What’s New With Parasiticides for Dogs and Cats

In the past few years, the introduction of isoxazolines and their combination with classic endoparasiticide molecules have drastically changed parasite control and prevention in companion animals. These “end-ectocide” combination preventives provide broad-spectrum parasite coverage in a single monthly product, making them easy for pet owners to administer and thereby often improving compliance.

Several isoxazoline stand-alone and combination preventives for dogs and cats with differing spectra of parasite coverage, application routes, and duration of efficacy are available in the United States; this article provides a quick-reference overview of current label indications.

What’s New in Canine Parasiticides?

In the United States, there are now 3 isoxazoline combination preventives that provide broad-spectrum coverage of both endo- and ectoparasites and 6 isoxazoline stand-alone preventives available for control of ectoparasites in dogs. While the products may appear similar on the surface, each preventive has nuanced label differences and specific highlights (TABLE 1).

Over the past 2 years, the isoxazoline combination preventives NexGard PLUS (Boehringer Ingelheim, nexgardforpets.com) and Credelio Quattro (Elanco, elanco.com) have entered the market, and Simparica TRIO (Zoetis, zoetispetcare.com) has undergone several label updates since its initial FDA approval in 2020. Most recently, Bravecto Quantum (Merck, us.bravecto.com), an injectable isoxazoline preventive, entered the U.S. market in July 2025.

Simparica TRIO

When originally approved, Simparica TRIO was labeled for prevention of heartworm disease caused by Dirofilaria immitis and treatment and control of the roundworms Toxocara canis and Toxascaris leonina, adult hookworms Ancylostoma caninum and Uncinaria stenocephala, Ctenocephalides felis fleas, and 5 tick species: Amblyomma americanum, Amblyomma maculatum, Dermacentor variabilis, Ixodes scapularis, and Rhipicephalus sanguineus.¹ Treatment and control of A caninum fourth-stage (L4) larvae have since been added to the Simparica TRIO label,² and the invasive Asian longhorned tick, Haemaphysalis longicornis, has been added to the labels of both Simparica TRIO and Simparica.^3,4 H longicornis was introduced to the northeastern region of the United States sometime in the early 2010s but has since been rapidly expanding its distribution south and westward.⁵ Outside of the United States, H longicornis has been implicated in the transmission of a number of tick-borne infections of zoonotic and veterinary importance,⁵ making efficacious control of this species on companion animals a growing concern.

Currently, Simparica TRIO and Simparica are the only isoxazoline-containing preventives to include A maculatum, the Gulf Coast tick, on their labels, and they cover the most tick species of the isoxazoline-containing preventives for dogs. Zoetis has also emphasized adding vector-borne disease prevention to its parasiticide labels. Both Simparica TRIO and Simparica are now labeled for the prevention of Lyme disease by killing the tick vector I scapularis before transmission of Borrelia burgdorferi can occur.^2,6 In the most recent label extension, Simparica TRIO was shown to be effective for preventing transmission of Dipylidium caninum, the flea tapeworm, by killing and controlling C felis fleas.⁷

Simparica TRIO may be prescribed for dogs as young as 8 weeks of age, differing from Simparica, which may only be prescribed for dogs aged 6 months and older.^1,3 This labeling difference is likely due to the higher minimum dose of sarolaner delivered by Simparica (2 mg/kg) versus Simparica TRIO (1.2 mg/kg).^1,4

The safety of macrocyclic lactone–containing preventives is of greater concern in dogs with the multidrug resistance-1 (MDR1) gene mutation due to their sensitivity to avermectins. Additionally, the use of moxidectin-containing products in dogs that are heartworm positive or have unknown heartworm status often causes concern due to moxidectin’s powerful microfilaricidal effect and potential for killing adult heartworms, sometimes called slow-kill. While the use of moxidectin in heartworm-positive dogs should always be cautioned, Simparica TRIO has demonstrated tolerance and safety in both avermectin-sensitive collies and microfilaremic dogs infected with adult heartworms following administration of up to 3 times the maximum labeled dose.¹

NexGard PLUS

When it received FDA approval in 2023, NexGard PLUS was labeled for prevention of heartworm disease caused by D immitis and for treatment and control of adult A caninum, Ancylostoma braziliense, and U stenocephala; adult T canis and T leonina; C felis fleas; and 4 tick species: A americanum, D variabilis, I scapularis, and R sanguineus.⁸ NexGard PLUS includes 3 different hookworm species on the label, more than any other isoxazoline-containing preventive for dogs. Both NexGard PLUS and NexGard have subsequently added H longicornis to their labels, increasing label coverage to 5 tick species.^9,10 NexGard PLUS and NexGard are also labeled for the improvement of clinical signs associated with flea allergy dermatitis through the killing and elimination of fleas,^9,10 a unique label claim among isoxazoline-containing preventives for dogs. NexGard PLUS and NexGard are additionally labeled for prevention of B burgdorferi infection through the killing of I scapularis before transmission can occur.^11,12 NexGard PLUS and NexGard contain the same minimum dosage of the insecticidal component afoxolaner (2.5 mg/kg).^9,10

Both NexGard PLUS and NexGard may be prescribed to dogs as young as 8 weeks, and NexGard PLUS was well tolerated in microfilaremic dogs infected with adult heartworms at up to 3 times the maximum labeled dose and in collies with the MDR1 gene mutation at up to 5 times the maximum labeled dose.⁸

Credelio Quattro

Credelio Quattro is the newest canine isoxazoline combination preventive to enter the U.S. market, receiving FDA approval in late 2024 and becoming publicly available in 2025.¹³ It is currently the only isoxazoline-containing preventive for dogs to incorporate praziquantel, adding treatment and prevention of 3 tapeworm species to its label: D caninum, Taenia pisiformis, and Echinococcus granulosus.¹³ Credelio Quattro was initially labeled for prevention of heartworm disease caused by D immitis and treatment and control of adult U stenocephala, T canis, and T leonina; C felis fleas; and 4 tick species: A americanum, D variabilis, I scapularis, and R sanguineus.¹³ The label has now been extended to include treatment and control of A caninum L4 larvae, immature adults, and adult worms.¹⁴ Compared with moxidectin or pyrantel alone, the combination of the 2 at the labeled doses showed increased efficacy against A caninum L4 larvae.¹⁵

Credelio Quattro may be prescribed for dogs as young as 8 weeks¹³ and has demonstrated tolerance and safety in microfilaremic dogs infected with adult D immitis at up to 3 times the labeled dose.¹⁶ Within 1 day of product administration at the labeled dose, experimentally infected dogs showed 38.8% reduction in the number of circulating microfilariae without induction of hypersensitivity reactions.¹⁶

Credelio Quattro has been shown to be safe in collies with the MDR1 gene mutation and was tolerated at doses up to 5 times the labeled dose while producing only mild dose-dependent adverse effects, which were also observed in normal beagles administered the same dosage.¹⁷ Similarly, NexGard PLUS was well tolerated in dogs with the MDR1 gene mutation at up to 5 times the maximum labeled dose.⁸ These safety margins differ somewhat from safety studies for Simparica TRIO, in which a dose 5 times the labeled dose produced mild and self-limiting signs, including ataxia and muscle twitching.¹ These differences may be attributable to the lower maximum dose of moxidectin delivered by Credelio Quattro (40 µg/kg) and NexGard PLUS (24 µg/kg) compared with Simparica TRIO (48 µg/kg).^1,8,13,17

Bravecto Quantum

Bravecto Quantum is the newest isoxazoline product for dogs to enter the U.S. market. Receiving FDA approval in July 2025, Bravecto Quantum is indicated for treatment and prevention of C felis flea infestations and treatment and control of the ticks I scapularis, D variabilis, and R sanguineus for 12 months.¹⁸ Bravecto Quantum is also labeled for treatment and control of A americanum for 8 months. With up to 1 year of ectoparasite control, Bravecto Quantum delivers the longest duration of ectoparasite control for dogs in a single injectable dose.

Bravecto Quantum may be prescribed for dogs beginning at 6 months of age and is administered by subcutaneous injection. Nonpainful injection site swelling was the most commonly reported adverse effect in dogs administered Bravecto Quantum; this effect typically resolved over time without intervention.¹⁸ Bravecto Quantum has demonstrated safety when administered at the labeled dosage.

What’s New in Feline Parasiticides?

There are several isoxazoline-containing preventives for cats on the U.S. market, including 3 broad-spectrum isoxazoline combination preventives and 2 isoxazoline stand-alone products (TABLE 2).

Revolution PLUS

In its original 2018 FDA approval, Revolution PLUS (Zoetis, zoetispetcare.com) was labeled for prevention of heartworm disease caused by D immitis and for treatment and control of Ancylostoma tubaeforme, Toxocara cati, Otodectes cynotis, C felis fleas, and 3 tick species: I scapularis, A maculatum, and D variabilis.¹⁹ Subsequently, the label was extended to include A americanum,²⁰ increasing the labeled coverage to 4 tick species, the highest of any isoxazoline-containing product for cats. Control of A americanum is particularly important for cats in the southcentral, southeastern, and mid-Atlantic United States, where this tick serves as the primary vector for transmitting the protozoa Cytauxzoon felis, which can cause an estimated 40% or higher mortality rate in cats despite attempted treatment.²¹ In the most recent label extension, Revolution PLUS was shown to be effective for preventing D caninum infection in cats by killing and controlling C felis fleas.²²

Bravecto PLUS

Initially FDA approved in 2019, Bravecto PLUS (Merck, us.bravecto.com) is labeled for prevention of heartworm disease caused by D immitis and treatment and control of adults, immature adults, and L4 larvae of A tubaeformae and T cati; C felis fleas; and 2 tick species: I scapularis and D variabilis.²³ Both the Bravecto PLUS and Bravecto labels have since been extended to include H longicornis, making them the only isoxazoline-containing products for cats that are labeled for treatment and control of this invasive tick species.^24,25

NexGard COMBO

NexGard COMBO (Boehringer Ingelheim, nexgardforpets.com) is the newest isoxazoline-containing product for cats, receiving initial FDA approval in 2023 for prevention of heartworm disease caused by D immitis as well as treatment and control of adults and L4 larvae of A tubaeforme, adult A braziliense, adult and L4 larvae of T cati, D caninum, C felis fleas, and 2 tick species: I scapularis and A americanum.²⁶ NexGard COMBO is the only isoxazoline-containing product for cats that contains praziquantel, making it efficacious for treating and controlling D caninum tapeworm infections.

Neurologic Considerations for Isoxazolines in Dogs and Cats

Many pet owners and veterinarians are conscious of concerns about neurologic adverse events related to isoxazoline use in dogs and cats, particularly following a public FDA alert on the topic in 2023.²⁷ The FDA continues to back the safety of isoxazolines in companion animals but advises that special consideration may be needed for animals with a history of neurologic conditions.²⁷ Animals may have adverse neurologic events with or without a history.

Isoxazolines act against arthropods by binding and inhibiting γ-aminobutyric acid (GABA) and glutamate-gated chloride channels (GluCls), resulting in continuous stimulation of the arthropod’s neurons, paralysis, and eventual death.²⁸ Mammals also express GABA and GluCls; however, limited evidence suggests that isoxazolines have a much higher affinity or specificity for arthropod receptors compared with mammalian receptors.²⁹ Receptor binding differences between the individual isoxazolines, as well as a definitive link between isoxazolines and neurologic effects in mammals, remain undescribed.

Although there are no data on the topic, in animals at elevated risk for adverse neurologic events, veterinarians should consider the potential risk of administering isoxazolines with greater bioavailability or extended duration of activity. While neurologic adverse events are possible, especially in higher-risk animals, isoxazolines appear to be safe in the vast majority of animals that receive these preventives.

Summary

Many parasite preventives for dogs and cats now exist in the U.S. market, and many offer robust control of both endo- and ectoparasites in a single product. Isoxazoline-containing products have grown to dominate the companion animal market due to their robust control of fleas and ticks and the convenient combination of isoxazolines with other molecules that control common intestinal parasites and prevent heartworm disease. With their spectra of parasite coverage and variety in the duration of efficacy, there are preventives to conveniently meet the parasite needs of every dog, cat, and pet owner.

Disclosures

Dr. Starkey has established professional and paid relationships with Merck, Zoetis, Elanco, and Boehringer Ingelheim.

Ms. Smith has served as a consultant for Zoetis.