Simparica Trio: Side Effects, Dosage, Alternatives, and More

Most pet parents know to stay on top of heartworm prevention (often after an annual vet visit and a heartworm test), but heartworm isn’t the only parasite that can cause trouble. Fleas, ticks, and intestinal worms can also take a toll on your dog’s health — and long before you notice obvious symptoms.

The good news is you don’t have to wait for scratching, scabs, or stomach issues to take action. Monthly preventives are designed to help stop these parasites before they become a bigger problem. One of the most popular options is Simparica Trio, a prescription chew that covers multiple parasites in one dose.

This guide breaks down everything you need to know about Simparico Trio, including how it works, what to know about dosing and side effects, and which alternatives might make more sense if it’s not the right fit for your dog.

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• What Is Simparica Trio?
• Alternatives to Simparica Trio
• Final Notes

What Is Simparica Trio?

Many diseases and illnesses are easier to prevent than treat, such as heartworm disease, Lyme disease, flea allergies, and intestinal parasites.

Simparica Trio is a prescription preventative medication for dogs designed to protect them from heartworm, ticks, fleas, roundworms, and hookworms. It's one of the most popular flea and tick care products because it protects against many parasites, including potentially deadly heartworms.

It also protects against parasites that can cause Lyme disease in dogs, acting as a three-in-one preventive and dewormer. 

In well-controlled lab studies, Simparica Trio was proven 100% effective in preventing the growth of heartworm in dogs. In addition, if you see dog scabs from fleas and need fast treatment, this is one of the best solutions available. In another study, Simparica Trio was proven to kill fleas in just four hours with an effectiveness of 100% after 8 hours, ultimately killing fleas before they could lay eggs.

And finally, in another study, this medication began killing ticks on dogs within 8 hours, drastically reducing the total number of live ticks in 24 hours.

How does Simparica Trio work?

Simparico Trio combines three active ingredients, each targeting different parasites:

• Moxidectin kills early-stage larvae in the bloodstream before they can mature and damage the heart and lungs.
• Sarolaner disrupts the nervous systems of fleas and ticks after they bite, killing them quickly.

• Pyrantel paralyzes roundworms and hookworms so they lose their grip in your dog’s gut and pass naturally.

Together, these ingredients work from the inside out, giving your dog broad protection with a single monthly chew.

Simparica Trio side effects

Simparica Trio is considered safe and is generally well tolerated in adult dogs. In a field safety and effectiveness study for heartworm prevention, most reported side effects were mild and temporary.

The most common side effects found were:

• Vomiting
• Diarrhea
• Lethargy
• Anorexia
• Increased thirst and urination
• Hyperactivity

Of course, not every medication is right for every dog, so you should contact your vet if your dog has any adverse reactions to this medication, regardless of how mild they may seem.

Simparica Trio dosage & administration

Simparica Trio is an oral medication given once monthly with a recommended dosage depending on body weight. The typical dosage is 0.54mg/lb of sarolaner, 0.011mg/lb moxidectin, and 2.27 mg/lb pyrantel.

Fortunately, you don’t need to do the math yourself. Your vet will prescribe the right strength, and the box lists the weight range so you can double-check it matches your dog. Just make sure you give it on schedule each month, because missed doses can leave gaps in protection — especially risky during peak flea and tick season.

Simparica Trio safety

Even with a well-known preventive like Simparica Trio, a few safety basics still matter. First, it’s for dogs only. Never give it to cats or share medication between pets (Zoetis, the company behind Simparico Trio, has a separate product designed specifically for cats).

If you forget a dose, give it as soon as you remember, then continue with your regular schedule from there. And should your dog not eat the entire chew (say, they spit it out, chew and drop part of it, or vomit soon after), don’t assume they’re covered — call your vet and ask whether to re-dose.

Like with all heartworm medicine, your vet should also test for heartworm before starting, since preventives don’t kill existing adult heartworms. If anything seems off after a dose (like repeated vomiting or diarrhea, extreme lethargy, wobbliness, or symptoms that last more than a day), contact your vet immediately.

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Simparica vs Simparica Trio

Simparica and Simparica Trio sound almost identical, but they’re used for different parasite plans. So how does their coverage stack up?

Simparica covers fleas and ticks only. It’s a practical choice if your dog already takes a separate heartworm preventive, or your vet has you on a two-product plan. It doesn’t prevent heartworm or target intestinal worms, so you’ll need another medication if those risks apply.

Simparica Trio offers broader coverage in a single monthly chew. Along with fleas and ticks, it includes heartworm prevention and treats roundworms and hookworms, which can simplify things if you’d rather not juggle multiple prescriptions.

The best choice comes down to your dog’s lifestyle and your vet’s recommendations. If your dog needs heartworm coverage (most do), Trio is usually the easier one-and-done option. If fleas and ticks are the only concern and you’re handling heartworm another way, Simparica could be just right.

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Why flea and tick protection is so important

Fleas and ticks are sneaky. Your dog can pick them up in less than five minutes outside, and you may not see a single sign until the scratching starts or your dog seems unusually tired and uncomfortable.

With fleas, the issue isn’t just itching. Many dogs react to flea saliva, so even a few bites can trigger nonstop scratching, hot spots, scabs, and hair loss. Heavier infestations can contribute to anemia, especially for puppies and smaller dogs. Dogs can also swallow fleas while grooming, which can lead to tapeworms. As a result, you might notice scooting, an upset stomach, or small rice-like segments around the butt or in the stool.

Ticks come with a different kind of risk. They can spread diseases like Lyme disease, ehrlichiosis, and anaplasmosis while they’re attached. Instead of obvious skin irritation, symptoms can look like limping, fever, unusual tiredness, or stiffness and joint pain. Left untreated, these infections can turn into longer-term problems.

That’s why prevention is everything. Consistent flea and tick protection helps stop parasites before they bite, reproduce, or pass along disease. It’s way easier (and less stressful) to prevent an infestation or infection than to treat one after the fact — for both you and your dog.

Alternatives to Simparica Trio

Because Simparica Trio isn’t always the best fit for every dog, your vet may recommend an alternative. Just pay attention to parasite coverage, since some options leave out heartworm prevention or intestinal worms. Your vet can also help you weigh practical factors like chew vs. topical, side effects, and cost. Here are a few common Simparica Trio alternatives:

NexGard SPECTRA

If you're looking for a monthly preventive that protects your pet from heartworm, ticks, fleas, and intestinal worms, NexGard SPECTRA is a common, cheaper alternative to Simparica Trio. Another monthly chewable tablet, it contains afoxolaner, a flea and tick preventative that eliminates fleas quickly by causing paralysis and subsequent death.

Cat owners should note that NexGard SPECTRA is for dogs only. The feline equivalent is NexGard COMBO, a monthly topical treatment that provides all-in-one coverage against fleas, ticks, heartworm disease, and common intestinal worms.

It's important to remember that not all NexGard products have the same levels of protection. For instance, NexGard chewables only protect against fleas, ticks, mites, and flea tapeworms, while NexGard SPECTRA protects against all of those parasites plus heartworm, hookworm, roundworm, and whipworm.

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Bravecto

Bravecto for dogs only targets fleas and ticks, so you won't get heartworm or intestinal parasite prevention. However, this medication might be a good alternative to Simparica Trio if you already use a heartworm preventive.

Bravecto stands out because it offers 12 weeks worth of protection against fleas and ticks, so you only need to give it to your dog once every three months. 

Bravecto is available in two forms — a chew and a topical solution, giving you options for how to administer it to your pet.

For cats, there’s also Bravecto Plus, which offers two months of protection against fleas, ticks, intestinal worms, and heartworm.

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Revolution Plus

You should never give your cat your dog’s medication, since they require their own formulations. But what you can do is give your cat a preventive created by the same company that brought you Simparica Trio — Zoetis. Revolution Plus is that preventive.

Revolution Plus for cats is a topical solution that prevents parasites, such as fleas, ticks, ear mites, roundworms, hookworms, and heartworms. With just one application a month, you can protect your cat, and it's safe for kittens as young as eight weeks old.

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Sentinel Spectrum

Sentinel Spectrum is another alternative to Simparica Trio for dogs. These monthly chews protect against heartworm disease, dog allergies to fleas, whipworms, hookworms, roundworms, and tapeworms. In a study, Sentinel Spectrum was proven safe for puppies ten weeks or older. In addition, these chews were taste-tested, with results indicating 99% of dogs are willing to eat them.

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Advantage Multi

Advantage Multi is a monthly topical broad-spectrum heartworm, parasite, and flea medicine for dogs. Unfortunately, it doesn't protect against ticks, so you'll need another solution provided by your vet. This alternative to Simparica Trio may be best suited for dogs who don't like receiving oral medications. It doesn't provide as much protection as other alternatives, but one monthly dose has been proven effective at killing worms.

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Get parasite treatment for your pets with Dutch

Simparica Trio covers a lot in one monthly chew, including heartworm prevention, flea and tick protection, and treatment for common intestinal worms. But that doesn’t mean it’s automatically the right choice for every dog.

Factors like age, weight, health history (including seizure concerns), lifestyle, and even how much your dog likes chews can all influence what works best. Your vet can help you confirm whether Simparica Trio is appropriate, choose the correct dose, and decide if an alternative makes more sense.

If keeping up with vet visits or pharmacy runs feels like a hassle, Dutch offers a more convenient option. You can consult with a licensed vet online, get a prescription when appropriate, and have Simparica Trio or another preventive delivered directly to your door, making it even easier to stay consistent with your dog’s parasite protection.

Sign up for Dutch and find out if Simparica Trio is the right fit for your dog.

Simparica Trio FAQs

Where can I buy Simparica Trio?

Simparica Trio is prescription-only, so you’ll need a vet to sign off first. After that, you can buy it through your vet’s office or order it from an online pharmacy. If you’d rather skip an in-person visit, an online vet service like Dutch can connect you with a vet who can review your dog’s medical history and prescribe Simparica Trio if it’s a good fit, and you can get it delivered right to your door.

How long do Simparica Trio side effects last?

Most side effects from Simparica Trio, such as mild vomiting, diarrhea, or lethargy, are temporary and typically resolve within 24 to 48 hours as your dog's system adjusts to the medication. But if symptoms persist beyond a few days, get worse, or if you notice more concerning signs like tremors, seizures, or extreme lethargy, contact your vet right away. In rare cases, neurological side effects may require medical attention and potentially discontinuing the medication.

What if I’m late giving a Simparica Trio dose?

If you’re late giving a Simparica Trio dose, give the missed dose as soon as you remember to restore protection, then resume your regular monthly schedule from that new date. If your dog is significantly overdue (especially in a high-risk region for heartworm or ticks), ask your vet how to safely get back on track (and whether re-testing is needed).

Setting phone reminders or marking your calendar can help maintain consistent monthly dosing, which is essential for continuous protection against heartworms, fleas, ticks, and intestinal parasites.

Does Simparica Trio require a prescription?

Yes, Simparica Trio is prescription-only in the United States, so you’ll need approval from a licensed veterinarian. This requirement exists because your vet needs to evaluate your dog's health status, confirm they're a suitable candidate for the medication, and determine the correct dosage based on their weight and medical history.

Fortunately, that no longer means a stressful in-person vet visit. With an online vet service like Dutch, you can talk to a licensed vet from the comfort of your own home and, if Simparica Trio is recommended, have the medication delivered.

Schedule an appointment with a Dutch vet to get started.

Is Simparica better than Capstar?

Simparica and Capstar address different needs in flea control. Simparica (or Simparica Trio) provides comprehensive monthly protection against fleas, ticks, and in the Trio formulation, heartworms and intestinal parasites. It kills fleas within hours and continues working for 30 days. Capstar, by contrast, is a fast-acting tablet that kills adult fleas within 30 minutes but offers no residual protection — its effects last only 24 hours.

Capstar works well for immediate flea infestations or before starting a long-term preventive, while Simparica is designed for ongoing prevention. Many pet owners use Capstar for quick knockdown during severe infestations, then transition to monthly preventives like Simparica for sustained protection.