Trifexis for Dogs: A Medication to Prevent Fleas and Worms

Trifexis (spinosad / milbemycin oxime) is a medication that prevents parasites in dogs. It combines two powerful preventatives: spinosad and milbemycin oxime.

Trifexis comes in a beef-flavored tablet and is only available via prescription. It prevents fleas, heartworms, and intestinal worms in dogs when given monthly.

Read on to learn more about Trifexis and how it may help your dog. 

Trifexis for dogs at a glance

What is Trifexis for dogs, and how does it work?

Trifexis is a commonly prescribed medication that prevents parasites in dogs. It’s approved by the FDA and given by mouth. It contains two different medications: spinosad and milbemycin oxime. 

Spinosad is a flea preventative also found in Comfortis. It circulates in a dog’s bloodstream for one month, and fleas that bite the dog ingest it. The medication affects a flea’s nervous system and causes it to die without harming the dog. 

Milbemycin oxime is a common heartworm and intestinal parasite preventative for dogs. You may know it by the name Interceptor. It prevents heartworm infection if given once a month. It also protects against three different intestinal worms: hookworms, roundworms, and whipworms. 

What is Trifexis used for in dogs?

When given monthly, Trifexis prevents these five common parasites in dogs: 

• Fleas: These parasites can cause significant skin disease in dogs. 

• Heartworms: These parasites are spread by mosquitoes. They mature into spaghetti-like worms that lodge in the blood vessels in a dog’s heart and lungs. It’s expensive and risky to treat heartworms. If left untreated, they can be deadly. 

• Hookworms: Hookworms attach to the lining of a dog’s intestines, sucking the dog’s blood. They can cause intestinal inflammation, diarrhea, and anemia (blood loss).  

• Roundworms: These worms live in a dog’s intestine, feeding off partially digested food. Roundworms cause diarrhea and weight loss. 

• Whipworms: Whipworms live in the large intestine and can cause inflammation, bloody diarrhea, and electrolyte imbalances.

How is Trifexis given for dogs?

Trifexis for dogs comes as a chewable, flavored tablet. It’s availables in several different sizes and is prescribed by a veterinarian based on your dog’s weight.

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You should give your dog Trifexis with a full meal. This improves absorption and makes the medication more effective. 

What are the common side effects of Trifexis in dogs?

Trifexis’ most common side effects include: 

• Vomiting

• Diarrhea

• Decreased appetite

• Lethargy

Giving Trifexis with a full meal can lower the risk of side effects. If your dog doesn’t feel well after taking Trifexis, reach out to your veterinarian. They may recommend a different medication to prevent parasites. 

What are the most serious risks of Trifexis for dogs?

The most serious risks of Trifexis involve dogs who already have heartworms or who have seizures. 

Giving Trifexis to a dog with a heartworm infection can kill off the heartworms in their bloodstream. This can cause severe illness or even death. To protect your pup, veterinarians recommend a heartworm test before giving Trifexis for the first time. Yearly testing is recommended for dogs taking Trifexis long term. 

Trifexis may increase the risk of seizures in dogs with epilepsy. Your veterinarian may recommend a different medication to prevent parasites if your dog has a history of seizures.

Does Trifexis interact with any other dog medications?

Trifexis may interact with the following medications: 

• Amitriptyline

• Antifungal medications, such as fluconazole or ketoconazole

• Cimetidine

• Cyclosporine

• Digoxin

• Diltiazem

• Fluoxetine

• Loperamide

• Spironolactone

• Tetracycline

Interactions between Trifexis and these medications are more common in dogs with the MDR1 mutation. This genetic mutation is most common in collies and other herding breeds. These dogs can safely take Trifexis. But they are more likely to have interactions if they take Trifexis with medications from the list above.

Make sure your veterinarian is aware of any medications your dog is taking. This includes prescription medications, over-the-counter remedies, and supplements. 

Don’t combine Trifexis with other flea, heartworm, or intestinal parasite preventatives. 

What should you do if your dog misses a dose of Trifexis?

If your dog misses a dose of Trifexis, you should give the missed dose as soon as possible. Then, adjust your dog’s Trifexis schedule going forward. 

For example, if you normally give Trifexis on the first of the month but forget to give it until the 15th, give your dog’s future doses on the 15th of the month. 

If your dog misses multiple doses of Trifexis, talk to your veterinarian. Your dog may need a heartworm test before taking Trifexis again, depending on how much time has passed since their last dose.

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Written by:

Catherine Barnette, DVM

Catherine Barnette, DVM, is a small animal veterinarian with 14 years of experience providing preventive care, medical workups, and surgical services in a number of general veterinary practices. She also served on her county's board of health for several years and taught biology laboratories for college students.

Edited by:

Renée Fabian, MA

Renée Fabian is the senior pet health editor at GoodRx. She’s worked for nearly 10 years as a journalist and editor across a wide range of health and well-being topics.

Reviewed by:

Ghanasyam Bey, DVM

Ghanasyam Bey, DVM, is from Cleveland, Ohio, and attended Princeton University for undergraduate studies. After a year of biology research at Duke University, he attended Ohio State College of Veterinary Medicine.

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