Trifexis Chewable Tablets for Dogs

Trifexis for Dogs protects petite dogs from fleas, heartworms, hookworms, roundworms, and whipworms. This FDA-Approved, chewable tablet features a scrumptious beef flavor that makes it easy to administer your pet's monthly dose. By combining spinosad and milbemycin oxide, this treatment combats parasites for a full month and begins working within 30 minutes of administering the first dose.

Triflexis is a prescription medication that is safe for dogs that are at least 8 weeks of age. There are also five different formulations of Triflexis to give the proper dosage based on your dog's weight: 5-10 lbs (Pink), 11-20 lbs (Orange), 21-40 lbs (Green), 41-60 lbs (Blue), and 61-120 lbs (Brown).

Key Benefits

• Protects against fleas, heartworm disease, hookworm, roundworm and whipworm.
• Oral beef-flavored tablet that's easy to administer
• Convenient once-a-month dosing
• Protect all month long with just one tablet
• Approved for puppies and dogs 8 weeks and older, and who weigh 5 pounds or more

Indications

Trifexis prevents heartworm disease. Trifexis kills fleas and prevents flea infestations, and treats and controls adult hookworm, roundworm and whipworm infections in dogs and puppies 8 weeks and older and 5 pounds or more.

How It Works

Spinosad, an active ingredient in Trifexis, starts to work within 30 minutes to kill fleas and has been proven to kill 100% of all biting fleas within 4 hours. Trifexis also kills flea eggs before they can mature, which helps to end the flea life cycle. Trifexis prevents heartworm disease by killing microfilariae and larvae from maturing into adult heartworms.

• NADA 141-321
• NDC 58198-4332-6 (Pink)
• NDC 58198-4333-6 (Orange)
• NDC 58198-4334-6 (Green)
• NDC 58198-4335-6 (Blue)
• NDC 58198-4336-6 (Brown)

View Trifexis Drug Facts Sheet.

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 EFFECTIVENESS).

Quick Tips

• Give Trifexis chewable tablets with food.
• Give Trifexis chewable tablets once a month.
• Please view the chart below for the correct dosage of Trifexis for your dog.
• Trifexis does not protect against ticks.
• If vomiting occurs within 1 hour of administration, redose the pet with another full dose.
• Consult your veterinarian for pregnant or lactating dogs.

Administer TRIFEXIS with food for maximum effectiveness. To ensure heartworm prevention, owners should observe the dog for one hour after dosing. If vomiting occurs within an hour of administration, redose with another full dose. If a dose is missed and a monthly interval between doses is exceeded, then immediate administration of TRIFEXIS with food and resumption of monthly dosing will minimize the opportunity for the development of adult heartworm infections and flea reinfestations.

Powerful 3-in-1 parasite protection in one convenient tablet

Just one beef-flavored tablet each month protects your dog against:

• Heartworm disease
• Fleas
• Intestinal parasites: adult hookworm*, roundworm and whipworm

*Ancylostoma caninum

Is Trifexis right for your dog?

If your dog spends time outdoors (or shares a home with outdoor pets), exposure to fleas, heartworm disease and intestinal parasites is a given. However, even dogs that spend the majority of their time indoors benefit from parasite protection.

The American Heartworm Society (AHS) and the Companion Animal Parasite Council (CAPC) recommend annual testing and year-round heartworm disease prevention to ensure your dog is heartworm-free.^1,2

Three key threats to your dog's health

Fleas

• Trifexis provides fast relief. It starts killing fleas within 30 minutes, before they can lay eggs, and keeps working to prevent flea infestations all month long.
• Fleas may cause extreme discomfort for your dog: scratching, chewing, biting, fur loss and restlessness.
• Fleas are the source of flea allergy dermatitis (FAD), a common veterinary skin condition.
• Severe infestations may cause anemia.³

Heartworm disease¹

• Heartworms are transmitted by mosquitoes and heartworm infection in dogs has been reported in all 50 states
• Symptoms include coughing, sluggishness and difficulty breathing; however some dogs show no signs of any kind.
• Treatment is difficult and costly, and complications may occur.
• If left untreated it can be fatal to your dog

Intestinal parasites

• Intestinal parasites can cause dehydration, anemia, diarrhea and even death in puppies.^4,5
• Unfortunately, these parasites are all around, and your dog can contract them almost anywhere on a daily walk, in your yard or at the local dog park.

Heartworm Prevention:

TRIFEXIS should be administered at monthly intervals beginning within 1 month of the dog's first seasonal exposure and continuing until at least 3 months after the dog's last seasonal exposure to mosquitoes (see EFFECTIVENESS). TRIFEXIS may be administered year round without interruption. When replacing another heartworm preventative product, the first dose of TRIFEXIS should be given within a month of the last dose of the former medication.

Flea Treatment and Prevention:

Treatment with TRIFEXIS may begin at any time of the year, preferably starting one month before fleas become active and continuing monthly through the end of flea season. In areas where fleas are common year-round, monthly treatment with TRIFEXIS should continue the entire year without interruption.

To minimize the likelihood of flea reinfestation, it is important to treat all animals within a household with an approved flea protection product.

ntestinal Nematode Treatment and Control:

TRIFEXIS also provides treatment and control of roundworms (T. canis, T. leonina), hookworms (A. caninum) and whipworms (T. vulpis). Dogs may be exposed to and can become infected with roundworms, whipworms and hookworms throughout the year, regardless of season or climate. Clients should be advised of measures to be taken to prevent reinfection with intestinal parasites.

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 ADVERSE REACTIONS).

Precautions:

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

Prior to administration of TRIFEXIS, dogs should be tested for existing heartworm infection. At the discretion of the veterinarian, infected dogs should be treated with an adulticide to remove adult heartworms. TRIFEXIS is not effective against adult D. immitis. While the number of circulating microfilariae may decrease following treatment, TRIFEXIS is not indicated for microfilariae clearance (see ANIMAL SAFETY).

Mild, transient hypersensitivity reactions manifested as labored respiration, vomiting, salivation and lethargy, have been noted in some dogs treated with milbemycin oxime carrying a high number of circulating microfilariae. These reactions are presumably caused by release of protein from dead or dying microfilariae.

Use with caution in breeding females (see ANIMAL SAFETY). The safe use of TRIFEXIS in breeding males has not been evaluated.

Use with caution in dogs with pre-existing epilepsy (see ADVERSE REACTIONS).

Puppies less than 14 weeks of age may experience a higher rate of vomiting (see ANIMAL SAFETY).

Adverse Reactions:

In a well-controlled US field study, which included a total of 352 dogs (176 treated with TRIFEXIS and 176 treated with an active control), no serious adverse reactions were attributed to administration of TRIFEXIS. All reactions were regarded as mild.

Over the 180-day study period, all observations of potential adverse reactions were recorded. Reactions that occurred at an incidence >1% (average monthly rate) within any of the 6 months of observation are presented in the following table. The most frequently reported adverse reaction in dogs in the TRIFEXIS group was vomiting.

^an=176 dogs

In the US field study, one dog administered TRIFEXIS experienced a single mild seizure 2 ½ hours after receiving the second monthly dose. The dog remained enrolled and received four additional monthly doses after the event and completed the study without further incident.

Following concomitant extra-label use of ivermectin with spinosad alone, a component of TRIFEXIS, some dogs have experienced the following clinical signs: trembling/twitching, salivation/drooling, seizures, ataxia, mydriasis, blindness and disorientation. Spinosad alone has been shown to be safe when administered concurrently with heartworm preventatives at label directions.

In US and European field studies, no dogs experienced seizures when dosed with spinosad alone at the therapeutic dose range of 13.5-27.3 mg/lb (30-60 mg/kg), including 4 dogs with pre-existing epilepsy. Four epileptic dogs that received higher than the maximum recommended dose of 27.3 mg/lb (60 mg/kg) experienced at least one seizure within the week following the second dose of spinosad, but no seizures following the first and third doses. The cause of the seizures observed in the field studies could not be determined.

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/AnimalVeterinary/SafetyHealth

Mode of Action:

The primary target of action of spinosad, a component of TRIFEXIS, is an activation of nicotinic acetylcholine receptors (nAChRs) in insects. Spinosad does not interact with known insecticidal binding sites of other nicotinic or GABAergic insecticides such as neonicotinoids, fiproles, milbemycins, avermectins and cyclodienes. Insects treated with spinosad show involuntary muscle contractions and tremors resulting from activation of motor neurons. Prolonged spinosad-induced hyperexcitation results in prostration, paralysis and flea death. The selective toxicity of spinosad between insects and vertebrates may be conferred by the differential sensitivity of the insect versus vertebrate nAChRs.

Milbemycin oxime, a component of TRIFEXIS, acts by binding to glutamate-gated chloride ion channels in invertebrate nerve and muscle cells. Increased permeability by the cell membrane to chloride ions causes hyperpolarization of affected cells and subsequent paralysis and death of the intended parasites. Milbemycin oxime may also act by disrupting the transmission of invertebrate neurotransmitters, notably gamma amino butyric acid (GABA).

Effectiveness:

Heartworm Prevention:

In a well-controlled laboratory study, TRIFEXIS was 100% effective against induced heartworm infections when administered for 3 consecutive monthly doses. Two consecutive monthly doses did not provide 100% effectiveness against heartworm infection. In another well-controlled laboratory study, a single dose of TRIFEXIS was 100% effective against induced heartworm infections.

In a well-controlled six-month US field study conducted with TRIFEXIS, no dogs were positive for heartworm infection as determined by heartworm antigen testing performed at the end of the study and again three months later

Flea Treatment and Prevention:

In a well-controlled laboratory study, TRIFEXIS demonstrated 100% effectiveness on the first day following treatment and 100% effectiveness on Day 30. In a well-controlled laboratory study, spinosad, a component of TRIFEXIS, began to kill fleas 30 minutes after administration and demonstrated 100% effectiveness within 4 hours. Spinosad, a component of TRIFEXIS, kills fleas before they can lay eggs. If a severe environmental infestation exists, fleas may persist for a period of time after dose administration due to the emergence of adult fleas from pupae already in the environment. In field studies conducted in households with existing flea infestations of varying severity, flea reductions of 98.0% to 99.8% were observed over the course of 3 monthly treatments with spinosad alone. Dogs with signs of flea allergy dermatitis showed improvement in erythema, papules, scaling, alopecia, dermatitis/pyodermatitis and pruritus as a direct result of eliminating the fleas.

Treatment and Control of Intestinal Nematode Infections:

In well-controlled laboratory studies, TRIFEXIS was ? 90% effective in removing naturally and experimentally induced adult roundworm, whipworm and hookworm infections.

Palatability:

TRIFEXIS is a flavored chewable tablet. In a field study of client-owned dogs where 175 dogs were each offered TRIFEXIS once a month for 6 months, dogs voluntarily consumed 54% of the doses when offered plain as if a treat, and 33% of the doses when offered in or on food. The remaining 13% of doses were administered like other tablet medications.

Animal Safety:

TRIFEXIS was tested in pure and mixed breeds of healthy dogs in well-controlled clinical and laboratory studies. No dogs were withdrawn from the field studies due to treatment-related adverse reactions.

In a margin of safety study, TRIFEXIS was administered orally to 8-week-old Beagle puppies at doses of 1, 3, and 5 times the upper half of the therapeutic dose band, every 28 days for 6 dosing periods. Vomiting was seen in all groups including control animals with similar frequency. Adverse reactions seen during the course of the study were salivation, tremors, decreased activity, coughing and vocalization.

Body weights were similar between control and treated groups throughout the study. Treatment with TRIFEXIS was not associated with any clinically significant hematology, clinical chemistry or gross necropsy changes. One 5X dog had minimal glomerular lipidosis observed microscopically. The clinical relevance of this finding is unknown.

Plasma spinosyn A, spinosyn D, milbemycin A3 5-oxime and milbemycin A4 5-oxime concentrations increased throughout the study. At each dosing period, plasma spinosyn A and spinosyn D concentrations were greater than proportional across the dose range 1 to 5X. Plasma milbemycin A4 5-oxime concentrations appeared to be dose proportional across range 1 to 5X by the end of the study. Plasma concentrations of spinosad and milbemycin oxime indicate that expected systemic exposures were achieved throughout the study.

In an avermectin-sensitive Collie dog study, TRIFEXIS was administered orally at 1, 3, and 5 times the upper half of the recommended therapeutic dose band every 28 days. No signs of avermectin sensitivity were observed after administration of TRIFEXIS during the study period to avermectin-sensitive Collie dogs. The adverse reactions observed in the treatment groups were vomiting and diarrhea. Body weights in all treatment groups were comparable to the control group. Hematology and clinical chemistry parameters showed no clinically significant changes from study start to end, and all dogs were considered healthy throughout the study.

In a heartworm positive safety study, TRIFEXIS was administered orally at 1, 3, and 5 times the upper half of the therapeutic dose band to Beagle dogs with adult heartworm infections and circulating microfilariae, every 28 days for 3 treatments. Vomiting was observed in one dog in the 1X group, in three dogs in the 3X group, and in one dog in the 5X group. All but one incident of vomiting was observed on the treatment day during the first treatment cycle. The vomiting was mild and self-limiting. Hypersensitivity reactions were not observed in any of the treatment groups. Microfilariae counts decreased with treatment.

In a reproductive safety study, TRIFEXIS was administered orally to female dogs at 1 and 3 times the upper half of the therapeutic dose band every 28 days prior to mating, during gestation and during a six-week lactation period. Dogs with confirmed fetal heartbeats on ultrasound examination were evaluated for reproductive safety. One 3X and one 1X group female did not become pregnant. No treatment-related adverse reactions or signs of avermectin toxicosis were noted for adult females. Adult females in the 3X group lost weight during the 6-week pre-mating period, while control group females gained weight during that time. The body weights of the treated groups were comparable to the control group during gestation and post-parturition phases of the study. Gestation length, litter average body weight, litter size, stillborn pups, pup survival and the proportion of pups with malformations were comparable between treated and control dam groups. Malformations in the 1X group included a pup with cleft palate and a littermate with anophthalmia, fused single nares, misshapen palate, hydrocephalus, omphalocele and malpositioned testes; a pup with a malformation of the anterior tip of the urinary bladder and umbilical blood vessel; and a pup with patent ductus arteriosus (PDA). Malformations in the 3X group included three littermates with PDA. Malformations in the control group included a pup with a malformed sternum and a pup with PDA and a malpositioned superior vena cava. Clinical findings in pups of the treated groups were comparable to the control group except for one 1X group pup that was smaller and less coordinated than its littermates and had tremors when excited. The relationship between spinosad and milbemycin oxime treatment and the 1X and 3X dogs that did not become pregnant, the specific pup malformations and the unthrifty 1X group pup are unknown. The incidence of cleft palate is not unexpected based on the historical data collected at the breeding site.

In a margin of safety study with spinosad alone, 6-week old Beagle puppies were administered average doses of 1.5, 4.4, and 7.4 times the maximum recommended dose at 28-day intervals over a 6-month period. Vomiting was observed across all treatments, including controls, and was observed at an increased rate at elevated doses. Vomiting most often occurred 1 hour following administration and decreased over time and stabilized when puppies reached 14 weeks of age.

Storage Information:

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