Sarolaner, moxidectin, and pyrantel (as pamoate salt): what the FDA reviewed for dog products
1 Freedom of Information summary from the FDA Center for Veterinary Medicine for products containing Sarolaner, moxidectin, and pyrantel (as pamoate salt), as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dogs.
Products
- Simparica TRIO® (NADA/ANADA 141-521)
Simparica TRIO® NADA 141-521, Original approval, February 27, 2020; sponsor Zoetis Inc.; species: Dogs; foi_id 8847; FDA PDF
Indication
Prevention of heartworm disease (D. immitis); treatment and control of roundworm (T. canis, T. leonina) and adult hookworm (A. caninum, U. stenocephala); kills adult fleas and treats/prevents flea infestations; treatment and control of tick infestations (A. americanum, A. maculatum, D. variabilis, I. scapularis, R. sanguineus) in dogs.
Dose regimen
minimum 0.54 mg/lb (1.2 mg/kg) sarolaner, 0.011 mg/lb (24 μg/kg) moxidectin, and 2.27 mg/lb (5 mg/kg) pyrantel, oral (chewable tablet), once a month, with or without food; six tablet strengths by body weight
Simparica TrioTM is given orally, once a month, at the recommended minimum dose of 0.54 mg/lb (1.2 mg/kg) sarolaner, 0.011 mg/lb (24 μg/kg) moxidectin, and 2.27 mg/lb (5 mg/kg) pyrantel (as pamoate salt).
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| half-life | 19 days sarolaner and 22 days moxidectin (average terminal half-lives) | heartworm-positive Beagles dosed at 1X and 3X three times at 28-day intervals; longer than in healthy beagles | In this study, while the values of the exposure parameters (AUC, Cmax, and Tmax) were comparable to other PK studies conducted in healthy beagle dogs, the average terminal half-lives were longer and were 19 days for sarolaner and 22 days for moxidectin. |
| other | sarolaner and moxidectin: dose-related increases in AUC and Cmax at 1X and 3X; pyrantel less than proportional | heartworm-positive dogs, 1X and 3X oral | Following oral dosing at 1X and 3X the maximum intended dose, sarolaner and moxidectin show dose related increases in AUC and Cmax but pyrantel showed less than proportional increases in AUC and Cmax. |
| other | MDR1-deficient Collies: greater AUC and Cmax and prolonged terminal half-lives for moxidectin and sarolaner (not pyrantel) vs Beagles | avermectin-sensitive Collies, 1X/3X/5X single oral dose | Compared to beagle dogs used in other studies, MDR1 deficient collies had greater exposure (AUC and Cmax) and prolonged terminal half-lives to moxidectin and sarolaner, but not to pyrantel. |
| auc | moxidectin AUClast geometric LS mean 954.9 ng*h/mL (final Simparica Trio); ratio T/R 92.97%, CI 89.61-96.48 | BE study A461N-US-17-861 vs non-final formulation #1 (reference AUClast 1027 ng*h/mL), 36 male Beagles, fasted, two-way crossover, single tablet with 0.24 mg moxidectin; row order: geometric LS mean, ratio, CI lower, CI upper | 954.9 92.97 89.61 96.48 |
| cmax | moxidectin Cmax geometric LS mean 14.3 ng/mL (final Simparica Trio); ratio 88.04%, CI 82.70-93.73 | BE study A461N-US-17-861 vs non-final formulation #1 (reference Cmax 16.3 ng/mL), 36 male Beagles, fasted | 14.3 88.04 82.70 93.73 |
| auc | moxidectin AUClast geometric LS mean 980.17 ng*h/mL (final); ratio 106.81%, CI 102.31-111.51 | BE study A461N-US-17-862 vs non-final formulation #2 (reference AUClast 917.69), 48 male Beagles, fasted, single tablet with 0.24 mg moxidectin and 12 mg sarolaner | 980.17 106.81 102.31 111.51 |
| auc | sarolaner AUClast geometric LS mean 162644.72 ng*h/mL (final); ratio 94.23%, CI 87.55-101.41 | BE study A461N-US-17-862 vs non-final formulation #2 (reference AUClast 172609.59), 48 male Beagles, fasted | 162644.72 94.23 87.55 101.41 |
| cmax | sarolaner Cmax geometric LS mean 397.79 ng/mL (final); ratio 90.03%, CI 83.38-97.20 | BE study A461N-US-17-862 vs non-final formulation #2 (reference Cmax 441.86), 48 male Beagles, fasted | 397.79 90.03 83.38 97.20 |
Target-animal safety
dose multiples 1X, 3X, 5X; duration once monthly for 7 consecutive doses (25 weeks), starting at 8 weeks of age; animals 32 Beagle dogs (16 male, 16 female).
Objective: To evaluate the safety margin of the sarolaner, moxidectin, and pyrantel combination (combination product) when administered orally at one (1X), three (3X), and five times (5X) the maximum labeled dose once monthly for 7 consecutive doses to Beagle dogs starting at 8 weeks of age. This study was conducted in compliance with Good Laboratory Practice (GLP) Regulations (21 CFR Part 58). Study Animals: 32 Beagle dogs (16 male, 16 female), 8 weeks of age and 1.8 to 2.9 kg body weight.
| Finding | Quote |
|---|---|
| Retinal dysplasia (OS folds) in one 1X dog at end-of-study ophthalmic exam; all other results similar to control | During the end-of-study ophthalmic examination the following change was found: one 1X dog had retinal dysplasia (OS folds). |
| Supports safe use in dogs 8 weeks and older at labeled dose | The study supports the safe use of Simparica TrioTM (sarolaner, moxidectin, and pyrantel) in dogs 8 weeks of age and older when used at the labeled dose. |
Effectiveness
Masked, multi-center GCP field study A161C-US-13-211: monthly oral sarolaner/moxidectin/pyrantel tablet (non-final formulation #1; min 2.0 mg/kg sarolaner, 24 μg/kg moxidectin, 5 mg/kg pyrantel) vs ivermectin/pyrantel active control for 11 doses; heartworm antigen and microfilariae testing Days 120, 240, 330; n = 272 treated and 138 active control (safety); 246 treated and 119 control evaluable for effectiveness; primary endpoint: Heartworm antigen and microfilariae tests at Day 330 (all treated dogs negative); result: None of the 246 treated dogs tested positive for adult heartworms at Days 120, 240 or 330
Study Animals: Two hundred seventy-two (272) dogs administered the sarolaner, moxidectin, pyrantel pamoate tablet and 138 dogs administered active control were evaluated for safety. Two hundred forty-six (246) dogs administered the sarolaner, moxidectin, pyrantel pamoate tablet and 119 dogs administered active control were included in the effectiveness evaluation.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Vomiting | 14.3% | 10.9% | Vomiting 14.3% 10.9% |
| Diarrhea | 13.2% | 8.0% | Diarrhea 13.2% 8.0% |
| Lethargy | 8.5% | 6.5% | Lethargy 8.5% 6.5% |
| Anorexia | 5.1% | 5.8% | Anorexia 5.1% 5.8% |
| Polyuria | 3.7% | 3.6% | Polyuria 3.7% 3.6% |
| Hyperactivity | 2.2% | 0.7% | Hyperactivity 2.2% 0.7% |
Extraction notes: Corrected FOI summary (80 pages, 27 studies). Adverse reactions are from the heartworm field study (Table II.2; treated n=272 vs ivermectin/pyrantel active control n=138; also polydipsia 2.2% vs 2.9%). Field-study result quote: 'None of the 246 dogs administered the sarolaner, moxidectin, pyrantel pamoate tablet that completed the study tested positive for adult heartworms on Days 120, 240, or 330.' Two further field studies (fleas, n=278 treated; ticks) and many laboratory studies are not captured here. Indication quote is only the first sentence of the label indication (the flea/tick sentence continues). BE table quotes are numeric row fragments (geometric LS mean of the final formulation, T/R ratio, 90% CI lower, upper) because the table sentences exceed grep length; the reference-formulation means (1027, 16.3, 917.69, 12.37, 172609.59, 441.86) are on the adjacent rows. The margin-of-safety study used non-final formulation #2 (bridged via BE study A461N-US-17-862). Other TAS studies: heartworm-positive dogs (24, 1X/3X x3, well tolerated; live worm recovery 89% control, 83% 1X, 74% 3X) and avermectin-sensitive Collies (32, 1X/3X/5X; mild self-limiting signs at 5X).
Reproduce: foi_structured_search(query="Sarolaner, moxidectin, and pyrantel (as pamoate salt)") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).