Fluralaner: what the FDA reviewed for dog products
9 Freedom of Information summaries from the FDA Center for Veterinary Medicine for products containing Fluralaner, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Cats; Dogs; Dogs and cats.
Products
- BRAVECTO® (NADA/ANADA 141-459)
- BRAVECTO® 1-MONTH (NADA/ANADA 141-532)
- BRAVECTO® QUANTUM (NADA/ANADA 141-599)
- Bravecto® (NADA/ANADA 141-426)
BRAVECTO® NADA 141-459, Supplemental approval, August 09, 2022; sponsor Intervet, Inc.; species: Cats; foi_id 12711; FDA PDF
Indication
Supplement adding treatment and control of Haemaphysalis longicornis (Asian longhorned tick) infestations for 12 weeks in cats and kittens 6 months of age and older weighing 2.6 lb or more.
Dose regimen
minimum 18.2 mg/lb (40 mg/kg) fluralaner, topical (spot-on solution), single dose every 12 weeks (every 8 weeks in case of potential D. variabilis exposure), Dosage unchanged by this supplement.
BRAVECTO® should be administered topically as a single dose every 12 weeks according to the Dosage Schedule below to provide a minimum dose of 18.2 mg/lb (40 mg/kg) body weight.
Effectiveness
Laboratory dose confirmation study S19248-00 (Waverly, NY; GCP): 20 healthy domestic shorthair cats randomized to untreated control (10) or fluralaner topical solution (10; 39.6-40.3 mg/kg on Day 0); ~50 adult female H. longicornis applied on Days -2, 28, 58, 88 with Elizabethan collars to prevent grooming; live/dead counts 48 h after treatment/infestation (Days 2, 30, 60, 90); masked. Second study S19249-00 (South Africa) had invalid Day 2 counts (grooming) but >90% effectiveness on Days 30-90.; primary endpoint: Live tick counts (least squares means) vs untreated control; result: S19248-00: 100%, 100%, 100% and 95.4% effectiveness on Days 2, 30, 60, 90 (P < 0.0001); S19249-00: 100%, 99.0%, 100% on Days 30, 60, 90.
The fluralaner group had greater than 90% reduction in live H. longicornis tick counts at 48 hours following drug administration or infestation for 90 days (infestation on Day 88).
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| No adverse reactions reported (laboratory studies) | Adverse Reactions: No adverse reactions were reported in this study. |
Extraction notes: Cat summary filed under a dog-flagged application; species recorded as Cats. Supplemental approval; no target animal safety studies required (refers to the July 20, 2016 original NADA 141-459 summary). n_dogs left null because the study animals are cats (20 per study, 10 treated/10 control).
Bravecto® NADA 141-426, Supplemental approval, January 12, 2023; sponsor Intervet, Inc.; species: Dogs; foi_id 13361; FDA PDF
Indication
Supplement adding treatment and control of Haemaphysalis longicornis (Asian longhorned tick) infestations for 12 weeks in dogs and puppies 6 months of age and older weighing 4.4 lb or more.
Dose regimen
minimum 11.4 mg/lb (25 mg/kg) fluralaner, oral (chewable tablet), single dose every 12 weeks (every 8 weeks for potential A. americanum exposure), Administered with food; dosage unchanged by this supplement.
BRAVECTO® should be administered orally as a single dose every 12 weeks according to the Dosage Schedule below to provide a minimum dose of 11.4 mg/lb (25 mg/kg) body weight.
Effectiveness
Laboratory dose confirmation study S19250-00 (Waverly, NY; GCP): 20 healthy Beagles randomized to untreated control (10) or fluralaner chews (10; 27.3-35.9 mg/kg oral on Day 0); ~50 adult female H. longicornis ticks applied on Days -2, 28, 58 and 88; live/dead tick counts 48 h after treatment/infestation on Days 2, 30, 60, 90; masked counts. A second identical study (S19251-00, South Africa) gave the same result.; primary endpoint: Live tick counts (least squares means) vs untreated control; >90% reduction required; result: 100% effectiveness on Days 2, 30, 60 and 90 in S19250-00 (control LS-mean live ticks 20.2, 18.4, 16.1, 13.9 vs 0.0 treated; p <= 0.0002); 100% at all counts in S19251-00 (p < 0.0001).
The fluralaner group had greater than 90% reduction in live H. longicornis tick counts at 48 hours following drug administration or infestation for 90 days (infestation on Day 88) compared to the control group.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| No adverse reactions reported (laboratory studies) | Adverse Reactions: No adverse reactions were reported in this study. |
Extraction notes: Supplemental approval; no target animal safety studies were required (summary refers to the original 2014 NADA 141-426 FOI summary). Effectiveness rests on two laboratory dose confirmation studies (20 dogs each, 10 treated/10 control); no field study.
BRAVECTO® 1-MONTH NADA 141-532, Original approval, July 09, 2020; sponsor Intervet, Inc.; species: Dogs; foi_id 9329; FDA PDF
Indication
Kills adult fleas; treatment and prevention of flea infestations (C. felis) and treatment and control of I. scapularis, D. variabilis and R. sanguineus infestations for one month in dogs and puppies 8 weeks of age and older weighing 4.4 lb or more; A. americanum for one month in dogs 6 months and older.
Dose regimen
minimum 4.5 mg/lb (10 mg/kg) fluralaner, oral (chewable tablet), single dose monthly, Administered with food, per body-weight dosage schedule (45-560 mg chews).
BRAVECTO® 1-MONTH should be administered orally as a single dose monthly according to the Dosage Schedule below to provide a minimum dose of 4.5 mg/lb (10 mg/kg) fluralaner.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| other | steady state reached with three treatments at 30-day intervals | margin of safety study, 8-week-old Beagles, 1X-5X of 22.5 mg/kg monthly x3 | Plasma concentrations of fluralaner showed that steady-state is achieved with three treatments administered at 30-day intervals. |
| other | Cmax accumulation first-to-third dose 1.1X to 5.0X (1X), 0.7X to 1.7X (3X), 0.6X to 2.5X (5X); AUClast accumulation 1.0X to 4.6X, 0.8X to 1.7X, 0.8X to 2.7X | margin of safety study; less than dose-proportional increase across 1X, 3X, 5X | The accumulation of the 1X, 3X, and 5X doses between the first and third dose ranged from 1.1X to 5.0X , 0.7X to 1.7X, 0.6X to 2.5X, respectively (based on maximum plasma concentration: Cmax) and 1.0X to 4.6X, 0.8X to 1.7X, 0.8X to 2.7X, respectively (based on the area under the plasma concentration-time curve from 0 to the last quantifiable concentration: AUClast). |
Target-animal safety
dose multiples 1X, 3X, 5X; duration three oral doses at one-month intervals (Days 1, 31, 61) of 1X/3X/5X the maximum labeled dose of 22.5 mg/kg; 92-day study; animals 32.
Study Animals: 32 healthy, weaned puppies (Beagles; 16 male and 16 female), 57-59 days of age, and 1.6 to 2.9 kg body weight.
| Finding | Quote |
|---|---|
| No clinically relevant treatment-related effects on body weight, food consumption, organ weights, hematology, CRP, coagulation or urinalysis. | Results: There were no clinically-relevant, treatment-related effects on body weights, food consumption, organ weights, hematology, C-reactive protein, coagulation profile, and urinalysis. |
| Diarrhea and mucoid/discolored feces most common, similar incidence in fluralaner and control groups. | Diarrhea and mucoid or discolored feces were the most common observations in this study, occurring at a similar incidence in the fluralaner and control groups. |
| Tremors in one dog each of the 1X, 3X and 5X groups 4 hours after the first dose; one 1X dog with splayed hind limbs and one with trembling. | One dog in the 1X group demonstrated trembling on Day 2. One dog each in the 1X, 3X, and 5X groups had tremors on Day 1 at 4 hours post-dose. |
| Serum ALT elevations in two dogs each of the 1X and 5X groups; elevated BUN in one 3X dog and BUN/creatinine in one 5X dog. | Two dogs each from the 1X and 5X groups had serum ALT elevations (49-105 U/L; reference range: 10-48 U/L). |
| Pituitary cysts in treated dogs (macroscopic in two 1X dogs; microscopic in three 1X, one 3X, two 5X). | Pituitary cysts were noted macroscopically in two dogs from the 1X group and microscopically in three dogs from the 1X group, one dog from the 3X group, and two dogs in the 5X group. |
| Conclusion: supports safe use at label dose; potential treatment-related effects listed. | Potential treatment-related effects include vomiting, diarrhea, mucoid or discolored stool, trembling, tremors, splayed hind limbs, mandibular lymphadenopathy, abdominal distention, increased serum alanine aminotransferase (ALT) values, increased blood urea nitrogen (BUN) and serum creatinine values, and pituitary cysts. |
Effectiveness
Multi-center pivotal field study S16367-00 (6 enrolling US sites, GCP): 271 client-owned dogs from 149 households; 201 dogs (112 households) given fluralaner chewable tablets at mealtime on Days 0, 30 and 60 vs 70 dogs (37 households) given afoxolaner chewable tablets (active control); households randomized 3:1; one primary dog per household assessed; investigators and flea counters masked.; n = 110 fluralaner and 37 active-control primary dogs at Visit 1; primary endpoint: Difference in live flea counts on primary dogs at Days 30, 60 and 90 vs pretreatment (geometric means from mixed model); result: Fluralaner effectiveness 99.6% (Day 30), 99.9% (Day 60), 99.9% (Day 90); afoxolaner 99.0%, 99.5%, 100.0%; P < 0.001 vs baseline. At least 90% of fluralaner dogs with FAD signs resolved by Day 90; 81.5% of doses consumed voluntarily within 5 minutes.
Results: For each Visit 2, 3, and 4, the effectiveness of fluralaner chewable tablets, based on geometric means, was greater than 99%. Tablet II.1: Field Study S16367-00 Effectiveness Against Fleas Visit Fluralaner Group Active Control Group Visit 1 Number of Primary Dogs 110 37 Visit 1 Geometric Mean Flea Count 50.9 48.8 Visit 2 Number of Primary Dogs 104 34 Visit 2 Geometric Mean Flea Count 0.2 0.5 Visit 2 Percent Effectiveness 99.6% 99.0% Visit 3 Number of Primary Dogs 102 34 Visit 3 Geometric Mean Flea Count 0.0 0.2 Visit 3 Percent Effectiveness 99.9% 99.5% Visit 4 Number of Primary Dogs 98 34 Visit 4 Geometric Mean Flea Count 0.0 0.0 Visit 4 Percent Effectiveness 99.9% 100.0%
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Pruritus | 7.0% | 10.0% | Pruritus 7.0% 10.0% |
| Diarrhea | 3.0% | 4.3% | Diarrhea 3.0% 4.3% |
| Vomiting | 3.0% | 4.3% | Vomiting 3.0% 4.3% |
| Decreased appetite | 3.0% | 0.0% | Decreased Appetite 3.0% 0.0% |
| Lethargy | 1.0% | 1.4% | Lethargy 1.0% 1.4% |
| Weight loss (>15%) | 0.5% | 0.0% | Weight loss (>15%) 0.5% 0.0% |
Extraction notes: Adverse reactions from Table II.4 of field study S16367-00 (fluralaner n=201 vs afoxolaner active control n=70, 90-day study), rows quoted as flattened (term, fluralaner %, control %); liver enzyme (ALT/ALP) elevations >2x upper reference occurred in 1.0% vs 1.4% (row split across lines, not quoted). One fluralaner dog with a seizure history seized 28 days after its first dose. Nine laboratory studies (fleas, R. sanguineus in 8-week-old puppies, A. americanum) are not itemized; A. americanum effectiveness was shown only in dogs 6 months and older. The sentence on less-than-dose-proportional increase spans a page header and is not quoted.
BRAVECTO® QUANTUM NADA 141-599, Original approval, July 10, 2025; sponsor Intervet, Inc.; species: Dogs; foi_id 17185; FDA PDF
Indication
Kills adult fleas; treatment and prevention of flea infestations (C. felis) and treatment and control of I. scapularis, D. variabilis and R. sanguineus infestations for 12 months, and A. americanum for 8 months, in dogs and puppies 6 months of age and older.
Dose regimen
15 mg/kg fluralaner, subcutaneous injection (extended-release suspension, 150 mg/mL; 0.10 mL/kg), single dose every 12 months (every 8 months for A. americanum), Powder constituted with supplied vehicle before injection.
Therefore, a single subcutaneous dose of 15 mg/kg was selected for BRAVECTO® QUANTUM.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| cmax | 444±169 ng/mL, observed 28 to 70 days after the first dose | 1X (15 mg/kg SC), n=8 dogs, margin of safety study S18237-00 | Pharmacokinetics: Maximum fluralaner concentrations (Cmax) of 444±169 ng/mL were observed over a range from 28 to 70 days following the first dose, in 8 dogs receiving the clinically recommended dosage. |
| other | dose-proportional exposure | 1X, 3X, 5X SC every 4 months | Exposure to fluralaner increased in a dose-proportional manner. |
| other | Cmax/AUC accumulation ratios first-to-fifth dose 3.9 (1X), 4.6 (3X), 3.5 (5X) | repeated SC administration 4 months apart | The observed Cmax and area under the curve (AUC) values after repeated administrations 4 months apart showed significant accumulation with ratios between the first and fifth doses of 3.9, 4.6, and 3.5 for the 1X, 3X, and 5X groups, respectively. |
| other | steady state by the fourth dose (357 days) at 1X and 3X and by the third dose (238 days) at 5X | SC dosing every 4 months | Steady state was reached by the fourth dose (357 days) in the 1X and 3X groups and by the third dose (238 days) in the 5X group. |
Target-animal safety
dose multiples 1X, 3X, 5X; duration six subcutaneous doses at 4-month intervals (Days 1, 120, 239, 358, 477, 596) of 15/45/75 mg/kg; necropsy Day 638; animals Thirty-two (16 males and 16 females).
Study Animals: Thirty-two intact, healthy puppies (beagles, 16 males and 16 females), 6 months of age, and 5.3 to 9.5 kg.
| Finding | Quote |
|---|---|
| Injection site swellings after every dose, resolving over time; up to 32 days after the first 1X dose and persisting through the dosing interval in some dogs after later doses and at 3X/5X. | The administration of BRAVECTO® QUANTUM resulted in injection site swellings that resolved over time. After administration of the first dose, injection site swellings were observed for up to 32 days in the 1X dogs. |
| No pain at injection sites; erythema occasional in all groups including control. | No pain observations were recorded during any injection site assessment. |
| Injection site histopathology: fibrosis, granulomatous inflammation, histiocytic infiltration. | On histopathology, abnormal microscopic observation of the injection sites in dogs administered BRAVECTO® QUANTUM included fibrosis (minimal to moderate), granulomatous inflammation (minimal to moderate), and/or histiocytic infiltration (minimal). |
| One 3X male found unresponsive on Day 475 with seizures, euthanized; cause of death polyarteritis, considered possibly drug related. | The cause of death was determined to be polyarteritis. |
| Conclusion: supports safe use; seizures and polyarteritis in one 3X dog possibly drug related. | The seizures and polyarteritis in the one 3X male dog were considered possibly drug related. |
| Foreign experience: pain on injection reported in five dogs in a large European field study. | In a large European field study, pain on injection of BRAVECTO® QUANTUM was reported in five dogs. |
Effectiveness
Multi-center pivotal field study S19038-00 (GCP): 435 client-owned dogs from 274 households randomized 6:3:2 by household to BRAVECTO QUANTUM 15 mg/kg SC every 12 months (Group 1: 225 dogs), every 6 months (Group 2: 51 dogs) or oral fluralaner chewable tablets every 12 weeks (active control: 96 dogs), plus an open-label 6-month group (63 dogs); one primary dog per household assessed; flea counters and investigators masked; visits through Day 365 and beyond.; n = 150 (Group 1), 30 (Group 2) and 55 (active control) primary dogs at Visit 1; primary endpoint: Live flea counts on primary dogs at Visits 2, 3, 5, 7 and 9 (Days 30-365) vs Visit 1 (geometric means); result: Effectiveness >99% at every post-treatment visit for both QUANTUM groups (Group 1: 99.2%, 99.9%, 99.9%, 99.9%, 99.8% on Days 30, 84, 180, 270, 365); p<0.0001 vs baseline. At least 91% of QUANTUM dogs with FAD signs improved by Visit 9.
Results: For each Visit 2, 3, 5, 7, and 9, the effectiveness of BRAVECTO® QUANTUM, based on geometric means, was greater than 99%. Within each treatment group, geometric mean flea counts were significantly different (p<0.0001) from Visit 1 at all post-treatment visits (Visits 2, 3, 5, 7, and 9). Table II.2. Field Study S19038-00 Live Flea Count and Percent Effectiveness Visit Fluralaner Group 1 Fluralaner Group 2 Active Control Group Visit 1 (Day 0) Number of Primary Dogs 150 30 55 Visit 1 (Day 0) Geometric Mean Flea Count 37.6 32.4 36.0 Visit 2 (Day 30) Number of Primary Dogs 138 25 50 Visit 2 (Day 30) Geometric Mean Flea Count 0.3 0.3 0.2 Visit 2 (Day 30) Percent Effectiveness 99.2% 99.1% 99.6%
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Lethargy (12-month interval group; 6-month group 1.8%) | 4.9% | 3.1% | Lethargy 4.9% 1.8% 3.1% |
| Decreased appetite (6-month group 1.8%) | 4.4% | 4.2% | Decreased appetite 4.4% 1.8% 4.2% |
| Vomiting (6-month group 0.9%) | 4.0% | 0% | Vomiting 4.0% 0.9% 0% |
| Diarrhea (6-month group 1.8%) | 2.7% | 3.1% | Diarrhea 2.7% 1.8% 3.1% |
| Injection site lumps or swelling (6-month group 0%) | 1.3% | 0% | Injection site lumps or swelling† 1.3% 0% 0% |
| Seizures (6-month group 0.9%) | 0.9% | 0% | Seizures‡ 0.9% 0.9% 0% |
Extraction notes: Adverse reactions from Table II.4 of field study S19038-00; each quoted row is flattened in the order: term, QUANTUM 12-month dosing interval (n=225), QUANTUM 6-month dosing interval (n=114), active control oral fluralaner (n=96). 'treated' is the 12-month column and 'control' the active-control column; the 6-month column is given in the term. Three QUANTUM dogs had seizures and one had a hypersensitivity reaction (hives, facial edema, vomiting) within 12 hours of the first dose. Dose regimen quote is from the dosage characterization section; the General Information regimen reads 'BRAVECTO® QUANTUM should be administered as a single subcutaneous dose every 12 months.' Margin of safety n=32 is spelled out ('Thirty-two') in the summary. Six laboratory studies (fleas, R. sanguineus, A. americanum, onset of effectiveness) are not itemized.
BRAVECTO® NADA 141-459, Original approval, July 20, 2016; sponsor Intervet, Inc.; species: Dogs and cats; foi_id 945; FDA PDF
Indication
Dogs: kills adult fleas; treatment and prevention of flea infestations (C. felis) and treatment and control of I. scapularis, D. variabilis and R. sanguineus infestations for 12 weeks, and A. americanum for 8 weeks, in dogs and puppies 6 months of age and older weighing 4.4 lb or more. Cats: fleas and I. scapularis for 12 weeks, D. variabilis for 8 weeks, in cats and kittens 6 months and older weighing 2.6 lb or more.
Dose regimen
minimum 11.4 mg/lb (25 mg/kg) fluralaner (dogs), topical (spot-on solution, 280 mg/mL), single dose every 12 weeks (every 8 weeks in case of potential A. americanum exposure), Cats: minimum 18.2 mg/lb (40 mg/kg) topically every 12 weeks (every 8 weeks for D. variabilis exposure).
Dogs BRAVECTO should be administered topically as a single dose every 12 weeks according to the Dosage Schedule below to provide a minimum dose of 11.4 mg/lb (25 mg/kg) body weight.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| bioavailability | approximately 25% (oral and topical) | Beagle dogs, studies S28003/S29386, 12.5-50 mg/kg topical or oral vs 12.5 mg/kg IV; n=6 per group | Conclusion: The bioavailability of fluralaner following oral and topical administration is approximately 25%. |
| half-life | 15 (2) days (mean (SD)) | 12.5 mg/kg IV, dogs; Cmax 7061 ng/mL, AUC0-inf 87141 day*ng/mL (geometric means, CV 14%); Table III.1 row order: dose, route, Cmax, Tmax, AUC, half-life, F | 12.5 IV 7061a (14%)b Not applicable 87141a (14%)b 15 (2) Not applicable |
| tmax | 42 days (median) [range 21, 63] | 12.5 mg/kg topical, dogs; Cmax 347 ng/mL (CV 31%), AUC 19242 day*ng/mL, half-life 17 (4) days, F 22% | 12.5 Topical 347 (31%) 42c [21, 63]d 19242 (23%) 17 (4) 22a (23%)b |
| cmax | 1995 ng/mL (geometric mean, CV 53%) | 12.5 mg/kg oral (chewable tablet), dogs; Tmax 1 day [0.1, 2], AUC 27553 day*ng/mL, half-life 13 (1) days, F 32% | 12.5 Oral 1995 (53%) 1 [0.1, 2] 27553 (56%) 13 (1) 32 (56%) |
| cmax | 707 ng/mL (geometric mean, CV 29%) | 25 mg/kg topical (label dose), dogs; Tmax 25 days [14, 56], AUC 46266 day*ng/mL, half-life 21 (3) days, F 27% | 25 Topical 707 (29%) 25 [14, 56] 46266 (31%) 21(3) 27 (31%) |
| cmax | 3577 ng/mL (geometric mean, CV 67%) | 25 mg/kg oral, dogs; Tmax 1 day [1, 2], AUC 42611 day*ng/mL, half-life 12 (3) days, F 24% | 25 Oral 3577 (67%) 1 [1, 2] 42611 (62%) 12 (3) 24 (62%) |
| auc | 87818 day*ng/mL (geometric mean, CV 21%) | 50 mg/kg topical, dogs; Cmax 1673 ng/mL, Tmax 25 days [7, 42], half-life 19 (5) days, F 25% | 50 Topical 1673 (21%) 25 [7, 42] 87818 (21%) 19 (5) 25 (21%) |
| other | single oral dose of the topical solution gave about seven-fold greater exposure than the third topical dose | oral safety study D009\006, 56 mg/kg orally once vs 56 mg/kg topical x3 | The systemic fluralaner exposure after a single oral dose was about seven-fold greater than the exposure after the third topical dose in the margin of safety study. |
Target-animal safety
dose multiples 1X, 3X, 5X; duration three topical doses at eight-week intervals (Days 0, 56, 112); necropsy Day 168; animals 32.
Study Animals: 32 healthy, weaned puppies (Beagles, 16 male and 16 female), 56 to 63 days of age, and 2.0 to 3.7 kg body weight.
| Finding | Quote |
|---|---|
| Dogs (56/168/280 mg/kg topical): no clinically relevant treatment-related effects; cosmetic changes at the application site only. | There were no clinically-relevant, treatment-related effects on physical examinations, body weights, food consumption, clinical pathology (hematology, clinical chemistries, coagulation profiles and urinalysis), gross pathology, histopathology, or organ weights. Cosmetic changes at the application site included matting/clumping/spiking of hair, wetness, or a greasy appearance. |
| Dogs: steady state between second and third doses; exposure proportional to dose. | The dogs achieved steady-state plasma concentrations between the second and third doses. Systemic exposure was proportional to dose during each dosing period. |
| Conclusion (dogs): supports safe use at the labeled dose and duration. | The study supports the safe use of fluralaner topical solution in dogs when used at the labeled dose and duration. |
| Oral safety study (56 mg/kg of the topical solution given orally once, 12 dogs): salivation in 5 of 6 treated dogs; one bloody diarrhea, one vomiting. | Salivation was observed in five of the six dogs orally administered fluralaner during the five minutes immediately after dosing. |
| Cats margin of safety study (93/279/465 mg/kg topical, 32 kittens): increased incidence of minimal renal tubular degeneration/regeneration at 3X and 5X. | Histopathological examination of the kidneys showed an i ncreased incidence of minimal tubular degeneration/regeneration in the higher dose groups (one kitten in the control group, none in the 1X group, five in the 3X group, and three in the 5X group). |
| Cats conclusion: renal tubular degeneration/regeneration considered a potential drug-related effect of unknown clinical impact. | Renal tubular degeneration/regeneration is considered a potential drug-related effect with unknown clinical impact. |
Effectiveness
Multi-center pivotal field study S11157-00 in dogs (12 US sites, GCP): 321 client-owned dogs from 165 households; 221 dogs (121 households) given fluralaner topical solution on Days 0 and 84 vs 100 dogs (44 households) given fipronil + (S)-methoprene topical on Days 0, 28, 56; households randomized 3:1; one primary dog per household assessed; flea counters and investigators masked.; n = 120 fluralaner and 44 control primary dogs at Visit 1; primary endpoint: Difference in live flea counts on primary dogs at Days 28, 56 and 84 vs pretreatment (geometric means); result: Fluralaner effectiveness 99.8% (Day 28), 99.9% (Day 56), 99.9% (Day 84) vs control 81.2%, 90.3%, 93.0%. At least 86% of fluralaner dogs with FAD signs resolved by Week 12.
Table II.2: Field Study S11157-00 Effectiveness against Fleas Visit Fluralaner Group Control Group Visit 1 Number of Dogs 120 44 Visit 1 Geometric Mean Flea Count 68.9 66.6 Visit 2 Number of Dogs 110 36 Visit 2 Geometric Mean Flea Count 0.1 12.5 Visit 2 Percent Effectiveness 99.8% 81.2% Visit 3 Number of Dogs 105 36 Visit 3 Geometric Mean Flea Count 0.1 6.4 Visit 3 Percent Effectiveness 99.9% 90.3% Visit 4 Number of Dogs 104 33 Visit 4 Geometric Mean Flea Count 0.1 4.7 Visit 4 Percent Effectiveness 99.9% 93.0%
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Vomiting | 6.3% | 6.0% | Vomiting 6.3% 6.0% |
| Alopecia | 4.1% | 2.0% | Alopecia 4.1% 2.0% |
| Diarrhea | 2.7% | 11.0% | Diarrhea 2.7% 11.0% |
| Lethargy | 2.7% | 2.0% | Lethargy 2.7% 2.0% |
| Seizures (two fluralaner-treated dogs with no prior history) | two dogs treated with fluralaner topical solution with no prior history of seizures each experienced a seizure. One dog had two seizures a day apart about 18 days after its first dose. |
Extraction notes: Corrected FOI summary covering dogs and cats; dog data are recorded in the main fields. Indication quote is taken from the dog Indication paragraph, which the PDF extraction garbled ('fle a', 'bl ack-legged'); the sentence continues 'in dogs and puppies 6 months of age and older, and weighing 4.4 pounds or greater' after a page header. PK values come from Table III.1 (geometric mean (CV) for Cmax/AUC/F, median [range] Tmax, mean (SD) half-life); each quoted row is flattened in the order dose, route, Cmax, Tmax, AUC0-inf, half-life, F, with footnote letters a-d attached to some values. Adverse reactions are from Table II.4 (fluralaner n=221, 105-day study; active control n=100, 84-day study); the 'Decreased appetite' (fluralaner 1.4%) and 'Moist dermatitis/rash' (0.9%) rows were scrambled by extraction and are omitted. Cats: margin of safety at 93/279/465 mg/kg; field study S11158-00 (311 cats, 224 fluralaner/87 control) gave 99.1%/99.5%/99.0% effectiveness at Visits 2-4 vs 46.5%/66.6%/75.8% control; two fluralaner cats had ataxia; cat AR table: vomiting 7.6% vs 6.9%, pruritus 5.4% vs 11.5%, diarrhea 4.9% vs 1.1%.
BRAVECTO® NADA 141-459, Supplemental approval, June 12, 2026; sponsor Intervet, Inc.; species: Cats; foi_id 18561; FDA PDF
Indication
Supplement adding treatment and control of Amblyomma maculatum (Gulf Coast tick) infestations for 12 weeks in cats and kittens 6 months and older weighing 2.6 lb or more, and extending the flea indication (kill adult fleas, treat and prevent C. felis infestations for 12 weeks) to kittens 12 weeks of age and older weighing 2.6 lb or more.
Dose regimen
minimum 18.2 mg/lb (40 mg/kg) fluralaner, topical (spot-on solution), single dose every 12 weeks (every 8 weeks in case of potential D. variabilis exposure), Dosage unchanged by this supplement.
BRAVECTO® should be administered topically as a single dose every 12 weeks according to the Dosage Schedule below to provide a minimum dose of 18.2 mg/lb (40 mg/kg) body weight.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| other | age-related PK after topical administration not evaluated in kittens; oral fluralaner gives substantially lower Cmax and AUC and shorter half-life in puppies 8 to 9 weeks old than in dogs 6 months and older | statement carried over from dog data; no kitten PK values reported | Age related changes in pharmacokinetics following topical administration have not been evaluated in kittens. Pharmacokinetic studies demonstrate that oral administration of fluralaner results in a substantially lower peak plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC), and a shorter plasma elimination half-life (T½), in young puppies (8 to 9 weeks of age) compared to dogs aged 6 months and older, at approximately the same oral dose. |
Effectiveness
Laboratory dose confirmation study S19172-00 (Turlock, CA; GCP): 20 healthy domestic shorthair cats randomized to untreated control (10) or BRAVECTO 39.6-40.2 mg/kg topically on Day 0; ~50 adult A. maculatum applied on Days -2, 28, 58, 88 (Elizabethan collars); counts 72 h after treatment/infestation on Days 3, 31, 61, 91; masked. Companion study S19171-00 (Waverly, NY) had invalid Day 3 counts (grooming) but 100%/99.6%/97.5% on Days 31/61/91. Kitten flea study S16279-00 (40 kittens, 12- and 16-week cohorts) showed 99.8-100% flea effectiveness through Day 86.; primary endpoint: Live tick counts (least squares means) vs untreated control; >90% reduction; result: S19172-00: 100% (Day 3), 100% (Day 31), 100% (Day 61), 93.8% (Day 91) effectiveness against A. maculatum (p<0.0001).
The BRAVECTO® group had greater than 90% reduction in live A. maculatum tick counts at 72 hours following drug administration or infestation for 91 days (infestation on Day 88).
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| No adverse reactions reported (laboratory studies) | Adverse Reactions: No adverse reactions were reported in this study. |
Extraction notes: Cat summary filed under a dog-flagged application; species recorded as Cats. Supplemental approval; no target animal safety studies required (refers to the 2016 original NADA 141-459 summary). Additional kitten tick studies (I. scapularis, D. variabilis in 12- and 16-week-old kittens) failed to demonstrate >90% effectiveness through 12 weeks in 3 of 4 studies, so tick indications remain restricted to cats 6 months and older. n_dogs null because animals are cats.
BRAVECTO® QUANTUM NADA 141-599, Supplemental approval, March 16, 2026; sponsor Intervet, Inc.; species: Dogs; foi_id 18255; FDA PDF
Indication
Supplement adding treatment and control of Haemaphysalis longicornis (Asian longhorned tick) and Amblyomma maculatum (Gulf Coast tick) infestations for 12 months in dogs and puppies 6 months of age and older.
Dose regimen
15 mg/kg fluralaner, subcutaneous injection (0.10 mL/kg), single dose every 12 months (every 8 months for A. americanum), Dosage unchanged by this supplement.
This supplemental approval does not change the previously approved 15 mg/kg as a single subcutaneous dose every 12 months for fleas and ticks (Ixodes scapularis, Dermacentor variabilis, and Rhipicephalus sanguineus) and every 8 months for Amblyomma americanum.
Effectiveness
Laboratory dose confirmation study S22131-00 (Bloemfontein, South Africa; GCP): 20 healthy dogs randomized to untreated control (10) or BRAVECTO QUANTUM 15 mg/kg (0.10 mL/kg) SC on Day 0; ~50 adult H. longicornis applied on Days -2 and 12 and then about monthly through Day 378; live/dead counts 48 h after treatment/infestation; masked. Three further studies: S22132-00 (H. longicornis, >=92.7% through Day 365), S20042-00 (A. maculatum, >=92.8% through Day 365 at 72 h) and S20046-00 (A. maculatum; 89.7% on Day 3, then >=96.9% through Day 365).; primary endpoint: Live tick counts (least squares means) vs untreated control; >=90% reduction; result: S22131-00: 100% reduction in live H. longicornis at every valid count from Day 2 through Day 380 (p<0.0001); Days 330 and 337 invalid due to inadequate control infestation.
The BRAVECTO® QUANTUM group had a 100% reduction in live H. longicornis tick counts at 48 hours following infestation from Day 2 through Day 380.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Slight heat reaction at injection site (one dog, Day 7, resolved by Day 8) | One dog in the BRAVECTO® QUANTUM group was observed with a slight heat reaction of the injection site on Day 7. |
Extraction notes: Supplemental approval; no target animal safety studies required (refers to the July 10, 2025 original NADA 141-599 summary). Four laboratory studies of 20 dogs each (10 treated/10 control); no field study. Study S20046-00 failed to demonstrate >=90% effectiveness against A. maculatum at 3 days post-treatment (89.7%) but did from Day 7 onward.
Bravecto® NADA 141-426, Original approval, May 25, 2014; sponsor Intervet, Inc.; species: Dogs; foi_id 1502; FDA PDF
Indication
Kills adult fleas; treatment and prevention of flea infestations (C. felis) and treatment and control of tick infestations (I. scapularis, D. variabilis, R. sanguineus) for 12 weeks, and A. americanum for 8 weeks, in dogs and puppies 6 months of age and older weighing 4.4 lb or more.
Dose regimen
minimum 11.4 mg/lb (25 mg/kg) fluralaner, oral (chewable tablet), single dose every 12 weeks (every 8 weeks in case of potential A. americanum exposure), Administered with food, per body-weight dosage schedule (112.5-1400 mg chews).
BRAVECTO should be administered orally as a single dose every 12 weeks according to the Dosage Schedule below to provide a minimum dose of 11.4 mg/lb (25 mg/kg) body weight.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| other | substantially lower Cmax and AUC and shorter elimination half-life in young puppies (8-9 weeks) than in dogs 6 months and older | approximately the same oral dose; basis for the 6-month minimum age | Pharmacokinetic studies demonstrate that fluralaner chews have a substantially lower peak plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC), and a shorter plasma elimination half-life (T½), in young puppies (8-9 weeks of age) compared to dogs aged 6 months and older, at approximately the same oral dose. |
| bioavailability | higher after oral than topical administration (not quantified in this summary) | oral vs topical fluralaner | Pharmacokinetic studies demonstrate that fluralaner has a higher bioavailability when provided by an oral versus topical route of administration. |
| other | exposure less than dose proportional; steady state by the third treatment period | margin of safety study, 1X-5X (56/168/280 mg/kg) oral every 8 weeks x3, fed puppies | Plasma concentrations of fluralaner confirmed systemic exposure of all treated dogs although the exposure was less than dose proportional. Dogs achieved steady-state fluralaner concentrations by the third treatment period. |
Target-animal safety
dose multiples 1X, 3X, 5X; duration three oral doses at eight-week intervals (Study Days 0, 56, 112); necropsy Day 168; animals 32.
32 healthy weaned puppies (Beagles, 16 male and 16 female), 54 to 62 days of age, and 2.0 to 3.6 kg body weight
| Finding | Quote |
|---|---|
| No clinically relevant treatment-related effects on physical exams, body weight, food consumption, clinical pathology, gross/histopathology or organ weights. | There were no clinically-relevant, treatment-related effects on physical examinations, body weights, food consumption, clinical pathology (hematology, clinical chemistries, coagulation profiles and urinalysis), gross pathology, histopathology, or organ weights. |
| Diarrhea, mucoid and bloody feces were the most common observations, at similar incidence in treated and control groups. | Diarrhea, mucoid and bloody feces were the most common observations in this study, occurring at a similar incidence in the treated and control groups. |
| One 3X dog was dull and inappetent with bloody diarrhea, vomiting and weight loss from five days after the first dose; one 1X dog vomited four hours after the first dose. | One dog in the 3X group was observed to be dull, inappetent, with evidence of bloody diarrhea, vomiting and weight loss beginning five days following the first dose. One dog in the 1X group vomited food four hours following the first dose. |
| Conclusion: up to 280 mg/kg (5X) three times eight weeks apart was well tolerated; potential effects diarrhea, mucoid/bloody feces, vomiting. | The oral administration of fluralaner chews at up to 280 mg/kg on three occasions eight weeks apart was well-tolerated in dogs. Potential treatment-related effects include diarrhea, mucoid and bloody feces, and vomiting. |
| Reproductive safety study (up to 3X, 168 mg/kg): abnormalities in 7 pups from 2 of 10 treated dams (limb deformity, enlarged heart, enlarged spleen, cleft palate); none in controls. | The following abnormalities were noted in 7 pups from 2 of the 10 dams in only the treated group during gross necropsy examination: limb deformity (4 pups), enlarged heart (2 pups), enlarged spleen (3 pups), and cleft palate (2 pups). |
| Reproductive study adults: one treated dog had a seizure 46 days after the third dose; diarrhea and salivation after dosing. | One treated and one control dog experienced diarrhea on the day of dosing, and one adult treated dog suffered a seizure during the course of the study (46 days after the third dose). |
Effectiveness
Multi-center pivotal field study S11002-00 (18 US sites): 294 client-owned dogs from 157 households; 224 dogs (118 households) given fluralaner chews once every 12 weeks x3 vs 70 dogs (39 households) given spinosad tablets every 4 weeks plus an amitraz collar (active control); households randomized 3:1; one primary dog per household assessed; flea counters and investigators masked.; n = 117 fluralaner and 39 control primary dogs at Visit 1; primary endpoint: Difference in live flea counts on primary dogs at Days 28, 56 and 84 vs pretreatment (geometric means); result: Fluralaner effectiveness >90% at every visit: 99.7% (Day 28), 99.8% (Day 56), 99.8% (Day 84); control 96.1%, 99.5%, 99.6%. FAD signs resolved in at least 80% of affected fluralaner dogs by Week 12; 80.7% of doses consumed voluntarily within 5 minutes.
For each of Visits 2, 3, and 4, the effectiveness of fluralaner, based on geometric means, was greater than 90%. Table 2: Field Study S11002-00 Effectiveness against Fleas Visit Fluralaner Group Control Group Visit 1 Number of Dogs 117 39 Visit 1 Geometric Mean Flea Count 32.2 32.6 Visit 2 Number of Dogs 113 38 Visit 2 Geometric Mean Flea Count 0.1 1.3 Visit 2 Percent Effectiveness 99.7% 96.1% Visit 3 Number of Dogs 108 34 Visit 3 Geometric Mean Flea Count 0.1 0.2 Visit 3 Percent Effectiveness 99.8% 99.5% Visit 3 Number of Dogs 106 32 Visit 3 Geometric Mean Flea Count 0.1 0.1 Visit 3 Percent Effectiveness 99.8% 99.6%
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Emesis | 7.1% | 14.3% | Emesis 7.1% 14.3% |
| Decreased appetite | 6.7% | 0.0% | Decreased Appetite 6.7% 0.0% |
| Diarrhea | 4.9% | 2.9% | Diarrhea 4.9% 2.9% |
| Lethargy | 5.4% | 7.1% | Lethargy 5.4% 7.1% |
| Polydipsia | 1.8% | 4.3% | Polydipsia 1.8% 4.3% |
| Flatulence | 1.3% | 0.0% | Flatulence 1.3% 0.0% |
Extraction notes: Corrected FOI summary. Adverse reactions are from Table 5 of field study S11002-00: fluralaner group percent of dogs during the 182-day study (n=224) vs control group during the 84-day study (n=70); rows quoted as flattened by PDF extraction (term, fluralaner %, control %). The effectiveness table in the summary labels the Day 84 rows as 'Visit 3' a second time (quoted verbatim; the third block corresponds to Visit 4). No numeric PK parameters are reported in this summary; PK entries are qualitative. Fourteen laboratory dose confirmation studies (fleas, speed of kill, I. scapularis, D. variabilis, R. sanguineus, A. americanum) are not itemized here; A. americanum effectiveness supported 8-week (not 12-week) duration.
BRAVECTO® 1-MONTH NADA 141-532, Supplemental approval, November 25, 2024; sponsor Intervet, Inc.; species: Dogs; foi_id 16308; FDA PDF
Indication
Supplement adding treatment and control of Haemaphysalis longicornis (Asian longhorned tick) infestations for one month in dogs and puppies 8 weeks of age and older weighing 4.4 lb or more.
Dose regimen
minimum 4.5 mg/lb (10 mg/kg) fluralaner, oral (chewable tablet), single dose monthly, Administered with food; dose unchanged by this supplement.
BRAVECTO® 1-MONTH should be administered orally as a single dose monthly according to the Dosage Schedule below to provide a minimum dose of 4.5 mg/lb (10 mg/kg) fluralaner.
Effectiveness
Laboratory dose confirmation study S20185-00 (Bloemfontein, South Africa; GCP): 18 healthy puppies 7.6-9 weeks old randomized to untreated control (9) or one fluralaner chewable tablet (9; 10-19.6 mg/kg) within 20 minutes of food on Day 0; ~50 adult H. longicornis applied on Days -2, 7, 14, 21, 28; live/dead counts 48 h later (Days 2, 9, 16, 23, 30); masked. Second study S21138-00 (Waverly, NY; 20 Beagle puppies, 15-21.2 mg/kg) gave 100% at every count.; primary endpoint: Live tick counts (least squares means) vs untreated control; >90% reduction; result: S20185-00: 100%, 100%, 100%, 99.6%, 100% effectiveness on Days 2, 9, 16, 23, 30 (p<0.0001); S21138-00: 100% on all count days.
The fluralaner group had greater than 90% reduction in live tick counts at 48 hours following drug administration or infestation for 30 days (infestations on Day 28) compared to the control group.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| No adverse reactions reported (laboratory studies) | Adverse Reactions: No adverse reactions were reported in this study. |
Extraction notes: Supplemental approval; no target animal safety studies required (refers to the July 9, 2020 original NADA 141-532 summary). Two laboratory dose confirmation studies in 8-week-old puppies (18 and 20 puppies); no field study.
Reproduce: foi_structured_search(query="Fluralaner") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).