Simparica (sarolaner) Chewables Tablets for Dogs

Simparica is a fast-acting oral flea and tick preventative that begins killing fleas and ticks within hours of administration and remains effective for one month to prevent re-infestations. It is indicated for the treatment and prevention of flea infestations (Ctenocephalides felis), and the treatment and control of tick infestations [Amblyomma americanum (Lone Star tick), Amblyomma maculatum (Gulf Coast tick), Dermacentor variabilis (American dog tick), Ixodes scapularis (deer tick/black-legged tick), and Rhipicephalus sanguineus (brown dog tick)]. Simparica begins to kill adult fleas within 3 hours and ticks within 8 hours of administration. Treatment with Simparica may begin at any time of the year and is safe to use year-round without interruption. Simparica is given monthly and requires a prescription from your veterinarian.

Key Benefits

• Each tablet provides a full month of protection against fleas and ticks
• Tasty, liver-flavored chewable tablet is easy to administer
• Chewable tablets can be given directly to your dog or broken up and mixed with food
• Kills over 95% of adult fleas within 8 hours
• Available in six weight categories: 2.8-5.5 lbs, 5.6-11 lbs, 11.1-22.0 lbs, 22.1-40 lbs, 44.1-88.0 lbs and 88.1-132 lbs

Indication:

Simparica kills adult fleas, and is indicated for the treatment and prevention of flea infestations (Ctenocephalides felis), and the treatment and control of tick infestations [Amblyomma americanum (lone star tick), Amblyomma maculatum (Gulf Coast tick), Dermacentor variabilis (American dog tick), Ixodes scapularis (black-legged tick), and Rhipicephalus sanguineus (brown dog tick)] for one month in dogs 6 months of age or older and weighing 2.8 pounds or greater.

How It Works

Simparica contains the active ingredient sarolaner, which 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. Simparica is administered once a month directly by mouth or can be crumbled and mixed with food. To minimize the likelihood of flea re-infestation, it is important to treat all dogs and cats within a household with an approved flea control product.

View Simparica Drug Facts Sheet.

Simparica is given orally once a month at the recommended minimum dosage of 0.91 mg/lb (2 mg/kg).

Simparica can be offered by hand, in the food, or administered like other tablet medications. Care should be taken that the dog consumes the complete dose, and treated animals should be observed for a few minutes to ensure that part of the dose is not lost or refuse. If a dose is missed, administer Simparica and resume a monthly dosing schedule.

Simparica should be administered at monthly intervals.

Flea Treatment and Prevention:

Treatment with Simparica may begin at any time of the year. In areas where fleas are common year-round, monthly treatment with Simparica can continue the entire year without interruption.

To minimize the likelihood of flea re-infestation, it is important to treat all dogs and cats within a household with an approved flea control product.

Tick Treatment and Control:

Treatment with Simparica can begin at any time of the year (see Effectiveness).

Contraindications:

There are no known contraindications for the use of Simparica.

Warnings:

Not for use in humans. Keep this and all drugs out of reach of children and pets. For use in dogs only. Do not use Simparica in cats.

Simparica should not be used in dogs less than 6 months of age (see Animal Safety).

Precautions:

Simparica may cause abnormal neurologic signs such as tremors, decreased conscious proprioception, ataxia, decreased or absent menace, and/or seizures (see Animal Safety). The safe use of Simparica has not been evaluated in breeding, pregnant, or lactating dogs.

Adverse Reactions:

Simparica was administered in a well-controlled US field study, which included a total of 479 dogs (315 dogs treated with Simparica and 164 dogs treated with active control once monthly for three treatments).

Over the 90-day study period, all observations of potential adverse reaction were recorded.

Additionally, one female dog aged 8.6 years exhibited lethargy, ataxia while posturing to eliminate, elevated third eyelids, and inappetence one day after receiving Simparica concurrently with a heartworm preventative (ivermectin/pyrantel pamoate). The signs resolved one day later. After the day 14 visit, the owner elected to withdraw the dog from the study. For a copy of the Safety Data Sheet (SDS) or to report adverse reactions call Zoetis Inc. at 1-888-963-8471. Additional information can be found at www.Simparica.com. 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.

Clinical Pharmacology:

Sarolaner is rapidly and well absorbed following oral administration of Simparica. In a study of 12 Beagle dogs the mean maximum plasma concentration (C_max) was 1100 mg/mL and the mean time to maximum concentration (T_max) occurred at 3 hours following a single oral dose of 2 mg/kg to fasted animals. The mean oral bioavailability was 86% and 107% in fasted and fed dogs, 2 mg/kg to fasted animals. The mean oral T_½ values for fasted and fed animals was 10 and 12 days respectively. Sarolaner is distributed widely; the mean volume of distribution (Vdss) was 2.81 L/kg bodyweight following at 2 mg/kg intravenous dose of sarolaner. Sarolaner is highly bound (≥99.9%) to plasma proteins. The metabolism of sarolaner appears to be minimal in the dog. The primary route of sarolaner elimination from dogs is biliary excretion with elimination via the feces.

Following repeat administration of Simparica once every 28 days for 10 doses to Beagle dogs at 1X, 3X, and 5X the maximum intended clinical dose of 4 mg/kg, stead-state plasma concentrations were reached after the 6th dose. Following treatment at 1X, 3X, and 5X the maximum intended clinical dose of 4 mg/kg, sarolaner systemic exposure was dose proportional over the range 1X to 5X.

Mode of Action:

The active substance of simparica, 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 result in uncontrolled neuromuscular activity leading to death in insects or acarines.

Effectiveness:

In a well-controlled laboratory study, Simparica began to kill fleas 3 hours after initial administration and reduce the number of live fleas by ≥96.2% within 8 hours after flea infestation through Day 35.

In a separate well-controlled laboratory study, Simparica demonstrated 100% effectiveness against adult fleas within 24 hours following treatment and maintained 100% effectiveness against weekly re-infestations for 35 days.

In a study to explore flea egg production and viability, Simparica killed fleas before they could lay eggs for 35 days. In a study to simulate a flea-infested home environment, with flea infestation established prior to the start of treatment and re-infestations on Days 7, 37 and 67, Simparica administered monthly for three months demonstrated >95.6% reduction in adult fleas within 14 days after treatment and reached 100% on Day 60.

In well-controlled laboratory studies, Simparica demonstrated ≥99% effectiveness against an initial infestation of Amblyomma americanum, Amblyomma maculatum, Dermacentor variabilis, Ixodes scapularis, and Rhipicephalus sanguineus 48 hours post-administration and maintained >96% effectiveness 48 hours post re-infestation for 30 days.

In a well-controlled 90-day US field study conducted in households with existing flea infestations of varying severity, the effectiveness of Simparica against fleas on Day 30, 60 and 90 visits compared to baseline was 99.4%, 99.8%, and 100%, respectively. Dogs with signs of flea allergy dermatitis and pruritus as a direct result of eliminating fleas.

Animal Safety:

In a margin of safety study, Simparica was administered orally to 8 week old Beagle puppies at doses of 0, 1X, 3X, and 5X the maximum recommended dose 94 mg/kg) at 28 day intervals for 10 doses (8 dogs per group). The control group received placebo tablets. No neurologic signs were observed in the 1X group. In the 3X group, one male dog exhibited tremors and ataxia post-dose on Day 0; one female dog exhibited tremors on Days 1, 2, 3, and 5; and one female dog exhibited tremors on Day 1. In the 5C group, one female dog has a seizure on Day 61 (5 days after third dose); one female dog had tremors post-dose on Day 0 and abnormal head coordination after dosing on Day 140; and one female dog exhibited seizures associated with the second and fourth doses and tremors associated with the second and third doses. All dogs recovered without treatment. Except for the observation of abnormal head coordination in one dog in the 5X group two hours after dosing on Day 140 (dose 6). There were no treatment-related neurological signs observed once the dogs reached the age of 6 months.

In a separate exploratory pharmacokinetic study, one female dog dose at 12 mg/kg 93X the maximum recommended dose) exhibited lethargy, anorexia, and multiple neurological signs including ataxia, tremors, disorientation, hypersalivation, diminished proprioception, and absent menace, approximately 2 days after a third monthly dose. The dog was not treated, and was ultimately euthanized. The first two doses resulted in plasma concentrations that were consistent with those of the other dogs in the treatment group. Starting at 7 hours after the third dose, there was a rapid 2.5 fold increase in plasma concentrations within 41 hours, resulting in a C_max more than 7 fold higher than the mean C_max at the maximum recommended use dose. No cause for the sudden increase in sarolaner plasma concentrations was identified.

Storage:

Store at or below 30°C (86°F) with excursions permitted up to 40°C (104°F).