FOI Summary; NADA 141-078 (original); HEARTGARD™ for Cats (ivermectin); December 23, 1996
--Editor's abstract

I. GENERAL INFORMATION

NADA Number: 141-078

Sponsor:

Merck Research Laboratories
Division of Merck & Co., Inc.
P.O. Box 2000
126 E. Lincoln Ave.
Rahway, New Jersey 07065-0914

Accepted Name: ivermectin

Trade Name: HEARTGARD™ for Cats

Marketing Status: A prescription (Rx) product which carries the following caution statement: "Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian."

II. INDICATIONS FOR USE

HEARTGARD™ for Cats is indicated for the prevention of feline heartworm disease by eliminating the tissue stage of heartworm larvae (Dirofilaria immitis) for a month (30 days) after infection, and for the removal and control of adult and immature (L4) hookworms (Ancylostoma tubaeforme and A. braziliense).

III. DOSAGE FORM, ROUTE OF ADMINISTRATION, AND DOSAGE

The ingredients in HEARTGARD™ for Cats are formulated in a palatable beef-based chewable in two sizes for cats of different weight classes. The chewables are to be administered orally at monthly intervals during the mosquito (vector of D. immitis) season, and provide a minimum of 24 mcg ivermectin per kg of body weight (10.9 mcg/lb) when given as follows:

 

         Cat Weight            Ivermectin
   _______________________     __________
    kg              lb
 __________       _______
  up to 2.3       up to 5        55 mcg
 2.3 to 6.8       5 to 15       165 mcg

For cats over 6.8 kg (15 lb) use the appropriate combination of chewables.

HEARTGARD™ for Cats is recommended for use in cats 6 weeks of age and older.

IV. EFFECTIVENESS

A. Dose Establishment

The dose was selected based on efficacy against adult A. tubaeforme which proved to be the dose-limiting parasite. In all efficacy trials, the percent efficacy was calculated for each treatment group as the Control Geometric Mean minus the Treated Geometric Mean divided by the Control Geometric Mean X100.

1. Hookworm Dose Determination Study: ASR 13872

a. Investigators: Dr. K. Todd and Dr. A. Paul, Univ. of Illinois, Urbana, Illinois

b. Study design:

1) Purpose: To determine the effective dose of ivermectin chewables against adult hookworms

2) Test animals: 32 cats (17 male, 15 female), 10 weeks to 7 months of age, 8 per group

3) Control: Vehicle chewables comprised of formulation excipients without active ingredient

4) Diagnosis: Cats were experimentally infected with infective larvae of Ancylostoma tubaeforme 22 days before treatment so that the infection was in the adult stage at the time of treatment.

5) Dosage form: Chewables

6) Route of administration: Oral

7 Dosages: 0, 12, 24, and 36 mcg/kg, tailored to body weight

8) Duration of study: Cats were necropsied on Day 7

9) Pertinent parameters measured: Worm counts at necropsy

c. Results: Efficacy of ivermectin against adult A. tubaeforme was 83.8%, 99.3% and 99.6% at 12, 24, and 36 mcg/kg, respectively. The dose plateaus at 24 mcg/kg.

d. Conclusion: 24 mcg/kg was selected as the dose of ivermectin providing >99% control of adult hookworms in cats

e. Adverse reactions: No adverse reactions were observed.

2. Heartworm Dose Determination Study: ASR 13660

a. Investigator: Dr. J. McCall, TRS Laboratories Inc., Athens, Georgia

b. Study design:

1) Purpose: To determine the effective dose of ivermectin chewables for preventing the development of heartworms (Dirofilaria immitis)

2) Test animals: 40 cats (20 male, 20 female), 8 to 8.5 months of age, 8 per group

3) Control: Vehicle chewables comprised of formulation excipients without active ingredient

4) Diagnosis: Cats were experimentally infected with infective larvae of D. immitis 30 days before treatment (cats in one group were infected 45 days before treatment)

5) Dosage form: Chewables

6) Route of administration: Oral

7) Dosages: 0, 12, 24, and 36 mcg/kg, tailored to body weight; administered 30 days after infection; and 12 mcg/kg, administered 45 days after infection (one group)

8) Duration of study: Cats were necropsied on Day 150

9) Pertinent parameters measured: Worm counts at necropsy

c. Results: Ivermectin was 100% effective at all dose levels in preventing the development of D. immitis.

d. Conclusion: Ivermectin administered at 12, 24, and 36 mcg/kg body weight prevents the development of D. immitis.

e. Adverse reactions: No adverse reactions were observed.

B. Dose Confirmation

1. Heartworm Dose Confirmation Studies: ASR 14324 and ASR 14328

a. Investigators: Dr. J. McCall, TRS Laboratories Inc., Athens, Georgia (ASR 14324); and Dr. L. Cruthers, Professional Laboratory and Research Services Inc., Corapeake, North Carolina (ASR 14328)

b. Study design:

1) Purpose: To confirm the efficacy of ivermectin chewables at 24 mcg/kg in preventing the development of Dirofilaria immitis

2) Test animals: ASR 14324: 20 cats (10 male, 10 female), 6.2 to 7.5 months of age, 10 cats per group; ASR 14328: 20 cats (10 males, 10 females), approximately 8 months of age, 10 cats per group

3) Control: Vehicle chewables comprised of formulation excipients without active ingredient

4) Diagnosi