Dr Tracy Douglas
Your guide to this article today is by veterinarian Dr Tracy Douglas Dr Tracy Douglas
Published 14:23 pm

Trifexis for dogs is a duly-approved broad-spectrum anthelminthic with flea-killing and heartworm-protective capabilities. Additionally, Trifexis is primarily used in the management of flea infestations, including the parasites that are carried by adult fleas into the intestines and cardiovascular systems of the dog. Plus, Trifexis is also available in flavorful chewable tablets that can be easily given to puppies as young as 2 months old or dogs that weigh at least 5 pounds.

prevention of heartworm disease - trifexis

Each chewable tablet of Trifexis provides 13.5 milligrams of Spinosad and 0.2 milligrams of Milbemycin oxime for every pound of a dog’s weight. Being an FDA-approved anthelminthic, Trifexis for dogs is only available with a prescription from a duly-licensed veterinarian.


There is a reason why Trifexis is named what it is. Its 3-pronged approach to canine parasite management warrants the use of “Tri’ in its name. Specifically, Trifexis is indicated in the following.

  • Prevention of heartworm disease

Heartworm disease is transmitted by mosquitoes. Sadly, there are no specific species of mosquito that have been identified as the definitive intermediate host of Dirofilaria immitis. However, the use of Trifexis has been proven to be 100% effective against Dirofilaria immitis if given monthly for 4 consecutive months. Less than this and the clinical effectiveness may not be guaranteed.

  • Prevention, treatment, and extermination of fleas

Laboratory studies show that Trifexis for dogs starts killing fleas in as short as 30 minutes after administration. Within the first 4 hours, there was a 100% effectiveness rate that continues until Day 30. The Spinosad component of Trifexis is known to kill adult fleas before these are able to lay eggs. In a course of 3 months, the flea effectiveness of Trifexis was established at 98% to 99.8%. This can lead to a significant reduction in the incidence of skin redness, hair loss, scaling, itching, and dermatitis in dogs with flea allergy dermatitis.

  • Control and treatment of hookworm, roundworm, and whipworm infections

Intestinal parasites can readily infect dogs anytime. Roundworms look more like spaghetti growing up to 4 inches in length while hookworms are shorter. Whipworms are very thin. Intestinal parasites are mostly transmitted by fleas ingested by your dog although other modes of transmission are possible. Trifexis for dogs has been shown in laboratory studies that it is effective in removing at least 90% of adult Ancylostoma caninum hookworms, Trichuris vulpis whipworms, and Toxascaris leonina and Toxocara canis roundworms.

Benefits of Trifexis for Dogs

There are many benefits to using Trifexis for dogs and they are as follows:

  • Trifexis starts killing fleas in as short as 30 minutes.
  • It also kills all fleas (100%) on your dog in as short as 4 hours and continues to do so until the 30th
  • Additionally, Trifexis provides 100% protection against heartworm disease if given monthly for 3 consecutive months.
  • Plus, it kills at least 90% of whipworm, roundworm, and hookworm infections in dogs.
  • Finally, it is safe and very easy to administer as it can and should be mixed with dog food.

How Trifexis For Dogs Works

The mechanism of action of Trifexis is directly related to the individual actions of its two principal components: Spinosad and Milbemycin oxime.

Spinosad has a very unique insecticidal activity. It can kill fleas both on contact and when fleas draw on blood that contains the Spinosad ingredient. It specifically targets the binding sites located on nicotinic acetylcholine receptors. This leads to hyperexcitation of neural transmission by acetylcholine. This results in forceful involuntary contractions or seizures in the flea. With prolonged exposure to Spinosad, the flea experiences prostration leading to paralysis and death. The paralysis is hastened by the secondary action of Spinosad as a GABA receptor agonist.

Milbemycin oxime, on the other hand, works primarily against roundworms, whipworms, and hookworms as well as other intestinal parasites. It is also the active ingredient of Trifexis that is directly responsible for the prevention of heartworm infections. Its mechanism of action is similar to avermectins whereby it opens the chloride channels of nerve cells. These neurons undergo hyperpolarization which then blocks the transmission of electrical signals. This leads to the paralysis of the intestinal parasites causing them to die. Milbemycin oxime is also known to disrupt the transmission of GABA, especially in certain invertebrate organisms.

Potential Side Effects

While Trifexis is considered to be generally safe, there have been incidences of mild to moderate side effects associated with its administration. The most common side effects that were noted included the following:

  • Vomiting
  • Itching or pruritus
  • Weakness or lethargy
  • Loose, soft, or watery stools
  • Signs of skin irritations and inflammation
  • Decreased appetite
  • Reddening of the dog’s outer ears

There have also been reports of more serious adverse reactions, although rare. These include the following:

  • Mild seizures
  • Drooling
  • Disorientation
  • Muscle twitching or tremors

Things You Should Know about Trifexis for Dogs

Trifexis for dogs is an FDA-approved medication for the control and management of flea infestations, heartworm infections, and intestinal worm infections. It is available in chewable tablet formulation and comes in different colors of packaging or boxes to denote the different strengths of the active ingredients Spinosad and Milbemycin oxime. Additionally, Trifexis is a safe and proven effective way for managing heartworms and fleas as well as roundworms, hookworms, and whipworms. It is administered as a once-monthly dosing. Depending on the geographic location of the dog, it may be necessary to administer Trifexis all year round. For maximum effectiveness, Trifexis should always be given with food.

What You Should Tell Your Vet before They Prescribe Trifexis for Dogs

One of the most important things you need to inform your vet before using Trifexis is whether or not your dog has a history of seizures. Also, if you intend on breeding your dog, your vet should know that, too.

How to Give Trifexis to Your Dog

Trifexis should always be administered with food to help ensure maximum effectiveness. The current treatment recommendation for Trifexis is once-monthly dosing with the following dosage guidelines for each pound of your dog’s body weight.

  • 5 milligrams of Spinosad
  • 2 milligrams of Milbemycin oxime

Given that Trifexis is available in various Spinosad-Milbemyxin oxime concentrations as depicted in the coloring of their packaging, you can administer the following Trifexis products depending on the weight of your dog.

  • For dogs weighing 5 to 10 pounds, get the PINK box that contains 140 mg Spinosad and 2.3 mg Milbemycin oxime
  • If your dog weights 10.1 to 20 pounds, get the ORANGE box that contains 270 mg Spinosad and 4.5 mg Milbemycin oxime
  • For dogs weighing 20.1 to 40 pounds, get the GREEN box that contains 560 mg Spinosad and 9.3 mg Milbemycin oxime
  • Dogs weighing 40.1 to 60 pounds, get the BLUE box that contains 810 mg Spinosad and 13.5 mg Milbemycin oxime
  • If your dog weighs 60.1 to 120 pounds, get the BROWN box that contains 1,620 mg Spinosad and 27 mg Milbemycin oxime

For dogs weighing more than 120 pounds, get a combination of boxes that will represent the desired dose. For instance, if you have a 130-pound pooch, then you need a BROWN box and a PINK box.

Further Trifexis Use

To prevent heartworm infestation, it is advised that Trifexis be given every month starting within a month after initial seasonal exposure to mosquitoes. This should continue on a monthly basis until about 3 months from the time your dog was last exposed to seasonal mosquitoes. It is equally important to watch your dog for about an hour after giving Trifexis because there is a tendency that dogs will vomit. If vomiting occurs within 1 hour of Trifexis administration, you should give another dose to your dog at once.

For the prevention and treatment of fleas, Trifexis can be initiated at any time regardless of the season. However, it is recommended that Trifexis treatment is initiated a month before these ectoparasites become fully active. The treatment should be continued on a monthly basis until the termination of the flea season. For flea-endemic areas, year-round treatment is necessary.

For the treatment of roundworms, whipworms, and hookworms, year-round treatment is necessary as dogs can get infected with these intestinal parasites regardless of climate or season.

What to Do If You Miss a Dose of Trifexis for Dogs

In the event that a dose of Trifexis was missed and that the interval between monthly dosing has been exceeded, it is critical that you administer the correct dose immediately. This will help minimize the risk of developing heartworm infections as well as the reinfestation of fleas.

What to Do in Case of Trifexis Overdose

Trifexis is safe for dogs. However, if you do notice something ‘off’ with your dog after administration of the medication, make sure to get in touch with your veterinarian.

trifexis for dogs

Some Trifexis for Dogs Interactions

There have been reports of dogs taking Trifexis that reacted negatively with the concomitant administration of Ivermectin. While there are products that actually have a combination of Ivermectin and Spinosad, it is still best to consult your veterinarian about it. Any concurrent administration with medication, herbal supplement, or even nutraceuticals should be consulted with a vet.

Trifexis for dogs is a broad-spectrum antihelminthic and flea preventative that has amazing insecticidal property against adult fleas and antiparasitic properties against heartworms, whipworms, hookworms, and roundworms. It is duly approved by the FDA for use in dogs and is generally safe, too.


Dr Tracy Douglas
General Practice Veterinarian, currently working at the Glenwood Veterinary Clinic, Glenwood Springs, Colorado. Dr. Douglas began her veterinary career as a Veterinary Nurse in Highton Veterinary Clinic, Highton Victoria, and then as an Emergency Veterinarian in Uintah Pet Emergency, Colorado Springs, Colorado. Tracy is particularly interested in surgery, neurology and internal medicine, which gives her a well-rounded knowledge on animal health and well-being. She received her Doctorate of Veterinary Medicine from the University of Melbourne, while her undergraduate bachelor of science is from the United States Military Academy at West Point, New York.


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