Afoxolaner: what the FDA reviewed for dog products
7 Freedom of Information summaries from the FDA Center for Veterinary Medicine for products containing Afoxolaner, 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® (NADA/ANADA 141-406)
NexGard® NADA 141-406, Supplemental approval, April 01, 2014; sponsor Boehringer lngelheim Animal Health USA, Inc.; species: Dogs; foi_id 912; FDA PDF
Indication
Supplement adds flea speed-of-kill language to the Effectiveness section of the package insert; indication unchanged (kills adult fleas; treatment and prevention of flea infestations; treatment and control of American Dog tick infestations for one month).
Dose regimen
1.14 mg/lb (2.5 mg/kg) minimum, oral (soft chewable), once a month
NEXGARD is given orally, once a month, at the minimum dosage of 1.14 mg/lb (2.5 mg/kg).
Effectiveness
Laboratory flea speed-of-kill study PR&D 0233403: untreated control vs single oral dose of NEXGARD (at least 2.5 mg/kg) on Day 0 after infestation with 100 fleas on Day -1; live fleas counted at 30 min, 2, 4, 8, 12 and 24 h (4 dogs/group/timepoint).; n = 48; primary endpoint: Percent effectiveness against C. felis based on geometric mean live flea counts vs control at each timepoint; result: 0.0% at 30 minutes, 15.0% at 2 h, 87.8% at 4 h, 99.5% at 8 h, 100.0% at 12 and 24 h; significant vs control at 8, 12 and 24 h (P<0.005). NEXGARD started to kill fleas 4 hours after administration and demonstrated >99% effectiveness at 8 hours.
48 Beagle dogs (24 males, 24 females), 13.8 – 37.5 months of age, weighing between 7.1 – 14.8 kg.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| None (speed-of-kill study) | There were no adverse reactions during this study. |
Extraction notes: Supplemental approval; CVM did not require target animal safety studies (refers to the original approval FOI Summary of September 14, 2013). Indication quote is verbatim from the General Information section, which omits 'is indicated' in this summary.
NexGard® NADA 141-406, Supplemental approval, February 23, 2015; sponsor Boehringer lngelheim Animal Health USA, Inc.; species: Dogs; foi_id 914; FDA PDF
Indication
Supplement adds treatment and control of Brown dog tick (Rhipicephalus sanguineus) 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) minimum, oral (soft chewable), once a month
NEXGARD is given orally, once a month at the minimum dosage of 1.14 mg/lb (2.5 mg/kg).
Effectiveness
Three laboratory dose-confirmation studies against induced adult R. sanguineus infestations (untreated control vs single oral dose ≥2.5 mg/kg on Day 0; weekly re-infestation with 50 ticks; live/dead tick counts at 48 h): PR&D 0233601 (South Africa; quoted animals), PR&D 0233004 (20 dogs) and PR&D 0233005 (20 dogs).; n = 16; primary endpoint: Percent reduction in geometric mean live tick counts vs control at 48 h post-infestation through Day 30 (control indication); increased dead tick counts (treatment indication); result: Study 0233601: ≥98.6% effective through Day 30 (100, 98.7, 99.3, 98.6, 99.3% on Days 2-30). Study 0233004 failed to demonstrate >90% effectiveness at Day 30 (83.9%). Study 0233005: ≥93.5% through Day 30. Combined average effectiveness 92.2% (>90%), which CVM accepted as demonstrating effectiveness for 30 days when assessed 48 h after administration or infestation.
16 Beagle dogs (7 males, 9 females), ≥ 6 months of age, weighing between 11.0-18.4 kg
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Diarrhea (study PR&D 0233005; two dogs) | One dog had diarrhea within one day post-treatment; this dog had diarrhea one day prior to treatment as well. A second dog had diarrhea 12 and 24 days post-treatment. | ||
| None (studies PR&D 0233601 and 0233004) | There were no adverse reactions during this study. |
Extraction notes: Supplemental approval; CVM did not require target animal safety studies (refers to the original approval FOI Summary of September 14, 2013). n_dogs refers to study PR&D 0233601 only.
NexGard® NADA 141-406, Supplemental approval, July 13, 2018; sponsor Boehringer lngelheim Animal Health USA, Inc.; species: Dogs; foi_id 3811; 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) minimum, oral (soft chewable), once a month
NexGard® is given orally once a month at the minimum dosage of 1.14 mg/lb (2.5 mg/kg).
Effectiveness
Laboratory study 0377501 (GCP): masked, randomized block; untreated control vs single oral NexGard dose (≥2.5 mg/kg) on Day 0; infestation on Day 28 with 50 wild-caught I. scapularis (63.1% B. burgdorferi infection rate); ticks counted/removed Day 33; serology (Lyme Quant C6, SNAP 4Dx) through Day 102 and PCR of 4 skin biopsies on Day 104. A second similar study (PR&D 0328901, 20 dogs) used serology only.; n = 20; primary endpoint: Live tick counts on Day 33 and B. burgdorferi infection status (positive on either serology test or any skin-biopsy PCR); result: All 10 NexGard dogs remained negative for B. burgdorferi by serology and PCR while all 10 control dogs became positive (p<0.0001); NexGard was 99.5% effective against wild-caught I. scapularis on Day 33. Second study: 0/10 treated vs 9/10 control dogs seropositive (p=0.0001), 100% tick effectiveness on Day 33.
Study Animals: 20 Beagle dogs (10 males, 10 females), 6.7-8.0 months of age, weighing between 5.8-9.2 kg.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| None (both laboratory studies) | There were no adverse reactions to NexGard® treatment. |
Extraction notes: Supplemental approval; CVM did not require target animal safety studies (the summary's reference to 'NADA 141-460, dated September 13, 2013' appears to be a typo for NADA 141-406, September 14, 2013). No new PK data.
NexGard® NADA 141-406, Supplemental approval, June 21, 2023; sponsor Boehringer lngelheim Animal Health USA, Inc.; species: Dogs; foi_id 14165; FDA PDF
Indication
Supplement provides a new modified formulation, adds treatment and control of Haemaphysalis longicornis (longhorned tick) infestations for one month, and adds label language on improvement of signs of flea allergy dermatitis as a direct result of eliminating fleas.
Dose regimen
1.14 mg/lb (2.5 mg/kg) minimum, oral (soft chewable), once a month
NexGard® is given orally once a month, at the minimum dosage of 1.14 mg/lb (2.5 mg/kg).
Effectiveness
Field study PR&D 03547: active-controlled (oral spinosad), masked, multi-site (6 US sites), randomized block 3:1, three monthly oral treatments over 90 days in 103 households (178 dogs) with natural flea infestations and at least 2 signs of flea allergy dermatitis on the sentinel dog; flea counts and FAD sign scores on sentinel dogs at Days 30, 60, 90.; n = 121 NexGard-treated and 36 spinosad-treated dogs completed all four visits; primary endpoint: Percent effectiveness against fleas vs baseline at Days 30, 60, 90 (≥90% and significantly different from baseline); proportion of dogs with improved FAD signs (alopecia, erythema, papules, excoriation, scales/crusts); result: NexGard ≥97.5% effective at every visit (97.5% Day 30, 99.7% Day 60, 99.9% Day 90; 63/63/59 dogs analysed); spinosad 93.2%, 97.9%, 99.3%. 70% of NexGard dogs showed improvement of individual FAD signs at Day 30, 87.8% at Day 60 and 91.1% at Day 90 (active control 53.3%, 81.8%, 81.3%). Longhorned tick laboratory studies PR&D 0434502 and 0434506 (20 dogs each): 98.5% and 100% effective 72/48 h after treatment and 100% at 72 h after weekly re-infestations through Day 31.
One hundred twenty-one (121) dogs treated with NexGard® and 36 dogs treated with oral spinosad completed all four visits of the study.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Pruritus | 6 (4.6%) | 2 (4.3%) | Pruritus 6 4.6 2 4.3 |
| Diarrhea (with and without blood) | 5 (3.8%) | 1 (2.2%) | Diarrhea (with and without blood) 5 3.8 1 2.2 |
| Emesis | 4 (3.1%) | 2 (4.3%) | Emesis 4 3.1 2 4.3 |
| Anorexia | 1 (0.8%) | 0 (0.0%) | Anorexia 1 0.8 0 0.0 |
| Lethargy | 1 (0.8%) | 2 (4.3%) | Lethargy 1 0.8 2 4.3 |
| Seizure | 0 (0.0%) | 1 (2.2%) | Seizure 0 0.0 1 2.2 |
Extraction notes: Supplemental approval; CVM did not require target animal safety studies (refers to the original approval FOI Summary of September 14, 2013); no PK data for the modified formulation are given in the summary. Adverse reaction rows are from field study Table II.9 (columns: NexGard N, NexGard % of n=130, active control N, active control % of n=46). Longhorned tick study tables were partly garbled by PDF extraction (e.g. '19. 5', a 'Study Day 34' row that is Day 24).
NexGard® NADA 141-406, Supplemental approval, March 16, 2026; sponsor Boehringer lngelheim Animal Health USA, Inc.; species: Dogs; foi_id 18256; FDA PDF
Indication
Supplement adds treatment and control of Amblyomma maculatum (Gulf Coast 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) minimum, oral (soft chewable), once a month
NexGard® is given orally once a month, at the minimum dosage of 1.14 mg/lb (2.5 mg/kg).
Effectiveness
Two masked, negative-controlled laboratory dose-confirmation studies (GCP) with single oral NexGard dose (afoxolaner as close as possible to 2.5 mg/kg without under-dosing) on Day 0 and ~50 adult A. maculatum per infestation; live/dead tick counts 72 h after treatment or infestation. Study 2023-3557 (Colbert, GA; fed; infestations Days -1, 14, 28; quoted treatment groups) and Study 2024-3687 (South Africa; fasted; 20 dogs; infestations Days -2 to 35).; 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: ≥98.8% reduction in live A. maculatum at 72 h through Day 31 (99.5% Day 3, 100% Day 17, 98.8% Day 31; p<0.0001). Study 2024-3687: ≥94.6% through Day 38 (100, 97.7, 98.5, 98.9, 97.0, 94.6% on Days 3-38). Dead tick counts higher in treated dogs at all timepoints.
Control 0 mg/kg 10 (4M, 6F) NexGard® 2.5 mg/kg 10 (3M, 7F)
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Diarrhea (study 2023-3557; considered a possible drug-related adverse reaction) | One dog in the NexGard® treated group had a single incidence of diarrhea noted five hours after treatment. | ||
| None (study 2024-3687) | No treatment-related adverse reactions were observed during the study. |
Extraction notes: Supplemental approval; FDA did not require target animal safety studies (refers to the original approval FOI Summary of September 14, 2013). No PK data. The General Information section of this summary was partly overwritten by table-of-contents text during parsing; dose quote taken from the Dosage Regimen line via grep. n_dogs quote is the flattened Table II.1 treatment-group row (Treatment, Minimum Dose, Number and Sex of Dogs) of study 2023-3557; study 2024-3687 also used 10 treated and 10 control dogs.
NexGard® NADA 141-406, Supplemental approval, May 15, 2014; sponsor Boehringer lngelheim Animal Health USA, Inc.; species: Dogs; foi_id 913; FDA PDF
Indication
Supplement adds treatment and control of Black-legged tick (Ixodes scapularis) and Lone Star tick (Amblyomma americanum) 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) minimum, oral (soft chewable), once a month
NEXGARD is given orally, once a month at the minimum dosage of 1.14 mg/lb (2.5 mg/kg).
Effectiveness
Four laboratory dose-confirmation studies (untreated control vs single oral dose ≥2.5 mg/kg on Day 0; weekly re-infestation with 50 ticks through Day 35): PR&D 0233301 and 0233303 for I. scapularis (48 h counts) and PR&D 0233106 and 0233109 for A. americanum (72 h counts). Quoted animals are from study PR&D 0233301.; n = 16; primary endpoint: Percent reduction in geometric mean live tick counts vs control (control indication) and increase in dead tick counts (treatment indication) at 48 h (I. scapularis) or 72 h (A. americanum) after infestation; result: I. scapularis: ≥94.2% (study 0233301; 98.4, 99.1, 99.6, 94.2% on Days 2-30) and ≥98.0% (study 0233303; 20 dogs) effective through Day 30. A. americanum: ≥98.9% (study 0233106; 20 dogs) and ≥97.8% (study 0233109; 20 dogs) effective at 72 h through Day 30. Live tick counts significantly reduced and dead tick counts significantly increased vs control in all studies.
16 Beagle dogs (8 males, 8 females), 6.3 to 7.5 months of age, weighing between 5.2 – 8.7 kg
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| None (all four laboratory studies) | There were no adverse reactions during this study. |
Extraction notes: Supplemental approval; CVM did not require target animal safety studies (refers to the original approval FOI Summary of September 14, 2013). n_dogs refers to study PR&D 0233301 only; the other three studies enrolled 20 dogs each (10 per group). In study 0233301 two control dogs had reduced-vitality tick populations on Day 7, which compromised that timepoint only.
NexGard® NADA 141-406, Original approval, September 14, 2013; sponsor Boehringer lngelheim Animal Health USA, Inc.; species: Dogs; foi_id 911; FDA PDF
Indication
Kills adult fleas; treatment and prevention of flea infestations (Ctenocephalides felis) and treatment and control of American Dog tick (Dermacentor variabilis) 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) minimum, oral (beef-flavored soft chewable), once a month, chewable sizes 11.3, 28.3, 68 and 136 mg by body-weight band
NEXGARD is given orally once a month, at the minimum dosage of 1.14 mg/lb (2.5 mg/kg).
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| other | 0.18 µg/mL mean plasma afoxolaner concentration 33 days post-treatment | 2.5 mg/kg single oral dose of an experimental oral solution, fed (with an additional fasted group); first exploratory dose-ranging study; similar fed or fasted | Plasma concentrations averaged 0.18 µg/mL 33 days post-treatment at the 2.5 mg/kg dose level, and were similar under fed or fasted conditions. |
| other | 0.18 µg/mL mean plasma concentration 33 days post-treatment | 2.5 mg/kg single oral dose, second exploratory dose-ranging study | Plasma concentrations averaged 0.18 µg/mL 33 days post-treatment at the 2.5 mg/kg dose level. |
| other | 0.1 µg/mL mean plasma concentration 28 days post-treatment | 2.5 mg/kg single oral dose, third exploratory study in Beagles (0.75-3.5 mg/kg range) | The 2.5 mg/kg dosage maintained a 0.1 µg/mL mean plasma concentration 28 days post-treatment and an average of 99.8% effectiveness against fleas on day 31 post-treatment. |
| other | plasma concentrations greater than 0.08 µg/ml were 100% effective against fleas (flea-effective concentration threshold) | Beagles given single oral doses of 0.75, 1.5, 2.5 or 3.5 mg/kg (third exploratory study) | In the third study, Beagles administered a single oral dose of 0.75, 1.5, 2.5, or 3.5 mg/kg afoxolaner confirmed that plasma concentrations greater than 0.08 µg/ml were 100% effective against fleas. |
| other | less than dose-proportional plasma afoxolaner concentrations after three monthly doses | margin-of-safety study, 8-week-old Beagles, 1X/3X/5X of 6.3 mg/kg, pre-dose samples | Following the three monthly doses, plasma afoxolaner concentrations were less than proportional with dose administered. |
| other | Day 125 plasma afoxolaner concentrations dose proportional up to 3X and more than dose proportional at 5X | margin-of-safety study, after three doses every 2 weeks (Days 84, 98, 112) following three monthly doses | Following the three doses administered every 2 weeks, plasma afoxolaner concentrations on Day 125 were dose proportional up to 3X and more than dose proportional at 5X. |
Target-animal safety
dose multiples 1X, 3X, 5X; duration three monthly treatments (Days 0, 28, 56) followed by three bi-weekly treatments (Days 84, 98, 112); six treatments per dog; necropsy Day 126; animals 32.
32 Beagle dogs (16 males, 16 females), 8 to 9 weeks of age, weighing between 2.3 and 4 kg.
| Finding | Quote |
|---|---|
| No deaths; no clinically relevant treatment-related changes in food consumption, body weight, physical examination, clinical pathology, gross pathology, histopathology or organ weights. | There were no deaths during the course of the study. There were no clinically relevant treatment-related changes in daily food consumption, body weight, physical examination variables, clinical pathology (hematology, clinical chemistries, or coagulation tests), gross pathology, histopathology, or organ weights. |
| Vomiting occurred throughout the study with similar incidence across all groups, including one 5X dog four hours after treatment. | Vomiting occurred throughout the study, with a similar incidence across all groups, including one dog in the 5X group that vomited four hours after treatment. |
| Conclusion: well tolerated in 8-week-old Beagles at 1, 3 or 5X the maximum exposure dose of 6.3 mg/kg for six doses. | Afoxolaner is well tolerated when administered to 8-week old Beagle dogs at 1, 3, or 5X the maximum potential exposure dose of 6.3 mg/kg at three, 28-day dose intervals followed by three, 2-week dose intervals for a total of 6 doses. |
Effectiveness
Field study PR&D 02341: masked, multi-center (17 sites; 15 used for safety, 14 for effectiveness), randomized block, active-controlled (spinosad ≥30 mg/kg) study; NEXGARD ≥2.5 mg/kg orally once monthly for 3 consecutive months in households with natural flea infestations; 2:1 allocation NEXGARD:spinosad; flea counts on sentinel dogs at Days 0, 30, 60, 90.; n = 415 NEXGARD-treated and 200 spinosad-treated dogs (safety); 186 NEXGARD and 96 spinosad dogs in the Day 30 effectiveness analysis; primary endpoint: Percent reduction in geometric mean live flea counts on sentinel dogs compared with baseline (Visit 1) at Days 30, 60 and 90; result: Afoxolaner: 98.0% (Day 30), 99.7% (Day 60), 99.9% (Day 90) reduction vs baseline; spinosad: 95.7%, 99.4%, 99.7%; all reductions statistically significant (p<0.001). Both groups >90% effective; no conclusions on ticks (insufficient tick-infested dogs).
415 NEXGARD-treated dogs and 200 spinosad-treated dogs were evaluated for safety. The effectiveness analysis for Day 30 was performed on 186 NEXGARD-treated dogs and 96 spinosad-treated dogs.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Vomiting (with and without blood) | 17 (4.1%) | 25 (12.5%) | Vomiting (with and without blood) 17 4.1 25 12.5 |
| Dry/flaky skin | 13 (3.1%) | 2 (1.0%) | Dry/ Flaky Skin 13 3.1 2 1.0 |
| Diarrhea (with and without blood) | 13 (3.1%) | 7 (3.5%) | Diarrhea (with and without blood) 13 3.1 7 3.5 |
| Lethargy | 7 (1.7%) | 4 (2.0%) | Lethargy 7 1.7 4 2.0 |
| Anorexia | 5 (1.2%) | 9 (4.5%) | Anorexia 5 1.2 9 4.5 |
| Seizure in a dog with a history of seizures | One dog with a history of seizures experienced a seizure on the same day after receiving the first dose and on the same day after receiving the second dose of NEXGARD. |
Extraction notes: Original approval. PK data are limited to plasma-concentration statements from exploratory dose-ranging studies and the margin-of-safety study (no half-life, Cmax or AUC reported). Adverse reaction rows are from field study Table 8 (columns: Afoxolaner N, Afoxolaner % of n=415, Spinosad N, Spinosad % of n=200); a second dog with a seizure history seized nineteen days after the third dose. Laboratory dose-confirmation studies: fleas (32 dogs; 100% at 24 h post-infestation through Day 35, 81.1% at 12 h on Day 28) and two D. variabilis studies (16 dogs each; ≥97.3% and ≥98.5% at 48 h through Day 30). Target animal safety: study PR&D 0234001, treatment groups 0, 6.3 (1X), 18.9 (3X), 31.5 (5X) mg/kg.
Reproduce: foi_structured_search(query="Afoxolaner") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).