FORMULATION: «spot-on» for topical administration


CHEMICAL CLASS of the active ingredient(s):


PARASITES CONTROLLED* (spectrum of activity):




  • Cats, 0.8 to <2.5 kg bw: 1 pipette with 0.3 ml (containing 3.60 mg esafoxolaner + 1.20 mg eprinomectin + 24.90 mg praziquantel)
  • Cats, 2.5 to <7.5 kg bw: 1 pipette with 0.9 ml afoxolaner (containing 10.80 mg esafoxolaner + 3.60 mg eprinomectin + 74.70 mg praziquantel)



  • LD50 (acute oral) in rats: n.a. for the spot-on.
  • Estimated Hazard Class according to the WHO: not applicable for veterinary medicines

In September 2018 the FDA of the USA has alerted pet owners and veterinarians about potential neurological adverse events following the use of products containing isoxazolines in dogs. In August 2021 the DFA has extended this alert to cats. Some treated animals have experienced adverse events such as muscle tremors, ataxia (lack of voluntary coordination of muscle movements), and seizures. This regards all products containing isoxazolines. Most treated animals will not show such adverse drug reactions, but some may be affected.

Suspected poisoning? Read the articles on afoxolaner safetyeprinomectin safety and praziquantel safety in this site.

WARNING !!!: Never use on cats products approved only for use on dogs, and vice-versa. Never use on cats or small dogs products approved for large dogs.

WARNING 1! All heartworm preventatives contain macrocyclic lactones (e.g. eprinomectin, ivermectin, milbemycin oxime, moxidectin, selamectin), which must be handled very carefully on dogs. The reason is that dogs of some breeds do not tolerate macrocyclic lactones or other medicines (e.g. emodepside) that can cross the blood-brain barrier. They can suffer more or less serious adverse effects if treated at dose rates slightly higher than the recommended ones. Consequently dosing must be as accurate as possible. This is the case for Collies and related breeds, which have a mutation in the MDR-1 gene that affects the blood-brain barrier and makes it more permeable to such compounds than in dogs without this mutation. Besides Collies, other dog breeds have shown similar problems, although the MDR-1 mutation has not been confirmed in all of them. The breeds more affected by this mutation are (% frequency): Collie (70%), Long-haired Whippet (65%), Australian Shepherd (50%, also mini),  McNab (30%), Silken Windhound (30%), English Shepherd (15%), Shetland Sheepdog (15%), English Shepherd (15%), German Shepherd (10%), Herding Breed Cross (10%). Other less affected breeds are: Old English Sheepdog, Border Collie, Berger Blanc Suisse, Bobtail, Wäller. The only way to be sure that a dog breed is affected by this mutation or not, is to test for it. As more dogs are tested it is likely that the mutation is discovered in other breeds, or that the frequencies change.

WARNING 2! Heartworm preventatives stop development of microfilariae to adult worms but do not cure infections with adult worms. These preventative medicines are different from those curative anthelmintics that kill the adult worms. But preventatives may kill a few adult worms. If this happens, such dead worms may block lung vessels, which can be seriously harmful, even fatal for the pet. Consequently, heartworm preventatives are usually not administered to pets that are already infected with adult worms (hence the need for periodic diagnostic tests), because the risk of serious complications is real. The infection has first to be treated with adequate curative anthelmintics before preventative products are administered. This is however not trivial, and also risky for the same reason.

General information on the safety of veterinary antiparasitics is available in specific articles in this site (click to visit):


Risk of resistance development? YES

There are reports on resistance of Dirofilaria heartworms to macrocyclic lactones (e.g. eprinomectinivermectin, milbemycin oxime, moxidectin, selamectin, etc.) in the USA, reported particularly in the South. In this region, this means that if a heartworm preventative fails to achieve the expected efficacy, chance is real that it is due to resistance. Elsewhere and for the time being, if a heartworm preventative fails to achieve the expected efficacy, chance is very high that either the product was unsuited for the control of Dirofilaria heartworms, or it was used incorrectly. However, resistance cannot be excluded. And considering the massive use of macrocyclic lactones worldwide for heartworm prevention, it wouldn't be surprising that resistance emerges in other regions in the next years.

Alternatives to prevent heartworm resistance through product rotation: Currently there are no alternative active ingredients for rotation that ensure monthly heartworm prevention: all available products belong to the macrocyclic lactones that have the same mechanism of action.

Afoxolaner has been introduced in 2014. It belongs to the isoxazolines, a new chemical class of insecticides recently discovered. Isoxazolines have a mode of action that is different from all other insecticides currently used against fleas or ticks, and shows no cross-resistance with them. Consequently there are no reports on resistance to isoxazolines. However, fleas have developed resistance to several other insecticides (e.g. carbamatesorganophosphates and synthetic pyrethroids) and are certainly capable of becoming resistant to isoxazolines as well. Experience shows that prolonged and uninterrupted use of any insecticide on fleas bears the risk of resistance development.

Alternatives to prevent flea resistance through product rotation:

*F = effective against fleas; T = effective against ticks.

These alternative products may not be available in all countries, or may not be available as spot-ons. Resistance of fleas to carbamatesorganophosphates and synthetic pyrethroids is not uncommon in several countries, including the USA.

There are no reports on resistance of cat tapeworms to praziquantel..

Learn more about resistance and how it develops.


Are the active ingredients of this product ORIGINAL* or GENERICS**?

  • Esafoxolaner: ORIGINAL (introduced in 2014 by MERIAL, first described by DU PONT DE NEMOURS)
  • Eprinomectin: GENERIC (introduced in the 1990s by MERIAL)
  • Praziquantel: GENERIC (introduced in the 1970s by BAYER)

*Meaning that they are still patent protected and generics are not yet available
**Meaning that they have lost patent protection and may be acquired from manufacturers of generic active ingredients other than the holder of the original patent

COUNTRIES where this product is marketed: EU

Click here to learn more about GENERIC vs. ORIGINAL drugs.


NEXGARD COMBO is a once-a-month spot-on for flea + tickearmite + roundwormtapeworm control and heartworm prevention in cats.

NEXGARD COMBO is not an all-in-one product, but almost. Some cat parasites are not controlled, e.g.mites other than earmites and lice. In fact, for the time being, there is no such a really all-in-one monthly tablet or spot-on available for dogs or cats.

Esafoxolaner brings the efficacy against external parasites (fleas & ticks) and has no effect on worms. Eprinomectin brings the efficacy against roundworms, including heartworm prevention, but not against tapeworms, and at the recommended dose has no efficacy against external parasites. Praziquantel is effective against tapeworms but not against roundworms or external parasites.

Esafoxolaner is the purified S-enantiomer of afoxolaner, a broad spectrum insecticide and acaricide belonging to the isoxazolines that was introduced for use in pets in the mid 2010s (by MERIAL). It has a systemic mode of action, i.e. after oral administration it gets into the blood of the pet and reaches the fleas and ticks during their blood meal. It starts to kill fleas about 8 hours and ticks about 48 hours after administration. Administered about every 4 weeks it controls established flea infestations and prevents flea population development in the pets environment, but only if all the dogs and cats in the same household are treated against fleas. Ticks are killed during about 4 weeks after treatment.

Eprinomectin is a macrocyclic lactone introduced in the 1990s (by MERIAL). It also has a systemic mode of action. It is effective against roundworms (including heartworm microfilariae), but not at all against tapeworms, fleas or ticks (at the recommended dose). For decades it was used exclusively on cattle. Eprinomectin has a similar spectrum of activity as ivermectin.

Praziquantel is a veteran isoquinoline anthelmintic introduced in the 1970s (by BAYER). It is still the most effective and most vastly used parasiticide against tapeworms, both in pets and livestock, but has no efficacy against roundworms or external parasites. There are hundreds of antiparasitic brands for pets containing praziquantel, but rather few as a spot-on.

Topical products (mainly spot-ons and insecticide-impregnated collars) have some advantages over systemic products (mainly tablets for oral administration and injectables):

  • Most topical products kill or sterilize the external parasites before they bite and suck blood on the pet, whereas systemic products kill or sterilize the parasites only after their blood meal.
  • Topical products cannot be vomited.
  • Spot-ons and collars are very convenient to administer.
  • There is a larger choice of topical products.

But topical products have also some disadvantages:

  • Topical products contaminate the pet's hair coat and it is advisable for children and also adults to avoid contact with the pet for several days after treatment.
  • Non systemic topical products may not control parasites in some parts of the pet's body (e.g. the ears, below the tail, between the legs, etc.), whereas systemic products reach the blood-sucking parasites through the blood wherever they are.
  • Efficacy of topical products may be reduced or shortened through exposure to dirt, sun, shampooing, washing, rain, baths, etc., whereas efficacy of orally administered products is independent from these factors.

For an overview and a list of the most popular pet antiparasitics for flea & heartworm control click here.


This article IS NOT A PRODUCT LABEL. It offers complementary information that may be useful to veterinary professionals and users that are not familiar with veterinary antiparasitics. 

Information offered in this article has been extracted from publications issued by manufacturers, government agencies (e.g. EMEA, FDA, USDA, etc.) or in the scientific literature. No guarantee is given on its accuracy, integrity, sufficiency, actuality and opportunity, and any liability is denied. Read the site's DISCLAIMER.

In case of doubt contact the manufacturer or a veterinary professional.