Lotilaner: what the FDA reviewed for dog products
3 Freedom of Information summaries from the FDA Center for Veterinary Medicine for products containing Lotilaner, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dogs.
Products
- Credelio™ (NADA/ANADA 141-494)
Credelio™ NADA 141-494, Original approval, January 19, 2018; sponsor Elanco US Inc.; species: Dogs; foi_id 3101; FDA PDF
Indication
Kills adult fleas; treatment of flea infestations (Ctenocephalides felis) and treatment and control of tick infestations (Amblyomma americanum, Dermacentor variabilis, Ixodes scapularis, Rhipicephalus sanguineus) for one month in dogs and puppies 8 weeks of age and older weighing 4.4 lb or more.
Dose regimen
9 mg/lb (20 mg/kg) minimum, Oral (chewable tablet), once a month, Must be administered with food (bioavailability lower and more variable when fasted)
CREDELIO is given orally once a month, at the minimum dosage of 9 mg/lb (20 mg/kg).
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| half-life | 9.6 days (average) | dogs 2 months of age; 43 mg/kg oral (approx. 1X maximum labeled dose), fed; margin-of-safety study GSO-13-010 | Dogs 2 months of age had a shorter elimination half-life (average of 9.6 days) than at 10 months of age (average of 28.4 days). |
| half-life | 28.4 days (average) | dogs 10 months of age; 43 mg/kg oral (approx. 1X), fed; study GSO-13-010 | Dogs 2 months of age had a shorter elimination half-life (average of 9.6 days) than at 10 months of age (average of 28.4 days). |
| tmax | between 6 hours and 3 days | dogs 2 months of age; 43 mg/kg oral (approx. 1X maximum labeled dose) | Following oral administration of 43 mg/kg (approximately 1X the maximum labeled dose), peak lotilaner concentrations were achieved between 6 hours and 3 days in dogs 2 months of age and between 1 and 7 days in dogs 10 months of age. |
| tmax | between 1 and 7 days | dogs 10 months of age; 43 mg/kg oral (approx. 1X maximum labeled dose) | Following oral administration of 43 mg/kg (approximately 1X the maximum labeled dose), peak lotilaner concentrations were achieved between 6 hours and 3 days in dogs 2 months of age and between 1 and 7 days in dogs 10 months of age. |
| bioavailability | lower and more variable in the fasted state (fed administration required) | oral; fasted vs fed dogs | Bioavailability of lotilaner is lower and more variable in the fasted state. |
| other | exposure less than dose proportional at 5X | 1X/3X/5X oral doses (43, 129, 215 mg/kg) every four weeks for eight months, study GSO-13-010 | Blood concentrations of lotilaner confirmed systemic exposure of all treated dogs although the exposure was less than dose proportional at 5X. |
Target-animal safety
dose multiples 0X, 1X, 3X, 5X; duration Eight months; dosed orally once every four weeks (Days 1, 29, 57, 85, 113, 141, 169, and 197); necropsy Day 225; animals 32 (16 male and 16 female), eight per group.
32 healthy weaned Beagle dogs (16 male and 16 female), approximately 8 weeks of age, weighing between 1.5 kg to 3.0 kg. Experimental Design: Dogs were randomized to one of four groups (0X, 1X, 3X, and 5X) of eight dogs per group (four per sex). The chewable tablets were administered orally once every four weeks for eight months (Days 1, 29, 57, 85, 113, 141, 169, and 197) at doses of 43 mg/kg, 129 mg/kg and 215 mg/kg (approximately 1, 3, and 5X the maximum labeled dose, respectively).
| Finding | Quote |
|---|---|
| No clinically relevant treatment-related effects on clinical observations, physical/neurological examinations, body weight, food consumption, ECG, clinical pathology, gross/microscopic pathology or organ weights | There were no clinically relevant, treatment-related effects on clinical observations, physical and neurological examinations, body weights, food consumption, electrocardiograms, clinical pathology (serum chemistries, hematology, coagulation profiles, and urinalysis), gross or microscopic pathology, and organ weights. |
| One 5X male dog had bilateral corneal opacities at the final ophthalmoscopic examination (minimal microscopic corneal changes); relationship to drug undetermined | One male dog in the 5X group had bilateral corneal opacities at the final ophthalmoscopic examination. |
| Relationship of the corneal changes to the drug could not be determined | A direct relationship of the corneal changes to the drug could not be determined. |
| Study supports safe use at the labeled dose and duration | The study supports the safe use of lotilaner chewable tablets in dogs when used at the labeled dose and duration. |
Effectiveness
Field study NAH-13-076: randomized, blinded, positive-controlled (afoxolaner) multi-site (9 effectiveness / 10 safety sites) study in client-owned dogs naturally infested with fleas; households randomized 2:1 lotilaner:afoxolaner; owners dosed within 30 min of feeding on Days 0, 30 and 60; flea counts on primary dogs Days 30, 60, 90; n = 312 enrolled from 180 households (259 completed); 198 lotilaner / 86 afoxolaner evaluated for safety; 111 / 50 for effectiveness; primary endpoint: Percent reduction in geometric mean live flea count from baseline (Day 0) on Days 30, 60 and 90 (primary dog per household); result: Lotilaner: 99.5% (Day 30), 100% (Day 60), 100% (Day 90) reduction from baseline geometric mean 42.3; afoxolaner: 98.4%, 99.7%, 99.9%; both significant (p < 0.001) and both >= 90% effective. Improvement in FAD clinical signs in 90.6-100% of lotilaner dogs. Too few tick-infested dogs to conclude on ticks.
The study enrolled 312 client-owned dogs from 180 households, with 259 dogs completing the study. The study enrolled dogs ranging in age from 8 weeks to 16 years of age, and 4.4 to 143 pounds of body weight. One hundred and ninety-eight (198) lotilaner-treated dogs and 86 afoxolaner-treated (control) dogs were evaluated for safety. One hundred and eleven (111) lotilaner- treated dogs and 50 afoxolaner-treated dogs were included in the assessment of effectiveness for at least one time point (Day 30, 60, and/or 90).
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Weight loss | 3 (1.5%) | 2 (2.3%) | Weight loss 3 (1.5%) 2 (2.3%) |
| Polyuria | 2 (1.0%) | 0 (0.0%) | Polyuria 2 (1.0%)* 0 (0.0%) |
| Diarrhea | 2 (1.0%) | 2 (2.3%) | Diarrhea 2 (1.0%) 2 (2.3%) |
| Elevated blood urea nitrogen (BUN) | 2 (1.0%) | 0 (0.0%) | Elevated blood urea nitrogen (BUN) 2 (1.0%)* 0 (0.0%) |
| Elevated creatinine | 1 (0.5%) | 0 (0.0%) | Elevated creatinine 1 (0.5%)* 0 (0.0%) |
| Dyspnea | 1 (0.5%) | 0 (0.0%) | Dyspnea 1 (0.5%) 0 (0.0%) |
Extraction notes: Adverse reaction rows are from Table II.4 of field study NAH-13-076; column order = lotilaner group (n=198) then afoxolaner group (n=86); asterisked rows relate to two geriatric dogs with mildly elevated BUN etc. Also reported: elevated potassium 1 (0.5%), elevated phosphorus 1 (0.5%), polyphagia 1 (0.5%) in lotilaner group; one dog had head tremors within 1.5 h of first dose (with vaccines/ear cleaning), resolved in 24 h. Effectiveness table (Table II.1) verbatim: 'Lotilaner (42.3) 99.5% (0.2) 100% (0.0) 100% (0.0) Afoxolaner (41.8) 98.4% (0.7) 99.7% (0.1) 99.9% (0.0)'. Dose selection: PK/PD modeling plus dose determination study (10-25 mg/kg); 'a minimum dose of 9 mg/lb (20 mg/kg) was selected for lotilaner'. Foreign experience: seizure in one dog with seizure history (Australia); one unexplained death 33 days post-dose; vomiting (7 dogs) and diarrhea (2 dogs) in European field studies. Additional laboratory dose-confirmation studies for fleas (12/24 h speed of kill) and each tick species are in the summary but not extracted.
Credelio™ NADA 141-494, Supplemental approval, October 24, 2025; sponsor Elanco US Inc.; species: Dogs; foi_id 17693; FDA PDF
Indication
Adds treatment and control of Haemaphysalis longicornis (longhorned tick) infestations for one month in dogs and puppies 8 weeks and older weighing 4.4 lb or more, and prevention of Borrelia burgdorferi infections as a direct result of killing Ixodes scapularis vector ticks.
Dose regimen
9 mg/lb (20 mg/kg) minimum, Oral (chewable tablet), once a month, Dose unchanged from original approval; administered with food
Credelio™ is given orally once a month, at the minimum dosage of 9 mg/lb (20 mg/kg).
Effectiveness
Laboratory dose confirmation study ELA241006 (Waverly, NY; GCP): dogs ranked by tick count and randomly allocated in blocks to vehicle control (10 dogs) or Credelio (10 dosed, 9 evaluable) given once orally at 21.1-25.3 mg/kg lotilaner in the fed state; approx. 50 adult female H. longicornis applied Days -7, -1, 5, 12, 19, 30; live and dead tick counts 48 h after treatment/infestation on Days 2, 7, 14, 21, 32; n = Twenty (12 male and 8 female); primary endpoint: Percent reduction in LS mean live tick counts vs control (>=90% for control indication) and numerically higher LS mean dead ticks (treatment indication) 48 h after treatment or infestation; result: 100% reduction in live H. longicornis counts at 48 h through Day 32 (p<0.001 all days); dead tick LS means 10.7-21.9 (treated) vs 0.9-4.3 (control), p<0.001
Study Animals: Twenty beagle dogs (12 male and 8 female) approximately 15 to 45 months of age, weighing 7.8 to 13.9 kg.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Diarrhea (laboratory study ELA231098) | One dog | One dog had diarrhea at 4 and 8 hours after Credelio™ administration. The dog fully recovered with supportive care. | |
| Diarrhea (laboratory study ELA230933) | One dog | One dog had diarrhea within one hour of dosing with Credelio™. The dog fully recovered without treatment. |
Extraction notes: Five laboratory studies, no field study. H. longicornis: ELA231042 (100% through Day 21), ELA231098 (100% Days 7-32), ELA241006 (100% Days 2-32; extracted as effectiveness). B. burgdorferi prevention: ELA230932 and ELA230933 (20 dogs each; single dose 28 days before infestation with wild-caught infected I. scapularis; 100% tick reduction on Day 33; 0/10 treated dogs infected vs 8/10 and 9/9 controls; p=0.0007 and p<0.0001). TAS: no new studies ('did not require target animal safety studies'); no PK content. Adverse reactions in lab studies had no per-group denominators beyond 10 dogs/group.
Credelio™ NADA 141-494, Supplemental approval, September 03, 2019; sponsor Elanco US Inc.; species: Dogs; foi_id 7663; FDA PDF
Indication
Adds prevention of flea infestations (Ctenocephalides felis) for one month; full indication: treatment and prevention of flea infestations and treatment and control of tick infestations (A. americanum, D. variabilis, I. scapularis, R. sanguineus) for one month in dogs and puppies 8 weeks and older weighing 4.4 lb or more.
Dose regimen
9 mg/lb (20 mg/kg) minimum, Oral (chewable tablet), once a month, Must be administered with food; dose unchanged from original approval
CREDELIO is given orally once a month, at the minimum dosage of 9 mg/lb (20 mg/kg).
Effectiveness
Laboratory egg-laying study ELA1700480: blinded, randomized, negative (vehicle) controlled; single oral dose of at least 20 mg/kg lotilaner (10 dogs) vs vehicle (10 dogs) approx. 30 min after feeding; experimental C. felis infestations Days -1, 6, 13, 20, 29; live flea and flea egg counts 24 h after treatment/infestation; n = 20 (9 males and 11 females); primary endpoint: Live flea counts on dogs and flea eggs collected from cages 24 h after treatment or infestation; prevention = essentially zero eggs from treated dogs on Day 7 and later; result: Lotilaner 100% effective against fleas at 24 h through Day 30 (p < 0.0001 on all count days); egg production 13.9 (Day 1) then 0.0 from Day 7 through Day 30 in treated dogs vs 139.2-527.0 in controls
20 dogs (9 males and 11 females), 13 to 28 months of age, weighing between 7.0 kg and 13.6 kg.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| None reported (laboratory study ELA1700480) | There were no adverse reactions reported during the study. |
Extraction notes: Supplement adding the flea-prevention indication; effectiveness based on laboratory study ELA1700480 plus the original field study NAH-13-076 (referenced). Effectiveness table (Table II.2) verbatim: '1 91.4 0.0 100% 7 92.6 0.0 100% 14 92.9 0.0 100% 21 93.1 0.0 100% 30 87.8 0.0 100%'. TAS: 'CVM did not require target animal safety studies for this supplemental approval.' No PK content.
Reproduce: foi_structured_search(query="Lotilaner") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).