Company: ELANCO

FORMULATION: chewable «tablets»


CHEMICAL CLASS of the active ingredient(s):


PARASITES CONTROLLED* (spectrum of activity)


EU: ≥20 mg/kg

  • Dogs, 1.4 to 2.8 kg bw: 1 tablet with 56 mg lotilaner + 2.11 mg milbemycine oxime (equivalent to ~40.0 to ~22.0 mg/kg lotilaner + ~1.51 to ~0.75 mg/kg milbemycin oxime)
  • Dogs, >2.8 to 5.5 kg bw: 1 tablet with 112 mg lotilaner + 4.22 mg milbemycine oxime (equivalent to ~38.6 to ~20.4 mg/kg lotilaner + ~1.46 to ~0.77 mg/kg milbemycin oxime)
  • Dogs, >5.5 to 11 kg bw: 1 tablet with 225 mg lotilaner + 8.44 mg milbemycine oxime (equivalent to ~40.2 to ~20.5 mg/kg lotilaner + ~1.51 to ~0.77 mg/kg milbemycin oxime)
  • Dogs, >11 to 22 kg bw: 1 tablet with 450 mg lotilaner + 16.88 mg milbemycine oxime (equivalent to ~40.5 to ~20.5 mg/kg lotilaner + ~1.52 to ~0.77 mg/kg milbemycin oxime)
  • Dogs, >22 - 45 kg bw: 1 tablet with 900 mg lotilaner + 33.75 mg milbemycine oxime (equivalent to ~40.7 to ~20.00 mg/kg lotilaner + ~1.53 to ~0.75 mg/kg milbemycin oxime))
  • Dogs, >45 appropriate combination of tablets


  • 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.

WARNING on macrocyclic lactones. 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 is affected 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 on heartworm prevention. 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. Preventatives may kill a few adult worms, but won't kill all of them. 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 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. Ask your veterinary doctor.

Most heartworm preventatives contain macrocyclic lactones at a dose that kills microfilariae and ensures adequate protection for about 1 month, i.e. treatment has to be repeated monthly. In endemic regions with mild to warm climate it is recommended to treat the pets during the whole year, because mosquitoes can be infective the whole year through.

Suspected poisoning? Read the articles on lotilaner safety and 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.

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


Risk of resistance development?

Lotilaner has been introduced in 2017. It is the forth isoxazoline to be introduced, four years after the first one, afoxolaner (the a.i. of NEXGARD). Isoxazolines are a new chemical class of insecticides recently discovered, and are so far used mainly in dogs. 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 flea, tick or mite resistance to isoxazolines yet. 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.

Resistance of fleas to carbamatesorganophosphates and synthetic pyrethroids is not uncommon in several countries, including the USA.

There are reports of resistance or tolerance of heartworm microfilariae (Dirofilaria spp) to ivermectin and other macrocyclic lactones in the USA (mainly in the South), probably including milbemycin oxime as well. This has happened after about 20 years of very intensive use of such compounds there. This may happen elsewhere as well. Currently there are no other once-a-month treatments for heartworm prevention other than those containing macrocyclic lactones.

These alternative products may not be available in all countries, or may not be available as tabets.

Learn more about resistance and how it develops.


Are the active ingredients of this product ORIGINAL* or GENERICS**? ORIGINAL (introduced in 2017 by ELANCO)

  • Lotilaner: ORIGINAL (introduced in 2017 by ELANCO)
  • Milbemycin oxime: GENERIC (introduced in le lates 1980s by CIBA-GEIGY)

*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.


CREDELIO PLUS from ELANCO is once-a-month chewable tablet for flea + tick + roundworm control (incl. heartworm prevention) in dogs.

Lotilaner is a broad-spectrum insecticide and acaricide belonging to the isoxazolines introduced in 2017 (by ELANCO). It has a systemic mode of action, i.e. after oral administration it gets into the blood of the pet and reaches fleas and ticks during their blood meal. Full efficacy (>95%) against fleas is achieved within 4 hours of attachment for one month after product administration. Fleas on the animal prior to administration are killed within 6 hours. For adult ticks, the onset of effect (death) is about 48 hours. Administered monthly, CREDELIO PLUS 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. Lotilaner has no effect whatsoever on parasitic worms.

It must be considered that there are other tick species in Europe and in the USA 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. It is not known whether CREDELIO PLUS controls such tick species as well.

Milbemycin oxime is a macrociclic lactone introduced in the late 1980s (by CIBA-GEIGY → NOVARTIS → ELANCO). It is a systemic broad-spectrum nematicide effective against roundworms and some external parasites. 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. Milbemycin oxime has no effect whatsoever on fleas and ticks.

Systemic products (e.g. tablets for oral administration or injectables) have several general advantages over topical products (spot-ons, 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, 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, tick, lice and/or mite and worm 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.