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Trifexis vs Simparica Trio: Comparing These Popular Dog Preventatives

Trifexis and Simparica Trio packaging
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Pet parents know that protection against parasites and heartworm disease is important, but deciding which medication is right for their dog can feel overwhelming. Trifexis and Simparica Trio are two popular parasite control medications used in dogs. They treat a lot of the same parasites, but also have essential differences that make them unique from each other. 

Read on for a full comparison of Trifexis vs. Simparica Trio so you can have informed conversations with your veterinarian about the best choice of parasite control medication for your dog. 

Simparica Trio vs. Trifexis: A Quick Comparison Guide

 TrifexisSimparica Trio 
Type of medicationInternal and external parasite protectionInternal and external parasite protection
Active ingredient(s)Spinosad, milbemycin oximeSarolaner, moxidectin, pyrantel
Used to TreatProtects dogs against heartworm disease, fleas, hookworms, roundworms, whipwormsProtects dogs against heartworm disease, ticks, fleas, roundworms, hookworms
Minimum Age to Start8 weeks of age, must weigh at least 5 pounds8 weeks of age, must weigh at least 2.8 pounds
Available FormsBeef-flavored chewable tabletLiver-flavored chewable tablet
Prescription or OTCPrescription by veterinarian only, may require proof of recent negative heartworm testPrescription by veterinarian only, may require proof of recent negative heartworm test
Dosing FrequencyOnce a monthOnce a month
When Does It Start Working?Starts killing fleas within 30 minutesKills ticks within 8 hours, fleas within 4 hours
PrecautionsShould not be used at the same time as ivermectin. Use with caution in pregnant, lactating, or breeding dogs. Use with caution in dogs with a history of seizures or epilepsy. Possible adverse neurological events including tremors, incoordination, and seizures. Use with caution and under supervision of a licensed veterinarian in dogs with a history of seizures or neurological disorders. Use with caution in pregnant, lactating, or breeding dogs.
Possible Side EffectsMost common adverse reactions include vomiting, decreased activity, itching, decreased appetite, and diarrhea. Most common adverse side effects include vomiting, diarrhea, low energy, and loss of appetite. 
Safe for Long-Term Use?YesYes
FDA approved?YesYes

Key Differences When Comparing Trifexis and Simparica Trio

Both Trifexis and Simparica Trio for dogs are considered to be excellent choices for parasite protection, but there are a few important differences that may make one product better for your dog than the other.

  • Simparica Trio kills five species of ticks, including Brown dog ticks, Gulf Coast ticks, deer ticks, American dog ticks, and Lone star ticks. Trifexis does not kill ticks or prevent ticks.
  • Simparica Trio is FDA approved to prevent infections that may cause Lyme disease.
  • Trifexis for dogs eliminates whipworm infections, Simparica Trio does not.
  • While both products are labeled for puppies 8 weeks of age and older, Simparica Trio can be used in smaller puppies (2.8 pounds) than Trifexis (5 pounds).
  • Simparica uses three ingredients (sarolaner, moxidectin, and pyrantel), Trifexis uses two ingredients (spinosad and milbemycin oxime). 
  • Trifexis starts killing fleas quickly within 30 minutes with 100 percent of fleas dead by 4 hours. Simparica Trio starts killing fleas within 4 hours with 100 percent of fleas dead by 12 hours.
  • Simparica may be prescribed by veterinarians ‘off-label’ to treat mites, including sarcoptic mites, demodex, and ear mites. 
  • While both of these medications are given once a month, Simparica Trio is a little more forgiving because it has a slightly longer window of efficacy than Trifexis. 

Pros and Cons: Trifexis Vs. Simparica Trio

While Trifexis and Simparica Trio have several overlapping benefits, there are some distinct pros and cons to each medication that can help you decide which product to use.

TrifexisKills fleas very quicklyKills whipwormsSpinosad is non-synthetic and derived from bacteria, considered to be a ‘green’ insecticideDoes not protect dogs against ticksCannot be used in dogs who are being treated with ivermectinCan cause nausea in some dogs. If this happens, break the tablet in half and give half the dose in the morning with food and the other half of the dose in the evening with food
Simparica TrioKills both fleas and 5 species of ticksProtects against Lyme diseaseTreats skin mitesSlightly longer window of efficacyShould not be used in dogs with any history of adverse neurological eventsDoes not treat whipwormsHigher price point

Comparing Side Effects of Simparica Trio vs. Trifexis

Both Trifexis and Simparica Trio are known to be safe and effective for most dogs, and are widely prescribed and used by pet parents and the veterinary community. However, Simparica Trio and other drugs in the isoxazoline class come with an FDA warning regarding the potential for neurological side effects, including tremors, incoordination, and seizures, in some pets being treated with these products. If your dog has a history of seizures or a neurological disorder, your veterinarian may err on the side of caution and recommend a flea and tick product that is not in the isoxazoline class.

In general, the incidence of both short-term and long-term side effects is low with both medications, but some dogs may experience gastrointestinal upset that can manifest as decreased appetite, decreased energy, vomiting, and/or diarrhea with either medication. If you notice any side effects in your dog, consult with your local veterinarian. 

Cost Comparison of Trifexis and Simparica Trio

Depending on where you shop, Simparica Trio is on average more expensive than Trifexis. This may be due to the fact that Simparica Trio also kills ticks and Trifexis does not. If you think that Trifexis is a cheaper alternative to Simparica Trio, remember: if your dog needs protection against ticks, you may still end up paying the same amount of money if you purchase Trifexis and a product to protect against ticks. 

Pet insurance may be able to help offset the cost of parasite control medication, but it depends on the policy. If you purchase a basic accident and illness policy, it likely will not cover flea, tick and heartworm medication. If you purchase an insurance policy that includes preventive care, then it likely will cover the cost of parasite control medication. Always read the fine print, and ask your veterinary care team for pet insurance recommendations that include flea, tick and heartworm medication. 

The Bottom Line: Trifexis Vs. Simparica Trio

Both of these medications are well tolerated by most dogs and offer effective, fast protection against fleas, heartworm disease, roundworms, and hookworms. If your dog needs protection against ticks, then Simparica Trio is a better choice. If your dog needs additional protection against whipworms and does not need tick protection, then Trifexis is a better choice. Your veterinarian will be your best resource to ask about what parasite protection your dog needs, and they can also provide valuable advice on whether to use Trifexis, Simparica Trio, or another flea, tick or heartworm medication.