Spinosad and milbemycin oxime

Indications

TRIFEXIS is indicated for the prevention of heartworm disease ( Dirofilaria immitis ). TRIFEXIS kills fleas and is indicated for the prevention and treatment of flea infestations ( Ctenocephalides felis ), and the treatment and control of adult hookworm ( Ancylostoma caninum ), adult roundworm ( Toxocara canis and Toxascaris leonina ) and adult whipworm ( Trichuris vulpis ) infections in dogs and puppies 8 weeks of age or older and 5 pounds of body weight or greater.

Dosage and Administration

TRIFEXIS is given orally, once a month at the minimum dosage of 13.5 mg/lb (30 mg/kg) spinosad and 0.2 mg/lb (0.5 mg/kg) milbemycin oxime body weight. For heartworm prevention, give once monthly for at least 3 months after exposure to mosquitoes (see

Contraindications

There are no known contraindications to the use of TRIFEXIS.

Warnings

Not for human use. Keep this and all drugs out of the reach of children. Serious adverse reactions have been reported following concomitant extra-label use of ivermectin with spinosad alone, a component of TRIFEXIS (see

Precautions

Treatment with fewer than 3 monthly doses after the last exposure to mosquitoes may not provide complete heartworm prevention (see

Description

TRIFEXIS (spinosad and milbemycin oxime) is available in five sizes for oral administration to dogs and puppies according to their weight. Each chewable flavored tablet is formulated to provide a minimum spinosad dose of 13.5 mg/lb (30 mg/kg) and a minimum milbemycin oxime dose of 0.2 mg/lb (0.5 mg/kg). Spinosad is a member of the spinosyns class of insecticides, which are non-antibacterial tetracyclic macrolides. Spinosad contains two major factors, spinosyn A and spinosyn D, derived from the naturally occurring bacterium, Saccharopolyspora spinosa . Spinosyn A and spinosyn D have the chemical compositions C 41 H 65 NO 10 and C 42 H 67 NO 10 , respectively. Milbemycin oxime is a macrocyclic lactone anthelmintic, containing two major factors, A 3 and A 4 of milbemycin oxime. The approximate ratio of A 3 :A 4 is 20:80. Milbemycin A 4 5-oxime has the chemical composition of C 32 H 45 NO 7 and milbemycin A 3 5-oxime has the chemical composition of C 31 H 43 NO 7 .

Information for Owners

Your veterinarian has chosen to prescribe TRIFEXIS Chewable Tablets for the prevention of heartworm disease ( Dirofilaria immitis ), to kill fleas and for the prevention and treatment of flea infestations ( Ctenocephalides felis ), and the treatment and control of adult hookworm ( Ancylostoma caninum ), adult roundworm ( Toxocara canis and Toxascaris leonina ) and adult whipworm ( Trichuris vulpis ) infections in dogs and puppies 8 weeks of age or older and 5 pounds of body weight or greater. Controlling these parasites is very important to the health of your dog. Please read this leaflet, which describes the proper use of TRIFEXIS. If you have any questions about this information, please consult your veterinarian. Additional information can be found at www.trifexis.com. What is TRIFEXIS? TRIFEXIS is a chewable, flavored tablet that you give orally to your dog once-a-month to kill fleas, to prevent flea infestations, to treat and control hookworms, whipworms and roundworms, and to prevent heartworm disease. TRIFEXIS is for monthly use in dogs and puppies 8 weeks of age or older and 5 pounds of body weight or greater. If you do not administer TRIFEXIS monthly throughout the year, the final dose must be given no fewer than three months following the last exposure to mosquitoes. Why has my veterinarian prescribed TRIFEXIS? Your veterinarian has prescribed TRIFEXIS as a way of preventing your dog from developing problems caused by infection with three commonly occurring parasite categories. Heartworm infection can make dogs very sick and can even be fatal. This parasite is spread to dogs by mosquitoes. TRIFEXIS can prevent flea infestations from becoming established, and can also remove any fleas that are on your dog at the time of treatment. TRIFEXIS will also treat and control common adult intestinal worm infections (roundworms, hookworms and whipworms). Should I give TRIFEXIS each month all year round? Consult your veterinarian regarding the need for year round use of TRIFEXIS. If you do not administer TRIFEXIS monthly throughout the year, the final dose must be given no fewer than three months following the last exposure to mosquitoes. Will TRIFEXIS kill heartworms? TRIFEXIS prevents heartworm disease by killing certain stages that develop after an infected mosquito bites a dog. As with other heartworm preventatives, TRIFEXIS does not kill adult heartworms. Speak to your veterinarian about treatment options if your dog is diagnosed with an adult heartworm infection. Will my dog still need to be tested for heartworm infection while taking TRIFEXIS? You should speak to your veterinarian about the frequency of heartworm testing while your dog is taking TRIFEXIS. How do I switch to TRIFEXIS from another heartworm preventative? Follow the advice of your veterinarian about switching heartworm preventatives. What should I discuss with my veterinarian regarding TRIFEXIS for my dog? Your veterinarian is your dog's healthcare expert and can make the best recommendation for medications for your dog. This includes the prevention, control and/or treatment of parasites such as fleas, heartworms and intestinal parasites that may cause conditions that include flea allergy dermatitis, anemia and heart disease. Key points of your discussion may include the following: • As with other heartworm preventatives, dogs should be tested for heartworm prior to beginning treatment with TRIFEXIS. • If a dose is missed and a monthly interval between doses is exceeded, then immediately give TRIFEXIS with food and resume monthly dosing. This practice will minimize the opportunity for heartworms to grow. Also, continuing normal monthly dosing will allow you to gain control of any flea or intestinal parasites that might have infected your dog. • To minimize the likelihood of fleas continuing to jump onto your dog, it is important to treat all household pets with an approved flea protection product. • TRIFEXIS is not for use in humans. Like all medications, keep TRIFEXIS out of reach of children. How should I give TRIFEXIS to my dog? Give TRIFEXIS with food for maximum effectiveness. TRIFEXIS is a chewable tablet and may be offered as a treat. Consult your veterinarian regarding the need for year round administration of TRIFEXIS. What if I give more than the prescribed amount of TRIFEXIS to my dog? Contact your veterinarian as soon as possible if you believe your dog has ingested more than the recommended dose of TRIFEXIS. In a study in which dogs were dosed at 1, 3, and 5 times the upper half of the recommended dose, dogs exhibited vomiting, tremors, decreased activity, salivation, coughing and vocalization. Should I restrict either my dog's activity or contact with my dog after the tablet is consumed? Since TRIFEXIS is an oral formulation, you may maintain normal activities and interactions with your dog. How quickly will TRIFEXIS kill fleas? In a laboratory study of spinosad alone, an active ingredient of TRIFEXIS, spinosad started to kill fleas within 30 minutes and killed 100% of the fleas within 4 hours. TRIFEXIS kills fleas before they can lay eggs. Does seeing fleas on my dog mean that the treatment is not working? TRIFEXIS kills fleas before they can lay eggs when used monthly according to the label directions. Remember that all animals in the household should be treated with an approved flea product to help control the flea population. Your dog can continue to be exposed to the fleas that live in the environment. When fleas jump onto your dog, they will be killed by TRIFEXIS. If within a month after your dog receives TRIFEXIS you see fleas on your dog, it is most likely that these are new fleas. These new fleas will be killed before they can produce eggs that contaminate the environment. Continued monthly use of TRIFEXIS can prevent any new infestations. What if I see worms in my dog's stool during the month after administration of TRIFEXIS? TRIFEXIS is indicated to treat and control intestinal parasite infections of adult hookworms, roundworms and whipworms. In occasional cases, it is possible that the action of TRIFEXIS in killing the intestinal worms will lead to the dog expelling them in the stool. If you have questions, consult with your veterinarian for measures you can take to prevent a reinfection with intestinal parasites. Is it safe to give my dog TRIFEXIS? TRIFEXIS has been demonstrated to be safe in pure and mixed breeds of healthy dogs when used according to label directions for dogs and puppies 8 weeks of age and older and five pounds of body weight or greater. You should discuss the use of TRIFEXIS with your veterinarian prior to use if your dog has a history of epilepsy (seizures). Puppies less than 14 weeks of age may experience a higher rate of vomiting. Is it safe to give my breeding dogs TRIFEXIS? Ask your veterinarian about the use of TRIFEXIS prior to use in breeding females. The safe use of TRIFEXIS in male dogs intended for breeding has not been evaluated. What side effects might occur with TRIFEXIS? Like all medications, sometimes side effects may occur. In some cases, dogs vomited after receiving TRIFEXIS. To ensure heartworm prevention, observe your dog for one hour after administration. If vomiting occurs within an hour of administration, redose with another full dose. During field studies, no severe or prolonged vomiting occurred. Additional adverse reactions observed in the clinical studies were itching, decreased activity, diarrhea, inflammation of the skin, redness of the skin, decreased appetite and redness of the ear. All reactions were regarded as mild. Since the introduction of TRIFEXIS, additional side effects reported are trembling/shaking, ataxia, seizures and hypersalivation. For technical assistance or to report suspected adverse drug events, contact Elanco US Inc. at 1-888-545-5973. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or http://www.fda.gov/reportanimalae Can other medications be given while my dog is taking TRIFEXIS? Yes, TRIFEXIS has been given safely with a wide variety of products and medications. Your veterinarian should be made aware of all products that you administered and/or intend to administer to your dog. How should TRIFEXIS be stored? Store at 68-77°F (20-25°C). Temporary periods of time outside this range between 59-86°F (15 -30°C) are permitted. www.trifexis.com Trifexis, Elanco and the diagonal bar logo are trademarks of Elanco or its affiliates. © 2024 Elanco or its affiliates PA104092X Elanco™ Principal Display Panel - Trifexis 140 mg Carton Label Trifexis ™ (spinosad + milbemycin oxime) FOR DOGS 5-10 lbs 6 CHEWABLE TABLETS 140 mg spinosad/ 2.3 mg milbemycin oxime CAUTION: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian. Prevents HEARTWORM Disease Kills FLEAS & Prevents Infestations Treats and Controls INTESTINAL WORMS Adult Hookworm, Roundworm, and Whipworm For use in dogs and puppies 8 weeks of age and older and 5 lbs of body weight or greater STARTS Killing Fleas in 30 mins. MONTHLY Use GIVE WITH A Meal Elanco ™ Figure Principal Display Panel - Trifexis 270 mg Carton Label Trifexis ™ (spinosad + milbemycin oxime) FOR DOGS 10.1-20 lbs 6 CHEWABLE TABLETS 270 mg spinosad/ 4.5 mg milbemycin oxime CAUTION: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian. Prevents HEARTWORM Disease Kills FLEAS & Prevents Infestations Treats and Controls INTESTINAL WORMS Adult Hookworm, Roundworm, and Whipworm For use in dogs and puppies 8 weeks of age and older and 5 lbs of body weight or greater STARTS Killing Fleas in 30 mins. MONTHLY Use GIVE WITH A Meal Elanco ™ Figure Principal Display Panel - Trifexis 560 mg Carton Label Trifexis ™ (spinosad + milbemycin oxime) FOR DOGS 20.1-40 lbs 6 CHEWABLE TABLETS 560 mg spinosad/ 9.3 mg milbemycin oxime CAUTION: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian. Prevents HEARTWORM Disease Kills FLEAS & Prevents Infestations Treats and Controls INTESTINAL WORMS Adult Hookworm, Roundworm, and Whipworm For use in dogs and puppies 8 weeks of age and older and 5 lbs of body weight or greater STARTS Killing Fleas in 30 mins. MONTHLY Use GIVE WITH A Meal Elanco ™ Figure Principal Display Panel - Trifexis 810 mg Carton Label Trifexis ™ (spinosad + milbemycin oxime) FOR DOGS 40.1-60 lbs 6 CHEWABLE TABLETS 810 mg spinosad/ 13.5 mg milbemycin oxime CAUTION: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian. Prevents HEARTWORM Disease Kills FLEAS & Prevents Infestations Treats and Controls INTESTINAL WORMS Adult Hookworm, Roundworm, and Whipworm For use in dogs and puppies 8 weeks of age and older and 5 lbs of body weight or greater STARTS Killing Fleas in 30 mins. MONTHLY Use GIVE WITH A Meal Elanco ™ Figure Principal Display Panel - Trifexis 1620 mg Carton Label Trifexis ™ (spinosad + milbemycin oxime) FOR DOGS 60.1-120 lbs 6 CHEWABLE TABLETS 1620 mg spinosad/ 27 mg milbemycin oxime CAUTION: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian. Prevents HEARTWORM Disease Kills FLEAS & Prevents Infestations Treats and Controls INTESTINAL WORMS Adult Hookworm, Roundworm, and Whipworm For use in dogs and puppies 8 weeks of age and older and 5 lbs of body weight or greater STARTS Killing Fleas in 30 mins. MONTHLY Use GIVE WITH A Meal Elanco ™ Figure

Storage

Store at 20-25°C (68-77°F), excursions permitted between 15-30°C (59-86°F).

FDA adverse event reports

The FDA Center for Veterinary Medicine publishes the adverse event reports it receives through openFDA. The counts below are the reports naming spinosad and milbemycin oxime as an active ingredient for each species this label names, as returned on 2026-09-16, coded by the VeDDRA reaction term the reporter chose. Reactions are counted per report, so one report can appear under several terms.

These are counts, not rates. Reporting is voluntary, the number of animals treated is not known, and a widely used product accumulates reports for that reason alone. A report records that an event followed a dose; it does not establish that the product caused it. The counts say nothing about how one product compares with another.