FORMULATION: «spot-on» solution for topical administration on the back of the animals (also called pipettes, squeeze-ons, drop-ons, etc.)


CHEMICAL CLASS of the active ingredient(s):


PARASITES CONTROLLED* (spectrum of activity)

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


  • Dogs, small <4.5 kg ≈ >10 lbs. bw: 1 pipette with 0.4 mL (equivalent >7.8 mg/kg imidacloprid, >0.4 mg/kg mg/kg pyriproxyfen, >39.1 mg/kg permethrin)
  • Dogs, medium 4.5 to 9.1 kg11 to 20 lbs. bw: 1 pipette with 1.0 mL (equivalent to 19.6 - 9.7 mg/kg imidacloprid, 1.0 - 0.5 mg/kg pyriproxyfen, >97.8 - 48.4 mg/kg permethrin)
  • Dogs, large 9.1 to 25 kg 21 to 55 lbs. bw:  1 pipette with 2.5 mL (equivalent to 24.2 - 8.8 mg/kg imidacloprid, 1.2 - 0.4 mg/kg pyriproxyfen, 120.9 - 44 mg/kg permethrin)
  • Dogs, very large >25 kg ≈ >55 lbs. bw: 1 pipette with 4.0 mL (equivalent to <14.1 mg/kg imidacloprid, <0.7 mg/kg pyriproxyfen, <70.4 mg/kg permethrin)

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


  • LD50 (acute oral) in rats: 1660->2000 mg/kg (according to MSDS)
  • LD50 (acute dermal) in rats: >2000 mg/kg (according to MSDS)
  • Estimated Toxicity Class according to the WHO: II Moderately hazardous (based on the LD50, learn more)

Suspected poisoning? Read the articles on imidacloprid safety, permethrin safety and pyriproxyfen safety in this site. 

WARNING !!!: Never use on cats pipettes approved only for dogs. Permethrin is toxic to cats! Never use on small dogs pipettes approved for large dogs. Learn more about spot-ons and their safety.

You may be interested in the following articles in this site dealing with the general safety of veterinary products:


Risk of resistance? YES, low to moderate in:

So far there are no reports on flea resistance to imidacloprid, more than 20 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 imidacloprid as well. Experience shows that prolonged and uninterrupted use of any insecticide on fleas (including imidacloprid) bears the risk of resistance development. There are no reports on resistance of fleas to pyriproxyfen either.

Resistance of mosquitoes to pyrethroids (including permethrin) is widespread worldwide, including in the USA. This is mostly not due to the use of pyrethroids on pets, but to large scale spraying of pyrethroids for vector control or pest control in agriculture. As a consequence protection provided by this product against mosquitoes may be lower or shorter than expected, considering also that neither imidacloprid nor pyriproxyfen are effective against mosquitoes.

Resistance of brown dog ticks (R. sanguineus) and stable flies to permethrin and other pyrethrois is not uncommon in many countries, including the USA. Since neither imidacloprid nor pyriproxyfen have any affect on brown dog ticks or stable flies, protection against these parasites may be lower than expected.

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 spot-ons.

Resistance of fleas, mosquitoes, brown dog ticks to carbamates and organophosphates 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**?

  • Imidacloprid: GENERIC (introduced in the 1990s)
  • Permethrin: GENERIC (introduced in the 1970s)
  • Pyriproxyfen: 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.

K9 ADVANTIX II is a BAYER's original follow-up brand of ADVANTAGE. But patent protection for imidacloprid and all other constituents has expired.

COUNTRIES where this product is marketed (maybe under another TM): USA.
GENERIC BRANDS available? YES, in some countries, with a more or less comparable composition

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


K9 ADVANTAGE II is a follow-up product for BAYER's ADVANTAGE, its first imidacloprid once-a-month spot-on for dogs and cats against fleas.

Administered about every 4 weeks, K9 ADVANTIX II controls established flea infestations and prevents flea populations to develop in the pets environment, but only if all the dogs and cats in the same household are treated against fleas. It also kills chewing lice (Trichodectes canis) and several tick species.

Imidacloprid is a broad-spectrum neonicotinoid insecticide introduced in the 1990s (by BAYER). It is abundantly used in pets, but very scarcely in livestock. It is massively used in agriculture and quite abundantly also against household pests. Imidacloprid in this formulation has no effect whatsoever on ticks, mosquitoes and biting flies.

Permethrin is a veteran synthetic pyrethroid introduced in the 1970s (by several companies). It is also a broad-spectrum non-systemic insecticide and acaricide massively used in pets, livestock, hygiene and agriculture worldwide. There are thousands of products with permethrin world-wide. It is effective against ticks, fleas and certain lice species of dogs, but has also a certain repellent effect against mosquitoes, ticks and flies. However, resistance of some of these parasites to permethrin and other pyrethroids is not uncommon, in the USA and elsewhere. This means that protection against these parasites due to permethrin may be lower or shorter than expected, particularly against mosquitoes, because the imidacloprid the formulation does not contribute to their control.

Pyriproxyfen (Nylar) is a veteran insect development inhibitor introduced in the 1980s (by SUMITOMO) scarcely used in pets and not at all in livestock. It is also used moderately in agriculture and vector control. In this product it stops development of flea eggs and larvae. It has no protective effect whatsoever against fleas, ticks, mosquitoes, and biting flies. Its task is to ensure that if a few fleas survive the killing effect of the flea adulticides (what usually happens) development of their offspring is inhibited, because the eggs of the surviving fleas will not develop further.

This combination of two or more active ingredients of different chemical classes makes also sense regarding resistance prevention, because it means attacking fleas through two different mechanisms of action, which is vastly assumed to help preventing or at least delaying resistance development.

Nowadays, after imidacloprid has lost patent protection, generic brands are abundant in some countries (e.g. in Latin America), but not everywhere (e.g. not or only very few in the USA or the EU).

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 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.
  • 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 systemic products is independent from these factors.

This product is one of many examples of a questionable practice regarding the use of pyrethroids at very high concentrations on pets, mainly on dogs. Photostable pyrethroids (including permethrin, cypermethrin, deltamethrin, cyphenothrin, phenothrin, etc.) can have a dose-dependent irritant effect on mammals. Most of them are toxic to cats at the therapeutic dose used on dogs. Pyrethroid-related irritation is a well-known problem in livestock. Ready-to-use pour-ons are frequently used on cattle, comparable to ready-to-use spot-ons por dogs, but usually at a concentration of 1%-5% active ingredient and at a much lower dose of 1-5 mg/kg. Even at this dose some cattle show signs of irritation, particularly dairy cows and calves. In this particular dog spot-on permethrin is delivered at a concentration of 44.0%, which results in a dose rate of up to 89.8 mg/kg for a 2 kg dog, and a dose of up to 115 mg/kg for a 9.5 kg dog, about 20 to 100 times more than on cattle. It is not surprising that not all dogs tolerate such a dose, particularly small breeds, puppies and weaker animals (sick, stressed, old). 

A comparable situation occurs with amitraz for dogs (and cats, to which amitraz is also toxic). There are no amitraz ready-to-use pour-ons for cattle, because cattle just don't tolerate it at high concentrations. Instead there are topical amitraz sprays or dips that are applied to cattle at concentrations of ~0.025% (250 ppm = mg/L), which results in a dose of 3-5 mg/kg body weight. Even at this dose cattle may not tolerate amitraz and show undesirable side-effects (sedation, depression, etc). Spot-ons for dogs may contain up to 10% amitraz and can result in doses of up to 45 mg/kg body weight! Chihuahuas and puppies are particularly at risk of amitraz side-effects.

It is also not surprising that such products erroneously administered to cats can be deadly.

In fact, serious problems with adverse reactions after use of certain spot-ons have been reported in the USA, especially on cats and small dogs. According to a report by the EPA from 2010, most problems occurred with spot-ons containing permethrin, phenothrincyphenothrin (all are synthetic pyrethroids) and amitraz, not approved for use on cats but erroneously used on them. There have been also numerous overdosing cases of small dogs, apparently because some users buy large vials for large dogs but use them several times in smaller dogs to save money. It seems also that small dogs are more sensitive than large ones and don't tolerate the treatment as well as large ones. It also seems that some insufficiently investigated inert ingredients (e.g. solvents) in the formulations are not as harmless as they were supposed to be.

Deeper information on the misuse of synthetic pyrethroids in dogs and pets can be found in: Anadón et al. 2009. Use and abuse of pyrethrins and synthetic pyrethroids in veterinary medicine. The Veterinary Journal 182, 7-20.

My personal opinion is that the fierce competition for market share in this largest and most profitable veterinary market has pushed some companies to take too many risks in order to launch products that are "different" to those of their competitors. In fact it has become very difficult to be "new" or really "superior" in a market driven mainly by generic active ingredients during the last decade. Once one company has taken the risk, others will follow and launch their "me-too" brand, to be sure they don't miss an opportunity.

For an overview and a list of the most popular pet antiparasitics for flea, tick, lice and/or mite 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. 

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