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Simparica TRIO (3.0 mg/0.06 mg/12.5 mg) (Canada)

This page contains information on Simparica TRIO (3.0 mg/0.06 mg/12.5 mg) for veterinary use.
The information provided typically includes the following:
  • Simparica TRIO (3.0 mg/0.06 mg/12.5 mg) Indications
  • Warnings and cautions for Simparica TRIO (3.0 mg/0.06 mg/12.5 mg)
  • Direction and dosage information for Simparica TRIO (3.0 mg/0.06 mg/12.5 mg)

Simparica TRIO (3.0 mg/0.06 mg/12.5 mg)

This treatment applies to the following species:
Company: Zoetis

sarolaner/moxidectin/pyrantel chewable tablets

DIN 02492652, DIN 02492687

DIN 02492660, DIN 02492695

DIN 02492679, DIN 02492709

Veterinary Use Only

Parasiticide for dogs

Description

SIMPARICA TRIO (sarolaner/moxidectin/pyrantel) is a flavored chewable tablet for administration to dogs 8 weeks of age and older. Each tablet is formulated to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin, and 5 mg/kg pyrantel (as pyrantel pamoate).

Simparica TRIO (3.0 mg/0.06 mg/12.5 mg) Indications

SIMPARICA TRIO is recommended for use in dogs and puppies 8 weeks of age and older, and weighing 1.3 kg or greater, for the following indications:

- For the prevention of heartworm disease caused by Dirofilaria immitis.

- For the treatment and control of tick infestations with Amblyomma americanum (lone star tick) and Ixodes scapularis (black-legged tick) for 5 weeks (35 days), and with Amblyomma maculatum (Gulf Coast tick), Dermacentor variabilis (American dog tick), and Rhipicephalus sanguineus (brown dog tick) for 4 weeks (28 days).

- For the treatment and prevention of flea infestations for 5 weeks (35 days); SIMPARICA TRIO kills adult fleas.

- For the treatment and control of roundworm (immature adult and adult Toxocara canis and adult Toxascaris leonina) and adult hookworm (Ancylostoma caninum and Uncinaria stenocephala) infections.

Dosage and Administration

The recommended minimum dosage is 1.2 mg/kg (0.54 g/lb) sarolaner, 24 µg/kg (0.011 mg/lb) moxidectin, and 5 mg/kg (2.27 mg/lb) pyrantel (as pyrantel pamoate). See dosing schedule below.

SIMPARICA TRIO is given orally on a monthly basis. SIMPARICA TRIO needs to be administered every 4 weeks in case of exposure to Amblyomma maculatum, Dermacentor variabilis, and Rhipicephalus sanguineus. In case of tick infestation, accurate tick identification is recommended prior to administering the product.

Visit https: / / biologicalsurvey.ca / public / Bsc / Controller / Page / AGR - 001 - Ticks - Monograph.pdf for more information on tick morphology and species differentiation.

Dosage Schedule:

Body Weight

Sarolaner per Tablet (mg)

Moxidectin per Tablet (mg)

Pyrantel per Tablet (mg)

Number of Tablets Administered

In kg

In lbs

1.3 to 2.5 kg

2.8 to 5.5 lbs

3.0

0.06

12.5

1

2.6 to 5.0 kg

>5.5 to 11.0 lbs

6.0

0.12

25.0

1

5.1 to 10.0 kg

>11.0 to 22.0 lbs

12.0

0.24

50.0

1

10.1 to 20.0 kg

>22.0 to 44.0 lbs

24.0

0.48

100.0

1

20.1 to 40.0 kg

>44.0 to 88.0 lbs

48.0

0.96

200.0

1

40.1 to 60.0 kg

>88.0 to 132.0 lbs

72.0

1.44

300.0

1

60.1 kg and up

>132.0 lbs and up

Administer the appropriate combination of tablets

SIMPARICA TRIO can be offered to the dog with or without food.

Care should be taken to ensure that the dog consumes the complete dose and that part of the dose is not lost or refused. If a monthly dose is missed, give SIMPARICA TRIO immediately and resume monthly dosing.

Heartworm Prevention

SIMPARICA TRIO should be administered at monthly intervals. It can be given year-round or, at minimum, within one month of the dog’s first seasonal exposure to mosquitoes and continued until at least one (1) month after the dog’s last seasonal exposure to mosquitoes. If a dose is missed, give SIMPARICA TRIO immediately and resume monthly dosing thereafter. This minimizes the risk for the development of adult heartworms. When changing from another monthly heartworm preventive product to SIMPARICA TRIO, the first dose of SIMPARICA TRIO should be given within a month of the last dose of the product previously used.

Flea Treatment and Prevention - Tick Treatment and Control

Canada has highly variable distribution and abundance of fleas and ticks due to climate variations across the country. Consequently, a comprehensive plan, based on regional risk assessment, is recommended to determine an appropriate dosing regimen. To minimize the likelihood of flea reinfestation, it is important to treat all dogs and cats within a household with an approved flea control product.

Intestinal Nematode Treatment and Control

For the treatment of roundworm (immature adult and adult Toxocara canis and adult Toxascaris leonina) and adult hookworm (Ancylostoma caninum and Uncinaria stenocephala) infections, SIMPARICA TRIO should be administered once as a single dose and monthly thereafter to control infections.

Contraindications

There are no known contraindications for the use of SIMPARICA TRIO.

CAUTIONS:

Sarolaner, one of the ingredients in SIMPARICA TRIO, is a member of the isoxazoline class. This class has been associated with neurological adverse reactions including tremors, ataxia, and seizures. Seizures have been reported in dogs receiving isoxazoline class drugs, even in dogs without a history of seizures. Use with caution in dogs with a history of seizures or neurological disorders.

The safe use of SIMPARICA TRIO has not been evaluated in breeding, pregnant, or lactating dogs.

Prior to administration of SIMPARICA TRIO dogs should be tested for existing heartworm infections. At the discretion of the veterinarian, infected dogs should be treated to remove adult heartworms. SIMPARICA TRIO is not effective against adult D. immitis.

Warnings

Keep out of reach of children.

Adverse Reactions

In a field safety and effectiveness study, SIMPARICA TRIO was administered to dogs for the prevention of heartworm disease. The study included a total of 410 dogs treated once monthly for 11 treatments (272 treated with SIMPARICA TRIO and 138 treated with ivermectin + pyrantel). Over the 330-day study period, all observations of potential adverse reactions were recorded. The most frequent reactions reported in the SIMPARICA TRIO group are presented in the following table, along with the corresponding results in the ivermectin + pyrantel group.

Adverse Reactions Occurring on a Per Animal Basis over the 330-day Study Period:

Clinical Sign

SIMPARICA TRIO

(n=272 dogs)

Ivermectin + Pyrantel

(n=138 dogs)

Vomiting

14.3%

10.9%

Diarrhea

13.2%

8.0%

Lethargy

8.5%

6.5%

Anorexia

5.1%

5.8%

Polyuria

3.7%

3.6%

Hyperactivity

2.2%

0.7%

Polydypsia

2.2%

2.9%

In a second field safety and effectiveness study, SIMPARICA TRIO was administered to 278 dogs with fleas. Adverse reactions in dogs treated with SIMPARICA TRIO included diarrhea.

In a third field safety and effectiveness study, SIMPARICA TRIO was administered to 120 dogs with roundworms. Adverse reactions in dogs treated with SIMPARICA TRIO included diarrhea and vomiting.

To report adverse reactions, call Zoetis Canada Inc. at 1-800-461-0917.

Clinical Pharmacology

Sarolaner is a member of the isoxazoline class of parasiticides and the chemical name is 1 - (5’ - ((5S) - 5 - (3,5 - Dichloro - 4 - fluorophenyl) - 5 - (trifluoromethyl) - 4,5 - dihydroisoxazol - 3 - yl) - 3’ - H - spiro(azetidine - 3,1’ - (2)benzofuran) - 1 - yl) - 2 - (methylsulfonyl)ethanone. SIMPARICA TRIO contains the S-enantiomer of sarolaner.

Moxidectin is a semi-synthetic methoxime derivative of nemadectin which is a fermentation product of Streptomyces cyaneogriseus subspecies noncyanogenus. Moxidectin is a pentacyclic 16-membered lactone macrolide. The chemical name for moxidectin is (6R,23E,25S)-5-O-Demethyl-28-deoxy- 25-[(1E)-1,3-dimethyl-1-buten-1-yl]-6,28-epoxy-23- (methoxyimino)milbemycin B.

Pyrantel belongs to a family classified chemically as tetrahydropyrimidines and the chemical name is (E) - 1,4,5,6 - Tetrahydro - 1 - methyl - 2 - [2 - (2 - thienyl)vinyl]pyrimidine4,4’ - methylenebis(3 - hydroxy - 2 - naphthoic acid) (1:1). It is a yellow, water-insoluble crystalline salt of the tetrahydropyrimidine base and pamoic acid containing 34.7% base activity.

Mode of Action

SIMPARICA TRIO contains three active pharmaceutical ingredients, sarolaner, moxidectin, and pyrantel pamoate.

Sarolaner is an acaricide and insecticide belonging to the isoxazoline group. Sarolaner inhibits the function of the neurotransmitter gamma aminobutyric acid (GABA) receptor and glutamate receptor and works at the neuromuscular junction in arthropods. This results in uncontrolled neuromuscular activity leading to death in insects or acarines.

Moxidectin is an endectocide in the macrocyclic lactone class. Moxidectin acts by interfering with the chloride channel-mediated neurotransmission in the parasite. This results in paralysis and death of the parasite.

Pyrantel pamoate is a nematocide belonging to the tetrahydropyrimidine class. Pyrantel acts as a depolarizing, neuromuscular-blocking agent in susceptible parasites, which causes paralysis and death or expulsion of the organism.

Pharmacokinetics

Following oral administration of SIMPARICA TRIO in Beagle dogs (13 to 15 months of age at the time of initial dosing), sarolaner and moxidectin were rapidly and well absorbed.

Following a single oral dose of SIMPARICA TRIO (sarolaner dose of 1.2 mg/kg), the sarolaner mean maximum plasma concentration (Cmax) was 523 ng/mL with a mean time to maximum concentration (Tmax) of 3.5 hours and an absolute bioavailability of 88%. At a moxidectin dose of 0.024 mg/kg, the moxidectin mean Cmax was 13.1 ng/mL with a mean Tmax of 2.4 hours and an absolute bioavailability of 67%.

Following intravenous (IV) dosing of a combination solution of sarolaner and moxidectin, the sarolaner volume of distribution (Vss) was 2.4 L/kg and systemic clearance (CL) was 6.0 mL/kg/hr. For moxidectin, the Vss was 7.65 L/kg and CL was 26.6 mL/kg/hr. The terminal half-lives were similar after oral and IV dosing for both sarolaner (12 days) and moxidectin (11 days).

The primary route of elimination of both sarolaner and moxidectin is biliary excretion with minimal metabolism.

Following an oral dose of SIMPARICA TRIO containing 5 mg/kg pyrantel (as pamoate salt), pyrantel has measurable plasma concentrations, but they are low and highly variable. Pyrantel pamoate is intended to remain in the gastrointestinal tract allowing for delivery of effective concentrations to gastrointestinal nematodes.

EFFICACY:

Heartworm Prevention

In two well-controlled laboratory studies, a single oral dose of SIMPARICA TRIO was 100% effective in preventing the development of adult D. immitis in dogs inoculated with third-stage larvae 30 days before treatment.

SIMPARICA TRIO was 100% effective in the prevention of heartworm disease in a multicenter study consisting of 246 dogs treated with SIMPARICA TRIO and 119 dogs given the active control (ivermectin + pyrantel). All dogs treated with SIMPARICA TRIO were negative for D. immitis antigen and blood microfilaria at study completion on day 330 and two dogs in the active control group were positive for D. immitis antigen on day 330.

Tick Treatment And Control

In a well-controlled laboratory study, SIMPARICA TRIO began to kill existing I. scapularis within 8 hours, SIMPARICA TRIO reduced the number of live ticks by ≥94.2% within 24 hours of infestation for 4 weeks.

In well-controlled laboratory studies, SIMPARICA TRIO demonstrated ≥98.9% effectiveness against an existing infestation of Amblyomma maculatum, Rhipicephalus sanguineus, and Dermacentor variabilis 48 hours post-administration and maintained ≥90.4% effectiveness 48 hours after reinfestation for 4 weeks. Against Ixodes scapularis, SIMPARICA TRIO demonstrated 100% effectiveness 48 hours after treatment of existing infestations and maintained ≥ 95.1% effectiveness 48 hours after reinfestation for 5 weeks. Against Amblyomma americanum, SIMPARICA TRIO demonstrated ≥99.4% effectiveness 72 hours after treatment of existing infestations and maintained ≥98.4% effectiveness 72 hours after reinfestation for 5 weeks.

Flea Treatment And Prevention

In a well-controlled laboratory study, SIMPARICA TRIO began to kill fleas at 4 hours and demonstrated 100% effectiveness at 8 hours after initial administration. After weekly reinfestations, SIMPARICA TRIO reduced the number of live fleas by ≥97.8% within 12 hours of infestation for 4 weeks.

In a separate well-controlled laboratory study, SIMPARICA TRIO demonstrated 100% effectiveness against adult fleas within 24 hours following treatment and maintained ≥99.7% effectiveness against weekly reinfestations for 5 weeks.

In a study to explore flea egg production and viability, SIMPARICA TRIO killed fleas before they could lay eggs during 5 weeks.

In a well-controlled 60-day US field study conducted in dogs with existing flea infestations of varying severity, the effectiveness of SIMPARICA TRIO against fleas on Day 30 and 60 visits was 98.5% and 99.7%, respectively, compared to baseline. Dogs with signs of flea allergy dermatitis showed improvement in erythema, papules, scaling, alopecia, dermatitis/pyodermatitis and pruritus as a direct result of eliminating fleas.

Intestinal Nematode Treatment And Control

Elimination of roundworms (immature adult and adult Toxocara canis and adult Toxascaris leonina) and adult hookworms (Ancylostoma caninum and Uncinaria stenocephala) was demonstrated in three well-controlled laboratory studies.

In a 10-day multi-center field study, SIMPARICA TRIO was effective against Toxocara canis and resulted in a 91.7% reduction of fecal egg counts.

ANIMAL SAFETY:

Safety In Puppies

SIMPARICA TRIO was administered orally to 8-week-old Beagle puppies at doses of 1, 3, and 5X the maximum labeled dose (2.4 mg/kg sarolaner, 48 µg/kg moxidectin, and 10 mg/kg pyrantel) at 28-day intervals for 7 treatments. Dogs in the control group received placebo. During the end-of-study ophthalmic examination, one 1X dog was found to have retinal dysplasia in the left eye. The cause of the retinal dysplasia was not determined. There were no clinically-relevant, treatment related effects on clinical observations, body weights, food consumption, clinical pathology (hematology, coagulation, serum chemistry, and urinalysis), gross pathology, histopathology, or organ weights.

Oral Safety In P-gp Deficient Collies (avermectin-sensitive)

SIMPARICA TRIO was administered orally at 1, 3 and 5X the maximum labeled dose to Collies which had been pre-screened for avermectin sensitivity. Dogs in the control group received placebo. Clinical signs (ataxia, muscle fasciculations, mydriasis) associated with avermectin sensitivity were observed in the 5X group. All dogs were completely recovered by the third day of the study.

Laboratory Safety Study In Heartworm-positive Dogs

SIMPARICA TRIO was administered orally at 1 and 3X the maximum labeled dose at 28 day intervals for 3 treatments to Beagle dogs with patent adult heartworm infections and circulating microfilariae. Dogs in the control group received placebo. Diarrhea occurred more commonly in the treated dogs and also more often in the 3X group compared with the 1X group. Two dogs (one each in 1X and 3X) developed a fever less than 24 hours after the first dose. The fever may have been a transient reaction to a rapid microfilaria reduction. Both dogs recovered without treatment.

Field Safety

In three well-controlled field studies, SIMPARICA TRIO was used concurrently with other medications such as vaccines, antimicrobials, anthelmintics, antiprotozoals, steroidal and non-steroidal anti-inflammatory agents, anesthetic agents and analgesics. No adverse reactions were associated with the concurrent use of SIMPARICA TRIO and other medications.

Storage

Store between 15 and 30°C.

PRESENTATION:

SIMPARICA TRIO chewable tablets are available in six flavoured tablet sizes (see DOSAGE AND ADMINISTRATION). Each tablet size is available in color-coded packages of one, three, or six tablets. Not all pack sizes may be marketed.

Zoetis is a trademark and Simparica TRIO is a registered trademark of Zoetis or its licensors, used under license by Zoetis Canada Inc.

Zoetis Canada Inc., Kirkland QC H9H 4M7

10022797-11-0

51036500

CPN: 1198570.1

ZOETIS CANADA INC.
16,740 TRANS-CANADA HIGHWAY, KIRKLAND, QC, H9H 4M7
Order Desk:   800-663-8888
Technical Services Canada:   800-461-0917
Technical Services USA:   800-366-5288
Website:   www.zoetis.ca
Every effort has been made to ensure the accuracy of the Simparica TRIO (3.0 mg/0.06 mg/12.5 mg) information published above. However, it remains the responsibility of the readers to familiarize themselves with the product information contained on the Canadian product label or package insert.

Copyright © 2021 Animalytix LLC. Updated: 2021-10-04