SIMPARICA CHEWABLES- sarolaner tablet, chewable 
Zoetis Inc.

----------

Simparica

 Simparica

(sarolaner) Chewables

FOR ORAL USE IN DOGS ONLY

Caution

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

Description

SIMPARICA is a flavored, chewable tablet for administration to dogs over 6 months of age according to their weight.  Each tablet is formulated to provide a minimum sarolaner dosage of 0.91 mg/lb (2 mg/kg ) body weight. 

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 contains the S-enantiomer of sarolaner.

The chemical structure of the S-enantiomer of sarolaner is:

 Chemical Structure of Simparica

Chemical Structure of Simparica

INDICATIONS

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.

DOSAGE AND ADMINISTRATION

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

Dosage Schedule:

Body Weight

SAROLANER per Tablet (mg)

Number of Tablets Administered

2.8 to 5.5 lbs

5

One

5.6 to 11.0 lbs

10

One

11.1 to 22.0 lbs

20

One

22.1 to 44.0 lbs

40

One

44.1 to 88.0 lbs

80

One

88.1 to 132.0 lbs

120

One

>132.1 lbs

Administer the appropriate combination of tablets

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 refused. 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 reactions were recorded.

Table 1. Dogs with adverse reactions

Adverse reaction

sarolaner

sarolaner

active control

active control

         

N

%
(n = 315)

N

#
(n =164)

Vomiting

3

0.95%

9

5.50%

Diarrhea

2

0.63%

2

1.20%

Lethargy

1

0.32%

2

1.20%

Inappetence

0

0%

3

1.80%

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 (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.

.

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.

NADA #141-452, Approved by FDA

Distributed by:

Zoetis Inc.

Kalamazoo, MI 49007

Made in Switzerland

Revised: June 2017

PRINCIPAL DISPLAY PANEL 5 mg Carton

Simparica

(sarolaner) Chewables

Kills fleas before they lay eggs

Kills 5 types of ticks

Protection for a full month

1 liver-flavored tablet controls fleas and ticks for a month

Net Contents: 1 tablet containing 5 mg sarolaner

See back panel for dosing intervals

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

NADA #141-452, Approved by FDA

PRINCIPAL DISPLAY PANEL 5 mg Carton

PRINCIPAL DISPLAY PANEL 5 mg Carton

PRINCIPAL DISPLAY PANEL 10 mg Carton

Simparica

(sarolaner) Chewables

Kills fleas before they lay eggs

Kills 5 types of ticks

Protection for a full month

1 liver-flavored tablet controls fleas

and ticks for a month

Net Contents: 1 tablet containing 10 mg sarolaner

See back panel for dosing intervals

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

NADA #141-452, Approved by FDA

PRINCIPAL DISPLAY PANEL 10 mg Carton

PRINCIPAL DISPLAY PANEL 10 mg Carton

PRINICIPAL DISPLAY PANEL 20 mg Carton

Simparica

(sarolaner) Chewables

Kills fleas before they lay eggs

Kills 5 types of ticks

Protection for a full month

1 liver-flavored tablet controls fleas

and ticks for a month

Net Contents: 1 tablet containing 20 mg sarolaner

See back panel for dosing intervals

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

NADA #141-452, Approved by FDA

PRINICIPAL DISPLAY PANEL 20 mg Carton

PRINICIPAL DISPLAY PANEL 20 mg Carton

PRINCIPAL DISPLAY PANEL 40 mg Carton

Simparica

(sarolaner) Chewables

Kills fleas before they lay eggs

Kills 5 types of ticks

Protection for a full month

1 liver-flavored tablet controls fleas

and ticks for a month

Net Contents: 1 tablet containing 40 mg sarolaner

See back panel for dosing intervals

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

NADA #141-452, Approved by FDA

PRINCIPAL DISPLAY PANEL 40 mg Carton

PRINCIPAL DISPLAY PANEL 40 mg Carton

PRINCIPAL DISPLAY PANEL 80 mg Carton

Simparica

(sarolaner) Chewables

Kills fleas before they lay eggs

Kills 5 types of ticks

Protection for a full month

1 liver-flavored tablet controls fleas

and ticks for a month

Net Contents: 1 tablet containing 80 mg sarolaner

See back panel for dosing intervals

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

NADA #141-452, Approved by FDA

PRINCIPAL DISPLAY PANEL 80 mg Carton

PRINCIPAL DISPLAY PANEL 80 mg Carton

PRINCIPAL DISPLAY PANEL 120 mg Carton

Simparica

(sarolaner) Chewables

Kills fleas before they lay eggs

Kills 5 types of ticks

Protection for a full month

1 liver-flavored tablet controls fleas

and ticks for a month

Net Contents: 1 tablet containing 120 mg sarolaner

See back panel for dosing intervals

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

NADA #141-452, Approved by FDA

PRINCIPAL DISPLAY PANEL 120 mg Carton

PRINCIPAL DISPLAY PANEL 120 mg Carton

SIMPARICA CHEWABLES 
sarolaner tablet, chewable
Product Information
Product TypePRESCRIPTION ANIMAL DRUGItem Code (Source)NDC:54771-2015
Route of AdministrationORAL
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
SAROLANER (UNII: DM113FTW7F) (SAROLANER - UNII:DM113FTW7F) SAROLANER5 mg
Inactive Ingredients
Ingredient NameStrength
HYDROLYZED SOY PROTEIN (ENZYMATIC; 2000 MW) (UNII: 1394NXB9L6)  
STARCH, CORN (UNII: O8232NY3SJ)  
SUCROSE (UNII: C151H8M554)  
WHEAT GERM (UNII: YR3G369F5A)  
ANHYDROUS DIBASIC CALCIUM PHOSPHATE (UNII: L11K75P92J)  
CORN SYRUP (UNII: 9G5L16BK6N)  
GELATIN (UNII: 2G86QN327L)  
Product Characteristics
ColorBROWNScoreno score
ShapeSQUARE (Square with rounded edges) Size6mm
FlavorLIVERImprint Code
Contains    
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:54771-2015-32 in 1 CARTON
13 in 1 BLISTER PACK
2NDC:54771-2015-11 in 1 CARTON
21 in 1 BLISTER PACK
3NDC:54771-2015-21 in 1 CARTON
33 in 1 BLISTER PACK
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
NADANADA14145202/24/2016
SIMPARICA CHEWABLES 
sarolaner tablet, chewable
Product Information
Product TypePRESCRIPTION ANIMAL DRUGItem Code (Source)NDC:54771-2016
Route of AdministrationORAL
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
SAROLANER (UNII: DM113FTW7F) (SAROLANER - UNII:DM113FTW7F) SAROLANER10 mg
Inactive Ingredients
Ingredient NameStrength
HYDROLYZED SOY PROTEIN (ENZYMATIC; 2000 MW) (UNII: 1394NXB9L6)  
STARCH, CORN (UNII: O8232NY3SJ)  
SUCROSE (UNII: C151H8M554)  
WHEAT GERM (UNII: YR3G369F5A)  
ANHYDROUS DIBASIC CALCIUM PHOSPHATE (UNII: L11K75P92J)  
CORN SYRUP (UNII: 9G5L16BK6N)  
GELATIN (UNII: 2G86QN327L)  
Product Characteristics
ColorBROWNScoreno score
ShapeSQUARE (Square with rounded edges) Size8mm
FlavorLIVERImprint Code
Contains    
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:54771-2016-11 in 1 CARTON
11 in 1 BLISTER PACK
2NDC:54771-2016-21 in 1 CARTON
23 in 1 BLISTER PACK
3NDC:54771-2016-32 in 1 CARTON
33 in 1 BLISTER PACK
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
NADANADA14145202/24/2016
SIMPARICA CHEWABLES 
sarolaner tablet, chewable
Product Information
Product TypePRESCRIPTION ANIMAL DRUGItem Code (Source)NDC:54771-2017
Route of AdministrationORAL
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
SAROLANER (UNII: DM113FTW7F) (SAROLANER - UNII:DM113FTW7F) SAROLANER20 mg
Inactive Ingredients
Ingredient NameStrength
HYDROLYZED SOY PROTEIN (ENZYMATIC; 2000 MW) (UNII: 1394NXB9L6)  
STARCH, CORN (UNII: O8232NY3SJ)  
SUCROSE (UNII: C151H8M554)  
WHEAT GERM (UNII: YR3G369F5A)  
ANHYDROUS DIBASIC CALCIUM PHOSPHATE (UNII: L11K75P92J)  
CORN SYRUP (UNII: 9G5L16BK6N)  
GELATIN (UNII: 2G86QN327L)  
Product Characteristics
ColorBROWNScoreno score
ShapeSQUARESize10mm
FlavorLIVERImprint Code
Contains    
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:54771-2017-11 in 1 CARTON
11 in 1 BLISTER PACK
2NDC:54771-2017-21 in 1 CARTON
23 in 1 BLISTER PACK
3NDC:54771-2017-32 in 1 CARTON
33 in 1 BLISTER PACK
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
NADANADA14145202/24/2016
SIMPARICA CHEWABLES 
sarolaner tablet, chewable
Product Information
Product TypePRESCRIPTION ANIMAL DRUGItem Code (Source)NDC:54771-2018
Route of AdministrationORAL
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
SAROLANER (UNII: DM113FTW7F) (SAROLANER - UNII:DM113FTW7F) SAROLANER40 mg
Inactive Ingredients
Ingredient NameStrength
HYDROLYZED SOY PROTEIN (ENZYMATIC; 2000 MW) (UNII: 1394NXB9L6)  
STARCH, CORN (UNII: O8232NY3SJ)  
SUCROSE (UNII: C151H8M554)  
WHEAT GERM (UNII: YR3G369F5A)  
ANHYDROUS DIBASIC CALCIUM PHOSPHATE (UNII: L11K75P92J)  
CORN SYRUP (UNII: 9G5L16BK6N)  
GELATIN (UNII: 2G86QN327L)  
Product Characteristics
ColorBROWNScoreno score
ShapeSQUARESize14mm
FlavorLIVERImprint Code
Contains    
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:54771-2018-11 in 1 CARTON
11 in 1 BLISTER PACK
2NDC:54771-2018-21 in 1 CARTON
23 in 1 BLISTER PACK
3NDC:54771-2018-32 in 1 CARTON
33 in 1 BLISTER PACK
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
NADANADA14145202/24/2016
SIMPARICA CHEWABLES 
sarolaner tablet, chewable
Product Information
Product TypePRESCRIPTION ANIMAL DRUGItem Code (Source)NDC:54771-2019
Route of AdministrationORAL
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
SAROLANER (UNII: DM113FTW7F) (SAROLANER - UNII:DM113FTW7F) SAROLANER80 mg
Inactive Ingredients
Ingredient NameStrength
HYDROLYZED SOY PROTEIN (ENZYMATIC; 2000 MW) (UNII: 1394NXB9L6)  
STARCH, CORN (UNII: O8232NY3SJ)  
SUCROSE (UNII: C151H8M554)  
WHEAT GERM (UNII: YR3G369F5A)  
ANHYDROUS DIBASIC CALCIUM PHOSPHATE (UNII: L11K75P92J)  
CORN SYRUP (UNII: 9G5L16BK6N)  
GELATIN (UNII: 2G86QN327L)  
Product Characteristics
ColorBROWNScoreno score
ShapeSQUARESize16mm
FlavorLIVERImprint Code
Contains    
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:54771-2019-11 in 1 CARTON
11 in 1 BLISTER PACK
2NDC:54771-2019-21 in 1 CARTON
23 in 1 BLISTER PACK
3NDC:54771-2019-32 in 1 CARTON
33 in 1 BLISTER PACK
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
NADANADA14145202/24/2016
SIMPARICA CHEWABLES 
sarolaner tablet, chewable
Product Information
Product TypePRESCRIPTION ANIMAL DRUGItem Code (Source)NDC:54771-2020
Route of AdministrationORAL
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
SAROLANER (UNII: DM113FTW7F) (SAROLANER - UNII:DM113FTW7F) SAROLANER120 mg
Inactive Ingredients
Ingredient NameStrength
HYDROLYZED SOY PROTEIN (ENZYMATIC; 2000 MW) (UNII: 1394NXB9L6)  
STARCH, CORN (UNII: O8232NY3SJ)  
SUCROSE (UNII: C151H8M554)  
WHEAT GERM (UNII: YR3G369F5A)  
ANHYDROUS DIBASIC CALCIUM PHOSPHATE (UNII: L11K75P92J)  
CORN SYRUP (UNII: 9G5L16BK6N)  
GELATIN (UNII: 2G86QN327L)  
Product Characteristics
ColorBROWNScoreno score
ShapeSQUARESize19mm
FlavorLIVERImprint Code
Contains    
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:54771-2020-11 in 1 CARTON
11 in 1 BLISTER PACK
2NDC:54771-2020-21 in 1 CARTON
23 in 1 BLISTER PACK
3NDC:54771-2020-32 in 1 CARTON
33 in 1 BLISTER PACK
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
NADANADA14145202/24/2016
Labeler - Zoetis Inc. (828851555)
Establishment
NameAddressID/FEIBusiness Operations
Siegfried AG482824026API MANUFACTURE
Establishment
NameAddressID/FEIBusiness Operations
Zoetis LLC039055157MANUFACTURE

Revised: 3/2018
Document Id: 1594ff27-1075-4cf1-89ab-7eab2edb542e
Set id: 91fc9ba1-35e6-4e37-8c37-c5e40699bd5b
Version: 7
Effective Time: 20180306
 
Zoetis Inc.