human OTCs in animals Scenario

Law Continued: Understanding Veterinary Credentials Can a physician write a prescription for his dog?

Law: Prescription Verification Veterinarians are NOT eligible for NPI numbers: CMS identifier DEA strongly opposes use of DEA number for non-controlled substances NCPDS recommends use of prescriber state license ID number to verify NOTE: Some non-controlled substances are reportable in the Virginia PMP (e.g. gabapentin and naloxone) and require the prescriber s DEA number for reporting.

Law: Generic Substitution Veterinarians are unaware of CMS requirements to dispense generics Veterinarians are unaware of the Dispense As Written signature line Call veterinarian to verify if Brand is required or if generic substitution is permitted

Elements of a Veterinary Prescription Label * Pharmacy name, address, and phone number Prescription number Date of initial dispensing Name and species of the animal patient Note: VA requires name of animal owner and species of patient for CII PMP reporting Directions for use Name and strength of the drug product (or active ingredients in a compounded prescription) Quantity or volume of drug product dispensed Name of the prescribing veterinarian Any withdrawal times stated for food-producing animals Name of the dispensing pharmacist Expiration or beyond-use date Number of refills *American Veterinary Medical Association-https://www.avma.org/KB/Policies/Pages/Guidelines-for-Veterinary-Prescription- Drugs.aspx

#4 Be Aware of The Most Common Dispensing Errors

AVMA Survey September 2014 (Cima, Greg. Substitution errors. JAVMA (2014): 462-465. Insulin substitutions Levothyroxine dosage changes RPh recommended human OTC NSAID instead of prescribed NSAID Veterinarians Perceptions NCSU Survey March 2015 (Sorah E, Davidson G. Royal K. Dispensing Errors for Non-Human Patients in the Community Pharmacy Setting: A Survey of Pharmacists and Veterinarians. Poster. SVHP Portland, ME, June 2015.) Insulin substitutions Levothyroxine dosage changes RPh recommended human OTC Inappropriate counseling Wrong drug salt dispensed

Other Potential Errors Drugs withdrawn for human safety are commonly used in animals Cisapride Bromides Phenylpropanolamine Diethylstilbestrol Metabolic capacity of a species may result in completely different drug disposition compared to humans Levothyroxine Digoxin Diazepam

#5 Understand the Patient s Metabolic Capacity

Feline Metabolic Limitations Glucuronide conjugation (deficient) Targeted Functional Groups: -OH, -COOH, NH 2, =NH, -SH moieties attached to either phenolic (ring) or alcoholic (straight-chain) Targeted Drugs: Acetaminophen, Azo Dyes, Benzodiazepines, Benzyl alcohol, Benzoic acid derivatives, Carprofen, Chloramphenicol, Codeine, Morphine, Lamotrigene, Phenazopyridine, Phenols, Propofol, Salicylates, Zidovudine Methylation (deficient in thiopurine methyltransferase) Targeted Functional Groups: --SH (purines) Targeted Drugs: Azathioprine, 6- mercaptopurine

Canine Metabolic Limitations Acetylation (absent) Targeted Functional Groups: Aromatic NH 2 Targeted Drugs: Dapsone, Hydralazine, Isoniazid, Procainamide, Sulfonamides

Metabolic Capacities: Canine Genetic Anomalies-ABCB1-Δ and BBB Affected Dog Breeds Breed Approximate Frequency of Mutation (%) Australian Shepherd 50 (standard and mini) Border Collie <5 Collie 70 English Shepherd 15 German Shepherd 10 Herding Breed Crosses 10 Long-Haired Whippet 65 McNab 30 Mixed breeds 5 Old English Sheepdog 5 Shetland Sheepdog 15 Silken Windhound 30 Targeted Drugs Acepromazine Butorphanol Chemotherapy agents Doxorubicin Paclitaxel Vinblastine Vincristine Loperamide Macrocyclic lactones Ivermectin Milbemycin Moxidectin (used in doses higher than labeled for heartworm prevention) Selamectin

#6 Understand the Patient s Gastrointestinal Physiology/Diet

Effects of Dietary Habit Carnivores Omnivores Herbivores More acidic gastrointestinal ph Low ph kills raw diet pathogens Shorter, faster gastrointestinal tract More alkaline gastrointestinal ph Volatile fatty acids from carbohydrate digestion Longer, slower gastrointestinal tract

Effect of Gastric ph on Drug Disposition Weak acids are more bioavailable in dogs and cats due to lower GI ph (lower dose compared to humans.) Weak acids are less bioavailable in horses due to higher GI ph. (higher dose compared to humans) Sustained-release or extended-release dosage forms designed for the human GI tract are unlikely to have the same release profile in non-human patients. Drug contents may be released prematurely or not at all, depending on ph and GI tract length.

#7 Know Likely Toxins for Each Species

Toxic Excipients and Foods in Dogs, Cats, and Birds Drug/Excipient/Food Species Affected Toxicity Alcohols Dogs, cats, birds Central nervous system toxicity Avocado Birds Pulmonary congestion, nonsuppurative inflammation of the liver, kidney, pancreas, skin, and proventriculus Benzocaine, benzoic acid derivatives Cats Red blood cell oxidative injury, hemolytic anemia Chocolate Dogs, birds Cardiovascular and central nervous system stimulation Cremophor Dogs Histamine release, anaphylaxis Fat, fatty foods Dogs Increased risk of pancreatitis Garlic, onions Dogs, cats Hemolytic anemia Grapes, raisins Dogs Renal toxicity Macadamia nuts Dogs Lethargy, hyperthermia, ataxia, vomiting Pennyroyal Cats Hepatotoxicity Polysorbate 80 Dogs Histamine release, anaphylaxis Raw yeast dough Dogs Alcohol poisoning, gastrointestinal dilatation and volvulus Xylitol Dogs, birds Profound hypoglycemia and hepatocellular necrosis

#8 Know Species Vital Sign Thresholds

Fever Thresholds in Various Species

Pulse and Respiratory Rate Ranges

Gestational Periods by Species

#9 Be Familiar With Veterinary-Only Drugs

Enrofloxacin (Baytril ) Marbofloxacin (Zinequin ) Veterinary Fluoroquinolones Pradofloxacin (Veraflox ) Danofloxacin (Advocin ) Orbifloxacin (Orbax )

Carprofen (Rimadyl ) Deracoxib (Deramaxx ) Firocoxib (Previcox ) Veterinary NSAIDs Robenacoxib (Onsior ) Grapiprant (Galliprant ) Flunixin (Banamine ) Phenylbutazone (Butazolidin )

Trilostane (Vetoryl ) Pergolide (Prascend ) Veterinary Endocrine Agents Estriol (Incurin ) Diethylstilbestrol (DES ) Domperidone (Equidone )

#10 Know Where to Report a Veterinary ADE

Veterinarian Can determine if truly an ADE or if related to disease May choose to report to FDA using form 1932a Adverse Drug Events FDA Form 1932a Veterinary Adverse Experience, Lack of Effectiveness or Product Defect Report https://www.fda.gov/animalveterinary/safetyhealth/reportaproblem/ucm05 5305.htm#Drugs_and_Devices May be reported by veterinarian, pet owner or pharmacist

Report Errors to? Pet owner For immediate discontinuation of therapy or other resolution Veterinarian Board of Pharmacy AVMA For needed monitoring or additional therapy To broaden database for dispensing errors Pharmacy Dispensing Complaint Form

Keep Keep these 10 tools sharp and readily retrievable Call Call veterinarians for questions Summary Report Report any adverse events or errors to veterinarian Learn Learn as much as you can about nonhuman patients

Questions?