Sarolaner, moxidectin, and pyrantel for dogs

Disclaimer: This information is provided for educational purposes only and should not replace professional veterinary advice. Always consult with your veterinarian before starting, stopping, or changing any medication for your pet. Your veterinarian can determine whether this medication is appropriate for your pet’s specific condition and health status.

Content review: This content has been written and reviewed by licensed veterinary professionals. For complete prescribing information, consult the official product labeling or speak with your veterinarian.

Simparica Trio is an FDA-approved parasite control product that’s indicated for the treatment and prevention of fleas, several tick species, and two types of intestinal worms. Simparica Trio also prevents heartworm disease. Guidelines from both the Companion Animal Parasite Council (CAPC) and the Canadian Parasitology Expert Panel (CPEP) emphasize the importance of regular protection against heartworms, fleas, ticks, and intestinal parasites, given their prevalence and the health risks they pose to both pets and people.

Simparica Trio is a flavored, chewable tablet that contains the active ingredients sarolaner, moxidectin, and pyrantel. It prevents heartworm disease, treats and prevents fleas, prevents tapeworms, and treats and controls roundworms, hookworms, and certain species of ticks. Simparica Trio also prevents Lyme disease by killing carrier ticks. The chewable tablets are given once a month to dogs and puppies eight weeks of age and older and weighing 2.8 pounds or greater. Simparica Trio is manufactured by ZoetisⓇ and is available by veterinary prescription only.

Important safety information: Sarolaner belongs to the isoxazoline class of drugs. The FDA reports that this class of drug has been associated with neurologic adverse effects, like tremors, ataxia, and seizures. Seizures have been reported in dogs receiving isoxazoline-class drugs, even in dogs without a history of seizures. Caution is advised when prescribing this drug for dogs with a history of seizures or neurological disorders. Research into a potential link between isoxazolines and seizures is ongoing, and experts continue to evaluate safety data to better understand these reports. The overall consensus is currently that isoxazolines are generally safe and effective when used as directed.

Simparica Trio contains a combination of three active ingredients to combat several specific parasites.

Sarolaner

Sarolaner works by rapidly killing adult fleas and certain tick species after they bite a dog who has taken the medication orally within the previous 30 days. Your veterinarian may prescribe Simparica Trio to your dog for flea and tick treatment or prevention.

Flea populations thrive because a single female can lay dozens of eggs every day, allowing infestations to grow quickly if fleas are not controlled. Sarolaner works by interrupting a flea’s nerve and muscle function. This loss of motor control greatly reduces the chance of fleas mating and laying eggs, leading to a reduction in the number of new fleas in the environment.

For sarolaner to be most effective, all pets in a household must be considered in the flea treatment or prevention plan. The right approach can vary depending on whether you have dogs, cats, or other pets because the safety of a product is different for each species. Since veterinary experts often recommend year-round flea and tick protection for all dogs, products containing sarolaner are commonly prescribed as part of an ongoing prevention strategy.

Studies show that rapid elimination of adult fleas reduces allergen exposure, which may lead to improvement in flea allergy symptoms. This includes a reduction of hair loss, itchiness, and skin infection and redness. Since flea saliva is a common allergen, vets often recommend preventatively treating dogs who have allergic dermatitis for fleas year-round.

Sarolaner also protects dogs against several common tick species, including the deer tick, which can spread the bacteria that causes Lyme disease. By killing ticks quickly, Simparica Trio helps prevent Lyme disease infections. Simparica kills several tick species, including the lone star tick, Gulf Coast tick, American dog tick, brown dog tick, and Asian longhorned tick.

Sarolaner also helps prevent tapeworm infections by eliminating fleas, which can carry tapeworm larvae.

Moxidectin

Moxidectin is one of several medications in the macrocyclic lactone family that are used to prevent heartworm disease. Other examples include ivermectin, selamectin, and milbemycin oxime.

Moxidectin in a monthly preventative does not treat adult heartworms. Dogs that already have adult heartworms need a different treatment plan, which is why regular testing and uninterrupted prevention are important.

Pyrantel

Pyrantel is an antiparasitic medicine that’s been used safely in dogs and cats for decades. In Simparica Trio, pyrantel’s role is to treat and control common intestinal worms: Toxocara canis and Toxascaris leonina (roundworms), and Ancylostoma caninum and Uncinaria stenocephala (hookworms). Not only are these parasites harmful to dogs, some can also spread to people, which is why routine deworming and prevention are important.

Pyrantel acts as a neuromuscular blocker in intestinal worms, which causes prolonged contraction of the worm’s muscles. This leads to spastic paralysis, meaning the worm can no longer move or stay attached to the intestinal wall. Once paralyzed, the worm passes out of the dog’s body through normal bowel movements.

When given monthly, the pyrantel in Simparica Trio removes existing roundworm and hookworm infections in dogs and helps prevent these parasites from persisting in their intestines.

Off-label use* notice: While Simparica Trio is FDA approved specifically for the treatment and prevention of fleas, some tick species, roundworms, and hookworms, and the prevention of heartworms, tapeworms, and Lyme disease, veterinarians may prescribe it for additional conditions beyond its approved indications, including:

• Demodectic mange
• Sarcoptic mange
• Ear mites
• Off-label use means using an FDA-approved medication at a dosage or for a condition or species that differs from what appears on the official drug label. Some geographical jurisdictions may differ in their official drug labels. While veterinarians often prescribe medications for off-label uses based on their clinical judgment, your veterinarian can determine whether this medication is appropriate for your pet’s specific needs.

Simparica Trio is given orally to dogs every 30 days. It can be given with or without food. The tablets are not scored, which means splitting them is not advised. Careful observation of your dog is important to ensure they have eaten the entire dose.

Simparica Trio comes in different sizes of chewable flavored tablets. The tablets are flavored with pork liver to give them a better taste. Because of this, they are not appropriate for dogs on a food allergy trial that excludes pork or for those with a known pork allergy. Packages are available with one, three, or six tablets. Each package is color coded to distinguish between tablet sizes.

Flea prevention and treatment

For flea prevention, dosing can begin at any time of year. Veterinary guidelines in the United States recommend year-round flea and tick prevention for all dogs, while Canadian recommendations vary by region and season, with year-round protection advised in higher-risk areas.

Simparica Trio is only effective against adult fleas, not flea eggs, larvae, or pupae. Approximately 30 days after administration, the medication wears off, so if monthly doses aren’t continued on time, the dog is at risk for new exposures and existing infestations can quickly rebound. Simparica Trio should be administered once a month for at least three months so that enough fleas that are newly hatched from the pupae are killed before they can mature and reproduce, breaking the flea life cycle.

With an existing flea infestation, treating all household pets for fleas is critical to eliminating environmental sources and preventing reinfection. The approach can vary depending on whether you have dogs, cats, or other pets, since products and safety differ by species.

Tapeworm prevention

For tapeworm prevention, treatment with Simparica Trio may begin at any time of year. Simparica Trio should be given once a month year-round or started at least one month before fleas become active.

Prevention and control of ticks and intestinal worms

For tick prevention and control, Simparica Trio should be given once a month year-round or at least one month before ticks become active. For treatment of roundworm and hookworm infections, Simparica Trio can be given as a single dose. For ongoing control, monthly doses may be prescribed.

Prevention of heartworm disease

Simparica Trio can be prescribed for heartworm prevention. Heartworms are parasitic worms transmitted to dogs by mosquitoes. Simparica Trio kills heartworms in their early larval stage. Dogs can be dosed year-round or at least one month before their first seasonal exposure to mosquitoes. Because Simparico Trio works by killing the larvae picked up during the previous month, dosing of Simparica Trio should continue until at least one month after the dog’s last exposure to mosquitoes.

If replacing another monthly heartworm preventative product with Simparica Trio, the first dose of Simparica Trio should be given within one month of the last dose of the former medication.

Always follow the directions on the drug label provided by your veterinarian.

Simparica Trio is tolerated well in most dogs.

During clinical studies, common (1–15 percent of dogs) reported adverse effects of using Simparica Trio include:

• Vomiting
• Diarrhea
• Lethargy
• Appetite loss (anorexia)
• Increased urination (polyuria)
• Restlessness and agitation (hyperactivity)
• Increased thirst (polydipsia)

Adverse effects in clinical studies that are reported as rare or of unknown frequency include:

• Neurological symptoms, including seizures

Adverse effects that have been reported since market introduction (from most to least frequently reported) include:

• Vomiting
• Diarrhea (with and without blood)
• Seizure
• Lethargy
• Loss of appetite (anorexia)
• Muscle tremors
• Wobbliness or lack of coordination (ataxia)
• Non-specific behavioral changes
• Itchy skin (pruritus)

Understanding side effects

Reading through the list of side effects may feel alarming, but it’s important to understand how these lists are created. In clinical studies, every symptom that occurs is recorded, whether or not the medication is the cause. For example, if a dog develops diarrhea while in a trial, it must be noted, even if the diarrhea was due to something unrelated. Dogs receiving a placebo often show the same kinds of symptoms. Scientists compare these groups carefully to determine whether a medication is safe and effective.

Reported side effects are those that are reported to Zoetis by a veterinary professional or pet owner who has administered Simparica Trio. Though the reported symptoms are seen after giving the medication, it’s very difficult to reliably confirm that the medication is the direct cause.

The list of side effects is comprehensive, but it doesn’t mean your dog is likely to have them. If you’re still unsure, your vet can help you weigh the risks and benefits for your unique situation.

Are side effects more likely to happen with the first dose?

Some side effects appear soon after the first dose because this is the first time the body has been exposed to this drug. Others may not emerge until a medication is used for a longer period of time. Even if a symptom appears shortly after starting a new medication, your vet may need to investigate further to determine whether the medication is truly the cause.

What should I do if I notice changes in my pet right after starting a new medication?

If your pet shows new symptoms after starting a medication, veterinary input is important for understanding whether the change is related to the drug or some other cause. This is especially important if you see serious signs needing urgent action, like:

• Difficulty breathing
• Trouble standing up
• Severe vomiting or diarrhea
• Pale gums
• Seizures
• Collapse

These symptoms are rarely related to sarolaner, moxidectin, or pyrantel, but they almost always indicate a need for immediate emergency veterinary care. Decisions about stopping, adjusting, or switching a medication are safest when made with guidance from your veterinarian.

Where can I find more information?

The drug label and package insert contain the most significant information, including the list of side effects seen during scientific studies. These studies are done in a controlled environment to limit external factors from influencing the data. Clinical studies are designed to carefully measure both the benefits and potential risks of a medication in a controlled environment.

For more details about Simparica Trio, visit the Zoetis website.

There are no known contraindications for using Simparica Trio with other medications. However, studies are limited. Always check with a veterinarian before giving your pet any new medications and make sure they are aware of all other medications and supplements you give your pet.

Various research studies show Simparica Trio to have a strong safety profile. Overall, Simparica Trio is well tolerated in dogs, but as with any medication, some dogs may be at higher risk for side effects than others. Your veterinarian can determine whether Simparica Trio is right for your dog. Main concerns include:

• Species and age: Simparica Trio is not for use in puppies under eight weeks of age.
• Weight: Simparica Trio is not for use in dogs weighing less than 2.8 pounds.
• Breed: Some herding breeds, like collies and Australian shepherds, can carry a genetic mutation called MDR1 that makes them sensitive to high doses of certain antiparasitic drugs. The moxidectin in Simparica Trio is given at a low preventative dose for heartworm, not the higher doses that can cause problems. According to the product’s prescribing information, collies with the MDR1 mutation tolerated Simparica Trio well, even when given three times the recommended monthly dose, with no observed neurological side effects. This means Simparica Trio is considered safe for these breeds when used as directed. If you have a herding breed or MDR1-positive dog, your veterinarian can help confirm the best prevention option for your dog.
• Existing and pre-existing health conditions: Dogs should be tested for heartworm disease before starting Simparica Trio. According to the product’s prescribing information, Simparica Trio has been shown to be safe when given to heartworm-positive dogs. Because it contains sarolaner, veterinarians may use extra caution in dogs with a history of seizures or other neurologic disorders. If your dog has an ongoing medical condition, always check with your veterinarian before starting any new medication.
• Pregnancy and nursing: Simparica Trio has not been tested for safety in pregnant or lactating dogs.

Veterinarians can take into account your dog’s specific health condition and circumstances. If at any time you have questions or concerns about the safety of a medication for your dog, your veterinarian can provide professional guidance tailored to your and your dog’s unique situation and needs.

There are important safety details you need to follow if you give your dog medications that contain sarolaner, moxidectin, or pyrantel.

Human safety

• Not for human use; keep out of reach of children.
• In case of accidental eye contact, flush immediately with water and seek medical attention if necessary.
• In case of accidental ingestion, seek medical attention immediately.

Storage

• Simparica Trio should be stored at or under 30° Celsius (86° Fahrenheit).
• Do not use after the expiration date on the label.
• Dispose of unused or expired medication according to local regulations or as directed by your veterinarian or pharmacist.

Use and administration

• Use Simparica Trio only as directed by a veterinarian, and follow the label instructions exactly. The medication should not be stopped and doses should not be skipped unless directed to do so by a veterinarian.
• Verify that your pet’s species, age, and weight match the prescribed dose.
• Don’t give Simparica Trio to a dog with a known allergy to sarolaner, moxidectin, pyrantel, or any other ingredients listed.
• Don’t give Simparica Trio to your dog if they have an allergy to pork or are in a food allergy trial that excludes pork.
• Don’t give Simparica Trio to a cat.

Overdosage

Contact your veterinarian or a poison control center immediately if your dog receives more than the prescribed amount of Simparica Trio.

Talk to your vet

Before starting Simparica Trio, your vet needs to know if your dog has ever had:

• Seizures or other neurological symptoms
• Heartworm disease
• Frequent upset stomach or other medical problems
• A previous adverse reaction to sarolaner, moxidectin, or pyrantel

Your vet needs to be aware of every medication and supplement your dog receives, including over-the-counter (OTC) products. This information helps prevent drug interactions, avoids duplicate therapies, and guides safe dosing and monitoring. It’s also important to let your vet know if your dog is pregnant, nursing, or you plan to breed your dog.

Accidental ingestion by people or other pets

Veterinary prescription medications are directly prescribed for an individual pet. Before prescribing a medication, a vet can take into account their species, weight, age, physical examination, and previously existing conditions, among other details. It’s unsafe to give a veterinary prescription to a human or to an animal other than the pet it’s prescribed for.

If another pet of any species, including another dog, accidentally receives or ingests the medication, contact a veterinarian, or poison control center immediately for advice.

For complete safety and handling information, including situations when it might be harmful to use this medication, see the package insert for the specific product containing sarolaner, moxidectin, or pyrantel.

Emergency contacts:

• Pet Emergency: Contact your local emergency veterinary clinic
• Pet Poison Helpline: (855) 764-7661 (fee may apply)
• ASPCA Animal Poison Control: (888) 426-4435 (fee may apply)
• Human Poison Control: Contact your local poison control center or emergency services
• FDA Adverse Event Reporting: Report suspected adverse reactions to the FDA Center for Veterinary Medicine at 1-888-FDA-VETS or online at www.fda.gov/reportanimalae
• To report a suspected adverse reaction to a veterinary drug in Canada, contact the Veterinary Drugs Directorate (VDD) by calling 1-877-838-7322 or emailing pv-vet@hc-sc.gc.ca
• Manufacturer: Contact Zoetis Services: Canada: 800-461-0917 US: 1-888-Zoetis1 (1-888-963-8471) UK: 0345 300 8034 or visit https://www.zoetis.com/contact-us

If a dose is missed, it can be given as soon as possible and then continued on the regular monthly schedule from there. Do not give double doses or extra doses.

Based on your pet’s individual circumstances and condition, your vet may recommend other kinds of medications and products in addition to or in place of Simparica Trio. Your vet may also take into account ease of administration when recommending an alternative to Simparica Trio.

Alternatives in the same family as sarolaner (isoxazolines)

Isoxazolines are a group of modern flea and tick medications that work in a similar way (they kill parasites on your dog after the parasite bites). Common options include sarolaner (Simparica), afoxolaner (NexGardⓇ/NexGard PLUSⓇ), fluralaner (BravectoⓇ chews and some topical forms), and lotilaner (CredelioⓇ, with newer US combos including Credelio Quattro™). All of these target fleas and several tick species, but they differ in dosing schedules, tick-species coverage, and add-on protections.

Most are monthly, while some fluralaner products protect for up to 12 weeks for certain ticks. Some products bundle heartworm and intestinal worm prevention (e.g., Simparica Trio, NexGard PLUS, Credelio Quattro), while single-ingredient versions focus on fleas and ticks only. Age/weight minimums and exact label claims vary by product and country, so the “best fit” depends on your dog’s size, lifestyle, and which parasites are common where you live. Isoxazoline products carry similar important safety language, noting that rare neurologic events have been reported. Overall, regulators consider the class safe and effective when used as directed.

Alternative or additional flea and tick treatments outside of the isoxazoline family include:

• Prescription oral and topical (spot-on) medications
• Over-the-counter medications
• Topical treatments

Compared with older, traditional flea products (e.g., OTC pyrethroid or fipronil/imidacloprid spot-ons), isoxazolines are systemic medications that kill fleas quickly after a bite, protect against multiple tick species, and keep working even with routine bathing. Recent veterinary guidance often supports the use of an oral isoxazoline as a first-line option, though many older products remain effective when used as labeled.

Alternatives in the same family as moxidectin (macrocyclic lactones)

Macrocyclic lactones are the family of medicines used for heartworm prevention. They all work by killing immature heartworm larvae transmitted by mosquitoes before the larvae can grow into adults. Common examples include:

• Ivermectin (HeartgardⓇ, Tri-HeartⓇ, and generics)
• Milbemycin oxime (InterceptorⓇ, Interceptor PLUSⓇ, SentinelⓇ products, NexGard SpectraⓇ)
• Selamectin (RevolutionⓇ, Revolution PlusⓇ)
• Moxidectin (Simparica Trio, Advantage MultiⓇ topical, ProHeartⓇ 6/12 injections)

All are effective against heartworm larvae, and many also treat some intestinal parasites or external parasites depending on the formulation. While they share the same general mechanism of action, they differ in which worms and parasites they cover, how they’re given (chew, topical, injection), and how long they last (one month vs. six or 12 months with injectables). Your veterinarian may recommend one over another depending on your dog’s lifestyle, tolerance for oral vs. topical dosing, or the need for extended protection.

Alternatives in the same family as pyrantel (anthelmintics for intestinal worms)

Pyrantel belongs to a group of medicines called tetrahydropyrimidines, which are used to treat roundworms and hookworms. Other families of anthelmintics are also widely used in veterinary medicine, and your veterinarian may recommend them based on the type of worm infection being treated. Examples include:

• Fenbendazole (PanacurⓇ, Safe-GuardⓇ; a benzimidazole): Effective against roundworms, hookworms, whipworms, and some tapeworm species, usually given as a short course
• Febantel (often combined with pyrantel and praziquantel in Drontal PlusⓇ): Broadens coverage to whipworms and tapeworms
• Praziquantel (found in DrontalⓇ, DroncitⓇ, and others): Specifically targets tapeworms

These medications differ in which parasites they help protect against and how they’re given, and are often combined for broader coverage. Pyrantel itself is generally safe, well tolerated, and widely used, but in some cases your vet may recommend one of these alternatives or combinations for complete intestinal parasite control.

Each product has different advantages and disadvantages and plays different roles in parasite treatment and prevention. Talk to a veterinarian to determine which options are right for you and your unique situation.

When exposed to or infected with parasites, a dog may be at risk for other conditions or diseases. If needed, your vet can recommend treatments additional to or in place of Simparica Trio. Here are some examples of conditions and diseases that are commonly associated with fleas, ticks, intestinal worms, and mosquitoes:

• Flea allergy dermatitis
• Atopic dermatitis
• Tapeworm
• Lyme disease
• Ehrlichiosis
• Anaplasmosis
• Heartworm disease
• Gastrointestinal issues
• Anemia
• Respiratory issues

• If anything unexpected happens when your dog is taking this medication, contact a veterinarian.
• Sarolaner, moxidectin, and pyrantel should be used only for the pet it was prescribed for and only for the specific condition your veterinarian intended.
• Follow the exact dosing instructions. Never adjust the dose, split doses, or share the medication with other pets.

• Zoetis: Simparica Trio product page
• Zoetis: Simparica Trio: For Animal Healthcare Professionals
• European Commission Health Document

This product information is based on FDA-approved labeling. For the most current prescribing information, safety updates, and regulatory status, consult the official product labeling or contact the manufacturer directly.

This educational content was developed independently by our veterinary editorial team without financial compensation, input, or approval from any pharmaceutical manufacturer. All information is based solely on FDA-approved labeling, published scientific literature, and independent veterinary professional judgment. While our organization may have separate business relationships with pharmaceutical companies, these do not influence our editorial content or medical recommendations.