FORMULATION: «tablets» for oral administration; may be chewable, flavored, coated, etc., depending on the country


CHEMICAL CLASS of the active ingredient(s):


PARASITES CONTROLLED* (spectrum of activity):



  • Dogs, 2.0 to 3.5 kg bw: 1 tablet with 9.375 mg afoxolaner (equivalent to 4.7 to 2.7 mg/kg afoxolaner) + 1.875 mg milbemycin oxime (equivalent to 0.9 to 0.5 mg/kg milbemycin oxime)
  • Dogs, >3.5 to 7.5 kg bw: 1 tablet with 18.75 mg afoxolaner (equivalent to 5.3 to 2.5 mg/kg afoxolaner) + 3.75 mg milbemycin oxime (equivalent to 1.1 to 0.5 mg/kg milbemycin oxime)
  • Dogs, >7.5 to 15.0 kg bw: 1 tablet with 37.50 mg afoxolaner (equivalent to 5.0 to 2.5 mg/kg afoxolaner) + 7.50 mg milbemycin oxime (equivalent to 1.0 to 0.5 mg/kg milbemycin oxime)
  • Dogs, >15.0 to 30.0 kg bw:1 tablet with 75.0 mg afoxolaner (equivalent to 5.0 to 2.5 mg/kg afoxolaner) + 15.0 mg milbemycin oxime (equivalent to 1.0 to 0.5 mg/kg milbemycin oxime)
  • Dogs, >30.0 - 60 kg bw kg bw: 1 tablet with 150.0 mg afoxolaner (equivalent to 4.7 to 2.3 mg/kg afoxolaner) + 30.0 mg milbemycin oxime (equivalent to 1.0 to 0.5 mg/kg milbemycin oxime)



  • LD50 (acute oral) in rats: n.a. for the tablets.
  • 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. 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 safety and on milbemycin oxime safety in this site.

WARNING !!!: Never use on cats tablets approved only for use on dogs, and vice-versa. Never use on cats or small dogs tablets approved for large dogs. Learn more about tablets and their safety.

WARNING 1! All heartworm preventatives contain macrocyclic lactones (e.g. 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 (ivermectin, milbemycin oxime, moxidectin, selamectin, etc.) in the USA, reported particularly in Louisiana. 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.

Afoxolaner has been introduced in 2014. It belongs to the isoxazolines (together with fluralaner, the active ingredient of BRAVECTO), a new chemical class of insecticides recently discovered, from which afoxolaner and fluralaner are the first commercial products at all. 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 tablets. Resistance of fleas to carbamatesorganophosphates and synthetic pyrethroids is not uncommon in several countries, including the USA.

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.

Learn more about resistance and how it develops.


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

  • Afoxolaner: ORIGINAL (introduced in 2013, first described by DU PONT DE NEMOURS)
  • Milbemycin oxime: GENERIC (introduced in the 1980s)

*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 SPECTRA is a once-a-month tablet for flea + tickroundwormheartworm prevention for dogs introduced by MERIAL. It is the logic development after the introduction of NEXGARD with afoxolaner, "only" against fleas & ticks.

Afoxolaner brings the efficacy against external parasites (fleas & ticks) and has no effect on worms. Milbemycin oxime brings the efficacy against roundworms, including heartworm prevention, and has no efficacy against external parasites at the dose administered.

NEXGARD SPECTRA is not an all-in-one tablet: important dog parasites are not controlled, e.g. mites, lice, mosquitoes, tapeworms and several important dog roundworms (e.g. Angiostrongylus vasorum, Crenosoma vulpis, Uncinaria stenocephala, etc.). And there are other tick species in Europe that can infect dogs in addition to the ones controlled by this product, e.g. Dermacentor marginatus, Dermacentor pictusHaemaphysalis spp, Hyalomma spp, Rhipicephalus bursa, etc. In fact, for the time being, there is no such an all-in-one monthly tablet or spot-on available for dogs or cats.

Afoxolaner is a broad spectrum insecticide and acaricide belonging to the isoxazolines that was introduced for use in pets in the 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.

Milbemycin oxime is a macrocyclic lactone effective against roundworms and some external parasites that was introduced in the late 1980s (by CIBA-GEIGY → NOVARTIS → ELANCO). It is exclusively used in pets, not in livestock or agriculture. It too has a systemic mode of action. After oral administration to dogs milbemycin oxime is quickly and almost completely absorbed. Peak plasma concentration is reached 2 to 4 hours later, and subsequently declines with a half-life of 1-3 days. Bioavailability is about 80%. As a general rule, due to a different pharmacokinetic behavior the anthelmintic effect is longer for milbemycin oxime than for ivermectin, although this strongly depends on the delivery form and the administered dose. A monthly treatment ensures adequate control of the roundworm species mentioned and prevents development of heartworm microfilariae.

The launch of NEXGARD and NEXGARD SPECTRA by MERIAL was quite interesting. After decades of dominating the pet flea+tick control market with the FRONTLINE product line based on monthly topical spot-ons, MERIAL introduced oral tablets, which for decades were considered as less attractive than topical spot-ons. After the launch of NEXGARD, "only" against fleas & ticks, came NEXGARD SPECTRA, a tablet effective also against roundworms and for heartworm prevention. But to this aim MERIAL preferred generic milbemycin oxime over its own ivermectin, which has dominated heartworm prevention for decades with their HEARTGARD product line. The reason is most likely the fact that milbemycin oxime is less toxic than ivermectin, which allows a higher dose that ensures both heartworm prevention and control of roundworms, with a lower risk of adverse reactions in dogs susceptible to macrocyclic lactones. Ivermectin alone (HEARTGARD ) prevents heartworms, but the dose has to be that low to prevent adverse reactions, that it does not control roundworms and has to be complemented with a nematicide, typically with pyrantel (HEARTGARD PLUS).

Systemic products (e.g. tablets for oral administration or injectables) have several general advantages over topical products (spot-on, insecticide-impregnated collars, shampoos, soaps, sprays, powders, etc):

  • They do not contaminate the pet's hair coat: avoiding contact with the pets after administration is not necessary for children or adults.
  • The active ingredient reaches the parasites through the blood, everywhere in the pet's body, whereas topical products may leave some body parts (e.g. the ears, between the legs, etc.) insufficiently protected.
  • Efficacy is independent from exposure to dirt, sun, shampooing, washings, rain, baths, dirt, etc., whereas topical products can be washed away, or broken down by sunlight, etc.

But they have also a few disadvantages:

  • External parasites have to bite and suck blood first before they are killed or sterilized., i.e. they may transmit several diseases before they are killed.
  • Orally administered products (tablets, suspensions, pastes, etc.) may be vomited and treatment needs to be repeated.
  • Administration of tablets may be less convenient than administration of spot-ons.
  • The choice of products for oral or injectable administration is smaller than for topical administration.

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.