Brand: TRIFEXIS ®
CHEMICAL CLASS of the active ingredient(s):
USA and other countries
- Dogs, 5 to 10 lbs. ≈ 2.3 to 4.5 kg bw: 1 tablet with 140 mg spinosad and 2.3 mg milbemycin oxime (equivalent to 60.9 to 31.1 mg/kg spinosad and 1.0 to 0.5 mg/kg milbemycin oxime)
- Dogs, 10.1 to 20 lbs. ≈ 4.6 to 9.1 kg bw: 1 tablet with 270 mg spinosad and 4.5 mg milbemycin oxime (equivalent to 58.7 to 29.7 mg/kg spinosad and 1.0 to 0.5 mg/kg milbemycin oxime)
- Dogs, 20.1 to 40 lbs. ≈ 9.2 to 18.1 kg bw: 1 tablet with 560 mg spinosad and 9.3 mg milbemycin oxime (equivalent to 60.9 to 30.9 mg/kg spinosad and 1.0 to 0.5 mg/kg milbemycin oxime)
- Dogs, 40.1 to 60 lbs. ≈ 18.2 to 27.2 kg bw: 1 tablet with 810 mg spinosad and 13.5 mg milbemycin oxime (equivalent to 44.5 to 29.8 mg/kg spinosad and 0.7 to 0.5 mg/kg milbemycin oxime)
- Dogs, 60.1 to 120 lbs. ≈ 27.3 to 54.4 kg bw: 1 tablet with 1620 mg spinosad and 27 mg milbemycin oxime (equivalent to 59.3 to 29.8 mg/kg spinosad and 1.0 to 0.5 mg/kg milbemycin oxime)
- Dogs, >120 lbs. ≈ >54.4 kg bw: administer the appropriate combination of tablets
EU and other countries
- Dogs, 3.9 to 6.0 kg ≈ 8.5 to 13.2 lbs. bw: 1 tablet with 270 mg spinosad and 4.5 mg milbemycin oxime (equivalent to 69.2 to 45.0 mg/kg spinosad and 1.2 to 0.8 mg/kg milbemycin oxime)
- Dogs, 6.1 to 9.4 kg ≈ 13.3 to 20.7 lbs. bw: 1 tablet with 425 mg spinosad and 7.1 mg milbemycin oxime (equivalent to 69.7 to 45.2 mg/kg spinosad and 1.2 to 0.8 mg/kg milbemycin oxime)
- Dogs, 9.5 to 14.7 kg ≈ 20.8 to 32.4 lbs. bw: 1 tablet with 665 mg spinosad and 11.1 mg milbemycin oxime (equivalent to 70.0 to 45.2 mg/kg spinosad and 1.2 to 0.8 mg/kg milbemycin oxime)
- Dogs, 14.8 to 23.1 kg ≈ 32.5 to 50.9 lbs. bw: 1 tablet with 1040 mg spinosad and 17.4 mg milbemycin oxime (equivalent to 70.3 to 45.0 mg/kg spinosad and 1.2 to 0.8 mg/kg milbemycin oxime)
- Dogs, 23.2 to 36.0 kg ≈ 51.0 to 79.4 lbs. bw: 1 tablet with 1620 mg spinosad and 27 mg milbemycin oxime (equivalent to 69.8 to 45.0 mg/kg spinosad and 1.2 to 0.8 mg/kg milbemycin oxime)
- Dogs, >36 kg ≈ >79.4 lbs. bw: administer the appropriate combination of tablets, ensuring a dose of 45-70 mg/kg spinosad and 0.75-1.18 mg/kg milbemycin oxime
* Can be slightly different in some countries: read the product label!
- LD50 (acute oral) in rats: n.a. for the tablets. >3600 mg/kg for the spinosad; 980 mg/kg for milbemycin oxime
- Estimated Hazard Class according to the WHO: not applicable for veterinary medicines
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 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.
You may be interested in the following articles in this site dealing with the general safety of veterinary products:
- Safety for humans
- Safety for domestic animals
- Safety for the environment
- Hazard classifications of pesticides
Risk of resistance? YES, low in fleas, mainly the cat flea, Ctenocephalides felis
So far there are no reports on flea resistance to spinosad. However, fleas have developed resistance to several other insecticides (e.g. carbamates, organophosphates and pyrethroids) and are certainly capable of becoming resistant to spinosad as well. Experience shows that prolonged and uninterrupted use of any insecticide on fleas (including spinosad) bears the risk of resistance development.
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.
Alternatives to prevent resistance through product rotation:
- Carbamates (F+T*), e.g. carbaryl, propoxur
- Indoxacarb (F*)
- Insect Development Inhibitors (F*), e.g. lufenuron, methoprene, pyriproxyfen
- Isoxazolines (F+T*), e.g. afoxolaner, fluralaner, sarolaner
- Macrocyclic lactones (F*), e.g. selamectin
- Neonicotinoids (F*), e.g. dinotefuran, imidacloprid, nitenpyram
- Organophosphates (F+T*), e.g. chlorpyrifos, coumaphos, diazinon, fenthionn, etc.
- Phenylpyrazoles (F+T*), e.g. fipronil, pyriprole
- Pyrethroids (F+T*), e.g. cyphenothrin, cypermethrin, deltamethrin, etofenprox, flumethrin, permethrin, etc. toxic to cats!
*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 carbamates, organophosphates and pyrethroids is not uncommon in several countries, including the USA.
Are the active ingredients of this product ORIGINAL* or GENERICS**?
- Spinosad: GENERIC (introduced in the 1990s)
- 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: USA, the EU, Canada, Australia, etc. In Australia under the brand PANORAMIS.
GENERIC BRANDS available? So far not available in most countries.
Click here to learn more about GENERIC vs. ORIGINAL drugs.
The logic of TRIFEXIS is to bring once-a-month flea and heartworm prevention together in one tablet that controls several other common dog roundworms as well (Toxocara canis, Ancylostoma caninum, Trichuris vulpis). Spinosad has no effect whatsoever on the worms, and milbemycin oxime is ineffective against the fleas.
Spinosad is a broad-spectrum insecticide of natural origin introduced in the 1990s (by ELI-LILLY). It is moderately used in pets, rather scarcely in livestock and moderately in agricultural pesticides. It has a systemic mode of action, i.e. after oral administration it gets into the blood of the pet and reaches the fleas during their blood meal. It kills the fleas very fast. 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.
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.
The 4-week treatment interval ensures continuous adequate heartworm prevention as well, a parasite that is transmitted by mosquitoes.
Systemic products (tablets for oral administration, 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:
- The parasite has to bite and suck blood first before it is killed or sterilized.
- 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.