Frontline Plus vs K9 Advantix II vs Advantage II: Which is the Best Topical Flea Medication?

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It seems that there is always a new flea and tick preventative popping up all the time, making it a challenge to know which is the best one to choose.

This article compares Frontline Plus vs Advantix II vs Advantage II flea medications all in one place to make it more convenient for dog owners to select the one that will work best for their dog.

Though all three of these products are topical one-month treatments, they do have their differences.

This article will dive into the different features, side effects, cost, and pros and cons to aid dog parents in making an educated decision when choosing the right flea and tick treatment.

Spoiler Alert: My top pick of the three is K9 Advantix II. It protects against more parasites and repels, not just kills, fleas and ticks.

Frontline Plus Review

  • Active Ingredients: Fipronil and (S)-methoprene
  • Type: Topical
  • Duration: 1 Month

Frontline Plus was first released in 1993 and EPA-approved in 1996[1].

However, the active ingredient in Frontline, fipronil, was initially formulated back between 1985-1987 as a broad-use insecticide.

Frontline is a spot-on flea and tick treatment that eliminates fleas and ticks and kills flea eggs and larvae, preventing the continued life cycle.

Frontline is applied directly to your pup’s skin, where it is absorbed and spreads throughout your dog’s hair follicles and skin.

Fipronil is kept in your dog’s oil glands under your dog’s skin.

Frontline starts killing fleas within 4-8 hours and ticks inside of 12 hours. Additionally, Frontline is an effective treatment against biting lice.

Fleas, ticks, and lice are not required to bite your dog for Frontline Plus to work.

Instead, parasites are eliminated when they come in contact with your dog’s hair and skin.

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24 hours after application Frontline is waterproof. And it is safe to start using Frontline on puppies as young as eight weeks old as well as on pregnant dogs.


  • Kills fleas and ticks on contact
  • Few side effects
  • Fast acting
  • Easy to apply
  • Waterproof
  • Safe for puppies and pregnant dogs


  • Does not repel fleas and ticks

To place your order for Frontline Plus, click here!

For a more in-depth review of Frontline Plus, click here!

K9 Advantix II Review

  • Active Ingredients: Imidacloprid, Permethrin, and Pyriproxyfen
  • Type: Topical
  • Duration: 1 Month

K9 Advantix II is a Bayer Animal Health flea and tick topical treatment.

Advantix II was launched at the North American Veterinary Conference in January of 2011 and became available to the public in March 2011[2].

Bayer was founded in 1867, with its pet products launching in 1919. Over the years, Bayer Animal Health products have been a leading company in keeping our pets healthy.

Advantix is a spot-on flea and tick treatment. After applying it to your dog’s skin, Advantix spreads over the skin, hair follicles, and sebaceous glands to deter and kill pests.

What sets Advantix apart from other flea and tick remedies is that it is also effective against mosquitoes, biting flies, and biting lice.

This is an added advantage to those who enjoy camping and hiking to help keep their canines free of flies and mosquitoes.

Advantix does not just kill parasites, but it also repels them, which is another added benefit to using Advantix over other common flea and tick products.


  • Repels and kills parasites
  • Repels flies, lice, and mosquitos in addition to fleas and ticks
  • Kills on contact; does not require bugs to bite the dog to work
  • Kills fleas within 12 hours


  • More expensive than other topical treatments
  • May cause skin irritation

If you are ready to start repelling fleas, ticks, and mosquitos, click here!

If you instead want to learn more about K9 Advantix II, click here!

Advantage II Review

  • Active Ingredients: Imidacloprid and Pyriproxyfen
  • Type: Topical
  • Duration: 1 Month

Advantage II is a topical flea treatment manufactured by Bayer Animal Health.

Advantage II does not help kill or prevent ticks.

Imidacloprid is the primary active ingredient that works on a flea’s nervous system, paralyzing and killing the parasite.

Pyriproxyfen, the other active ingredient, is an insect growth regulator, meaning that it is responsible for killing the larvae and eggs, discontinuing a flea’s life cycle.

Advantage II kills fleas at all life stages, preventing flea infestations. Though it does not repel fleas, it does kill the fleas on contact, so they do not have to bite your dog to be effective.

Also, Advantage II is a useful option for biting lice. It will kill and prevent lice infestations.


  • Kills fleas and lice on contact
  • Interrupts the parasite’s lifecycle, effectively preventing infestation
  • Is safe to use on puppies as young as seven weeks old
  • Is waterproof after 24-hours of application


  • Is not effective against ticks
  • Does not repel fleas

If you are interested in placing your order for Advantage II, click here!

Frontline vs Advantix vs Advantage Compared

When comparing flea and tick products, it is often helpful to look at the facts side by side.

Below is a chart that compares Frontline vs Advantix vs Advantage, plus a few highlights of which product is best for various categories.

 Frontline PlusK9 AdvantixAdvantage II
Kills Fleas and TicksYesYesFleas Only
Repels Fleas and TicksNoYesNo
Other Parasites Biting LiceLice, Mosquitos, and Biting Flies Biting Lice
Active IngredientsFipronil and (S)-methopreneImidacloprid, Permethrin, and PyriproxyfenImidacloprid and Pyriproxyfen
Prescription Needed?NoNoNo
Waterproof or Water ResistantWaterproof after 24 hoursWaterproof after 24 hoursWaterproof after 24 hours
Price per Month (Based on a Small Sized Dog)$9.59$11.33$10.99
Minimum Age Requirement8 Weeks7 Weeks7 Weeks

Side Effects

Frontline Plus

  • Skin irritation or hair loss 
  • Irritation to the eyes

Advantix II

  • Skin irritation and redness
  • Itchiness
  • Vomiting
  • Diarrhea 
  • Lethargy

Advantage II

  • Skin irritation and redness
  • Redness
  • Vomiting
  • Diarrhea

Which is Safest?

Winner: Frontline Plus

Frontline Plus has the least number of side effects of the three products.

Also, Frontline Plus’s side effects do not include GI upset like its competitors.

Which Works Fastest?

Winner: Frontline Plus

Frontline Plus starts going to work on fleas in just four hours.

Advantix and Advantage both take 12-hours.

Which is Cheapest?

Winner: Frontline Plus

When comparing the three products for small breed dogs, Frontline Plus is the most economical per month.

Which Lasts Longer?

Winner: Tie

All three products last thirty days.

Overall Winner

Winner: K9 Advantix II

All three products are fairly similar. They all:

  • Are topical
  • Last up to thirty days
  • Kill on contact

However, K9 Advantix II stands out above the rest.

I like K9 Advantix II because it repels fleas and other insects, whereas most topical treatments only kill the parasites.

Plus, Advantix is effective against other insects such as mosquitos and biting flies.


I know that Frontline Plus came first for most of the categories, but Advantix II came in as the overall winner.

Though Advantix costs more and has more side effects, it also protects against more parasites and repels them.

That being said, I will say it is not a product I currently use. My oldest dog, Sophie, who is 15.5 years old, uses Frontline because she has several health issues, so I opted for the safest option.

So, although my top pick is not the topical treatment I always use, it just reflects that there isn’t just one optimal solution for all dogs.

Use Frontline Plus if:

  • You have a dog that has health issues
  • You have a dog that is on a lot of medications

Use K9 Advantix II if:

  • You have a healthy dog
  • You do not have cats – Advantix requires cats to stay away from dogs who are treated with Advantix for 48 hours.

Use Advantage II if:

  • You do not have ticks in your area and are looking for a safe product to use around cats.


Is Imidacloprid Considered Toxic to Humans?

Imidacloprid has a low toxicity level to humans but may cause minor reactions such as vomiting, headache, and diarrhea[3]

Is Fipronil Considered Toxic to Humans?

If ingested, Fipronil may cause severe reactions such as tonic-clonic convulsions, paresthesia seizures, pneumonia, and death.

Can You Use Topical Treatments Together?

It is not advised to use multiple flea and tick medications unless recommended by your veterinarian in severe cases.


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