(S)-Methoprene: what the FDA reviewed for dog products
1 Freedom of Information summary from the FDA Center for Veterinary Medicine for products containing (S)-Methoprene, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dogs.
Products
- Hartz® Flea Control Capsules™ Zodiac® Fleatrol Flea Caps™ (NADA/ANADA 141-162)
Hartz® Flea Control Capsules™ Zodiac® Fleatrol Flea Caps™ NADA 141-162, Original approval, January 24, 2000; sponsor Wellmark International; species: Dogs; foi_id 533; FDA PDF
Indication
Prevention and control of flea populations in dogs nine weeks of age and older and 4 pounds or more (insect growth regulator; inhibits flea egg development, does not kill adult fleas).
Dose regimen
10 mg (S)-Methoprene per pound of body weight (22 mg/kg) minimum, oral (capsule), once per week, given according to a body-weight capsule schedule (1-4 capsules of 154/308/462 mg)
The capsules are given orally once per week at the recommended minimum dosage of 10 mg (S)-Methoprene per pound of body weight (22 mg/kg) according to the following schedule.
Target-animal safety
dose multiples 1X, 3X, 5X, 10X; duration once weekly for 13 weeks (1X, 3X, 5X; 90-day study); 10X once weekly for 4 weeks (28 days); animals 32.
32 Beagle puppies (16 males and 16 females), approximately 6-weeks old, 1.62-2.10 kg body weight. Groups 1-4 (6/group) and Groups 5 and 6 (4/group), divided equally by sex
| Finding | Quote |
|---|---|
| No adverse effects on body weight, food consumption, ophthalmology, clinical pathology, urinalysis, organ weights, gross pathology or histology; clinical signs were depression, ataxia and tremors. | There were no adverse effects on body weight, food consumption, ophthalmology, clinical pathology, urinalyses, organ weights, gross pathology or histology. The clinical signs included depression, ataxia (loss of balance) and tremors. |
| Depression, ataxia and tremors occurred at 1X, 3X, 5X and 10X in 6-week-old puppies (all returned to normal by the next observation). | (S)-Methoprene capsules caused clinical signs including depression, ataxia and tremors when administered at 1X, 3X, 5X and 10X the recommended dose in 6 week old puppies. |
| Depression recurred on days 0 and 7 in two 3X dogs and one 10X dog; by day 14 only one dog showed mild depression. | Two dogs in the 3x treatment group and 1 in the 10x group exhibited depression twice on days 0 and 7. By day 14 only 1 dog exhibited mild depression. |
| Conclusion: safe up to 5X the recommended dose in puppies 9 weeks of age and older and 4 pounds or more. | (S)-Methoprene capsules (22 mg/kg), administered up to 5X the recommended dose, are safe for administration to puppies, 9 weeks of age and older and 4 pounds body weight or greater. |
Effectiveness
Clinical field trial at 11 veterinary practices; positive control (lufenuron tablets, minimum 10 mg/kg once monthly) vs (S)-Methoprene minimum 22 mg/kg orally once weekly for 5 months in naturally flea-infested client-owned dogs; a topical adulticide mist was applied weekly for the first 8 weeks.; n = 165; primary endpoint: Adult flea counts at months 0-5 and percent inhibition of fleas computed from geometric mean counts; result: (S)-Methoprene percent inhibition of fleas 73.5% (month 1), 87.5% (month 2), 85.7% (month 3), 89.8% (month 4), 92.8% (month 5) and 87.1% for months 1-5 combined, versus 85.6% for the lufenuron positive control; capsules worked as effectively as the positive control. Sixty-one of the 165 analysed dogs received (S)-Methoprene.
A total of 246 (118 males, 127 females) dogs were enrolled in the study (the sex of one animal was not reported). Of these, 165 client owned dogs ranging in age from 6 months to 16 years and weighing between 4 to 130 pounds, were included in the statistical analysis. Sixty-one of the 165 dogs were treated with (S)-Methoprene.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Vomiting, diarrhea, lethargy/depression, nervousness (field trial, (S)-Methoprene group; no counts given) | Vomiting, diarrhea, lethargy/depression and nervousness were observed in the (S)- Methoprene group. | ||
| Depression (target animal safety study, 6-week-old Beagle puppies; incidence by dose group) | 1X 2/6; 3X 3/6, 3/6, 1/6; 5X 1/6, 3/6; 10X 1/4, 3/4 | 1x 2/6 3x 3/6 3/6 1/6 5x 1/6 3/6 10x 1/4 3/4 | |
| Ataxia (target animal safety study, 6-week-old Beagle puppies; incidence by dose group) | 1X 2/6; 3X 2/6, 4/6, 3/6, 1/6; 5X 5/6, 3/6, 2/6; 10X 2/4, 4/4, 2/4, 1/4 | 1x 2/6 3x 2/6 4/6 3/6 1/6 5x 5/6 3/6 2/6 10x 2/4 4/4 2/4 1/4 | |
| Tremors (target animal safety study, day 0) | 1/6 (1X); 1/4 (10X) | Tremors were exhibited in 1/6 and 1/4 dogs in the 1x and 10x treatment groups, respectively on day 0. |
Extraction notes: Species not listed as a separate General Information field; 'Dogs' taken from the indication statement. Summary is an older (2000) format with no PK section. Effectiveness also supported by a dose-titration study (24 dogs; 20 mg/kg gave >90% reduction in adult flea emergence), a dose-confirmation study (20 dogs; 96.1% reduction at 22 mg/kg) and a 91-day simulated home environment study (20 dogs; 93.8% reduction in adult fleas by day 49). Field trial: 246 dogs enrolled, 165 analysed, 61 treated with (S)-Methoprene (the '61' is spelled out in the text so it is not in the n_dogs field). Target animal safety table rows were flattened by PDF extraction: for the depression and ataxia rows the successive fractions per dose group are the Day 0, Day 7, Day 14 (and for ataxia Day 21, Day 56) columns in order, with blank cells dropped; in the ataxia table the 3x row's last value (1/6) is the Day 56 column. Additional safety studies: 1-generation reproduction study at 3X in 52 Beagles (no drug-related effects except green-discoloured feces from capsule dye) and a 5X study in combination with topical flea adulticides in 24 puppies (no adverse effects).
Reproduce: foi_structured_search(query="(S)-Methoprene") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).