SIMPARICA TRIO

DESCRIPTION

SIMPARICA TRIO (sarolaner, moxidectin, and pyrantel chewable tablets) is a flavored, chewable tablet for administration to dogs 8 weeks of age and older. Each tablet is formulated to provide minimum dosages of 0.54 mg/lb (1.2 mg/kg) sarolaner, 0.011 mg/lb (24 μg/kg) moxidectin, and 2.27 mg/lb (5 mg/kg) pyrantel (as pamoate salt).

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] pyrimidine 4,4’ methylenebis [3-hydroxy-2-naphthoate] (1:1). It is a yellow, water-insoluble crystalline salt of the tetrahydropyrimidine base and pamoic acid containing 34.7% base activity.

INDICATIONS

SIMPARICA TRIO is indicated for the prevention of heartworm disease caused by Dirofilaria immitis and for the treatment and control of roundworm (immature adult and adult Toxocara canis and adult Toxascaris leonina) and hookworm (L4, immature adult, and adult Ancylostoma caninum and adult Uncinaria stenocephala) infections. SIMPARICA TRIO kills adult fleas (Ctenocephalides felis) and is indicated for the treatment and prevention of flea infestations, and the treatment and control of tick infestations with Amblyomma americanum (lone star tick), Amblyomma maculatum (Gulf Coast tick), Dermacentor variabilis (American dog tick), Ixodes scapularis (blacklegged tick), and Rhipicephalus sanguineus (brown dog tick) for one month in dogs and puppies 8 weeks of age and older, and weighing 2.8 pounds or greater. SIMPARICA TRIO is indicated for the prevention of Borrelia burgdorferi infections as a direct result of killing Ixodes scapularis vector ticks.

DOSAGE AND ADMINISTRATION

SIMPARICA TRIO is given orally once a month, at the recommended minimum dose of 0.54 mg/lb (1.2 mg/kg) sarolaner, 0.011 mg/lb (24 μg/kg) moxidectin, and 2.27 mg/lb (5 mg/kg) pyrantel (as pamoate salt).

Dosage Schedule

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 dose is missed, give SIMPARICA TRIO immediately and resume monthly dosing.

Heartworm Prevention:
SIMPARICA TRIO should be administered at monthly intervals year‑round or at least within one month of the animal’s first seasonal exposure to mosquitoes and continuing until at least 1 month after the dog’s last seasonal exposure. If a dose is missed, give SIMPARICA TRIO immediately and resume monthly dosing. When replacing a monthly heartworm preventive product, SIMPARICA TRIO should be given within one month of the last dose of the former medication.

Flea Treatment and Prevention:
Treatment with SIMPARICA TRIO may begin at any time of the year. SIMPARICA TRIO should be administered year‑round at monthly intervals or started at least one month before fleas become active. To minimize the likelihood of flea re‑infestation, it is important to treat all dogs and cats within a household with a flea control product.

Tick Treatment and Control:
Treatment with SIMPARICA TRIO can begin at any time of the year. SIMPARICA TRIO should be administered year‑round at monthly intervals or started at least one month before ticks become active.

Intestinal Nematode Treatment and Control:
For the treatment of roundworm (immature adult and adult Toxocara canis and adult Toxascaris leonina) and hookworm (L4, immature adult, and adult Ancylostoma caninum and adult Uncinaria stenocephala) infections, SIMPARICA TRIO should be administered once as a single dose. Monthly use of SIMPARICA TRIO will control any subsequent infections.

CONTRAINDICATIONS

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

WARNINGS

Not for use in humans. Keep this and all drugs out of reach of children.

Keep SIMPARICA TRIO in a secure location out of reach of dogs, cats and other animals to prevent accidental ingestion or overdose.

PRECAUTIONS

Sarolaner, one of the ingredients in SIMPARICA TRIO, 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 dogs receiving isoxazoline class drugs, even in dogs without a history of seizures. Use with caution in dogs with a history of seizures or neurologic disorders.

Prior to administration of SIMPARICA TRIO, dogs should be tested for existing heartworm infections. Infected dogs should be treated with an adulticide to remove adult heartworms. SIMPARICA TRIO is not effective against adult D. immitis.

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

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 an active control). 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.

Table 1. Dogs with Adverse Reactions

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.

CLINICAL PHARMACOLOGY

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.

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 insects. 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.

Storage Instructions

Store at or below 30°C