Approval Date: June 4, 1998

Freedom of Information Summary
NADA 140-915

I. GENERAL INFORMATION:

NADA	140-915
Sponsor:	Novartis Animal Health Post Office Box 26402 Greensboro, NC 27404-6402
Generic Name:	Milbemycin Oxime Tablets
Trade Name:	SAFEHEARTä
Marketing Status:	Rx, For use by or on the order of a licensed veterinarian
Effect of Supplement	Approval of the supplemental NADA will change NADA 140-915 by adding a lower dosage for use in the prevention of heartworm disease only in dogs and puppies and a new tradename, Safeheartä . The original conditions of approval for Interceptorâ under NADA 140-915 remain unchanged by this supplement.

II. INDICATIONS FOR USE

SAFEHEARTä Tablets are indicated for use in the prevention of heartworm disease in dogs and puppies four weeks of age or greater and two pounds body weight or greater

III. DOSAGE

A.	DOSAGE FORM	Oral Tablets
B.	ROUTE OF ADMINISTRATION	SAFEHEARTä Tablets should be given by direct oral dosing.
C.	RECOMMENDED DOSAGES:	SAFEHEARTä Tablets are given orally, once a month, at the recommended minimum dosage of 0.1 mg milbemycin oxime per kg of body weight (0.05 mg/lb).
	Recommended Dosage Schedule	Body Weight Tablet Size 2 -50 lbs. One Tablet (2.3 mg) 50.1 - 125 lbs. One Tablet (5.75 mg)
	NOTES	Dogs over 125 lbs. are provided the appropriate combination of tablets.

 

IV. EFFECTIVENESS

Milbemycin oxime is an anthelmintic compound which, when given orally to animals, is effective in eliminating the tissue stage of heartworm larvae. The anthelmintic activity is believed to be a result of interference with invertebrate neurotransmission.

A. Dose Establishment Studies

Dose establishment studies in support of this product are referenced in the Freedom of Information (FOI) Summary for the original NADA 140-915 approval.

B. Well-Controlled Clinical Field Trial

Study No. CAH-4303-95-0096

Purpose: To evaluate the efficacy of milbemycin oxime when administered monthly at a minimum of 0.1 mg/kg by the pet owner for heartworm prevention.

Investigators/Study Locations:

Dr. William Craig Ingram Park Animal Hospital San Antonio, TX

Dr. Karen Kennedy Guilford-Jamestown Veterinary Hospital Greensboro, NC

Dr. Dan J. McIlhany Towne North Animal Hospital San Antonio, TX

 

Type of Study: Clinical trial in client-owned dogs.

Animals: One hundred thirty-four (134) of the 150 client-owned dogs enrolled completed the 12 month study. Sixty-six (66) of the dogs that completed the study were in the low dose treatment group and sixty-eight (68) were in the positive control group.

Dosage Form: SAFEHEARTä Tablets

Route of Administration: Oral

Dose Tested: Minimum dose of 0.1 mg/kg

Frequency of Treatment: Monthly for 12 months. All dogs were tested for D. immitis microfilaria and antigen at months 5 and 12.

Control: Interceptorâ (milbemycin oxime) Flavor Tabs (minimum dose of 0.5 mg/kg)

NADA 140-915

Duration of Study: Twelve months

Results: All dogs from both treatment groups were negative for D. immitis microfilaria and adult antigen at months 5 and 12.

Conclusions: The low dose of milbemycin oxime (0.1 mg/kg) provides effective heartworm prevention in the dog.

Adverse Reactions: The following clinical observations were noted during the study.

	Number of Enrolled Dogs
Observations	Safeheartä (n = 75)	Interceptorâ (n = 75)
Anorexia/¯ appetite	4	0
Vomiting	3	3
Diarrhea	3	1
Lethargy	2	1

 

V. ANIMAL SAFETY

Target animal safety studies in support of this supplement are referenced in the FOI Summary for the original NADA 140-915 approval.

VI. HUMAN SAFETY

Data on human safety, pertaining to consumption of drug residues in food were not required for approval of this supplemental NADA. This drug is to be labeled for use in dogs which are non-food animals. 

VII. AGENCY CONCLUSIONS:

The data in support of this supplement comply with the requirements of Section 512 of the Act and Part 514 of the implementing regulations. The data demonstrate that SAFEHEARTä (milbemycin oxime) Tablets, when used under labeled conditions of use, are safe and effective.

According to the Center’s supplemental approval policy (21 CFR 514.106) this is a Category II change. This supplement provides for a change in dose for dogs from a minimum of 0.5 mg/kg to a minimum of 0.1 mg/kg with a corresponding restriction in indications to the prevention of heartworm disease only.

The drug is restricted to use by or on the order of a licensed veterinarian because professional expertise is judged to be critical for the diagnosis of heartworms and for the safe use of the product.

Under section 512(c)(2)(F)(iii) of the FFDCA, this approval for non food producing animals qualifies for THREE years of marketing exclusivity beginning on the date of approval because the supplemental application contains substantial evidence of the effectiveness of the drug involved, or any studies of animal safety, required for the approval of the application and conducted or sponsored by the applicant. The three years of marketing exclusivity applies only to the new dose and restricted indication for which the supplemental application was approved.

Patent # 4,547,520 expires on June 14, 2004

 

VIII. LABELING (Attached)

Veterinary Insert
Client Insert
Blister Pack
Tablet Carton
Display Carton
Shipper Carton

Copies of applicable labels may be obtained by writing to the:

Freedom of Information Office
Center for Veterinary Medicine, FDA
7500 Standish Place
Rockville, MD 20855