TRIFEXIS- spinosad and milbemycin oxime tablet

Trifexis by

Drug Labeling and Warnings

Trifexis by is a Animal medication manufactured, distributed, or labeled by Elanco US Inc., Elanco SAS France, Eurofins Pharma Quality Control, Eurofins Lancaster Laboratories, Inc, Elanco Clinton Laboratories, Corteva Agriscience LLC, Livzon Group Fuzhou Fuxing Pharmaceutical Co., Ltd., Zhejiang Hisun Pharmaceutical Co., Ltd.. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

SPL UNCLASSIFIED SECTION

(spinosad + milbemycin oxime)

Chewable Tablets

Caution: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian.

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 C41H65NO10 and C42H67NO10, respectively. Milbemycin oxime is a macrocyclic lactone anthelmintic, containing two major factors, A3 and A4 of milbemycin oxime. The approximate ratio of A3:A4 is 20:80. Milbemycin A4 5-oxime has the chemical composition of C32H45NO7 and milbemycin A3 5-oxime has the chemical composition of C31H43NO7.

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 EFFECTIVENESS).

Dosage Schedule:

Body Weight	Spinosad; Per Tablet (mg)	Milbemycin oxime; Per Tablet (mg)	Tablets; Administered
5 to 10 lbs	140	2.3	One
10.1 to 20 lbs	270	4.5	One
20.1 to 40 lbs	560	9.3	One
40.1 to 60 lbs	810	13.5	One
60.1 to 120 lbs	1620	27	One
Over 120 lbs	Administer the appropriate combination of tablets

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.

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.

Intestinal 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.

Average Monthly Rate (%) of Dogs With Adverse Reactions

an=176 dogs
Adverse Reaction	TRIFEXIS Chewable; Tabletsa	Active Control; Tabletsa
Vomiting	6.13	3.08
Pruritus	4.00	4.91
Lethargy	2.63	1.54
Diarrhea	2.25	1.54
Dermatitis	1.47	1.45
Skin Reddening	1.37	1.26
Decreased appetite	1.27	1.35
Pinnal Reddening	1.18	0.87

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/reportanimalae

Post Approval Experience (Mar 2012):

The following adverse reactions are based on post-approval adverse drug event reporting.The adverse reactions are listed in decreasing order of frequency: vomiting, depression/lethargy, pruritus, anorexia, diarrhea, trembling/shaking, ataxia, seizures, hypersalivation, and skin reddening.

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).

How Supplied:

TRIFEXIS is available in five tablet sizes. Each tablet size is available in color-coded packages of 6 tablets.

5-10 lbs (140 mg spinosad and 2.3 mg milbemycin oxime)

10.1-20 lbs (270 mg spinosad and 4.5 mg milbemycin oxime)

20.1-40 lbs (560 mg spinosad and 9.3 mg milbemycin oxime)

40.1-60 lbs (810 mg spinosad and 13.5 mg milbemycin oxime)

60.1-120 lbs (1620 mg spinosad and 27 mg milbemycin oxime)

Approved by FDA under NADA # 141-321

Manufactured for:
Elanco US Inc.
Greenfield, IN 46140

www.trifexis.com

Trifexis, Elanco and the diagonal bar logo are trademarks of Elanco or its affiliates.

CA4332

CA4333

CA4334

CA4335

CA4336

Revised: May 2020

Elanco™

Information for Dog 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.To help you remember the monthly dosing schedule, stick-on labels are included for your calendar.

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.

PA102948X

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™

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™

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™

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™

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™

INGREDIENTS AND APPEARANCE

TRIFEXIS 
spinosad and milbemycin oxime tablet

Product Information
Product Type	PRESCRIPTION ANIMAL DRUG	Item Code (Source)	NDC: 58198-0042
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
spinosad (UNII: XPA88EAP6V) (spinosad - UNII:XPA88EAP6V)	spinosad	140 mg
milbemycin oxime (UNII: 0502PUN0GT) (milbemycin oxime - UNII:0502PUN0GT)	milbemycin oxime	2.3 mg

Inactive Ingredients
Ingredient Name	Strength
MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U)
HYDROXYPROPYL CELLULOSE (1600000 WAMW) (UNII: RFW2ET671P)
SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
MAGNESIUM STEARATE (UNII: 70097M6I30)
CROSCARMELLOSE SODIUM (UNII: M28OL1HH48)

Product Characteristics
Color	brown (Brown)	Score	no score
Shape	ROUND (Round)	Size	9mm
Flavor		Imprint Code	T
Contains

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 58198-0042-1	10 in 1 BOX
2	NDC: 58198-0042-6	6 in 1 CARTON
2		6 in 1 BLISTER PACK

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NADA	NADA141321	10/18/2012

TRIFEXIS 
spinosad and milbemycin oxime tablet

Product Information
Product Type	PRESCRIPTION ANIMAL DRUG	Item Code (Source)	NDC: 58198-0043
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
spinosad (UNII: XPA88EAP6V) (spinosad - UNII:XPA88EAP6V)	spinosad	270 mg
milbemycin oxime (UNII: 0502PUN0GT) (milbemycin oxime - UNII:0502PUN0GT)	milbemycin oxime	4.5 mg

Inactive Ingredients
Ingredient Name	Strength
MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U)
HYDROXYPROPYL CELLULOSE (1600000 WAMW) (UNII: RFW2ET671P)
SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
MAGNESIUM STEARATE (UNII: 70097M6I30)
CROSCARMELLOSE SODIUM (UNII: M28OL1HH48)

Product Characteristics
Color	brown (Brown)	Score	no score
Shape	ROUND (Round)	Size	11mm
Flavor		Imprint Code	7
Contains

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 58198-0043-1	10 in 1 BOX
2	NDC: 58198-0043-6	6 in 1 CARTON
2		6 in 1 BLISTER PACK

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NADA	NADA141321	10/18/2012

TRIFEXIS 
spinosad and milbemycin oxime tablet

Product Information
Product Type	PRESCRIPTION ANIMAL DRUG	Item Code (Source)	NDC: 58198-0044
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
spinosad (UNII: XPA88EAP6V) (spinosad - UNII:XPA88EAP6V)	spinosad	560 mg
milbemycin oxime (UNII: 0502PUN0GT) (milbemycin oxime - UNII:0502PUN0GT)	milbemycin oxime	9.3 mg

Inactive Ingredients
Ingredient Name	Strength
MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U)
HYDROXYPROPYL CELLULOSE (1600000 WAMW) (UNII: RFW2ET671P)
SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
MAGNESIUM STEARATE (UNII: 70097M6I30)
CROSCARMELLOSE SODIUM (UNII: M28OL1HH48)

Product Characteristics
Color	brown (Brown)	Score	no score
Shape	ROUND (Round)	Size	15mm
Flavor		Imprint Code	T
Contains

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 58198-0044-1	10 in 1 BOX
2	NDC: 58198-0044-6	6 in 1 CARTON
2		6 in 1 BLISTER PACK

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NADA	NADA141321	10/18/2012

TRIFEXIS 
spinosad and milbemycin oxime tablet

Product Information
Product Type	PRESCRIPTION ANIMAL DRUG	Item Code (Source)	NDC: 58198-0045
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
spinosad (UNII: XPA88EAP6V) (spinosad - UNII:XPA88EAP6V)	spinosad	810 mg
milbemycin oxime (UNII: 0502PUN0GT) (milbemycin oxime - UNII:0502PUN0GT)	milbemycin oxime	13.5 mg

Inactive Ingredients
Ingredient Name	Strength
MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U)
HYDROXYPROPYL CELLULOSE (1600000 WAMW) (UNII: RFW2ET671P)
SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
MAGNESIUM STEARATE (UNII: 70097M6I30)
CROSCARMELLOSE SODIUM (UNII: M28OL1HH48)

Product Characteristics
Color	brown (Brown)	Score	no score
Shape	ROUND (Round)	Size	17mm
Flavor		Imprint Code	7
Contains

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 58198-0045-1	10 in 1 BOX
2	NDC: 58198-0045-6	6 in 1 CARTON
2		6 in 1 BLISTER PACK

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NADA	NADA141321	10/18/2012

TRIFEXIS 
spinosad and milbemycin oxime tablet

Product Information
Product Type	PRESCRIPTION ANIMAL DRUG	Item Code (Source)	NDC: 58198-0046
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
spinosad (UNII: XPA88EAP6V) (spinosad - UNII:XPA88EAP6V)	spinosad	1620 mg
milbemycin oxime (UNII: 0502PUN0GT) (milbemycin oxime - UNII:0502PUN0GT)	milbemycin oxime	27 mg

Inactive Ingredients
Ingredient Name	Strength
MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U)
HYDROXYPROPYL CELLULOSE (1600000 WAMW) (UNII: RFW2ET671P)
SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
MAGNESIUM STEARATE (UNII: 70097M6I30)
CROSCARMELLOSE SODIUM (UNII: M28OL1HH48)

Product Characteristics
Color	brown (Brown)	Score	no score
Shape	ROUND (Round)	Size	21mm
Flavor		Imprint Code	T
Contains

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 58198-0046-1	10 in 1 BOX
2	NDC: 58198-0046-6	6 in 1 CARTON
2		6 in 1 BLISTER PACK

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NADA	NADA141321	10/18/2012

Labeler - Elanco US Inc. (966985624)

Establishment
Name	Address	ID/FEI	Business Operations
Elanco SAS France		736833104	MANUFACTURE, ANALYSIS

Establishment
Name	Address	ID/FEI	Business Operations
Eurofins Pharma Quality Control		291433006	ANALYSIS

Establishment
Name	Address	ID/FEI	Business Operations
Eurofins Lancaster Laboratories, Inc		069777290	ANALYSIS

Establishment
Name	Address	ID/FEI	Business Operations
Elanco Clinton Laboratories		039138631	ANALYSIS, LABEL, PACK

Establishment
Name	Address	ID/FEI	Business Operations
Corteva Agriscience LLC		837038785	API MANUFACTURE

Establishment
Name	Address	ID/FEI	Business Operations
Livzon Group Fuzhou Fuxing Pharmaceutical Co., Ltd.		421260459	API MANUFACTURE

Establishment
Name	Address	ID/FEI	Business Operations
Zhejiang Hisun Pharmaceutical Co., Ltd.		654211754	API MANUFACTURE