Approval Date: Sep. 9, 1996
I. GENERAL INFORMATION:
Animal Health Division
Post Office Box 18300
Greensboro, NC 27419-8300
Milbemycin Oxime Tablets
Effect of Supplement:
This supplement expands the indications to include the removal and control of adult roundworms Toxascaris leonina. Laboratory data support the efficacy of the drug against this species.
II. INDICATIONS FOR USE
INTERCEPTOR FLAVOR TABS are indicated for use in the prevention of heartworm disease caused by Dirofilaria immitis, the control of adult Ancylostoma caninum (hookworm), and the removal and control of adult Toxocara canis and Toxascaris leonina (roundworms), and Trichuris vulpis (whipworm) infections in dogs and in puppies four weeks of age or greater and two pounds of body weight or greater.
III. DOSAGE FORM(S), ROUTE OF ADMINISTRATION AND RECOMMENDED DOSAGE
The ingredients of INTERCEPTOR FLAVOR TABS are formulated into various sized tablets to be administered orally (swallow or chew), as appropriate for the weight of the dog (see below), at monthly dosing intervals. The tablets supply the recommended minimum dose level of 0.5 mg milbemycin oxime per kilogram (0.23 mg/lb.) of body weight.
Tablet Milbemycin Oxime
|Dog Weight||Per Month||Per Tablet|
|Up to 10 lbs.||1||2.3 mg|
|11 to 25 lbs.||1||5.75 mg|
|26 to 50 lbs.||1||11.5 mg|
|51 to 100 lbs.||1||23.0 mg|
Dogs over 100 lbs. are provided the appropriate combination of these tablets.
A. Dose Establishment
No additional dose establishment work was required. The minimum target dose of milbemycin oxime 0.5 mg/kg body weight was established in the original NADA 140-915 for the currently approved label indications.
One dose confirmation study (Trial AH-93-0045) was conducted to evaluate the effectiveness of milbemycin oxime in the removal and control of the adult roundworm, Toxascaris leonina. Twenty-four dogs were infected with eggs of Toxascaris leonina by oral inoculation 75-77 days pre-treatment. Twelve dogs were given a treatment of 0.5 mg/kg minimum dose of milbemycin oxime one time and 12 were untreated. All dogs were necropsied 7 days post-treatment, and all intestinal parasites were recovered, identified and counted.
17190 Polk Road
Stanwood, MI 49346
Dwight D. Bowman, Ph.D.
- 21.5 to 27 week old Beagle dogs
- 13 males and 11 females
- 5.3 to 10.6 kg
One adult worm was recovered from the 12 treated dogs compared to 159 worms from the 12 untreated control dogs. The milbemycin oxime treatment was calculated to be 99.4% efficacious.
This study demonstrated the efficacy of Interceptor Flavor Tabs against T. leonina.
C. 1989 Clinical Field Trial
A clinical field trial (MT-147-00-89) was conducted during 1989-90 to evaluate the safety and efficacy of monthly administration of milbemycin oxime for the additional indications of removal and control of roundworms and whipworms when used under typical veterinary conditions. Safety and efficacy data from animals infected with roundworms was extracted to support the label change for this supplement to the NADA. In this study, 100% (62 of 62) of the roundworm cases were successfully treated by study completion (See Table 1).
(Eds note: The following table consists of 4 columns.)
TABLE 1 : Effects of Milbemycin Oxime on Removal and Control of Adult Roundworm Infections in Dogs During Clinical Field Trials.
|Investigator/Location||Treatment||No. of Dogs Completing Study||Roundworm Infections|
|Totals||Milbemycin||86||62/62 = 100%|
|Filaribits||85||67/66 = 98%|
2 - "Cured" means no eggs found at final fecal examination.
D. Prevalence Study
National Prevalence of Canine Parasites based on Centrifugal Sucrose Flotation Examinations of Fecal Specimens, B. L. Blagburn, D. S. Lindsay, J. L. Vaughan, R. C. Lynn, W. J. Kelch, G. C. Ritchie, D. I. Hepler, July 6-10, 1995, Joint Meeting of the American Association of Veterinary Parasitologists/American Society of Parasitologists, Pittsburg, PA.
Fecal specimens (6,458 in total) were collected from dogs housed in animal shelters and analyzed by Dr. Byron L. Blagburn, Auburn University. The animal shelters were selected from the largest cities in each state. Fresh fecal specimens, collected individually into 120 ml plastic specimen cups were examined using the centrifugal sucrose flotation procedure. Specimen cups were placed in styrofoam shipping boxes containing "cold pack" inserts, and shipped to Dr. Blagburn's laboratory at Auburn University via overnight courier. Specimens could contain more than one type of parasite. Thus, the percentages presented below indicate the percent of specimens that contained the particular parasite and do not add to 100 percent.
|Parasite||% of Total|
Conclusion: Based upon the 99.4% efficacy demonstrated in the dose confirmation study, the 100% efficacy in the MT-147-00-89 Clinical Field Trial (including the probability albeit low that some of the roundworms may have been Toxascaris leonina cases), this data is adequate to support the expansion of the roundworm claim.
V. ANIMAL SAFETY
This supplemental NADA does not require re-evaluation of target animal safety data submitted in support of the initial NADA No. 140-915. Please refer to the original Freedom of Information Summary (NADA 140-915) for additional information on target animal safety studies.
VI. HUMAN SAFETY:
Data on human safety, pertaining to consumption of drug residues in food, were not required for approval of this supplemental NADA. The drug is to be labeled for use in dogs, which are non-food animals.
VII. AGENCY CONCLUSIONS:
The data in support of this supplemental NADA application complies with the requirements of Section 512 of the Act and Section 514.111 of the implementing regulations. It demonstrates that Interceptor® Flavor Tabs, when used under the 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 an additional claim for the removal and control of the adult roundworm, Toxascaris leonina. This approval relied upon the safety and effectiveness data in the parent application and evaluation of new efficacy data submitted in the supplemental application.
Under section 512(c)(2)(F)(iii) of the Federal Food, Drug, and Cosmetic Act (FFDCA), this approval qualifies for THREE years of marketing exclusivity beginning on the date of approval because the supplemental application contains reports of new clinical or field investigations (other than bioequivalence studies) essential to the approval of the application and conducted or sponsored by the applicant. The three years of marketing exclusivity applies only to the additional roundworm claim (Toxascaris leonina) for which the supplemental application was approved. This exclusivity period will expire three years from the date of the approval letter.
The drug is restricted to use by or on the order of a licensed veterinarian because professional expertise is required to determine the existence of hookworm roundworm and/or whipworm infection. In addition, professional expertise is required to determine the existence of heartworm infection, and then properly treat existing heartworm infection prior to starting treatment with Interceptor ® (milbemycin oxime) Flavor Tabs in a prevention program.
VIII. LABELING (Attached)
- Veterinary Package insert
- Client Package insert
Copies of these labels may be obtained by writing to the:
Freedom of Information Office
Center for Veterinary Medicine, FDA
7500 Standish Place
Rockville, MD 20855