2023 Veterinary Therapeutics: Updates, Highlights, & Practical Considerations

Jim Budde, PharmD, RPh, DICVP, Plumb's Veterinary Drugs

ArticleLast Updated December 202312 min read
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This article highlights some of the key drugs recently approved for treatment of small animals in the United States and details pharmacology, contraindications, dosages, adverse effects, and other information required for safe use. Also included are new dosage forms, updated indications, and first generic approvals.

New Approvals for Cats

Bexagliflozin

Approved Use

Bexagliflozin is an oral agent FDA-approved for treatment of diabetes mellitus in otherwise healthy cats.

Pharmacology

Bexagliflozin inhibits sodium-glucose–linked transporter (SGLT) 2 in the kidneys, decreasing renal glucose reabsorption and increasing urinary glucose excretion.1 Bexagliflozin also inhibits SGLT1 in the GI tract, possibly contributing to GI adverse effects (eg, loose stool, diarrhea).

Contraindications

Bexagliflozin is contraindicated in cats previously or currently treated with insulin, cats with insulin-dependent diabetes mellitus, and cats with (or that have evidence of) hepatic disease or reduced renal function. Bexagliflozin increases the risk for potentially fatal diabetic ketoacidosis (DKA) and euglycemic DKA, which can occur at any time during treatment, including in cats with improved glycemic control. This drug should be immediately discontinued if DKA is diagnosed or suspected.

This drug should not be given to cats that are anorexic, dehydrated, or lethargic; cats with laboratory values consistent with DKA; cats with history of pancreatitis or current clinical signs or objective evidence (eg, feline pancreas-specific lipase [fPL] >5.3 µg/L, diagnostic imaging) consistent with pancreatitis; or cats with serum beta-hydroxybutyrate >37 mg/dL or >25 mg/dL and history of renal disease or metabolic acidosis.

Adverse Effects

Common adverse effects include GI signs (eg, vomiting, diarrhea, anorexia), lethargy, dehydration, weight loss, UTI, and elevations in various laboratory parameters (eg, BUN, urine specific gravity, fPL, symmetric dimethylarginine, AST). Rare adverse effects include pancreatitis, pancreatic necrosis, hepatopathy, hepatic lipidosis, anemia, hemolytic anemia, peritonitis, urothelial carcinoma, and death. Clinical signs of hypoglycemia were not observed during field trials, but hypoglycemic glucose measurements were seen.1 Bexagliflozin-induced glucosuria can result in osmotic diuresis that increases the risk for dehydration.

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Dosage

Bexagliflozin (15 mg/cat PO every 24 hours) can be administered to cats ≥6.6 lb (3 kg), regardless of blood glucose value. This drug should be administered at approximately the same time every day, with or without food. Temporary discontinuation should be considered during periods of decreased caloric intake (eg, surgery).

Additional Information

The risk for potentially fatal DKA and euglycemic DKA is increased with bexagliflozin treatment. Careful patient selection is required, and diligent monitoring of drug safety and efficacy is needed. The manufacturer-provided client information sheet should be included each time this drug is prescribed and dispensed.

Velagliflozin

Approved Use

Velagliflozin is an oral agent FDA-approved for treatment of diabetes mellitus in otherwise healthy cats.

Pharmacology

Velagliflozin works by inhibiting SGLT2 in the kidneys, decreasing renal glucose reabsorption and increasing urinary glucose excretion.2

Contraindications

Velagliflozin is contraindicated in cats previously or currently treated with insulin, cats with insulin-dependent diabetes mellitus, and cats with (or that have evidence of) hepatic disease or reduced renal function. Velagliflozin increases the risk for potentially fatal DKA and euglycemic DKA, which can occur at any time during treatment, including in cats with improved glycemic control. This drug should be immediately discontinued if DKA is diagnosed or suspected.

Velagliflozin should not be initiated in cats with anorexia, dehydration, lethargy, ketonuria or ketonemia, current or history of DKA, clinical signs or other objective evidence (eg, fPL level >12 µg/L, diagnostic imaging) consistent with pancreatitis within the previous month, history of pancreatitis, or chronic or unresponsive diarrhea. Velagliflozin should also be avoided in cats with cachexia or BUN >2 mg/dL or bilirubin >0.5 mg/dL.

Adverse Effects

Common adverse effects include GI signs (eg, vomiting, diarrhea, anorexia), lethargy, dehydration, weight loss, UTI, and elevations in various laboratory parameters (eg, BUN, fPL, bilirubin). Rare adverse effects include pancreatitis, pancreatic necrosis, hepatopathy, hepatic lipidosis, and death. Velagliflozin-induced glucosuria can result in osmotic diuresis that increases the risk for dehydration.

Dosage

Velagliflozin (1 mg/kg PO every 24 hours) can be administered regardless of blood glucose value. This drug should be administered at approximately the same time every day. Temporary discontinuation should be considered during periods of decreased caloric intake (eg, surgery).

Additional Information

The risk for potentially fatal DKA and euglycemic DKA is increased with velagliflozin treatment. Careful patient selection is required, and diligent monitoring of drug safety and efficacy is needed. The manufacturer-provided client information sheet should be included each time this drug is prescribed and dispensed.

Esafoxolaner/Eprinomectin/Praziquantel Combination for Cats

Approved Use

Esafoxolaner/eprinomectin/praziquantel combination topical solution is indicated for prevention of heartworm disease caused by Dirofilaria immitis; treatment and control of roundworms, hookworms, and tapeworms; treatment and prevention of flea infestations; and treatment and control of black-legged tick and lone star tick infestations in cats ≥8 weeks of age.3

Pharmacology

Esafoxolaner inhibits insect and acarine gamma-aminobutyric acid (GABA)-gated chloride channels in the parasite CNS, and eprinomectin binds selectively to glutamate-gated chloride ion channels in invertebrate nerve and muscle cells. Both actions result in parasite neuronal hyperexcitation, paralysis, and death. Fleas and ticks are eliminated within 24 and 48 hours, respectively, after treatment.4

Praziquantel is thought to interact with phospholipids in the cestode integument, causing rapid calcium influx. In vitro, the drug appears to paralyze the worm’s sucker function at low concentrations and contracts and paralyzes the worm’s strobila at high concentrations. Praziquantel also causes irreversible focal vacuolization with subsequent disintegration at specific sites of the cestodal integument.

Contraindications

The US product label states there are no known contraindications3; however, in other countries, this product is contraindicated in patients hypersensitive to any of the components.4

Adverse Effects

The esafoxolaner/eprinomectin/praziquantel combination product was well tolerated in preapproval studies. In cats, reported rates of dermatologic adverse effects (eg, hair changes, itching, bacterial skin infection, alopecia, application site redness) were ≈1% to 4% and more common than in cats receiving an alternative topical parasiticide.3

Dosage

Esafoxolaner/eprinomectin/praziquantel (0.12 mL/kg) is topically administered directly on the skin. Monthly application is recommended year-round for parasite prevention or control. This product can also be used as a single-dose treatment for roundworms, hookworms, and tapeworms.3

Molidustat

Approved Use

Molidustat is conditionally FDA-approved (pending full demonstration of effectiveness) for control of nonregenerative anemia associated with chronic kidney disease in cats.

Pharmacology

Molidustat is a reversible inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase (PH). HIF is a protein that stimulates transcription of hypoxia-sensitive genes (eg, genes responsible for erythropoietin production, iron homeostasis),5,6 and PH is an enzyme involved in HIF catabolism. HIF-PH inhibitors (eg, molidustat) stabilize HIF concentrations, promote intracellular HIF accumulation, and subsequently increase transcription of HIF-regulated genes. Molidustat can result in a dose-dependent increase of endogenous erythropoietin production and subsequent RBC production (ie, erythropoiesis) in cats with chronic kidney disease.7

Contraindications

Molidustat is contraindicated in cats hypersensitive to it or the drug’s inactive ingredients. This drug should not be administered to cats that are pregnant, lactating, or intended for breeding.

Adverse Effects

Vomiting was observed in ≈50% of cats.7

Dosage

Molidustat (5 mg/kg PO every 24 hours) can be administered for up to 28 consecutive days.7 Treatment must be discontinued when hematocrit (HCT) or packed cell volume (PCV) exceeds the upper limit of the reference interval or after 28 consecutive days of administration. Treatment may be repeated following a minimum of 7 days without treatment and when HCT or PCV falls below the lower limit of the reference interval. Extra-label use (ie, unapproved species, dose, route, frequency, duration) of a conditionally approved drug is prohibited by the FDA.

Additional Information

HCT and PCV should be monitored prior to initiating therapy, at weekly intervals beginning ≈2 weeks after treatment, and periodically after cessation of treatment.


New Approvals for Dogs

Fuzapladib

Approved Use

Fuzapladib is conditionally FDA-approved (pending full demonstration of effectiveness) to control clinical signs in dogs with acute pancreatitis.

Pharmacology

Fuzapladib limits the neutrophil-mediated inflammatory response in dogs with pancreatitis and may reduce pancreatic lesion size and extrapancreatic organ involvement.8

Contraindications

Fuzapladib is contraindicated in dogs hypersensitive to it. This drug has not been studied in dogs with cardiac, hepatic, or renal disease; dogs <6 months of age; or dogs that are pregnant, lactating, or intended for breeding.

Adverse Effects

Adverse effects observed in the field trial included GI effects (eg, anorexia, diarrhea, hypersalivation), hepatopathy, jaundice, respiratory tract effects (eg, pneumonia, tachypnea, dyspnea), cardiac effects (eg, arrhythmia, hypertension, cardiac arrest), hyperthermia, pruritus, and cerebral edema.8

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Dosage

Fuzapladib (0.4 mg/kg IV bolus over 15-60 seconds) is administered every 24 hours for 3 days. Extra-label use (ie, unapproved species, dose, route, frequency, duration) of a conditionally approved drug is prohibited by the FDA.

Additional Information

Reconstitution instructions should be followed carefully, as the amount of the supplied diluent (5 mL) exceeds the volume required for reconstitution (3.5 mL).

Canine Parvovirus Monoclonal Antibody

Approved Use

Canine parvovirus monoclonal antibody (parvovirus mAb) is conditionally licensed by the USDA for the treatment of canine parvovirus.

Pharmacology

Parvovirus mAb selectively binds to circulating canine parvovirus, neutralizing the virus and preventing viral infiltration into host cells.9

Contraindications

Canine parvovirus mAb should not be administered in dogs <8 weeks of age. Use in pregnant dogs has not been studied. Parvovirus mAb is a canine-specific product that should not be used in other species.

Adverse Effects

Injection site reactions (eg, erythema, inflammation, edema, pain) occurred in ≈4% of dogs.9 Systemic adverse effects may include diarrhea and pruritus.

Dosage

Parvovirus mAb (0.2 mL/kg [NOT mg/kg] IV) is administered once as a single treatment.

Additional Information

Parvovirus mAb must be stored frozen at or below −5°F (−15°C). It is important to store the product inside the specialized delivery packaging by placing the delivery box (with the product inside) directly into the freezer. Parvovirus mAb is conditionally licensed by the USDA, which assures product safety and purity and a reasonable expectation of efficacy while further efficacy studies are conducted.

Afoxolaner/Moxidectin/Pyrantel Combination for Dogs

Approved Use

Afoxolaner/moxidectin/pyrantel combination tablets are indicated for prevention of heartworm disease caused by D immitis, treatment and control of roundworms and hookworms, treatment and prevention of flea infestations, and treatment and control of black-legged tick and lone star tick infestations in dogs ≥8 weeks of age.10

Pharmacology

All antiparasitic agents in this combination product result in paralysis and death of susceptible parasites. Afoxolaner causes prolonged neuronal hyperexcitation by inhibiting insect and acarine GABA-gated chloride channels in the parasite CNS. Moxidectin selectively binds to glutamate-gated chloride ion channels in invertebrate nerve and muscle cells and enhances the release of GABA at presynaptic neurons. Pyrantel causes neuronal depolarization via binding at nematode nicotinic cholinergic receptors, acts as a neuromuscular blocking agent, and inhibits cholinesterase.

Contraindications

Although the manufacturer states there are no known contraindications,10 this combination product should not be administered to patients hypersensitive to any of the active or inactive product components.

Adverse Effects

The afoxolaner/moxidectin/pyrantel combination product was well tolerated in preapproval studies. The most common adverse effects were diarrhea (6.7%) and vomiting (4.5%).10 Drugs in the isoxazoline class can cause neurologic adverse effects (including muscle tremors, ataxia, and seizures) in patients with and without history of neurologic disorders.10,11

Dosage

Afoxolaner (2.5 mg/kg)/moxidectin (12 µg/kg)/pyrantel (5 mg/kg) PO once per month is the minimum dosage. Dogs >132.2 lb (60 kg) require a combination of chewable tablet sizes. Year-round administration is recommended for parasite prevention or control.

Bedinvetmab

Approved Use

Bedinvetmab is indicated for the control of pain associated with osteoarthritis in dogs.

Pharmacology

Bedinvetmab is a canine immunoglobulin G mAb that binds to nerve growth factor (NGF), thereby decreasing NGF-mediated processes involved in pain.

Contraindications

Fetal abnormalities, increased stillbirths, and increased postpartum fetal mortality have been noted in rodents and primates receiving anti-NGF mAbs. Bedinvetmab is contraindicated in dogs that are breeding, pregnant, lactating, or intended for breeding.12 Hypersensitivity reactions may occur, necessitating discontinuation of the drug. This drug has not been evaluated in dogs with history of cruciate ligament rupture in the past 6 months or in dogs <12 months of age. Bedinvetmab is a canine-specific product that should not be administered in other species.

Adverse Effects

Bedinvetmab may cause increased BUN, UTI, inappropriate urination, bacterial skin infection, dermatitis, a dermal mass or cyst, erythema, lethargy, vomiting, decreased appetite, a cough, and/or lameness. In studies, treatment-emergent immunogenicity was uncommon in dogs that received bedinvetmab for up to 9 months.13,14

Dosage

Bedinvetmab (0.5 mg/kg SC) can be administered once per month.

Gilvetmab

Approved Use

Gilvetmab is conditionally licensed by the USDA for the treatment of mast cell tumors and melanoma in dogs.

Pharmacology

Gilvetmab is an antagonist immunoglobulin G antibody that selectively binds to canine programmed cell death receptor-1 (PD-1) on CD4+ and CD8+ T lymphocytes.15 PD-1 antibodies block tumor-induced suppression of the T cell-mediated immune response, freeing the immune system to recognize and destroy cancer cells.16,17 PD-1 antibodies are one type of immune checkpoint inhibitor.

Contraindications

Gilvetmab is a canine-specific product that should not be used in other species. Gilvetmab is contraindicated in dogs hypersensitive to it or that have severe adverse reactions when receiving this drug. Gilvetmab should be used with caution in dogs hypersensitive to gentamicin, a preservative in the commercial solution.

Adverse Effects

Systemic adverse effects may include lethargy, fatigue, reduced appetite, vomiting, diarrhea, or pruritus. Hypersensitivity reactions (eg, facial, eye, or ear swelling; localized erythema) occurred in 6% of healthy beagles.15

Dosage

Gilvetmab (10 mg/kg as an IV infusion over 30 minutes) can be repeated every 2 weeks for up to 10 treatments.

Additional Information

Diphenhydramine (2 mg/kg IM or PO) should be administered prior (IM, 15-30 minutes; PO, 4 hours) to gilvetmab administration to prevent or reduce infusion reactions. Gilvetmab is conditionally licensed by the USDA while further efficacy, safety, and potency studies are conducted.


Drugs With Long-Standing Approval for Human Use Newly Approved for Veterinary Use

Phenobarbital

Phenobarbital tablets are conditionally FDA-approved for the control of seizures associated with idiopathic epilepsy in dogs. This product is available in 16.2-, 32.4-, 64.8-, and 97.2-mg unflavored, bisected tablets. Extra-label use (ie, unapproved species, dose, route, frequency) of a conditionally approved drug is prohibited by the FDA; this product must be used at the labeled dosage and in dogs only.

Metronidazole

Metronidazole oral suspension is FDA-approved for the treatment of Giardia duodenalis in dogs. The 125-mg/mL product has a poultry liver flavor in an oily suspension base and is available in 30- and 100-mL bottles. This product has been available in several countries (eg, Australia, Canada, the United Kingdom).


New Dosage Forms

Oclacitinib is now available as chewable tablets.


Updated Indications

An additional indication was added to both afoxolaner and fluralaner labels for the treatment and control of Haemaphysalis longicornis (ie, Asian longhorned tick).


First Generic Approvals

First generic approvals were given for maropitant tablets (dogs), firocoxib tablets (dogs), acepromazine tablets (dogs), and imidacloprid/moxidectin topical solution (cats).