Approval Date: June 17, 1998

Freedom of Information Summary
NADA 141-084

I. GENERAL INFORMATION:

NADA	141-084
Sponsor:	Novartis Animal Health US, Inc. Post Office Box 26402 Greensboro, NC 27404
Generic Name:	Milbemycin Oxime/Lufenuron Tablets
Trade Name:	SENTINEL™ Flavor TabsÒ
Marketing Status:	Rx: U.S. Federal law restricts this drug to use by or on the order of a licensed veterinarian
Effect of Supplement:	Approval of this supplemental NADA will change NADA 141-084 by adding a flavored tablet formulation with the same indications. The flavored tablets (in three tablet sizes) will replace the swallow tablets for dogs ³ 11 pounds. The swallow tablet will remain for dogs between 2-10 lbs.

II. INDICATIONS FOR USE

SENTINEL Flavor Tabs are indicated for use in dogs and puppies four weeks of age and older and eleven pounds body weight or greater, for the prevention of heartworm disease caused by Dirofilaria immitis, for the prevention and control of flea populations, the control of adult Ancylostoma caninum (hookworm), and the removal and control of adult Toxocara canis, Toxascaris leonina (roundworm) and Trichuris vulpis (whipworm) infections.

III. DOSAGE FORM, ROUTE OF ADMINISTRATION AND RECOMMENDED DOSAGE

SENTINEL Flavor Tabs are given orally, once a month, at the recommended minimum dosage of 0.23 mg/lb (0.5 mg/kg) milbemycin and 4.55 mg/lb (10 mg/kg) lufenuron.

Recommended Dosage Schedule

 

Body Weight	Milbemycin Oxime Per Tablet	Lufenuron Per Tablet	Product
2 to 10 lbs.	2.3 mg	46 mg	SENTINEL
11-25 lbs.	5.75 mg	115 mg	SENTINEL Flavor Tabs
26-50 lbs.	11.5 mg	230 mg	SENTINEL Flavor Tabs
51-100 lbs.	23.0 mg	460 mg	SENTINEL Flavor Tabs

Dogs over 100 lbs. are provided the appropriate combination of tablets.

IV. EFFECTIVENESS

The effectiveness of SENTINEL Flavor Tabs is based upon existing Novartis product approvals for milbemycin oxime (INTERCEPTORÒ Tablets, NADA 140-915) and lufenuron (PROGRAMÒ Tablets, NADA 141-035), the combination product (SENTINEL tablets NADA 141-084), and the following study comparing SENTINEL tablets and SENTINEL Flavor Tabs.

1) Hookworm Efficacy Study with Flavored Tablet

Purpose:

SENTINEL tablets and SENTINEL Flavor Tabs were compared for efficacy against hookworms (Ancylostoma caninum).

Investigator:

Dwight Bowman, Ph.D.

Study Location:

CHK - R&D
Stanwood, Michigan

Type of Study:

Natural infections of hookworms Ancylostoma caninum.

Animals:

Thirty adult dogs (15 males, 15 females) were divided into three groups of ten dogs each.

Dosage Forms:

Group 1: Placebo Tablets

Group 2: SENTINEL (milbemycin oxime/lufenuron) tablets

Group 3: SENTINEL Flavor Tabs (milbemycin oxime/lufenuron)

Route of Administration:

Oral

Dose Tested:

Milbemycin Oxime 0.5 mg/kg

Lufenuron 10 mg/kg

Frequency of Treatment:

One treatment.

 

Controls:

Placebo control (group 1)

 

Duration of Study:

The dogs were euthanized 9 days after treatment and worms were recovered, identified and counted.

 

Results:

Efficacy was calculated by comparing the number of worms recovered from each of the two treatment groups versus control animals. The following table shows the mean (geometric) number of worms recovered and the percent efficacy for each group.

 

Treatment	Mean # of Worms	% Efficacy
Placebo	14.4	---
SENTINEL	0.0	100
SENTINEL Flavor Tabs	0.07	99.5

Using Wilcoxon Rank Sum Tests, the comparisons of Placebo versus SENTINEL FLAVOR TABS (p < .0001), Placebo versus SENTINEL (p < .0001), and SENTINEL FLAVOR TABS versus SENTINEL (p = .3681) indicated that both SENTINEL FLAVOR TABS and SENTINEL tablets were significantly different from Placebo tablets and were not different from one another. Both SENTINEL FLAVOR TABS and SENTINEL tablets were ³ 99.5% effective in eliminating hookworms from infected dogs when compared to Placebo tablets. There was no difference in effectiveness between SENTINEL FLAVOR TABS- and SENTINEL-treated dogs.

 

Conclusions:

The flavored tablet formulation was equally efficacious as the non-flavored tablet formulation against Ancylostoma caninum infections.

 

Adverse Reactions:

None reported.

 

2) Clinical Palatability/Acceptability Trial

Purpose: To assess the palatability/acceptability of SENTINEL Flavor Tabs in a clinical trial

 

Investigator/Study Locations:

Dr. Charles Ward The Animal Hospital 112 W. Main Carrboro, NC 27510		Dr. Benjamin Jones Friendly Animal Clinic 712 Guilford College Rd. Greensboro, NC 27410
Dr. Pat Cryan Cryan Veterinary Hospital 298 N. West Street Westerville, OH 43081		Dr. Robert Cape Greene Meadows Veterinary Hospital 127 Greene Meadows Dr. South Westerville, OH 43081
Dr. Jodi Black Best Friends Veterinary Service 1328 Hwy. 65 Eckert, CO 81418		Dr. Mark Leavell Radford Hills Animal Clinic 1109 N. Judge Ely Abilene, TX 79601
Dr. Jerry Greene Academe Animal Hospital 912 East Fletcher Avenue Tampa, FL 33612		Dr. Todd Henderson San Angelo Veterinary Hospital 108 N. Milton San Angelo, TX 76901
Dr. Leonard Sigdestad Loma Linda Animal Hosp. 2605 S. Waterman Ave. San Bernardino, CA 92408

Type of Study:

Palatability/Acceptability

 

Animals:

Two hundred twenty-five client-owned dogs were enrolled in the study, though only 223 were dosed. One dog was found to be heartworm positive and one dog was hit by a car and killed prior to dosing. Fifteen dogs were dosed with the drug and completed the study but were excluded from analysis for the following reasons: owner non-compliance (4) or use of concomitant drugs that could potentially affect appetite (11). A total of 208 dogs (109 F, 99 M) ranging in age from 2 months to 13 years and in weight from 2 to 100 pounds were included in the analysis of palatability/acceptability.

 

Dosage Forms:

SENTINEL Flavor Tabs (Milbemycin Oxime/Lufenuron)

Route of Administration: Oral

Dose Tested: Milbemycin Oxime 0.5 mg/kg
Lufenuron 10 mg/kg

Frequency of Treatment: One dose

Controls: None

Duration of Study:

Dogs were offered the tablets by hand and palatability/ acceptability was assessed within 3 minutes. If the dogs did not consume the tablets within this period, the owners were instructed to place the tablets in the food bowl and wait an additional 3 minutes. If this was unsuccessful, the tablets were placed in the dogs’ mouths followed by direct manually dosing, if necessary.

Results:

Results are displayed in the following table.

Absolute and Cumulative responses provided by Owners.

 

Question	#Yes	%	Cum. N	Cum %
1 Consumed the tablet when offered from the hand	173	83.0%	--	--
2 Consumed the tablet when offered from food bowl	7	3.4%	180	86.5%
3 Consumed the tablet when placed in dogs mouth	13	6.3%	193	92.8%
4 Accepted the tablet when attempted to "pill" the dog	12	5.8%	205	98.6%
5 Refused tablet	3	1.4%	208	100%

 

Conclusions:

SENTINEL Flavor Tabs are palatable to dogs.

Adverse Reactions:

None reported.