Brand: ACTIVYL ® TICK PLUS
Company: MERCK ANIMAL HEALTH
- INDOXACARB: 150 mg/mL (= 15.00%) in the EU; 130.1 mg/mL (= 13.01%) in the USA
- PERMETHRIN: 500 mg/mL (= 48.00%) in the EU; 425 mg/mL (= 42.5%) in the USA
CHEMICAL CLASS of the active ingredient(s):
- Indoxacarb: OXADIAZINE
- Permethrin: SYNTHETIC PYRETHROID
PARASITES CONTROLLED* (spectrum of activity)
* Can be slightly different in some countries: read the product label!
in the EU
- Dogs, small 1.2 to 5 kg ≈ 2.6 to 11 lbs. bw: 1 pipette with 0.5 mL (equivalent 62.5 to 15.0 mg/kg indoxacarb, 200.0 to 48.0 mg/kg permethrin)
- Dogs, medium 5 to 10 kg ≈11 to 22 lbs. bw: 1 pipette with 1.0 mL (equivalent to 30.0 - 15.0 mg/kg indoxacarb, 96.0 - 48.0 mg/kg permethrin)
- Dogs, large 10 to 20 kg ≈22 to 44 lbs. bw: 1 pipette with 2.0 mL (equivalent to 30.0 - 15.0 mg/kg indoxacarb, 96.0 - 48.0 mg/kg permethrin)
- Dogs, very large 20 to 40 kg ≈44 to 88 lbs. bw: 1 pipette with 4.0 mL (equivalent to 30.0 - 15.0 mg/kg indoxacarb, 96.0 - 48.0 mg/kg permethrin)
- Dogs, extremely large 40 to 60 kg ≈88 to 132 lbs. bw: 1 pipette with 6.0 mL (equivalent to 22.5 - 15.0 mg/kg indoxacarb, 72.0 - 48.0 mg/kg permethrin)
in the USA
- Dogs, small 4.1 to 11 lbs. 1.86 to 5 kg bw: 1 pipette with 0.5 mL (equivalent 54.2 to 13.0 mg/kg indoxacarb, 177.1 to 42.5 mg/kg permethrin)
- Dogs, medium 11.1 to 22 lbs. ≈5 to 10 kg bw: 1 pipette with 1.0 mL (equivalent to 26.0 - 13.0 mg/kg indoxacarb, 85.0 - 42.5 mg/kg permethrin)
- Dogs, large 22.1 to 44 lbs. ≈10 to 20 kg bw: 1 pipette with 2.0 mL (equivalent to 26.0 - 13.0 mg/kg indoxacarb, 85.0 - 42.5 mg/kg permethrin)
- Dogs, very large 44.1 to 88 lbs. ≈20 to 40 kg bw: 1 pipette with 4.0 mL (equivalent to26.0 - 13.0 mg/kg indoxacarb, 85.0 - 42.5 mg/kg permethrin)
- Dogs, extremely large 88.1 to 132 lbs. ≈40 to 60 kg bw: 1 pipette with 6.0 mL (equivalent to 19.5 - 13.0 mg/kg indoxacarb,63.8 - 42.5 mg/kg permethrin)
* Can be slightly different in some countries: read the product label!
- LD50 (acute oral) in rats: >2000 mg/kg (according to MSDS)
- LD50 (acute dermal) in rats: >2000 mg/kg (according to MSDS)
- Estimated Toxicity Class according to the WHO: III Slightly hazardous (based on the LD50, learn more)
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.
Risk of resistance? YES, low to moderate in:
So far there are no reports on flea resistance to indoxacarb. However, fleas have developed resistance to several other insecticides (e.g. carbamates, organophosphates and pyrethroids), including permethrin, and are certainly capable of becoming resistant to indoxacarb as well. Experience shows that prolonged and uninterrupted use of any insecticide on fleas (including indoxacarb) bears the risk of resistance development.
Resistance of brown dog ticks (R. sanguineus) to permethrin and other pyrethrois is not uncommon in many countries, including the USA. Since indoxacarb has no effect whatsoever on brown dog ticks, efficacy and protection against these parasites may be lower than expected.
Alternatives to prevent resistance through product rotation:
- Amitraz (T*): toxic to cats!
- Carbamates (F+T*), e.g. carbaryl, propoxur
- Insect Development Inhibitors (F*), e.g. lufenuron
- 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
- Spinosyns (F*), e.g. spinetoram, spinosad
*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 and brown dog ticks to carbamates and organophosphates is not uncommon in several countries, including the USA.
Are the active ingredients of this product ORIGINAL* or GENERICS**?
- Indoxacarb: GENERIC (introduced in the 2000s)
- Permethrin: GENERIC (introduced in the 1970s)
*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.
ACTIVYL TICK PLUS is MERCK AH's (formerly INTERVET) original once-a-month spot-on brand only for dogs againts fleas and ticks based on indoxacarb, a pesticide licensed from DUPONT. Patent protection for indoxacarb has expired.
COUNTRIES where this product is marketed (maybe under another TM): USA, EU and other countries.
GENERIC BRANDS available? NO; so far no other brands with indoxacarb for use on dogs or cats have been introduced.
Click here to learn more about GENERIC vs. ORIGINAL drugs.
Administered about every 4 weeks, ACTIVYL TICK PLUS controls established flea and tick 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.
Indoxacarb is a broad-spectrum oxadiazine insecticide introduced in the 2000s (by DUPONT). It is used rather modestly in dogs and cats, not at all in livestock antiparasitics, and moderately in pesticides for agriculture and vector control. It is a so-called pro-drug: it becomes toxic only after it is absorbed and transformed inside the organism of selected insect species, mainly through esterase enzymes. The chemical class of the oxadiazines is relatively new, with a mechanism of action that is different from all other insecticides used against fleas. Indoxacarb has no effect whatsoever on ticks.
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 indoxacarb in the formulation does not contribute to their control.
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. But for this product this applies only for fleas, because indoxacarb has no effect whatsoever on ticks.
- 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 48.0%, which results in a dose rate of up to 200 mg/kg. about 40 to 200 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, phenothrin, cyphenothrin (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 support 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.
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