Animal & Veterinary
NADA 141-035 Program® Cat Tabs - supplemental approval (January 23, 1997)
Approval Date: January 23, 1997
I. GENERAL INFORMATION:
|Sponsor:||Novartis Animal Health US, Inc.
Post Office Box 18300
Greensboro, NC 27419-8300
|Trade Name:||Program® Cat Tabs|
|Marketing Status:||Over the Counter (OTC)|
|Effect of Supplement:||Approval of the supplemental NADA will change NADA 141-035 by adding the indication for the use of lufenuron tablets in cats and kittens, six weeks of age or older, at a minimum dose of 30 mg/kg for the control of flea populations. The cat [sic] will have labeling separate from the original dog approval.|
II. INDICATIONS FOR USE
PROGRAM Cat Tablets are indicated for use in cats and kittens, six weeks of age and older, for the control of flea populations.
|A.||DOSAGE FORM||Oral Tablets|
|B.||ROUTE OF ADMINISTRATION||
PROGRAM Cat Tablets should be given by direct oral dosing or broken into wet food. In either case, give in conjunction with a full meal.
The tablet may need to be broken prior to direct oral dosing for ease of administration to small cats and kittens. In multi-cat households, cats should be separated during treatment to achieve adequate dosing in each cat.
PROGRAM Cat Tablets are given orally, once a month, at the recommended minimum dosage of 13.6 mg lufenuron per pound (30mg/kg) of body weight.
Recommended Dosage Schedule ----------------------------------------- Body Weight Dose & Tablet Color Lufenuron Per Tablet ------------- ------------------- -------------------- Up to 6 lbs. One red tablet 90.0 mg 7 to 15 lbs. One yellow tablet 204.9 mg Cats over 15 lbs are provided the appropriate combination of tablets.
Lufenuron is an insect development inhibitor which breaks the flea life cycle at the egg stage. The adult female flea is exposed to the drug when feeding on a treated cat. The drug, which has no deleterious effect on the adult flea, acts to inhibit the development of flea eggs. The mode of action is interference with the synthesis, polymerization and deposition of chitin, the major supportive component of the flea egg case and cuticle that forms the exoskeleton of larval stages.
A. Range-Finding Study in Cats to Determine Blood Levels of Lufenuron and Its Efficacy Against Adult Flea Emergence Using Different Dosage Forms of PROGRAM.
Purpose: PROGRAM Tablets and PROGRAM Suspension were compared for flea control and changes in lufenuron blood levels
Investigator: Mark S. Holbert. B.S.
Sugar Land, Texas
Type of Study: Experimental infestations of the cat flea, Ctenocephalides felis.
Animals: Twenty-two adult domestic mixed breed cats, 11 males and 11 females, ranging in weight from 2.0 to 3.2 kg were used. The 22 animals were divided into 4 groups, 1 untreated control group of 4 animals and 3 treated groups of 6 animals.
Group 2: Lufenuron Tablets, crushed and mixed with food
Group 3: Lufenuron Tablets, pilled with tablet pieces followed immediately by food
Group 4: Lufenuron Suspension, mixed with food
Route of Administration: Oral
Dose Tested: 30 mg/kg body weight
Frequency of Treatment: Two treatments, Day 0 and Day 30
Controls: Group 1: Untreated control group
Duration of Study: Cats were experimentally infested with 100 cat fleas on study Days -1, 24, 29, and 54. The cats in Groups 2 through 4 were treated with lufenuron on Days 0 and 30. Flea eggs were collected from each cat on Days 5, 30, 35, and 60. The number of adult fleas emerging from these eggs were counted 36 days after they were collected. Blood was collected at 8, 24, 48, 96 hours and 7, 21, and 29 days after treatment. The 24-, 48-, 96-hour and Day 29 blood samples were analyzed for lufenuron.
Results: Efficacy was calculated by comparing the development of eggs collected from fleas feeding on each of the 3 lufenuron-treated groups versus control animals. The following table shows the percent efficacy for each treatment group for each day eggs were collected.
Percent Efficacy Compared to Control ------------------------------------------ Group Day 5 Day 30 Day 35 Day 60 ----- ----- ------ ------ ------ 1 N/A N/A N/A N/A 2 97.0 96.4 97.7 95.5 3 90.7 88.0 98.7 92.6 4 86.8 94.1 97.6 88.2
The 95% confidence interval method was used to determine if the two forms of PROGRAM Tablets (crushed in food or manually dosed as pieces) were therapeutically equivalent to PROGRAM Suspension. The 95% confidence interval was calculated on the difference between the percent of eggs with non-emerging adults using the following pairwise treatment group comparisons:
- Group 2 versus Group 4,
- Group 3 versus Group 4
- Group 1 versus Group 2
- Group 1 versus Group 3 and
- Group 1 versus Group 4
Each treated group had a non-emergence rate statistically significantly different from and better than the control group (comparisons 3, 4 and 5 above). Comparison 2 above (between groups 3 and 4) had a 95% confidence interval on the difference of (-0.00544, 0.01764) and Comparison 1 above (between groups 2 and 4) had a 95% confidence interval on the difference of (0.01056, 0.03104).
The following table shows the mean lufenuron concentrations.
Mean Blood Concentration (± Standard Deviation) ---------------------------------------------------- Group Day 1 Day 2 Day 4 Day 29 ------------------------------------------------------------------- 2 542 ± 372 294 ± 264 299 ± 283 165 ± 172 3 344 ± 240 210 ± 152 171 ± 136 96 ± 59 4 435 ± 267 325 ± 285 192 ± 63 135 ± 59
The area under the curve (AUC) calculations to Day 29 show that the crushed tablets (Group 2) and the suspension mixed with food (Group 4) have similar bioavailabilities which are both greater than the manually dosed tablets (Group 3). However, due to the small number of animals studied and the large degree of intersubject variability, the test for treatment effects lacks the necessary power to derive meaningful statistical conclusions. Based on the efficacy parameter (egg hatch), there is no clinical difference between treatment Groups 2, 3 and 4.
Conclusions: PROGRAM Tablets, when administered to cats by either direct oral dosing of tablet pieces or crushed in wet food are therapeutically equivalent to PROGRAM Suspension administered in food.
This study indicates that PROGRAM Cat Tablets are therapeutically equivalent to PROGRAM Suspension, therefore the efficacy data provided in support of PROGRAM Suspension can be referenced from NADA 141-026. Refer to the original Freedom of Information Summary for NADA 141-026 for additional information on efficacy studies conducted with PROGRAM Suspension.
Adverse Reactions: None reported.
B. PROGRAM (Lufenuron) Swallow Tablets: Evaluation of Dosage Form Acceptability in Cats Study # CAH-6258-95-0297
Purpose: To evaluate the acceptability of PROGRAM (lufenuron) Tablets when administered orally to cats
Jodi Black, DVM
Best Friends Veterinary Service
1328 Highway 65
Elkert, CO 81418 Mark Silvers, DVM
Cat Clinic of Greensboro
2138-B Lawndale Drive
Greensboro, NC 27408
Type of Study: Field dosage form acceptability trial
Animals: 101 client owned cats with 99 completing the study and included in the analysis of dosage form acceptability. Of these 99 cats, 42 were female and 57 were male. These cats ranged in age from 8 weeks to 12 years and in weight from 1.25 to 16.8 pounds.
Dosage Form: Oral tablet
Route of Administration: The cat owners were instructed to dose the cat just prior to feeding by first placing the tablet directly in the mouth. If dosing by this method was unsuccessful, the tablet was to be broken into a small portion of wet food and offered to the cat.
Dose Tested: Minimum of 30 mg/kg, according to the dosing scale
Frequency of Treatment: Once
Duration of Study: September 26 through October 10, 1995
Results: Of the 99 cats completing the study, 93 were successfully dosed for a 94% acceptance rate. Of the 93 cats accepting the tablet, 66 accepted the tablet when placed directly in the mouth and 27 accepted the tablet when broken into food.
Manually Dosed 66/99 67% Dosed in Food 27/99 27% ---------------------------- Total Dosed 93/99 94%
Some owners reported on the case report forms that the size of the pill made dosing difficult, prevented manual administration of the pill, or simply looked large compared to the size of the cat.
Conclusions: PROGRAM Tablets are an acceptable dosage form for administration to cats.
Adverse Reactions: None reported.
V. ANIMAL SAFETY
Study A cited above indicates that PROGRAM Cat Tablets are therapeutically equivalent to PROGRAM Suspension, therefore the safety data provided in support of PROGRAM Suspension can be referenced from NADA 141-026. Refer to the original Freedom of Information Summary for NADA 141-026 for additional information on target animal safety studies conducted with PROGRAM Suspension.
VI. HUMAN FOOD SAFETY:
Data on human safety, pertaining to consumption of drug residues in food, were not required for approval of this Supplement. This drug is to be labeled for use in cats 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 PROGRAM Cat Tablets (lufenuron), 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 an additional species (cat) at a minimum dose of 30 mg/kg for the control of flea populations. The approval of this change has no adverse effect on the safety and effectiveness of the this new animal drug application. Accordingly, this approval did not require a reevaluation of the safety and effectiveness data in the parent application.
Because adequate directions for the safe and effective lay use of PROGRAM Cat Tabs could be written, the product has been labeled for over-the-counter distribution.
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 species for which the supplemental application was approved
VIII. LABELING (Attached)
- Blister Cards (6 Tablets)
- 90 mg
- 204.9 mg
- Bulk Package (60 Tablets)
- 90 mg
- 204.9 mg
- Dispensing Envelo pe
- Outer flap
- Inner flap
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