Evaluation of gastroprotectant administration in hospitalized cats in a tertiary referral hospital.

OBJECTIVES: The primary objective of this study was to evaluate the prescription patterns and appropriateness of the use of gastroprotectant medication in cats. METHODS: Pharmacy dispensation logs from an academic tertiary referral center were reviewed between 1 January 2018 and 31 December 2018. Cats that were administered proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), sucralfate, misoprostol, antacids or a combination were included. Data regarding medication, dosage, formulation, duration of administration, completeness of discharge instructions and clinical rationales for administration were obtained from medical records. The appropriateness of gastroprotectant use was assessed according to the American College of Veterinary Internal Medicine consensus statement guidelines. RESULTS: Of the 110 cases, 67 (60.9%) were prescribed a gastroprotectant medication without an appropriate indication. The most common reason for prescription was acute kidney injury in 26/67 (38.8%). PPIs were the most common gastroprotectant medication administered in 95/110 (86.3%) cats, followed by sucralfate in 18/110 (16.4%) and H2RAs in 11/110 (10%). Of the 35 cases in which gastroprotectant therapy was indicated, the medication chosen or dosage administered was considered suboptimal in 16 (45.7%). Instructions regarding the duration of administration, potential adverse effects and timing of administration in relation to meals or other medications were inconsistently provided in discharge instructions to pet owners. Of the 29 cases discharged with omeprazole, only 13 (44.8%) instructions included a duration of administration, while 6 (20.7%) recommended continuing gastroprotectants indefinitely until further notice, 16 (55.2%) discussed the timing of the administration in relation to a meal and six (20.7%) mentioned potential adverse effects; none advised tapering of omeprazole before discontinuation. CONCLUSIONS AND RELEVANCE: When prescribed, gastroprotectant medications were frequently prescribed injudiciously to cats in this referral population over a 12-month period. Discharge instructions to pet owners also often lacked information and recommendations regarding optimal administration, potential adverse effects, and tapering or discontinuation of the medications.

Assessing the urinary concentration of nitrofurantoin and its antibacterial activity against Escherichia coli, Staphylococcus pseudintermedius, and Enterococcus faecium isolated from dogs with urinary tract infections.

Nitrofurantoin, a broad-spectrum nitrofuran class antibiotic, is applied as a first-line antibiotic in treating human urinary tract infections (UTIs) due to its great efficacy and high achievable concentration. The interest in using this antibiotic in companion animals has increased due to the growing demand for effective antibiotics to treat UTIs caused by multidrug-resistant bacteria. Currently, the susceptibility interpretations for nitrofurantoin are based on the breakpoints set for humans, while the canine-specific breakpoints are still unavailable. In this study, we assessed the concentration of nitrofurantoin reaching the dog's urine using the recommended oral dosing regimen. In addition, we examined the efficacy of this breakpoint concentration against the common canine UTI pathogens, Escherichia coli, Staphylococcus pseudintermedius, and Enterococcus faecium. Eight experimental beagle dogs were treated with ~5 mg/kg of nitrofurantoin macrocrystal PO 8qh for 7 days. The urine samples were collected via cystocentesis at 2, 4, and 6 h after administration on day 2 and day 7 and used to quantify nitrofurantoin concentrations by ultra-high performance liquid chromatography. The results showed that 26.13-315.87 µg/mL nitrofurantoin was detected in the dogs' urine with a mean and median concentration of 104.82 and 92.75 µg/mL, respectively. Additionally, individual dogs presented with urinary nitrofurantoin concentrations greater than 64 µg/mL for at least 50% of the dosing intervals. This concentration efficiently killed E. coli, and S. pseudintermedius, but not E. faecium strains carrying an MIC90 value equal to 16, 16, and 128 µg/mL, respectively. Taken together, these results suggest that the value of 64 µg/mL may be set as a breakpoint against UTI pathogens, and nitrofurantoin could be an effective therapeutic drug against E. coli and S. pseudintermedius for canine UTIs.

Veterinary Education's Role in the Opioid Epidemic: Integration of an Online Safe Opioid Prescribing Course into the Core Curriculum.

As the COVID-19 pandemic continues, the opioid epidemic has worsened. Opioid-related deaths continue to rise, and many of these deaths can be traced to a prescription opioid. Because veterinarians prescribe opioids, many organizations and federal agencies have called for increased veterinary education on the topic. In this teaching tip, we review the current literature surrounding the veterinary profession's link to the opioid epidemic and one potential way that educational institutions can successfully and efficiently incorporate safe opioid prescribing training into the curriculum using an online course.

Bioencapsulation is a feasible method of terbinafine administration in Emydomyces testavorans-infected western pond turtles (Actinemys marmorata).

OBJECTIVE: To evaluate the pharmacokinetics of terbinafine administered to western pond turtles (Actinemys marmorata) via oral gavage and bioencapsulated in earthworms. ANIMALS: 7 western pond turtles. PROCEDURES: A randomized complete crossover single-dose pharmacokinetic study was performed. Compounded terbinafine (25 mg/mL; 30 mg/kg) was administered through oral gavage (OG) directly into the stomach or bioencapsulated (BEC) into an earthworm vehicle. Blood (0.2 mL) was drawn from the jugular vein at 0, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 120 hours after administration. Plasma terbinafine levels were measured using high-performance liquid chromatography. RESULTS: Peak plasma terbinafine concentrations of 786.9 ± 911 ng/mL and 1,022.2 ± 911 were measured at 1.8 ± 2.8 and 14.1 ± 12.3 hours after OG and BEC administration, respectively. There was a significant (P = .031) increase in area under the curve with BEC compared to OG. Using steady-state predictions, with once-daily terbinafine administration, 3/7 and 7/7 turtles had plasma concentrations persistently greater than the minimum inhibitory concentration (MIC) for Emydomyces testavorans for the OG and BEC administration routes of administration, respectively. With administration every 48 hours, 3/7 turtles for the OG phase and 6/7 turtles for the BEC phase had concentrations greater than the E. testavorans MIC throughout the entire dosing interval. CLINICAL RELEVANCE: Administration of terbinafine (30 mg/kg) every 24 or 48 hours via earthworm bioencapsulation in western pond turtles may be appropriate for the treatment of shell lesions caused by E. testavorans. Clinical studies are needed to assess the efficacy of treatment.

Pharmacokinetics of a 503B outsourcing facility-produced theophylline in dogs.

Theophylline is an important drug for treatment of canine chronic bronchitis and bradyarrhythmias, but new products require validation since pharmacokinetics in dogs can vary by formulation. A new, 503B outsourcing facility-produced theophylline product (OFT) is available for veterinary use. Outsourcing facilities have many advantages over traditional compounding sources including current good manufacturing practice compliance. The purpose of this study was to establish the pharmacokinetics of OFT in dogs. Eight healthy dogs received 11 mg/kg intravenous aminophylline and 10 mg/kg oral OFT followed by serial blood sampling in a two-way, randomized, crossover design with 7-day washout. Plasma theophylline concentrations were quantified by liquid chromatography-mass spectrometry. Bioavailability, maximum concentration, time to maximum concentration, half-life and area under the curve were: 97 ± 10%, 7.13 ± 0.71 µg/mL, 10.50 ± 2.07 h, 9.20 ± 2.87 h, and 141 ± 37.6 µg*h/mL, respectively. Steady-state predictions supported twice daily dosing of the OFT, but specific dosage recommendations are hindered by lack of a canine-specific therapeutic range for plasma theophylline concentration. These findings suggest that the OFT is well absorbed and can likely be dosed twice daily in dogs, but future pharmacodynamic and clinical studies are needed to establish a definitive therapeutic range for theophylline in this species.

A randomised, controlled trial to determine the effect of levothyroxine on Standardbred racehorses.

BACKGROUND: The use of thyroid supplement is pervasive in athletic horses although its effects on measures of performance are not known. OBJECTIVES: One purpose of this study was to determine whether supra-physiologic doses of levothyroxine affect the velocities at which blood lactate was greater than 4 mmol/L (VLa4 ) and heart rate was over 150 (V150 ) and 200 (V200 ) beats per minute respectively. Additionally, a survey of post-race blood samples was also conducted to determine whether high thyroxine concentrations were common in racehorses. STUDY DESIGN: A randomised, crossover, trial was performed in six healthy Standardbred racehorses. METHODS: Study 1: T4 was determined in 50 post-race samples from a single Standardbred meet. Study 2: Research horses were trained to fitness and then randomised to one of three treatments: carrier, 0.1 mg/kg thyroxine or 0.25 mg/kg thyroxine for 2 weeks. Horses completed a standardised exercise treadmill test (SET) to fatigue on the last day of treatment. Serum free and total thyroxine and triiodothyronine were determined on the day of SET testing. Blood lactate and ECG data were collected during the SET at 6, 8, 10, 11, and 12 m/s and during recovery. The effect of treatment and SET on heart rate and blood lactate was examined using generalised linear mixed models. Post hoc analysis was adjusted for multiple comparisons using Tukey's Test. Data were expressed as mean ± standard deviation and P < .05 was considered significant. RESULTS: Study 1: The median T4 value in this population of horses was 2.00 µg/dL (laboratory's normal range 1.5-4.5 µg/dL) and 3 of 50 racehorses had values above the laboratory reference range. Study 2: Levothyroxine at 0.25 mg/kg resulted in higher heart rates during SET (199 ± 30, 223 ± 17 and 239 ± 9 bpm at 6, 8 and 10 m/s respectively) and recovery (144 ± 20 and 119 ± 15 at 5 and 15 min) as compared to placebo (176 ± 18, 203 ± 10 and 219 ± 6 bpm at 6, 8, and10 m/s and 126 ± 5, 102 ± 11 at 5-15 minutes respectively). Three of six horses developed cardiac arrhythmias including atrial fibrillation. MAIN LIMITATIONS: A relatively small number of animals were used and a SET is not identical to actual racing conditions. CONCLUSIONS: Supra-physiologic thyroxine supplementation caused a decreased V200 during a standard exercise test and may result in cardiac arrhythmias.

Drug content on receipt and over time for compounded formulations of famciclovir.

OBJECTIVES: The aim of this study was to determine famciclovir content (strength) in compounded formulations and to determine if potency changed over time. METHODS: Four concentrations of oral oil suspension in three distinct flavors, three concentrations of oral paste, three chew treats and 62.5 mg tablets from one compounding pharmacy were evaluated for famciclovir content. Specific sample preparation procedures were used for each drug formulation prior to determination of famciclovir content through mass spectrometry tandem liquid chromatography. Analysis was performed on arrival from the compounder and on days 7, 14, 28, 56 and 120. Samples were run in triplicate and concentration determined by comparison with a standard curve. Content was considered appropriate if within 90-110% of the labeled concentration. RESULTS: On arrival from the compounding pharmacy, 5/12 oral oil suspensions of varying concentrations were <90% of the labeled concentration and 3/3 oral pastes were >110%. Famciclovir content in oil suspensions ranged from 72% to 118% of the label value while oral pastes ranged from 95% to 202% of the label concentration over the 120 study days, and all concentrations varied in an unpredictable fashion. Tablets contained 90-110% of the labeled value throughout the study period. Chew treats could not be successfully analyzed. CONCLUSIONS AND RELEVANCE: This study found substantial variation in famciclovir content in the compounded products evaluated, which, in turn, raises concerns that substandard dosing could result in lack of efficacy or a failed treatment trial. Drug toxicity might also be encountered. Veterinarians must be aware that while compounded medications can improve compliance, they might not deliver the drug dose expected.

The Current Landscape of Veterinary Compounding in the Veterinary Setting.

Compounding for veterinarians is regulated by the U.S. Food and Drug Administration, but day-to-day regulation is deferred to the state authorities. Veterinarians must meet certain standards when prescribing or dispensing a compounded medication. Veterinarians are expected to maintain current knowledge of the benefit of compounded preparations and prescribe and dispense in keeping with the best evidence related to animal and human health. Whether veterinarians recognize or adhere to these standards is unknown. A self-administered survey was distributed electronically to 30,000 email addresses on record with the Veterinary International Network. The survey asked questions about the regulations and standards associated with the use of or prescription of compounded medications. Of the distributed surveys, 1,520 survey responses were received, for a 5.1% response rate. All surveys were included in the final analysis. Respondents with a higher training level in compounding had a greater perceived skill level regarding compounding of medications (r = 0.26, P<0.0001). Similarly, respondents with a higher training level had a greater knowledge of state laws and regulations (r = 0.14, P<0.0001). Those with formal training had better scores on the assessment questions than those with informal or no training (P=0.01). Approximately one-third of the respondents felt that they were not knowledgeable at all about compounding rules and regulations. The most common compounded medications used in practice by veterinarians are methimazole, metronidazole, and doxycycline. Veterinarians mostly recognized that compounding backordered, commercially available products is permitted. Formal training improves familiarity with compounding rules, regulations, and current practices. Therefore, efforts should be directed at improving veterinary knowledge of laws and regulations surrounding the practice of compounding medications.

The Current Landscape of Veterinary Compounding in the Pharmacy Setting.

Medicating animals poses unique challenges that are often best dealt with via compounding. Pharmacists receive compounding training while in pharmacy school, but this training is not veterinary specific. Pharmacists are expected to have enough knowledge to properly verify prescriptions that are received at their practice site while keeping with the most up-to-date guidelines related to animal and human health. Whether pharmacists have the proper training to verify and/or compound veterinary specific medications is unknown. A self-administered survey was distributed electronically to 4,550 email addresses on record with the American College of Veterinary Pharmacists, the International Academy of Compounding Pharmacists, and the Society of Veterinary Hospital Pharmacists. The survey asked questions about regulations and standards associated with the use of prescription or compounded medications. Of the 4,550 distributed surveys, 153 were received, for a 3.4% response rate. Of the responses received, only 131 were used in the final data analysis. Most respondents correctly answered the assessment question regarding the ability to compound backordered, commercially available products. A majority of respondents incorrectly answered the question regarding the proper flavoring for a medication for a ferret. Those with more training perceived themselves to have a higher level of skill (r = 0.41, P<0.001). Similarly, those with formal veterinary training had better scores on Question 4 of the assessment questions, which requires knowledge of feline toxicities (P=0.029). The most common compounded medications dispensed in practice by pharmacists are methimazole, metronidazole, and gabapentin. Pharmacists mostly recognized that compounding backordered, commercially available products is permitted. Formal training improves familiarity with current compounding rules, regulations, and best practices. Formal training in veterinary pharmacy and veterinary compounding should be promoted and encouraged. Efforts should also be made at improving pharmacists' understanding of both veterinary and compounding laws and regulations.

Effects of high doses of levothyroxine sodium on serum concentrations of triiodothyronine and thyroxine in horses.

OBJECTIVE: To investigate the effect of high doses of orally administered levothyroxine sodium (LT4) on serum concentrations of triiodothyronine (T3) and thyroxine (T4) in euthyroid horses. ANIMALS: 12 healthy adult horses. PROCEDURES: 10 horses initially received water (vehicle) or 240 mg (5X treatment) or 480 mg (10× treatment) of LT4, and blood samples were collected at baseline (0 hours) and 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 48, 72, 96, and 120 hours after treatment to measure serum T3 and T4 concentrations. Three horses then received 480 mg of LT4 for 14 days, and T4 concentration was measured on days 0, 14, 21, 28, and 35. Changes in T3 and T4 concentrations were compared over time and among treatments. RESULTS: One-time administration of LT4 resulted in variable but significant increases in both T3 and T4 concentrations for up to 120 hours; however, T3 and T4 concentrations rarely exceeded reference intervals with either treatment. Prolonged administration of 480 mg of LT4 resulted in a 15-fold increase in T4 concentration after 14 days, but concentration returned to day 0 values within 21 days after LT4 administration was discontinued. CONCLUSIONS AND CLINICAL RELEVANCE: In euthyroid horses, administration of a high dose of LT4 resulted in mild increases in thyroid hormone concentrations; however, prolonged administration of high doses of LT4 resulted in markedly increased thyroid hormone concentrations that returned to pretreatment values within 3 weeks after discontinuation of LT4 administration. These results indicated complex kinetics of LT4 and suggested a possible saturation of T4 excretion in euthyroid horses.

Feline Transdermal Formulation Considerations.

Transdermal delivery of drugs is comparatively new in feline patients. However, transdermal formulations can be a desirable option for treating feline patients that are not willing participants to medication administration. However, achieving drug penetration across the skin is not always easy, and there are a wide variety of variables that can further affect penetration. This, coupled with a lack of studies, make transdermal administration an unknown with regards to efficacy and safety for many drugs. This article focuses on drugs that are administered transdermally with the intent of producing systemic effects.

Effects of a single preappointment dose of gabapentin on signs of stress in cats during transportation and veterinary examination.

OBJECTIVE To determine the effects of oral gabapentin administration prior to veterinary examination on signs of stress in cats. DESIGN Randomized, blinded, crossover clinical trial. ANIMALS 20 healthy pet cats with a history of fractious behavior or signs of stress during veterinary examination. PROCEDURES Cats were scheduled for 2 veterinary visits 1 week apart and randomly assigned to receive a capsule containing 100 mg of gabapentin (13.0 to 29.4 mg/kg [5.9 to 13.4 mg/lb]) or placebo (lactose powder) prior to the first visit and the opposite treatment prior to the second visit. Owners were instructed to administer the assigned capsule orally 90 minutes prior to placing the cat into a carrier and transporting it to the veterinary hospital. Standardized physical examinations and blood pressure readings were performed. Owners assigned a cat stress score during transportation and examination, and the veterinarian assigned a compliance score at the visit. Scores were compared between treatments, controlling for various factors. RESULTS Owner-assessed cat stress scores during transportation and veterinary examination and veterinarian-assessed compliance scores were significantly lower when cats received gabapentin than when they received the placebo. Sedation was a common effect of gabapentin administration, and ataxia, hypersalivation, and vomiting were also reported. All effects resolved within 8 hours after gabapentin administration. CONCLUSIONS AND CLINICAL RELEVANCE Owners' perception of stress in their cats is a primary reason for failing to seek veterinary care. Results of this study suggested that gabapentin is a safe and effective treatment for cats to help reduce stress and aggression and increase compliance for transportation and veterinary examination.

When to Compound Medications for Veterinary Patients.

This article serves as a brief discussion about some of the restrictions applicable to compounding medications for veterinary patients based on U. S. Food and Drug Administration compliance policy guidelines and provides a brief summary of when it is appropriate to compound medications for veterinary patients.

Consultation for Human, Veterinary, and Compounded Medications.

Providing consultation on medications is a daily responsibility for pharmacists. However, counseling components for veterinary or compounded medications can differ from those for manufactured medications for humans. This article lists the content that should be provided during consultation, describes differences between counseling for human and veterinary patients, and provides references that can be used. Because many veterinary medications are compounded, this article also provides information that should accompany compounded preparations.