Afoxolaner, Moxidectin, Pyrantel Pamoate: what the FDA reviewed for dog products
4 Freedom of Information summaries from the FDA Center for Veterinary Medicine for products containing Afoxolaner, Moxidectin, Pyrantel Pamoate, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dogs.
Products
- NexGard® PLUS (NADA/ANADA 141-554)
NexGard® PLUS NADA 141-554, Supplemental approval, April 23, 2025; sponsor Boehringer lngelheim Animal Health USA, Inc.; species: Dogs; foi_id 16845; FDA PDF
Indication
Supplement adds prevention of Borrelia burgdorferi infections as a direct result of killing Ixodes scapularis vector ticks.
Dose regimen
1.14 mg/lb (2.5 mg/kg) afoxolaner, 5.45 mcg/lb (12 mcg/kg) moxidectin, and 2.27 mg/lb (5.0 mg/kg) pyrantel, oral (soft chewable), once a month
This supplemental approval does not change the previously approved dose of 1.14 mg/lb (2.5 mg/kg) of afoxolaner, 5.45 mcg/lb (12 mcg/kg) of moxidectin, and 2.27 mg/lb (5.0 mg/kg) of pyrantel, given orally once a month.
Effectiveness
Two masked, negative-controlled (sham-dosed), completely randomized laboratory studies (GCP): Study 2021083 (Athens, GA; quoted animals) and Study 2021084 (Colbert, GA; 20 dogs). Single oral NexGard PLUS dose (2.5 mg/kg afoxolaner, 12 mcg/kg moxidectin, 5 mg/kg pyrantel; fed) on Day 0; Day 28 infestation with ~50 wild-caught adult I. scapularis (60% and 38.5% B. burgdorferi infection rates); live tick counts Day 33; SNAP 4Dx Plus and Lyme Quant C6 serology through Day 103; PCR of 4 skin biopsies on Day 104.; n = 20; primary endpoint: Percent reduction in arithmetic mean live tick counts on Day 33 and proportion of dogs infected with B. burgdorferi (any positive serology after Day 28 or positive biopsy PCR); result: Both studies: 100% reduction in live I. scapularis on Day 33 (p<0.0001); 0/10 NexGard PLUS dogs vs 10/10 control dogs infected with B. burgdorferi (serology and PCR). A single dose 28 days before infestation prevented B. burgdorferi infection by killing the vector ticks.
Study Animals: Twenty (20) beagle dogs (11 males and 9 females), 7.4 to 8.2 months of age and weighing 6.42 to 10.04 kg, were included in the study.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| None (study 2021083) | There were no treatment-related adverse reactions during the study. | ||
| Diarrhea (study 2021084; one dog, 6 h post-treatment) | Diarrhea was reported for one NexGard® PLUS treated dog at the six-hour post-treatment time point. |
Extraction notes: Supplemental approval; FDA did not require target animal safety studies (refers to the original approval FOI Summary of July 19, 2023). No PK data. n_dogs refers to study 2021083 (10 per group); study 2021084 also enrolled 20 dogs (10 per group). The General Information section was partly overwritten by table-of-contents text during parsing.
NexGard® PLUS NADA 141-554, Supplemental approval, January 20, 2026; sponsor Boehringer lngelheim Animal Health USA, Inc.; species: Dogs; foi_id 17910; FDA PDF
Indication
Supplement adds treatment and control of Amblyomma maculatum (Gulf Coast tick) infestations for one month in dogs and puppies eight weeks and older weighing four pounds or more.
Dose regimen
1.14 mg/lb (2.5 mg/kg) afoxolaner, 5.45 mcg/lb (12 mcg/kg) moxidectin, and 2.27 mg/lb (5.0 mg/kg) pyrantel, oral (soft chewable), once a month
This supplemental approval does not change the previously approved dose of 1.14 mg/lb (2.5 mg/kg) of afoxolaner, 5.45 mcg/lb (12 mcg/kg) of moxidectin, and 2.27 mg/lb (5.0 mg/kg) of pyrantel, given orally once a month.
Effectiveness
Two masked, negative-controlled, completely randomized laboratory dose-confirmation studies (GCP) with a single oral NexGard PLUS dose (afoxolaner as close as possible to 2.5 mg/kg without under-dosing; fed) on Day 0 and ~50 adult A. maculatum on Days -1, 14, 28; live/dead tick counts 72 h after treatment or infestation (Days 3, 17, 31). Study 2023-3557 (Colbert, GA; quoted treatment groups) and Study 2024-4349 (South Africa; 20 beagle/mixed-breed dogs).; n = 10 treated and 10 control; primary endpoint: Percent reduction (≥90%) in least-squares mean live tick counts vs control (control indication); numerically higher arithmetic mean dead ticks (treatment indication); result: Study 2023-3557: ≥99% reduction in live A. maculatum at 72 h through Day 31 (99.5, 99.0, 100%; p<0.0001). Study 2024-4349: ≥92.8% (99.2, 97.2, 92.8% on Days 3, 17, 31; p<0.0001). Dead tick counts higher in treated dogs at all post-treatment timepoints.
Control 0 mg/kg 10 (4M, 6F) NexGard® PLUS 2.5 mg/kg afoxolaner + 12 mcg/kg moxidectin + 5 mg/kg pyrantel 10 (7M, 3F)
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Diarrhea (study 2023-3557; considered a possible drug-related adverse reaction) | 1 dog (single incidence) + 1 dog (8 and 24 hours after treatment) | One dog in the NexGard® PLUS treated group had a single incidence of diarrhea noted six hours after treatment, and 1 NexGard® PLUS treated dog had diarrhea 8 and 24 hours after treatment. | |
| None (study 2024-4349) | No treatment-related adverse reactions were reported in the NexGard® PLUS treated dogs during the study. |
Extraction notes: Supplemental approval; FDA did not require target animal safety studies (refers to the original approval FOI Summary of July 19, 2023). No PK data. n_dogs quote is the flattened Table II.1 treatment-group rows (Treatment, Minimum Dose, Number and Sex of Dogs) of study 2023-3557; study 2024-4349 also used 10 treated (10F) and 10 control (1M, 9F) dogs. The General Information section was partly overwritten by table-of-contents text during parsing.
NexGard® PLUS NADA 141-554, Original approval, July 19, 2023; sponsor Boehringer lngelheim Animal Health USA, Inc.; species: Dogs; foi_id 14288; FDA PDF
Indication
Prevention of heartworm disease (Dirofilaria immitis); treatment and control of adult hookworm (A. caninum, A. braziliense, U. stenocephala) and roundworm (T. canis, T. leonina) infections; kills adult fleas, treatment and prevention of flea infestations, and treatment and control of I. scapularis, R. sanguineus, D. variabilis and A. americanum tick infestations for one month in dogs and puppies 8 weeks and older weighing 4 pounds or more.
Dose regimen
1.14 mg/lb (2.5 mg/kg) afoxolaner, 5.45 mcg/lb (12 mcg/kg) moxidectin, and 2.27 mg/lb (5.0 mg/kg) pyrantel (as pamoate salt), minimum, oral (beef-flavored soft chewable, five strengths), once a month, may be given with or without food
NexGard® PLUS is given orally once a month at the minimum dosage of 1.14 mg/lb (2.5 mg/kg) afoxolaner, 5.45 mcg/lb (12 mcg/kg) moxidectin, and 2.27 mg/lb (5.0 mg/kg) pyrantel (as pamoate salt).
Target-animal safety
dose multiples 1X, 3X, 5X; duration six oral treatments 28 days apart (Days 0, 28, 56, 84, 112, 140); 168-day GLP study; necropsy Day 168; animals 32.
Study Animals: Thirty-two (32) Beagle dogs (16 males, 16 females), aged 8 to 9 weeks and weighing 1.95 to 3.00 kg, were included in the study.
| Finding | Quote |
|---|---|
| No test-article-related effects on food consumption, body weight, physical or ophthalmic examinations, or anatomical/clinical pathology; no signs of avermectin sensitivity. | There was no evidence of test article-related alterations in food consumption, body weight, physical examination variables (heart rate, respiratory rate, body temperature), ophthalmic examination variables, and anatomical or clinical pathology findings. No signs of avermectin sensitivity were observed. |
| Mild, self-limiting diarrhea (with and without blood) possibly treatment-related (more incidences in NexGard PLUS groups than control, including within 48 h of treatment). | Mild, self-limiting diarrhea (with and without blood) was observed sporadically and was possibly related to treatment, as there were more incidences in the groups administered NexGard® PLUS than the control group throughout the study, including within 48 hours after treatment. |
| Vomiting sporadic in all groups including control, not treatment-related. | Vomiting was observed sporadically across all groups, including the control group, and did not appear to be related to treatment. |
| Heartworm-positive dog study (PR&D 0430201; 1X and 3X, three doses ~28 days apart, 24 dogs): mild self-limiting diarrhea in one 1X and three 3X dogs, vomiting in two 3X dogs; no avermectin toxicity or hypersensitivity; microfilariae counts significantly lower than control. | Mild, self-limiting diarrhea was observed in one dog in the 1X group and in three dogs in the 3X group within 8 hours of treatment. |
| MDR1-deficient Collie study (PR&D 0423901; 1X, 3X, 5X; 24 dogs): no clinical signs of avermectin toxicity; vomiting in 3X and 5X groups within 8 h; self-limiting diarrhea in all treated groups. | No clinical signs of avermectin toxicity were noted in any dog at any time during the study. Vomiting was observed in the 3X and 5X groups within 8 hours of treatment and resolved without intervention. |
Effectiveness
Field study PR&D 04197 (GCP): masked, multicenter (6 US clinics in heartworm-endemic regions), randomized block, active-controlled (topical imidacloprid 10 mg/kg + moxidectin 2.5 mg/kg) heartworm-prevention study; owners administered NexGard PLUS monthly (12 treatments, Days 0-330) with or without food to heartworm-negative dogs; heartworm antigen and microfilariae testing Days 60, 120, 180, 240, 330.; n = 134 NexGard PLUS and 138 active control dogs (safety); 120 and 124 dogs (effectiveness); primary endpoint: Heartworm antigen and blood microfilariae test results during 330 days (effectiveness shown if 100% negative; no statistical analysis then required); result: 100% effectiveness: none of the 120 NexGard PLUS dogs tested positive for adult heartworms at any time point. Laboratory studies: 100% effective against induced D. immitis in two studies (PR&D 0409401, 0427201; 10 treated/10 control each, six monthly doses); 100%/≥99.8% against fleas (PR&D 0431501); 97-100% (≥98.4% after re-infestation) against A. americanum (PR&D 0424001, 0425701); effective against induced and naturally acquired T. canis (PR&D 0410401, 0426601).
One hundred thirty-four (134) dogs administered NexGard® PLUS and 138 dogs administered the active control were evaluated for safety. One hundred twenty (120) dogs administered NexGard® PLUS and 124 dogs administered the active control were included in the effectiveness evaluation.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Diarrhea | 9 (6.7%) | 7 (5.1%) | Diarrhea 9 (6.7%) 7 (5.1%) |
| Vomiting | 6 (4.5%) | 7 (5.1%) | Vomiting 6 (4.5%) 7 (5.1%) |
| Lethargy | 3 (2.2%) | 5 (3.6%) | Lethargy 3 (2.2%) 5 (3.6%) |
| Itching | 3 (2.2%) | 3 (2.2%) | Itching 3 (2.2%) 3 (2.2%) |
| Dermatitis | 2 (1.5%) | 1 (0.7%) | Dermatitis 2 (1.5%) 1 (0.7%) |
| Muscle tremor | 1 (0.7%) | 1 (0.7%) | Muscle tremor 1 (0.7%) 1 (0.7%) |
Extraction notes: Original approval of the three-way combination. No PK section in the summary (dosage characterization relies on prior NADA 141-406 and 140-971 data plus moxidectin exploratory studies at 3-100 mcg/kg; 12 mcg/kg x 6 monthly doses selected). Target animal safety from margin-of-safety study PR&D 0416301 (0X sham, 1X = 5 mg/kg afoxolaner + 24 mcg/kg moxidectin + 10 mg/kg pyrantel pamoate, 3X, 5X; 8 dogs/group; fasted). Adverse reaction rows are field study Table II.2 (NexGard PLUS n=134, active control n=138; anorexia 1 (0.7%) vs 4 (2.9%) omitted). The General Information section was partly overwritten by table-of-contents text during parsing; dose and indication quotes taken via grep. The hookworm-specific laboratory studies were not reviewed in detail for this record.
NexGard® PLUS NADA 141-554, Supplemental approval, October 07, 2024; sponsor Boehringer lngelheim Animal Health USA, Inc.; species: Dogs; foi_id 15947; FDA PDF
Indication
Supplement adds treatment and control of Haemaphysalis longicornis (longhorned tick) infestations for one month and label language on a second flea field study and improvement of flea allergy dermatitis signs following afoxolaner treatment; base indication unchanged.
Dose regimen
1.14 mg/lb (2.5 mg/kg) afoxolaner, 5.45 mcg/lb (12 mcg/kg) moxidectin, and 2.27 mg/lb (5.0 mg/kg) pyrantel (as pamoate salt), minimum, oral (soft chewable), once a month
NexGard® PLUS is given orally once a month at the minimum dosage of 1.14 mg/lb (2.5 mg/kg) afoxolaner, 5.45 mcg/lb (12 mcg/kg) moxidectin, and 2.27 mg/lb (5.0 Freedom of Information Summary NADA 141-554 Page 6 of 9 mg/kg) pyrantel (as pamoate salt).
Effectiveness
No new studies in this supplement. Effectiveness against H. longicornis is extrapolated from two well-controlled laboratory studies of afoxolaner alone (NexGard, NADA 141-406, June 21, 2023), accepted because A. americanum (the less susceptible tick, against which NexGard PLUS was tested at original approval) is the dose-limiting species; the FAD label language rests on the 90-day afoxolaner field study under the same supplement.; result: Approval granted by reference to afoxolaner studies (2.5 mg/kg) under NADA 141-406; no NexGard PLUS-specific results reported.
Two well-controlled laboratory studies demonstrated the effectiveness of afoxolaner, one of the active ingredients in NexGard® PLUS, at the dose of 2.5 mg/kg body weight, for the treatment and control of Haemaphysalis longicornis (longhorned tick) infestations.
Extraction notes: Supplemental approval with no new studies, PK or target animal safety data (CVM did not require TAS studies; refers to the original approval FOI Summary of July 19, 2023). The dose quote reproduces a page header ('Freedom of Information Summary NADA 141-554 Page 6 of 9') that interrupts the Dosage Regimen sentence in the extracted text. The General Information section was partly overwritten by table-of-contents text during parsing.
Reproduce: foi_structured_search(query="Afoxolaner, Moxidectin, Pyrantel Pamoate") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).