Brand: FRONTLINE ® COMBO

Company: MERIAL 


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

ACTIVE INGREDIENT(S)*:

  • FIPRONIL: 100 mg/mL (=10%), in some countries 98 mg/mL (=9.8%)
  • METHOPRENE
    • 90 mg/mL for dogs and puppies (=9.0%), in some countries 88 mg/mL (=8.8%)
    • 120 mg/mL for cats and kittens (=12.0%), in some countries 118 mg/mL (=11.8%)

CHEMICAL CLASS of the active ingredient(s):


INDICATIONS: DOGS and CATS

PARASITES CONTROLLED* (spectrum of activity)

  • Fleas
  • Ticks
  • Chewing lice (Felicola subrostratus, Trichodectes canis)

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


RECOMMENDED DOSE*:

  • Dogs, small 2 to 10 kg = ≤22 lbs. bw: 1 pipette with 0.67 mL (equivalent to 33.5 - 6.7 mg/kg fipronil + 30.2 - 6.0 mg/kg methoprene)
  • Dogs, medium 10 to 20 kg23 to 44 lbs. bw: 1 pipette with 1.34 mL (equivalent to 13.3 - 6.7 mg/kg fipronil + 11.9 - 6.0 mg/kg methoprene)
  • Dogs, large 20 to 40 kg 45 to 88 lbs. bw:  1 pipette with 2.68 mL (equivalent to 13.3 - 6.7 mg/kg fipronil + 11.9 - 6.0 mg/kg methoprene)
  • Dogs, very large >40 kg =>88 lbs. bw: 1 pipette with 4.02 mL (equivalent to ≤10.0 mg/kg fipronil and ≤9.0 mg/kg methoprene)
  • Cats 1 kg =≥2.2 lbs. bw: 1 pipette with 0.5 mL (equivalent to ≤50.0 mg/kg fipronil and ≤60.0 mg/kg methoprene)

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


SAFETY

  • LD50 (acute oral) in rats: 750 mg/kg (according to MSDS)
  • LD50 (acute dermal) in rats: >5000 mg/kg (according to MSDS)
  • Estimated Hazard class calculated according to the WHO: II Moderately hazardous (based on the LD50, learn more)

Suspected poisoning? Read the article on fipronil safety in this site. Methoprene is an insect development inhibitor virtually non-toxic to dogs, cats, humans and other mammals. 
WARNING !!!: Never use on cats pipettes approved for dogs. 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:


RESISTANCE PREVENTION

Risk of resistance? YES, low to moderate for:

So far there are only very few confirmed reports on flea resistance to fipronil, 25 years after its introduction for flea control. But there are rumors that the number of product failures is increasing, mainly in the US. Fleas have developed resistance to several other insecticides (e.g. carbamates, organophosphates and pyrethroids) and are certainly capable of becoming resistant to fipronil as well. Experience shows that prolonged and uninterrupted use of any insecticide on fleas (including fripronil) bears the risk of resistance development.

There are no reports on resistance of brown dog ticks to fipronil, but moderate resistance to pyrethroids has been reported in several countries (e.g. Brazil, Panama, Spain, USA).

So far there are no reports on flea resistance to methoprene.

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 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 US.

Learn more about resistance and how it develops.


MARKETING

Are the active ingredients ORIGINAL* or GENERICS**?

  • Fipronil: GENERIC (introduced in the 1990s)
  • Metophrene: 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.

COUNTRIES where this product is marketed (maybe under another TM): Worldwide, including the US, the EU, Australia, etc.
GENERIC BRANDS available? YES, by the dozens, with a more or less comparable composition

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


COMMENTS

FRONTLINE COMBO (in some countries FRONTLINE PLUS) is the combination of fipronil (kills fleas and ticks) with methoprene (inhibits the development of fleas). It is a follow-up product for FRONTLINE TOP SPOT, MERIAL's original fipronil spot-on formulation without methoprene introduced in th 1990s.

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. It also kills several tick species (e.g. Dermacentor spp, Ixodes spp, Rhipicephalus sanguineusAmblyomma americanum, etc,) and chewing lice (Felicola subrostratus, Trichodectes canis).

Fipronil is a broad-spectrum insecticide and acaricide belonging to the phenylpyrazoles introduced in the late 1980s (by RHÔNE MÉRIEUX → MERIAL). It is massively used in pets and agriculture, and also moderately used against household pests and in some countries in livestock too.

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 combining active ingredients is to ensure that if a few fleas survive the killing effect of fipronil (what usually happens) development of their offspring is inhibited, because the eggs of the surviving fleas won't developed.

This combination of two 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 fipronil lost patent protection there are dozens of flea spot-ons for dogs and cats with generic fipronil, alone or in several mixtures with other active ingredients. But not all the brands are available in all countries.

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.

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


DISCLAIMER

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.

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