Two recent events have drastically changed parasite control and prevention in companion animals: the introduction of isoxazolines and the combined formulation of this class of ectoparasiticides with endoparasiticides. These \u201cend-ectocide\u201d combination preventives are popular with veterinarians and pet owners alike. Broad-spectrum parasite coverage in a single monthly product offers ease of use and peace of mind to pet owners, and these features often lend themselves to improved owner compliance, one of the hardest-fought battles for veterinarians. This article describes some of the newest parasiticides that have come to market for companion animals as well as updated labels for existing preventives, providing a quick-reference resource for general practitioners.<\/p>\n
Take-Home Points<\/strong><\/p>\n <\/div><\/div><\/p>\n In the past few years, the introduction of isoxazolines and their combination with classic endoparasiticide molecules have drastically changed parasite control and <\/span>prevention in companion animals. These \u201cend-ectocide\u201d 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. <\/span><\/p>\n 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.<\/span><\/p>\n In the United States, there are now 3 isoxazoline combination preventives that provide broad-spectrum coverage of both endo- and ectoparasites and 6\u00a0isoxazoline 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 (<\/span>TABLE 1<\/b><\/span>).<\/span><\/p>\n Over the past 2 years, the isoxazoline combination preventives NexGard PLUS (Boehringer Ingelheim, <\/span>nexgardforpets.com<\/span><\/a>) and Credelio Quattro (Elanco, <\/span>elanco.com<\/span><\/a>) have entered the market, and Simparica TRIO (Zoetis, <\/span>zoetispetcare.com<\/span><\/a>) has undergone several label updates since its initial FDA approval in 2020. Most recently, Bravecto Quantum (Merck, <\/span>us.bravecto.com<\/span><\/a>), an injectable isoxazoline preventive, entered the U.S. market in July 2025.<\/span><\/p>\n When originally approved, Simparica TRIO was labeled for prevention of heartworm disease caused by Dirofilaria immitis<\/i> and treatment and control of the roundworms Toxocara canis<\/i> and Toxascaris leonina<\/i>, adult hookworms Ancylostoma caninum<\/i> and Uncinaria stenocephala<\/i>, Ctenocephalides felis<\/i> fleas, and 5 tick species: Amblyomma americanum<\/i>, Amblyomma maculatum<\/i>, Dermacentor variabilis<\/i>, Ixodes scapularis<\/i>, and Rhipicephalus sanguineus.<\/i>1<\/sup> Treatment and control of A caninum <\/i>fourth-stage (L4) larvae have since been added to the Simparica TRIO label,2<\/sup> and the invasive Asian longhorned tick, Haemaphysalis longicornis<\/i>, has been added to the labels of both Simparica TRIO and Simparica.3,4<\/sup> H longicornis<\/i> 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<\/sup> Outside of the United States, H longicornis<\/i> has been implicated in the transmission of a number of tick-borne infections of zoonotic and veterinary importance,5<\/sup> making efficacious control of this species on companion animals a growing concern.<\/span><\/p>\n Currently, Simparica TRIO and Simparica are the only isoxazoline-containing preventives to include A\u00a0maculatum<\/i>, 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<\/i> before transmission of Borrelia burgdorferi<\/i> can occur.2,6<\/sup> In the most recent label extension, Simparica TRIO was shown to be effective for preventing transmission of Dipylidium caninum<\/i>, the flea tapeworm, by killing and controlling C felis<\/i> fleas.7<\/sup><\/span><\/p>\n 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<\/sup> This labeling difference is likely due to the higher minimum dose of sarolaner delivered by Simparica (2\u00a0mg\/kg) versus Simparica TRIO (1.2 mg\/kg).1,4<\/sup><\/span><\/p>\n The safety of macrocyclic lactone\u2013containing preventives is of greater concern in dogs with the multidrug resistance-1 (MDR1<\/i>) 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\u2019s 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\u00a0times the maximum labeled dose.1<\/sup><\/span><\/p>\n When it received FDA approval in 2023, NexGard PLUS was labeled for prevention of heartworm disease caused by D immitis<\/i> and for treatment and control of adult A caninum<\/i>, Ancylostoma braziliense,<\/i> and U\u00a0stenocephala<\/i>; adult T canis<\/i> and T leonina<\/i>; C felis <\/i>fleas; and 4 tick species: A americanum<\/i>, D variabilis<\/i>, I\u00a0scapularis<\/i>, and R sanguineus.<\/i>8<\/sup> 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<\/i> to their labels, increasing label coverage to 5 tick species.9,10<\/sup> NexGard <\/span>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<\/sup> a unique label claim among isoxazoline-containing preventives for dogs. NexGard PLUS and NexGard are additionally labeled for prevention of B\u00a0burgdorferi<\/i> infection through the killing of I\u00a0scapularis<\/i> before transmission can occur.11,12<\/sup> NexGard PLUS and NexGard contain the same minimum dosage of the insecticidal component afoxolaner (2.5 mg\/kg).9,10<\/sup><\/span><\/p>\n 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<\/i> gene mutation at up to 5 times the maximum labeled dose.8<\/sup><\/span><\/p>\n 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<\/sup> 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\u00a0caninum<\/i>, Taenia pisiformis<\/i>, and Echinococcus granulosus.<\/i>13<\/sup> Credelio Quattro was initially labeled for prevention of heartworm disease caused by D immitis<\/i> and treatment and control of adult U stenocephala<\/i>, T\u00a0canis<\/i>, and T leonina<\/i>; C felis <\/i>fleas; and 4 tick species: A americanum<\/i>, D variabilis<\/i>, I scapularis<\/i>, and R\u00a0sanguineus.<\/i>13<\/sup> The label has now been extended to include treatment and control of A caninum<\/i> L4 larvae, immature adults, and adult worms.14<\/sup> Compared with moxidectin or pyrantel alone, the combination of the 2\u00a0at the labeled doses showed increased efficacy against A caninum <\/i>L4 larvae.<\/i>15<\/sup><\/span><\/p>\n Credelio Quattro may be prescribed for dogs as young as 8 weeks13<\/sup> and has demonstrated tolerance and safety in microfilaremic dogs infected with adult D immitis<\/i> at up to 3 times the labeled dose.16<\/sup> 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<\/sup><\/span><\/p>\n Credelio Quattro has been shown to be safe in collies with the MDR1<\/i> 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<\/sup> Similarly, NexGard PLUS was well tolerated in dogs with the MDR1<\/i> gene mutation at up to 5 times the maximum labeled dose.8<\/sup> 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<\/sup> These differences may be attributable to the lower maximum dose of moxidectin delivered by Credelio Quattro (40 \u00b5g\/kg) and NexGard PLUS (24\u00a0\u00b5g\/kg) compared with Simparica TRIO (48 \u00b5g\/kg).1,8,13,17<\/sup><\/span><\/p>\n 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<\/i> flea infestations and treatment and control of the ticks I scapularis<\/i>, D\u00a0variabilis<\/i>, and R sanguineus<\/i> for 12 months.18<\/sup> Bravecto Quantum is also labeled for treatment and control of A\u00a0americanum<\/i> for 8 months. With up to 1\u00a0year of ectoparasite control, Bravecto Quantum delivers the longest duration of ectoparasite control for dogs in a single injectable dose.<\/span><\/p>\n 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<\/sup> Bravecto Quantum has demonstrated safety when administered at the labeled dosage.<\/span><\/p>\n 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 (<\/span>TABLE 2<\/b><\/span>).<\/span><\/p>\n In its original 2018 FDA approval, Revolution PLUS (Zoetis, <\/span>zoetispetcare.com<\/span><\/a>) was labeled for prevention of heartworm disease caused by D immitis<\/i> and for treatment and control of Ancylostoma tubaeforme<\/i>, Toxocara cati<\/i>, Otodectes cynotis<\/i>, C felis<\/i> fleas, and 3 tick species: I scapularis<\/i>, A\u00a0maculatum<\/i>, and D variabilis.<\/i>19<\/sup> Subsequently, the label was extended to include A\u00a0americanum,<\/i>20<\/sup> increasing the labeled coverage to 4\u00a0tick species, the highest of any isoxazoline-containing product for cats. Control of A americanum<\/i> 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<\/i>, which can cause an estimated 40% or higher mortality rate in cats despite attempted treatment.21<\/sup> In the most recent label extension, Revolution PLUS was shown to be effective for preventing D caninum<\/i> infection in cats by killing and controlling C felis<\/i> fleas.22<\/sup><\/span><\/p>\n\n
What\u2019s New in Canine Parasiticides?<\/h2>\n
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<\/a><\/p>\nSimparica TRIO<\/h3>\n
NexGard PLUS<\/h3>\n
Credelio Quattro<\/h3>\n
Bravecto Quantum<\/h3>\n
What\u2019s New in Feline Parasiticides?<\/h2>\n
<\/a><\/p>\nRevolution PLUS<\/h3>\n
Bravecto PLUS<\/h3>\n