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


CHEMICAL CLASS of the active ingredient(s): 


PARASITES CONTROLLED* (spectrum of activity): Fleas, heartworms (Dirofilaria immitis) and other roundworms (Toxocara canis, Ancylostoma caninum, Trichuris vulpis)


European Union and other countries

  • Dogs, small ≤4.5 kg = <10 lbs. bw: 1 tablet with 46 mg lufenuron and 2.3 mg milbemycin oxime >(equivalent to >10.2 mg/kg lufenuron and >0.5 mg/kg milbemycin oxime)
  • Dogs, medium 5 to 11 kg11 to 24 lbs. bw: 1 tablet with 115 mg lufenuron and 5.75 mg milbemycin oxime (equivalent to 23.0 - 10.5 mg/kg lufenuron and 1.2 to 0.5 mg/kg milbemycin oxime)
  • Dogs, large 12 to 22 kg 25 to 48 lbs. bw:  1 tablet with 230 mg lufenuron and 11.5 mg milbemycin oxime (equivalent to 19.2 -  10.5 mg/kg lufenuron and 1.0 to 0.5 mg/kg milbemycin oxime)
  • Dogs, very large 23 to 45 kg 49 to 99 lbs. bw:  1 tablet with 460 mg lufenuron and 23 mg milbemycin oxime (equivalent to 20.0 - 10.2 mg/kg lufenuron and 1.0 to 0.5 mg/kg milbemycin oxime)

* Can be slightly different in some countries: read the product label!


  • LD50 (acute oral) in rats: n.a. for the combination tablet. For lufenuron >2000 mg/kg; for milbemycin oxime 980 mg/kg
  • Estimated Hazard Class according to the WHO: not applicable for veterinary medicines

Suspected poisoning? Read the article on lufenuron safety and milbemycin oxime safety in this site.

WARNING !!!: Never use on cats tablets approved only for dogs. Never use on 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:


Risk of resistance? YES, low in:

  • Fleas, mainly the cat flea, Ctenocephalides felis

So far there are no reports on flea resistance to lufenuron, 25 years after its introduction for flea control. However, fleas have developed resistance to several other insecticides (e.g. carbamates, organophosphates and pyrethroids) and are certainly capable of becoming resistant to lufenuron as well. Experience shows that prolonged and uninterrupted use of any insecticide on fleas (including lufenuron) 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 milbemycine 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:

*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.

Learn more about resistance and how it develops.


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

  • Lufenuron: 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: Worldwide, including the USA, the EU, Canada, Australia, etc. In the USA, Canada and other countries under the brand SENTINEL.
GENERIC BRANDS available? YES, but rather few and not in all countries.

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


PROGRAM PLUS (in some countries SENTINEL) is one of NOVARTIS (now ELANCO) follow-up brands of INTERCEPTOR (only milbemycin oxyme) and PROGRAM (only lufenuron), both original brands from NOVARTIS.

The logic of PROGRAM PLUS 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). Lufenuron has no effect whatsoever on the worms, and milbemycin oxime is ineffective against fleas.

Lufenuron is an insect development inhibitor introduced in the lates 1980s (by CIBA-GEIGY → NOVARTIS → ELANCO). It is moderately used in pets, but not in livestock. It is also used in agricultural pesticides. Lufenuron has a systemic mode of action, i.e. after oral administration it get's into the blood of the pet and reaches the fleas during their blood meal. Administered about every 4 weeks it prevents flea infestations by inhibiting the development of eggs and larvae, but only if all the dogs and cats in the same household are treated against fleas. However, since it does not kill adult fleas, it is not suitable for treating established flea infestations.

Milbemycin oxime is a macrociclic lactone introduced in the late 1980s (by CIBA-GEIGY → NOVARTIS → ELANCO). It is abundantly used in pets, but neither in livestock, nor in pesticides for agriculture or for vector control. It 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.

Both for flea and heartworm prevention best results are obtained with this product when administered preventatively starting before the onset of the flea and mosquito season.

Systemic products (tablets for oral administration, 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, 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.

A personal message

I was very heavily involved in the discovery of lufenuron in the 1990s during my years in NOVARTIS AH. Click here if you want to know more about the discovery and development of lufenuron and PROGRAM.


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.