Simparica Chewables: Product Information (Page 2 of 2)

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 (Cmax ) was 1100 ng/mL and the mean time to maximum concentration (Tmax ) 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, respectively. The mean oral T1/2 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 a 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, steady-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 gammaaminobutyric 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.

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Effectiveness

In a well-controlled laboratory study, SIMPARICA began to kill fleas 3 hours after initial administration and reduced 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 infestations 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 showed improvement in erythema, papules, scaling, alopecia, dermatitis/pyodermatitis 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 (4 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 the3X 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 5X group, one female dog had 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 dosed at 12 mg/kg (3X 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 Cmax more than 7-fold higher than the mean Cmax at the maximum recommended use dose. No cause for the sudden increase in sarolaner plasma concentrations was identified.

Storage Information

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

How Supplied

SIMPARICA (sarolaner) Chewables are available in six flavored tablet sizes: 5, 10, 20, 40, 80, and 120 mg. Each tablet size is available in color-coded packages of one, three, or six tablets.

Approved by FDA under NADA # 141-452
zoetis
Distributed by:
Zoetis Inc.
Kalamazoo, MI 49007

Revised: June 201950070902

PRINCIPAL DISPLAY PANEL 5 mg Carton

5 mg Carton
(click image for full-size original)

PRINCIPAL DISPLAY PANEL 10 mg Carton

10 mg Carton
(click image for full-size original)

PRINICIPAL DISPLAY PANEL 20 mg Carton

20 mg Carton
(click image for full-size original)

PRINCIPAL DISPLAY PANEL 40 mg Carton

40 mg Carton
(click image for full-size original)

PRINCIPAL DISPLAY PANEL 80 mg Carton

80 mg Carton
(click image for full-size original)

PRINCIPAL DISPLAY PANEL 120 mg Carton

120 mg Carton
(click image for full-size original)
SIMPARICA CHEWABLES sarolaner tablet, chewable
Product Information
Product Type PRESCRIPTION ANIMAL DRUG Item Code (Source) NDC:54771-2015
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
SAROLANER (SAROLANER) SAROLANER 5 mg
Product Characteristics
Color BROWN Score no score
Shape SQUARE (Square with rounded edges) Size 6mm
Flavor LIVER Imprint Code
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:54771-2015-1 1 BLISTER PACK in 1 CARTON contains a BLISTER PACK
1 1 TABLET, CHEWABLE in 1 BLISTER PACK This package is contained within the CARTON (54771-2015-1)
2 NDC:54771-2015-2 1 BLISTER PACK in 1 CARTON contains a BLISTER PACK
2 3 TABLET, CHEWABLE in 1 BLISTER PACK This package is contained within the CARTON (54771-2015-2)
3 NDC:54771-2015-3 2 BLISTER PACK in 1 CARTON contains a BLISTER PACK
3 3 TABLET, CHEWABLE in 1 BLISTER PACK This package is contained within the CARTON (54771-2015-3)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NADA NADA141452 02/24/2016
SIMPARICA CHEWABLES sarolaner tablet, chewable
Product Information
Product Type PRESCRIPTION ANIMAL DRUG Item Code (Source) NDC:54771-2016
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
SAROLANER (SAROLANER) SAROLANER 10 mg
Product Characteristics
Color BROWN Score no score
Shape SQUARE (Square with rounded edges) Size 8mm
Flavor LIVER Imprint Code
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:54771-2016-1 1 BLISTER PACK in 1 CARTON contains a BLISTER PACK
1 1 TABLET, CHEWABLE in 1 BLISTER PACK This package is contained within the CARTON (54771-2016-1)
2 NDC:54771-2016-2 1 BLISTER PACK in 1 CARTON contains a BLISTER PACK
2 3 TABLET, CHEWABLE in 1 BLISTER PACK This package is contained within the CARTON (54771-2016-2)
3 NDC:54771-2016-3 2 BLISTER PACK in 1 CARTON contains a BLISTER PACK
3 3 TABLET, CHEWABLE in 1 BLISTER PACK This package is contained within the CARTON (54771-2016-3)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NADA NADA141452 02/24/2016
SIMPARICA CHEWABLES sarolaner tablet, chewable
Product Information
Product Type PRESCRIPTION ANIMAL DRUG Item Code (Source) NDC:54771-2017
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
SAROLANER (SAROLANER) SAROLANER 20 mg
Product Characteristics
Color BROWN Score no score
Shape SQUARE Size 10mm
Flavor LIVER Imprint Code
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:54771-2017-1 1 BLISTER PACK in 1 CARTON contains a BLISTER PACK
1 1 TABLET, CHEWABLE in 1 BLISTER PACK This package is contained within the CARTON (54771-2017-1)
2 NDC:54771-2017-2 1 BLISTER PACK in 1 CARTON contains a BLISTER PACK
2 3 TABLET, CHEWABLE in 1 BLISTER PACK This package is contained within the CARTON (54771-2017-2)
3 NDC:54771-2017-3 2 BLISTER PACK in 1 CARTON contains a BLISTER PACK
3 3 TABLET, CHEWABLE in 1 BLISTER PACK This package is contained within the CARTON (54771-2017-3)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NADA NADA141452 02/24/2016
SIMPARICA CHEWABLES sarolaner tablet, chewable
Product Information
Product Type PRESCRIPTION ANIMAL DRUG Item Code (Source) NDC:54771-2018
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
SAROLANER (SAROLANER) SAROLANER 40 mg
Product Characteristics
Color BROWN Score no score
Shape SQUARE Size 14mm
Flavor LIVER Imprint Code
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:54771-2018-1 1 BLISTER PACK in 1 CARTON contains a BLISTER PACK
1 1 TABLET, CHEWABLE in 1 BLISTER PACK This package is contained within the CARTON (54771-2018-1)
2 NDC:54771-2018-2 1 BLISTER PACK in 1 CARTON contains a BLISTER PACK
2 3 TABLET, CHEWABLE in 1 BLISTER PACK This package is contained within the CARTON (54771-2018-2)
3 NDC:54771-2018-3 2 BLISTER PACK in 1 CARTON contains a BLISTER PACK
3 3 TABLET, CHEWABLE in 1 BLISTER PACK This package is contained within the CARTON (54771-2018-3)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NADA NADA141452 02/24/2016
SIMPARICA CHEWABLES sarolaner tablet, chewable
Product Information
Product Type PRESCRIPTION ANIMAL DRUG Item Code (Source) NDC:54771-2019
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
SAROLANER (SAROLANER) SAROLANER 80 mg
Product Characteristics
Color BROWN Score no score
Shape SQUARE Size 16mm
Flavor LIVER Imprint Code
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:54771-2019-1 1 BLISTER PACK in 1 CARTON contains a BLISTER PACK
1 1 TABLET, CHEWABLE in 1 BLISTER PACK This package is contained within the CARTON (54771-2019-1)
2 NDC:54771-2019-2 1 BLISTER PACK in 1 CARTON contains a BLISTER PACK
2 3 TABLET, CHEWABLE in 1 BLISTER PACK This package is contained within the CARTON (54771-2019-2)
3 NDC:54771-2019-3 2 BLISTER PACK in 1 CARTON contains a BLISTER PACK
3 3 TABLET, CHEWABLE in 1 BLISTER PACK This package is contained within the CARTON (54771-2019-3)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NADA NADA141452 02/24/2016
SIMPARICA CHEWABLES sarolaner tablet, chewable
Product Information
Product Type PRESCRIPTION ANIMAL DRUG Item Code (Source) NDC:54771-2020
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
SAROLANER (SAROLANER) SAROLANER 120 mg
Product Characteristics
Color BROWN Score no score
Shape SQUARE Size 19mm
Flavor LIVER Imprint Code
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:54771-2020-1 1 BLISTER PACK in 1 CARTON contains a BLISTER PACK
1 1 TABLET, CHEWABLE in 1 BLISTER PACK This package is contained within the CARTON (54771-2020-1)
2 NDC:54771-2020-2 1 BLISTER PACK in 1 CARTON contains a BLISTER PACK
2 3 TABLET, CHEWABLE in 1 BLISTER PACK This package is contained within the CARTON (54771-2020-2)
3 NDC:54771-2020-3 2 BLISTER PACK in 1 CARTON contains a BLISTER PACK
3 3 TABLET, CHEWABLE in 1 BLISTER PACK This package is contained within the CARTON (54771-2020-3)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NADA NADA141452 02/24/2016
Labeler — Zoetis Inc. (828851555)

Revised: 01/2021 Zoetis Inc.

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