Lufenuron, Milbemycin Oxime: what the FDA reviewed for dog products
3 Freedom of Information summaries from the FDA Center for Veterinary Medicine for products containing Lufenuron, Milbemycin Oxime, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dogs.
Products
- Sentinel® Flavor Tabs® (NADA/ANADA 141-084)
Sentinel® Flavor Tabs® NADA 141-084, Original approval, April 10, 1997; sponsor Intervet, Inc.; species: Dogs; foi_id 3598; FDA PDF
Indication
Dogs and puppies 4 weeks of age and older and 2 lb or more: prevention of heartworm disease (Dirofilaria immitis), prevention and control of flea populations, control of adult hookworm (Ancylostoma caninum), and removal and control of adult roundworm (Toxocara canis, Toxascaris leonina) and whipworm (Trichuris vulpis) infections.
Dose regimen
0.5 mg/kg (0.23 mg/lb) milbemycin oxime and 10 mg/kg (4.55 mg/lb) lufenuron (minimum), oral (tablet), once a month, tablet strength selected by body-weight band (2.3/46 mg to 23.0/460 mg milbemycin/lufenuron)
Tablets are given orally, once a month, at the recommended minimum dosage of 0.23 mg/lb (0.5 mg/kg) milbemycin and 4.55 mg/lb (10 mg/kg) lufenuron.
Target-animal safety
dose multiples 1X, 3X, 5X; duration 6-month study: single daily doses for three sequential days starting on days 0, 28, 53, 87, 112, 140, 171 and 200 (necropsy week 29); animals 24 males, 24 females.
Forty-eight (24 males, 24 females) 2 month old Beagle puppies were divided into four groups of six males and six females.
| Finding | Quote |
|---|---|
| All dogs survived; diarrhea/soft stools, vomiting and red raised skin lesions considered probably related to active or vehicle tablets; salivation in 7 dogs (2 at 1X, 2 at 3X, 3 at 5X), mostly at or within 1 hour of dosing. | Diarrhea/soft stools, vomiting, and red, raised skin lesions. Salivation was noted in 7 dogs (2 at 1X, 2 at 3X and 3 at 5X). Six of these 7 dogs salivated either at the time of dosing or within 1 hour after a treatment. |
| No treatment effect on body weight change, food consumption, organ weights, hematology, serum chemistry, urinalysis or ophthalmic examinations. | Mean body weight changes, food consumption and organ weights were unaffected by treatment. No abnormal changes were apparent when hematology, serum chemistry and urinalysis parameters were evaluated. Ophthalmic examinations revealed no adverse findings. |
| Conclusion of the 6-month study: safe in dogs and puppies 2 months of age and older at up to 5X the recommended dose. | SENTINEL is safe for use in dogs and puppies 2 months of age and older at doses up to 5X the recommended dose. |
| Separate 2-month study starting at 2 weeks of age: CNS/behavioral signs (incoordination, generalized tremors, inability to arouse, tail twitching) in 2-week-old puppies at 3X and 5X and in 4-week-old puppies at 5X; all affected animals recovered fully. | SENTINEL caused changes in CNS/behavior (incoordination, generalized tremors, inability to arouse and/or tail twitching) in 2-week-old puppies treated at 3X and 5X the recommended dose and in 4-week-old puppies treated at 5X the recommended dose |
| Separate acute 10X study (5 mg/kg milbemycin oxime + 100 mg/kg lufenuron, single dose, 12 adult beagles): safe; vomiting in 3 placebo and 4 combination dogs, salivation in 1 combination dog. | Milbemycin oxime/lufenuron combination tablets are safe when administered orally to beagle dogs at dose levels of 5 mg/kg milbemycin oxime and 100 mg/kg lufenuron (10X the month ad usum level). Vomiting was observed in 3 placebo (vehicle)-treated dogs and in 4 combination- treated dogs. |
Effectiveness
General Clinical Trial: uncontrolled multi-site field study in client-owned dogs with natural infections (fleas, roundworms, hookworms, whipworms); SENTINEL given monthly for six months; 269 dogs enrolled, 247 in final efficacy analysis. Roundworm and whipworm evaluated after 3 months, fleas after 6 months.; n = 269; primary endpoint: Percent reduction / control of each parasite (fecal flotation for GI nematodes; monthly flea counts); result: Roundworm 96.5% reduction (57 dogs) / 100.0% control (38); hookworm 87.3% control (103); whipworm 89.3% reduction (56) / 93.0% control (43); flea count reduction 82.5% (161 dogs), adequate flea control in 85.7%; heartworm prevention could not be evaluated within 6 months.
Two hundred sixty-nine (269) client owned dogs were enrolled in the study and two hundred forty-seven (247) were included in the final efficacy analysis.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Diarrhea (General Clinical Trial, n=269) | 8 (3.0%) | Observation Number of Dogs Percent of Dogs (n=269) Diarrhea 8 3.0% Vomiting 6 2.2% Anorexia 4 1.5% | |
| Vomiting (General Clinical Trial, n=269) | 6 (2.2%) | Observation Number of Dogs Percent of Dogs (n=269) Diarrhea 8 3.0% Vomiting 6 2.2% Anorexia 4 1.5% | |
| Anorexia (General Clinical Trial, n=269) | 4 (1.5%) | Observation Number of Dogs Percent of Dogs (n=269) Diarrhea 8 3.0% Vomiting 6 2.2% Anorexia 4 1.5% | |
| Diarrhea (Roundworm Clinical Trial; SENTINEL n=38 vs pyrantel pamoate n=19) | 1 (2.6%) | 1 (5.3%) | Diarrhea 1 (2.6%) 1 (5.3%) |
| Vomiting (Roundworm Clinical Trial; SENTINEL n=38 vs pyrantel pamoate n=19) | 3 (7.9%) | 0 (0.0%) | Vomiting 3 (7.9%) 0 (0.0%) |
Extraction notes: Effectiveness rests mainly on the Interceptor (NADA 140-915) and Program (NADA 141-035) approvals plus five component non-interference studies (heartworm, flea, roundworm, hookworm, whipworm; 40 dogs each) and two field trials; the General Clinical Trial had no control group (its 'Control %' columns are parasite control claims, not a control group). Efficacy table rows are flattened in the PDF text so results are summarised in the result field only. TAS design_quote is the 6-month 1X/3X/5X study; n_animals given as sex split because '48' appears only as 'Forty-eight'. Roundworm-trial AR quotes are bare table rows (columns: Combination n=38, Pyrantel n=19).
Sentinel® Flavor Tabs® NADA 141-084, Supplemental approval, June 11, 2003; sponsor Intervet, Inc.; species: Dogs; foi_id 618; FDA PDF
Indication
Dogs and puppies four weeks and older and two pounds or more: prevention of heartworm disease (D. immitis), prevention and control of flea populations, control of adult A. caninum, removal and control of adult T. canis, T. leonina and T. vulpis (labeling revised for concurrent use with CAPSTAR).
Dose regimen
0.23 mg/lb (0.5 mg/kg) milbemycin oxime and 4.55 mg/lb (10 mg/kg) lufenuron (minimum), Oral, once a month, Concurrent CAPSTAR dosing schedule addressed in NADA 141-204
SENTINEL® Flavor Tabs® are given orally, once a month, at the recommended minimum dosage of 0.23 mg/lb (0.5mg/kg) milbemycin oxime and 4.55 mg/lb (10 mg/kg) lufenuron.
Extraction notes: Labeling supplement (Category II) for concurrent use with CAPSTAR (nitenpyram) as a 'FLEA MANAGEMENT SYSTEM'; effectiveness and safety of the concurrent use are documented in NADA 141-204 and of the product in the original approval (April 10, 1997). No studies, no PK in this summary.
Sentinel® Flavor Tabs® NADA 141-084, Supplemental approval, June 17, 1998; sponsor Intervet, Inc.; species: Dogs; foi_id 2556; FDA PDF
Indication
Dogs and puppies four weeks and older and eleven pounds or more: prevention of heartworm disease (D. immitis), prevention and control of flea populations, control of adult A. caninum, removal and control of adult T. canis, T. leonina and T. vulpis (flavored tablet formulation added).
Dose regimen
0.23 mg/lb (0.5 mg/kg) milbemycin oxime and 4.55 mg/lb (10 mg/kg) lufenuron (minimum), Oral, once a month, Flavor Tabs in three sizes for dogs 11-100 lb; swallow tablet retained for 2-10 lb
SENTINEL Flavor Tabs are given orally, once a month, at the recommended minimum dosage of 0.23 mg/lb (0.5 mg/kg) milbemycin and 4.55 mg/lb (10 mg/kg) lufenuron.
Effectiveness
Formulation-comparison hookworm efficacy study (natural A. caninum infections; Stanwood, MI): three groups of ten dogs given placebo, SENTINEL tablets, or SENTINEL Flavor Tabs once at 0.5 mg/kg milbemycin oxime / 10 mg/kg lufenuron; worms recovered at necropsy 9 days after treatment; n = Thirty (15 males, 15 females; three groups of ten); primary endpoint: Geometric mean hookworm count and percent efficacy vs placebo (Wilcoxon rank sum); result: SENTINEL Flavor Tabs 99.5% efficacy (geometric mean 0.07 worms) vs SENTINEL tablets 100% (0.0) vs placebo 14.4 worms; both formulations significantly different from placebo (p < .0001) and not different from each other (p = .3681)
Thirty adult dogs (15 males, 15 females) were divided into three groups of ten dogs each.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| None reported (hookworm efficacy study and clinical palatability trial) | Adverse Reactions: None reported. |
Extraction notes: Supplement adding a flavored formulation; effectiveness otherwise based on INTERCEPTOR (NADA 140-915), PROGRAM (141-035) and SENTINEL tablets. Efficacy table verbatim: 'Placebo 14.4 --- SENTINEL 0.0 100 SENTINEL Flavor Tabs 0.07 99.5'. Clinical palatability trial: 208 client-owned dogs analyzed; 173 (83.0%) consumed the tablet from the hand, 3 (1.4%) refused. TAS based on existing approvals; no PK.
Reproduce: foi_structured_search(query="Lufenuron, Milbemycin Oxime") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).