Esafoxolaner, eprinomectin and praziquantel

Indications

NexGard® COMBO is indicated for the prevention of heartworm disease caused by Dirofilaria immitis and for the treatment and control of roundworm (fourth stage larval and adult Toxocara cati ), hookworm (fourth stage larval and adult Ancylostoma tubaeforme ; adult Ancylostoma braziliense ), and tapeworm ( Dipylidium caninum ) infections. NexGard® COMBO kills adult fleas ( Ctenocephalides felis ) and is indicated for the treatment and prevention of flea infestations and the treatment and control of Ixodes scapularis (black-legged tick) and Amblyomma americanum (lone star tick) infestations for one month in cats and kittens 8 weeks of age and older, and weighing 1.8 lbs or greater.

Dosage and Administration

NexGard® COMBO is dosed at a minimum of 0.055 mL/lb (0.12 mL/kg), which delivers a minimum dose of 0.65 mg/lb (1.44 mg/kg) esafoxolaner, 0.22 mg/lb (0.48 mg/kg) eprinomectin, and 4.53 mg/lb (9.98 mg/kg) praziquantel. For heartworm disease prevention, apply once monthly for at least three months after last exposure to mosquitoes ( see Effectiveness). Administer the entire contents of a NexGard® COMBO unit applicator topically once a month as specified in the following table: Dosing Schedule Cat Weight (lb) Volume (mL) Esafoxolaner (mg) Eprinomectin (mg) Praziquantel (mg) 1.8- 5.5 0.3 3.6 1.2 24.9 5.6-16.5 0.9 10.8 3.6 74.7 16.6-22 0.3 + 0.9 14.4 4.8 99.6 22.1-33 0.9 + 0.9 21.6 7.2 149.4 A veterinarian or veterinary technician should demonstrate or instruct the pet owner regarding the appropriate technique for applying NexGard® COMBO topically to cats and kittens prior to first use. Keep product in original packaging until ready to use. 1. Use scissors to cut the blister along the dotted line. 2. Then pull the lid away. 3. Remove the applicator from the package and hold it upright. Pull back the plunger slightly. 4. Twist and pull off the cap. 5. Part the hair on the midline of the neck, between the base of the skull and the shoulder blades until the skin is visible. Place the tip of the applicator on the skin and apply the entire contents directly onto the skin in one spot. The product should be applied to dry skin on an area where the cat cannot lick it off. If the weight of the cat requires a second application, apply the contents in the same manner as described above in the same location. 6. Wash hands after use with soap and water. Heartworm Prevention: For the prevention of heartworm disease, NexGard® COMBO should be administered once a month year-round. At a minimum, administration of NexGard® COMBO should start at least 1 month before the cat’s first expected exposure to mosquitoes and monthly thereafter until at least 3 months after the cat’s last seasonal exposure to mosquitoes (see Effectiveness ). If a dose is missed and a 30-day interval between doses is exceeded, administer NexGard® COMBO immediately and resume the monthly dosing schedule. Treatment with fewer than 3 monthly doses may not provide complete heartworm prevention. When replacing another monthly heartworm preventive product in a heartworm prevention program, the first treatment with NexGard® COMBO should be given within one month of the last dose of the former medication. At the discretion of the veterinarian, cats older than 6 months of age may be tested to determine the presence of existing heartworm infection before treatment with NexGard® COMBO. Cats already infected with adult heartworms can be given NexGard® COMBO monthly to prevent further infections. Flea Treatment and Prevention: For the treatment and prevention of flea infestations, the use of NexGard® COMBO may begin at any time of year. NexGard® COMBO should be administered year-round at monthly intervals or begin at least one month before fleas become active. However, an environmental infestation may persist for a short time after beginning treatment with NexGard® COMBO because of the development of adult fleas from eggs that were laid prior to the initiation of treatment. Tick Treatment and Control: For the treatment and control of infestations with Ixodes scapularis and Amblyomma americanum , the use of NexGard® COMBO may begin at any time of year. NexGard® COMBO should be administered year-round at monthly intervals or begin at least one month before the ticks become active. Treatment and Control of Roundworms, Hookworms, and Tapeworms: NexGard® COMBO provides treatment and control of roundworms (adult and fourth stage larval Toxocara cati ), hookworms (adult and fourth stage larval Ancylostoma tubaeforme ; adult Ancylostoma braziliense ), and tapeworms ( Dipylidium caninum ). For the treatment of hookworm, roundworms and tapeworm infections, NexGard® COMBO should be administered once as a single dose. Monthly use of NexGard® COMBO will control any subsequent infections. Cats may be exposed to and can become infected with roundworms, hookworms, and tapeworms throughout the year, regardless of season or climate. Diagrams for opening and administering.

Contraindications

There are no known contraindications for the use of NexGard® COMBO. Human Warnings: Not for human use. Keep this and all drugs out of sight and reach of children. Avoid direct contact with application site for 4 hours or until visibly dry. This product may act as a mild to moderate eye irritant. Keep product in the original packaging until use. Wash hands after product administration. If the product accidentally gets into the eyes, rinse thoroughly with water. If wearing contact lenses, flush the eyes first with water and then remove the lenses and continue to flush thoroughly with water. In case of accidental ingestion, or if skin or eye irritation occurs, contact a poison control center or physician for treatment advice.

Precautions

Esafoxolaner, one of the ingredients in NexGard® COMBO, is a member of the isoxazoline class. This class has been associated with neurologic adverse reactions including tremors, ataxia, and seizures. Seizures have been reported in cats receiving isoxazoline class drugs, even in cats without a history of seizures. Use with caution in cats with a history of seizures or neurologic disorders. Do not administer orally. Cats may salivate excessively if NexGard® COMBO is accidentally administered orally or is ingested through licking/grooming the application site (see Target Animal Safety ). The safety of NexGard® COMBO has not been fully evaluated in breeding, pregnant, or lactating cats. The safety of NexGard® COMBO has not been tested in kittens less than 8 weeks of age or weighing less than 1.8 lbs (0.8 kg).

Adverse Reactions

In a field safety and effectiveness study, which included a total of 201 households and 380 treated cats (244 cats treated with NexGard® COMBO, 136 cats treated with an active control), the safety of NexGard® COMBO was evaluated over a 90-day period through in-clinic physical examinations or through reporting of abnormalities by the owner. The most frequently reported reactions in the NexGard® COMBO and active control groups are presented in the following table. Adverse Reactions by Treatment Group EVENT Treatment Group NEXGARD® COMBO Active Control n1 % (n=244) n2 % (n=136) Vomiting 16 6.56 8 5.88 Application Site Hair Change 9 3.69 0 0.00 Anorexia 7 2.87 4 2.94 Lethargy 6 2.46 5 3.68 Bacterial skin infection 4 1.64 1 0.74 Itching 4 1.64 0 0.00 Sneezing 4 1.64 5 3.68 Skin Peeling 3 1.23 2 1.47 Diarrhea 3 1.23 3 2.21 Epiphora 3 1.23 1 0.74 Hypersalivation 3 1.23 0 0.00 Hyperthermia 3 1.23 0 0.00 Alopecia 2 0.82 0 0.00 Dermal thickening 2 0.82 0 0.00 Ear Pruritus 2 0.82 1 0.74 Application Site Redness 2 0.82 0 0.00 Conjunctivitis 1 0.41 1 0.74 1 Number of cats treated with NexGard® COMBO with the identified abnormality. 2 Number of cats treated with Active Control with the identified abnormality.

Description

NexGard® COMBO is a topical solution containing esafoxolaner, eprinomectin and praziquantel available in 0.3 mL and 0.9 mL unit applicators to treat cats from 1.8 lbs to 33 lbs. Each mL of NexGard® COMBO contains 12 mg of esafoxolaner, 4 mg of eprinomectin, and 83 mg of praziquantel. Inactive ingredients: dimethyl isosorbide, unstabilized glycerol formal, and butylated hydroxytoluene. Esafoxolaner is a member of the aryl isoxazoline class of compounds. Its chemical name is 4-[(5S)-5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4, 5-dihydro-1,2-oxazol-3-yl]-N-{2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl}-1-naphthamide. Eprinomectin belongs to the avermectin class of anthelmintics and is a mixture of homologous components referred to as eprinomectin B1a and B1b. The chemical name for eprinomectin B1a is (4”R)-acetylamino-5-O-demethyl-4”-deoxyavermectin A1a. The chemical name for eprinomectin B1b is (4”R)-acetylamino-5-O-demethyl-25-de(1-methylpropyl)- 4”-deoxy-25-(1-methylethyl)avermectin A1a. Praziquantel is a pyrazinoisoquinoline anthelmintic. Its chemical name is 2-(Cyclohexylcarbonyl)- 1,2,3,6, 7,11b-hexahydro-4H-pyrazino[2,1-a]-isoquinolin-4-one.

Storage

Store at 59° - 86°F (15° - 30°C). Brief periods up to 104°F (40°C) are permitted. Protect from light. Approved by FDA under NADA # 141-570 Marketed by: Boehringer Ingelheim Animal Health USA Inc. Duluth, GA 30096 NEXGARD® is a registered trademark and NEXGARD COMBO is a trademark of Boehringer Ingelheim Animal Health France, used under license. ©2023 Boehringer Ingelheim Animal Health USA Inc. All rights reserved. 184238-003 Rev. 04/2023 Fact Sheet for Veterinarians: Emergency Use Authorization of NexGard COMBO (esafoxolaner, eprinomectin, and praziquantel topical solution) for New World Screwworm (NWS) NexGard COMBO (esafoxolaner, eprinomectin, and praziquantel topical solution) Topical solution For topical use in cats Original EUA Authorized Date: 02/18/2026 Emergency Use Authorization for NexGard COMBO (esafoxolaner, eprinomectin, and praziquantel topical solution) for NWS The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for the emergency use of the approved product NexGard COMBO (esafoxolaner, eprinomectin, and praziquantel topical solution) for the treatment of infestations caused by NWS ( Cochliomyia hominivorax ) larvae (myiasis) in cats and kittens. NexGard COMBO is not approved for this use. NexGard COMBO (esafoxolaner, eprinomectin, and praziquantel topical solution) (NADA 141-570) is approved for other uses in cats and kittens. 1 Limitations of Authorized Use NexGard COMBO (esafoxolaner, eprinomectin, and praziquantel topical solution) is authorized for this use only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of NexGard COMBO (esafoxolaner, eprinomectin, and praziquantel topical solution) under section 564(b)(1) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. § 360bbb-3(b)(1), unless the declaration is terminated or the authorization is revoked sooner. Justification for Emergency Use of Animal Drugs for NWS The Secretary of the U.S. Department of Health and Human Services (HHS) has: • determined that there is a significant potential for a public health emergency that has a significant potential to affect national security or the health and security of United States citizens living abroad and that involves NWS (Cochliomyia hominivorax); and • declared that circumstances exist justifying the authorization of emergency use of animal drugs to treat or prevent NWS myiasis in animals. 2 An EUA is an FDA authorization for the emergency use of an unapproved product or unapproved use of an approved product (i.e., drug, biological product, or device) in the United States under certain circumstances declared by the Secretary of HHS to justify emergency use authorization, including, among others, a determination that there is a public health emergency or a significant potential for a public health emergency that may affect national security and that involves a biological agent. 3 Criteria for issuing an EUA include: • The biological agent(s) can cause a serious or life-threatening disease or condition; • Based on the totality of available scientific evidence (including data from adequate and well-controlled clinical trials, if available), it is reasonable to believe that: o the product may be effective in diagnosing, preventing, or treating the serious or life-threatening disease or condition; and o the known and potential benefits of the product - when used to diagnose, prevent, or treat such disease or condition - outweigh the known and potential risks of the product; and • There is no adequate, approved 4 , and available alternative to the product for diagnosing, preventing, or treating the serious or life-threatening disease or condition. 5 Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian. Product Description Refer to the NexGard COMBO (esafoxolaner, eprinomectin, and praziquantel topical solution) package insert for full Product Description information.

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 esafoxolaner and eprinomectin and praziquantel 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.