Spinosad and milbemycin oxime: what the FDA reviewed for dog products
1 Freedom of Information summary from the FDA Center for Veterinary Medicine for products containing Spinosad and 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
- Trifexis™ (NADA/ANADA 141-321)
Trifexis™ NADA 141-321, Original approval, January 04, 2011; sponsor Elanco US Inc.; species: Dogs; foi_id 878; FDA PDF
Indication
Prevention of heartworm disease (Dirofilaria immitis); kills fleas and prevention/treatment of flea infestations (Ctenocephalides felis); treatment and control of adult hookworm, roundworm and whipworm infections in dogs and puppies 8 weeks of age or older and 5 pounds or greater.
Dose regimen
minimum 30 mg/kg (range 30 to 60 mg/kg) spinosad and 0.5 mg/kg (range 0.5 to 1.0 mg/kg) milbemycin oxime, oral, once monthly, administered with food; field safety study dosed monthly for six consecutive months
Monthly use of TRIFEXIS Chewable Tablets administered orally under field conditions in the United States is safe for dogs at a minimum dose of 30 mg/kg (range 30 to 60 mg/kg) of spinosad and 0.5 mg/kg (range 0.5 to 1.0 mg/kg) of milbemycin oxime.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| other | plasma spinosyn A and D concentrations greater than dose proportional across 1 to 5X | margin of safety study, 8-week-old Beagles, monthly oral dosing at 1X/3X/5X for six 28-day periods | At each dosing period, plasma spinosyn A and spinosyn D concentrations were greater than dose proportional across the dose range 1 to 5X. |
Target-animal safety
dose multiples 1X, 3X, 5X; duration six 28-day dosing periods (once monthly), starting at 8 weeks of age; animals 32 Beagle dogs.
Evaluate the safety of TRIFEXIS Chewable Tablets when first administered to 8-week old dogs at 1X, 3X, and 5X the upper half of the recommended therapeutic dose based for six dosing periods. 2) Number of Animal s: 32 Beagle dogs
| Finding | Quote |
|---|---|
| All dogs survived; emesis in all groups including control | All dogs survived to their scheduled termination at the end of six 28- day dosing periods. |
| Emesis observed in all groups including control with similar frequency | Emesis was observed in all groups including the control group with similar frequency. |
| Treatment-related clinical signs: salivation, tremors, decreased activity, vocalization, coughing | Clinical findings that were considered treatment- related were salivation in one dog in the 1X group, and two dogs in the 3X group, tremors in one dog in the 3X group and one dog in the 5X group, decreased activity in one 1X dog and two 5X dogs, vocalization in one 5X dog, and coughing in one 3X dog. |
| Minimal glomerular lipidosis in one 5X dog, clinical relevance unknown | One 5X dog had minimal glomerular lipidosis observed microscopically. |
| Well tolerated at 1X, 3X, 5X monthly for six dosing periods | The oral administration of TRIFEXIS Chewable Tablets at 1X, 3X, and 5X the upper half of the therapeutic dose band once monthly for six dosing periods in dogs was well tolerated in this study. |
Effectiveness
Laboratory dose confirmation study (T3A260812) in dogs experimentally infected with 40 +/- 2 D. immitis L3, masked, vehicle-controlled, 4 groups of 10; necropsy heartworm counts on Day 120; n = 40; primary endpoint: Adult heartworm count at necropsy (geometric mean vs control); result: 100% effectiveness with three consecutive monthly doses (Group 4); one heartworm recovered in one dog with two monthly doses (Group 2); control GM 19.7
Study Animals: 40 dogs 3) Treatm ent Groups: Table 1. Study T3A260812 Treatment Groups Group Infection Day Treatment Days* Treatment Dose Number and Gender of Dogs 1 Day -30 Days 0,15, 30, 45, 60 Control (final oral dosage form without actives) 0 mg/kg BW** 10 (5 M, 5 F)
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Vomiting | 6.13 | 3.08 | Vomiting 6.13 3.08 |
| Pruritus | 4.00 | 4.91 | Pruritus 4.00 4.91 |
| Lethargy | 2.63 | 1.54 | Lethargy 2.63 1.54 |
| Diarrhea | 2.25 | 1.54 | Diarrhea 2.25 1.54 |
| Dermatitis | 1.47 | 1.45 | Dermatitis 1.47 1.45 |
| Skin Reddening | 1.37 | 1.26 | Skin Reddening 1.37 1.26 |
Extraction notes: No dedicated PK section; the single PK entry is a qualitative dose-proportionality statement from the margin-of-safety study. Effectiveness: the summary contains only laboratory studies (no field effectiveness study); the pivotal heartworm dose-confirmation study T3A260812 is recorded here, result quote: 'There were no heartworms recovered in Treatment Group 4, demonstrating 100% effectiveness against heartworm infection when spinosad and milbemycin oxime was administered once a month for three consecutive months after infection.' Adverse reactions are average monthly rates (%) from field safety study T3AAM0801 (Table 22; n=176 dogs per group; control = lufenuron + milbemycin oxime active control). Seizure in one TRIFEXIS dog reported. TAS: also avermectin-sensitive Collie (24 dogs, 1X/3X/5X, no sensitivity signs), female reproduction (39 females, 1X/3X) and heartworm-positive (32 dogs, 1X/3X/5X) studies.
Reproduce: foi_structured_search(query="Spinosad and milbemycin oxime") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).