Brand: OVITROL ® X-TEND for DOGS
FORMULATION: «spot-on» solution for topical administration on the back of the animals (also called pipettes, squeeze-ons, drop-ons, etc.)
- ETOFENPROX: 300 mg/ml (=30.0%)
- METHOPRENE: 36.0 mg/mL (=3.6%)
- Piperonyl Butoxide (=PBO): 50 mg/kg (=5%): no direct therapeutic effec
CHEMICAL CLASS of the active ingredient(s):
- Etofenprox: PYRETHROID
- Methoprene: JUVENILE HORMONE ANALOGUE
- PBO: SYNERGISTS
PARASITES CONTROLLED* (spectrum of activity)
* Can be slightly different in some countries: read the product label!
- Dogs, small 6 to 12 lbs. ≈ 2.7 to 5.4 kg bw: 1 tube with 1.5 mL (equivalent to 166.7 - 83.3 mg/kg etofenprox, 20 to 10 mg/kg methoprene)
- Dogs, medium 13 to 31 lbs. ≈ 5.9 to 14 kg bw: 1 tube with 3.0 mL (equivalent to 152.5 - 64.3 mg/kg etofenprox, 18.3 to 7.7 mg/kg methoprene)
- Dogs, large 32 to 55 lbs. ≈ 14.5 to 25 kg bw: 1 tube with 4.5 mL (equivalent to 93.1 - 54.0 mg/kg etofenprox, 11.2 to 6.5 mg/kg methoprene)
- Dogs, very large 56 to 80 lbs. ≈ 25.5 to 36 kg bw: 1 tube with 6.0 mL (equivalent to 70.3 - 50.0 mg/kg etofenprox, 8.4 to 6.0 mg/kg methoprene)
- Dogs, extremely large ≥81 lbs. ≈ ≥36.5 kg bw: 1 tube with 9.0 mL (equivalent to ≤74 mg/kg etofenprox, ≤8.9 mg/kg methoprene)
* Can be slightly different in some countries: read the product label!
- LD50 (acute oral) in rats: >5000 mg/kg (estimate based on the LD50 of the active ingredient)
- Estimated Hazard class calculated according to the WHO: U unlikely to present acute hazard (based on the LD50, learn more)
Suspected poisoning? Read the articles on etofenprox safety and methoprene safety in this site.
WARNING !!!: Never use on cats pipettes approved only for dogs or vice-versa. 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:
- Safety for humans
- Safety for domestic animals
- Safety for the environment
- Hazard classifications of pesticides
Risk of resistance? YES, significant for:
- fleas, mainly the cat flea, Ctenocephalides felis
- brown dog ticks, Rhipicephalus sanguineus
Resistance to pyrethroids (including etofenprox) is common in fleas and mosquitoes worldwide, and in brown dog ticks (Rhipicephalus sanguineus) in some countries (e.g. the USA, Panama, Brazil and Spain). Mosquito resistance is mostly due to large scale spraying of pyrethroids for vector control or pest control in agriculture. As a consequence protection provided by this product against fleas, mosquitoes and brown dog ticks may be lower or shorter than expected.
This product contains piperonyl butoxide (= PBO), a synergist that has no direct effect on the parasites, but is supposed to neutralize pyrethroid resistance causeed by enhanced detoxifixation through mixed function oxidase (MFO) enzymes. PBO inhibits these enzymes. However detoxification through MFOs is only one among several possible resistance mechanisms (e.g. other detoxifying enzymes, target site insensitivity, reduced penetration, behavioral change, etc). This means that the chance that the added synergist overcomes resistance to etofenprox in fleas, mosquitoes and ticks is rather modest. And it is impossible to know in advance whether they will work or not.
So far there are no reports on resistance of fleas to methoprene.
Alternatives to prevent resistance through product rotation:
- Amitraz (T*): toxic to cats!
- Carbamates (F+T*), e.g. carbaryl, propoxur
- Indoxacarb (F*)
- 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 be not available as spot-ons.
Resistance of fleas and brown dog ticks 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 ORIGINAL* or GENERICS**?
- Etofenprox: GENERIC (introduced in the 1980s)
- Methoprene: GENERIC (introduced in the 1970s)
- PBO: GENERIC (introduced in the 1940s)
*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 (maybe under another TM): USA
GENERIC BRANDS available? YES, perhaps not with the same composition
Click here to learn more about GENERIC vs. ORIGINAL drugs.
OVITROL X-TEND for dogs is a once-a-month flea+tick spot-on from VET-KEM combining etofenprox (kills fleas, kills and repels ticks and mosquitoes) with methoprene that inhibits the development of fleas.
Administered about every 4 weeks 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/repels brown dog ticks (Rhipicephalus sanguineus) and mosquitoes.
Etofenprox is a veteran broad-spectrum insecticide and acaricide pyrethroid introduced in the 1980s (by MITSUI). It is abundantly used in agriculture and against household pests. It is effective against fleas, ticks and mosquitoes. However, resistance of fleas and mosquitoes to pyrethroids is not uncommon, in the USA and elsewhere. This means that protection against these parasites may be lower or shorter than expected.
Methoprene (also called (S)-methoprene) is a veteran insect development inhibitor introduced in the 1970s (by ZOECON) used moderately in pets and agriculture. It has no effect whatsoever on ticks, only on fleas. The logic of adding an IGR is to ensure that if a few fleas survive the killing effect of etofenprox (what usually happens), development of their offspring is inhibited because the eggs of the surviving fleas will not develop.
The combination of more than one active ingredient of different chemical classes makes also sense regarding resistance prevention, because it means attacking fleas or ticks through two or more different mechanisms of action, which is vastly assumed to help preventing or at least delaying resistance development.
As previously mentioned, the synergists in the formulation (PBO) has neither a direct effect on fleas, ticks or mosquitoes, nor enhance the efficacy of etofenprox. The chance that it neutralizes resistance to etofenprox is very modest.
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. Etofenprox is less toxic and irritant than other synthetic pyrethroids, but adverse drug reactions are not surprising when administered at such high doses as in this case.
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 etofenprox is delivered at a concentration of 30.0%, which results in a dose rate of up to up to ~167 mg/kg, about 30 to >100x 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 an EPA report 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 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 "new" or at least "different" to those of their competitors. In fact it has become very difficult to be "new", really "superior" or simply "different" 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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