2022 Veterinary Therapeutics: Updates, Highlights, & Practical Considerations
Jim Budde, PharmD, RPh, DICVP, Plumb's Veterinary Drugs
Several novel veterinary drug products have been approved by the FDA; This article highlights some of the new drugs marketed for use in small animals and summarizes pharmacology, dosages, adverse effects, and other key information required for safe use. Also included are drugs previously approved by the FDA that have been granted additional indications, as well as first generic approvals for topical formulations.
New Approvals in Veterinary Therapeutics
The medetomidine/vatinoxan combination product is a sedative–analgesic injection FDA-approved for use in dogs to help facilitate examinations, clinical procedures, and minor surgical procedures.
Vatinoxan, a peripherally acting alpha-2–adrenergic antagonist, attenuates the adverse cardiovascular effects (eg, bradycardia) of medetomidine, an alpha-2–adrenergic agonist. Vatinoxan can alter the pharmacokinetics of medetomidine (as well as other sedatives and anesthetics [eg, midazolam, alfaxalone]),1,2 resulting in a typically shorter duration of sedation of the combination product (ie, medetomidine/vatinoxan) than an equivalent dose of medetomidine alone. Medetomidine/vatinoxan should thus not be administered interchangeably with single-agent medetomidine in sedative and anesthetic protocols.
This combination drug is contraindicated in dogs hypersensitive to medetomidine or vatinoxan; dogs with cardiac disease, respiratory disorders, shock, or severe debilitation; dogs that have or are at risk for developing hypoglycemia; and dogs stressed due to heat, cold, or fatigue. Medetomidine/vatinoxan should not be administered to dogs with pre-existing hypotension, hypoxia (hypoxemia), or bradycardia and should be used with caution in dogs with hepatic or renal disease, as safe use with these conditions has not been evaluated.3 This drug should not be administered to cats, as significant hypotension has been noted.4-6
Medetomidine/vatinoxan is well tolerated in dogs. In clinical trials, decreased body temperature (≤99°F [37°C]) was observed in ≈50% of treated dogs, but clinical hypothermia was rare.3
Medetomidine/vatinoxan dosage should be calculated based on medetomidine 1 mg/m2 IM; the product label contains a weight-based dosage table.3
Atipamezole (5,000 µg/m2 IM) can reverse the central and cardiovascular effects of the combination product (ie, medetomidine’s effects); sedation reversal occurs 5 to 10 minutes after atipamezole administration.3
Crofelemer is conditionally FDA-approved (pending full demonstration of effectiveness) for treatment of chemotherapy-induced diarrhea in dogs. Other causes of diarrhea (eg, infection, toxicosis) should be ruled out prior to crofelemer use.
Crofelemer inhibits 2 types of chloride channels at the luminal membrane of intestinal epithelial cells, blocking chloride ion secretion and accompanying high-volume water loss that occurs with diarrhea. At approved dosages, crofelemer is not absorbed from the GI tract.
Crofelemer is contraindicated in patients hypersensitive to it. Administration in combination with other antidiarrheal agents (eg, hyoscyamine, loperamide) has not been studied and warrants caution.
At approved dosages, adverse effects are uncommon.
Dogs ≤140 lb (63.6 kg) can be administered 125 mg/dog PO every 12 hours for 3 days. Dogs >140 lb (63.6 kg) can be administered 250 mg/dog PO every 12 hours for 3 days.8 This drug can be administered with food or on an empty stomach and should be given as intact tablets (ie, not split, broken, or crushed); one additional dose can be administered if the tablets are chewed. Extra-label use of conditionally approved drugs is not permitted by the FDA.
Frunevetmab is the first safe and effective FDA-approved drug to control pain associated with osteoarthritis in cats.
Frunevetmab is a cat-specific immunoglobulin G monoclonal antibody that binds to nerve growth factor (NGF), decreasing NGF-induced peripheral sensitization, neurogenic inflammation, and increased perception of pain.9
Fetal abnormalities, increased stillbirths, and increased postpartum fetal mortality have been noted in rodents and primates receiving anti‑NGF monoclonal antibodies, and frunevetmab is contraindicated in breeding cats and in pregnant or lactating queens.10 Frunevetmab is also contraindicated in cats hypersensitive to it. This is a feline-specific product that should not be used in any other species.10
Adverse effects include injection site pain (≈11%), injection site reactions (≈5%; eg, scabbing, dermatitis, alopecia, pruritus, swelling), and GI signs (≈7%-13%; eg, vomiting, diarrhea, anorexia). Worsening of existing renal insufficiency (6.6%), dehydration (4.4%), weight loss (3.3%), and gingival disorders (2.2%) have also been reported. Cats can form antifrunevetmab antibodies that may result in loss of effectiveness.10
Target dosage range is 1 to 2.8 mg/kg SC per month.
Frunevetmab has not been studied in combination with other medications, including NSAIDs. In humans given a humanized anti-NGF concurrently with long-term NSAIDs, incidence of rapidly progressing osteoarthritis was increased.11,12 The significance of this finding for veterinary patients is uncertain; rapidly progressing osteoarthritis has not been reported in cats.Analgesic effect is ≈2 to 3 weeks after administration.7,13,14 Pet owners considered treatment to be successful in ≈75% of arthritic cats given frunevetmab in the target dosage range.13 The long-term safety and efficacy of this drug are unknown.
Buprenorphine transdermal solution (C-III)
Buprenorphine transdermal solution is FDA-approved for one-time administration to control postoperative pain in cats, providing an additional option for short-term analgesia.
This drug is formulated for rapid absorption and sequestration into the stratum corneum of cats, resulting in continuous systemic buprenorphine delivery.
Buprenorphine transdermal solution has not been evaluated in cats with renal, hepatic, cardiac, or respiratory disease and should be used with caution in these patients. Because this opioid formulation delivers the drug into the systemic circulation, this drug should be used cautiously in patients with head trauma, increased CSF pressure, or other CNS dysfunction (eg, coma), as any degree of respiratory depression could result in excessive partial pressure of arterial carbon dioxide with a subsequent increase in intracranial pressure.
Hyperthermia and sedation appear to be the most common adverse effects.
Tube size (0.4 mL or 1 mL) should be based on patient body weight and the target dose (2.7-6.7 mg/kg) administered via topical application of the entire tube contents directly on healthy skin at the dorsal cervical area of the base of the skull 1 to 2 hours preoperatively. Analgesia occurs within 1 to 2 hours of application and lasts up to 4 days.15
This product is a highly concentrated buprenorphine solution and should not be dispensed for at-home administration. Clinicians and veterinary staff should be trained in safe handling and proper administration techniques to minimize the risk for accidental exposure, which could result in life-threatening respiratory depression. Impermeable gloves, protective glasses, and a laboratory coat should be worn when applying the solution. Following administration, a drying time of ≥30 minutes should be allowed before contact is made with the application site. Buprenorphine is a Schedule III (C-III) controlled substance, and it is important to follow local, state, and federal requirements for storage, record keeping, disposal, and reporting. The package insert contains a warning related to potential human abuse of opioids and the risk for drug diversion and/or abuse that should be considered when storing, administering, and disposing of buprenorphine transdermal solution.15
Updated Indications in Veterinary Therapeutics
Fluralaner is now indicated for 2-month treatment and control of Haemaphysalis longicornis (ie, Asian longhorned tick) infestations in cats and kittens.16
Pimobendan is conditionally FDA-approved (pending full demonstration of effectiveness) for use in delaying the onset of congestive heart failure in dogs with stage B2 preclinical myxomatous mitral valve disease.17
The combination sarolaner/moxidectin/pyrantel chewable tablet is FDA-approved for the prevention of Borrelia burgdorferi infections as a direct result of killing Ixodes scapularis vector ticks and for the treatment and control of fourth-stage larvae and immature adult hookworm (Ancylostoma caninum).18
First Generic Approvals
The first generic approvals were given for imidacloprid and moxidectin topical solution and florfenicol, terbinafine, and mometasone otic solution.
ADVERSE DRUG EFFECTS
The FDA continues to monitor drug safety after approval is granted. Suspected adverse effects should be reported to the product’s manufacturer or the FDA here.