Imidacloprid, Moxidectin: what the FDA reviewed for dog products
7 Freedom of Information summaries from the FDA Center for Veterinary Medicine for products containing Imidacloprid, Moxidectin, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dog; Dogs.
Products
- Advantage Multi™ for Dogs (NADA/ANADA 141-251)
- Barrier® for dogs (NADA/ANADA 200-718)
- IMOXI™ Topical Solution for Dogs (NADA/ANADA 200-615)
- Midamox® for Dogs (NADA/ANADA 200-716)
- MoxiCloprid™ for Dogs (NADA/ANADA 200-818)
- PARASEDGE® Multi for Dogs (NADA/ANADA 200-700)
MoxiCloprid™ for Dogs NADA 200-818, Original approval, August 05, 2025; sponsor Bimeda Animal Health Ltd.; species: Dogs; foi_id 17355; FDA PDF
Indication
Prevention of heartworm disease (Dirofilaria immitis) and treatment of circulating D. immitis microfilariae in heartworm-positive dogs; kills adult fleas / treatment of flea infestations (Ctenocephalides felis); treatment and control of sarcoptic mange (Sarcoptes scabiei var. canis); treatment and control of hookworms (Ancylostoma caninum, Uncinaria stenocephala), roundworms (Toxocara canis, Toxascaris leonina) and whipworm (Trichuris vulpis).
Dose regimen
minimum 10 mg/kg imidacloprid and 2.5 mg/kg moxidectin (4.5 mg/lb and 1.1 mg/lb); entire tube matched to body-weight band, Topical, once a month
The recommended minimum dose is 4.5 mg/lb (10 mg/kg) imidacloprid and 1.1 mg/lb (2.5 mg/kg) moxidectin, once a month, by topical administration.
Effectiveness
No study: generic ANADA granted a biowaiver (waiver of in vivo bioequivalence) based on formulation characteristics; relies on the RLNAD Advantage Multi for Dogs (NADA 141-251); result: Biowaiver granted; effectiveness and target animal safety rest on the RLNAD
Based on the formulation characteristics of the generic product, Bimeda Animal Health Ltd., was granted a biowaiver for the generic product MoxiCloprid™ for Dogs (imidacloprid + moxidectin) topical solution.
Extraction notes: Generic ANADA with biowaiver; no PK, target animal safety, effectiveness or adverse reaction data (effectiveness field records the biowaiver only). Intestinal-parasite stage table in the indication was flattened by PDF extraction; indication text paraphrases it.
IMOXI™ Topical Solution for Dogs NADA 200-615, Original approval, December 19, 2019; sponsor Vetoquinol USA, Inc.; species: Dogs; foi_id 8067; FDA PDF
Indication
Prevention of heartworm disease (Dirofilaria immitis) and treatment of circulating D. immitis microfilariae in heartworm-positive dogs; kills adult fleas / treatment of flea infestations (Ctenocephalides felis); treatment and control of sarcoptic mange (Sarcoptes scabiei var. canis); treatment and control of hookworms (Ancylostoma caninum, Uncinaria stenocephala), roundworms (Toxocara canis, Toxascaris leonina) and whipworm (Trichuris vulpis).
Dose regimen
minimum 10 mg/kg imidacloprid and 2.5 mg/kg moxidectin (4.5 mg/lb and 1.1 mg/lb); entire tube matched to body-weight band, Topical, once a month
The recommended minimum dose is 4.5 mg/lb. (10 mg/kg) imidacloprid and 1.1 mg/lb. (2.5 mg/kg) moxidectin, once a month, by topical administration.
Effectiveness
No study: generic ANADA granted a biowaiver (waiver of in vivo bioequivalence) based on formulation characteristics; relies on the RLNAD Advantage Multi for Dogs (NADA 141-251); result: Biowaiver granted; effectiveness and target animal safety rest on the RLNAD
Based on the formulation characteristics of the generic product, Vetoquinol USA, Inc., was granted a biowaiver for the generic product IMOXI™ Topical Solution for Dogs (imidacloprid + moxidectin). The generic drug product is a topical solution, contains the same active ingredients in the same concentrations and dosage form as the RLNAD, and contains no inactive ingredients that may significantly affect the bioavailability of the active ingredients.
Extraction notes: Generic ANADA with biowaiver; the summary contains no PK, target animal safety, effectiveness or adverse reaction data (effectiveness field records the biowaiver only). Intestinal-parasite stage table in the indication was flattened by PDF extraction; indication text paraphrases it from the catalogue summary.
Advantage Multi™ for Dogs NADA 141-251, Original approval, December 20, 2006; sponsor Elanco US Inc.; species: Dogs; foi_id 803; FDA PDF
Indication
Prevention of heartworm disease (Dirofilaria immitis); kills adult fleas and treats flea infestations (Ctenocephalides felis); treatment and control of hookworms (Ancylostoma caninum, Uncinaria stenocephala), roundworms (Toxocara canis, Toxascaris leonina) and whipworm (Trichuris vulpis).
Dose regimen
Minimum 10 mg/kg imidacloprid + 2.5 mg/kg moxidectin (4.5 mg/lb + 1.1 mg/lb), Topical, Once a month, Tube size by body weight: 0.4 mL (3-9 lb), 1.0 mL (9.1-20 lb), 2.5 mL (20.1-55 lb), 4.0 mL (55.1-88 lb); dogs over 88 lb use a combination of tubes; do not administer orally
The recommended minimum dose is 4.5 mg/lb (10 mg/kg) imidacloprid and 1.1 mg/lb (2.5 mg/kg) moxidectin, once a month by topical administration, as specified by the following table.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| cmax | Imidacloprid 69.5 mcg/L mean (range 27.6 – 207.4) | Serum; 10 adult Beagles; 0.1 mL/kg topical (10 mg/kg imidacloprid + 2.5 mg/kg moxidectin); first monthly dose (Days 0-28); Study #141.329 | Day 0 – 28, Dosed on Day 0 69.5 mean; 27.6 – 207.4 31 hrs mean; 8 hrs – 3 days Days 3 to 7 (3 to 7 days post dosing) |
| tmax | Imidacloprid 31 hrs mean (range 8 hrs – 3 days) | Same study, first dose interval; imidacloprid quantifiable only 3 to 7 days post dosing (LOQ 10 mcg/L) | Day 0 – 28, Dosed on Day 0 69.5 mean; 27.6 – 207.4 31 hrs mean; 8 hrs – 3 days Days 3 to 7 (3 to 7 days post dosing) |
| cmax | Moxidectin 18.1 mcg/L mean (SD 5.1) | Serum; first dose interval (Days 0-28); row order: Cmax mean; SD, AUC0-28d mean; SD, Tmax mean; range, concentration at Day 28 | Day 0 -- 28 18.1 mean; 5.1 SD 324.6 mean; 68.5 SD 9.3 days mean; 1 – 21 days On Day 28: 10.5 mean; 2.9 SD |
| auc | Moxidectin 324.6 mcg·day/L mean (SD 68.5) over the 28-day interval | First dose interval; same flattened row | Day 0 -- 28 18.1 mean; 5.1 SD 324.6 mean; 68.5 SD 9.3 days mean; 1 – 21 days On Day 28: 10.5 mean; 2.9 SD |
| tmax | Moxidectin 9.3 days mean (range 1 – 21 days) | First dose interval; serum moxidectin still 10.5 mcg/L (SD 2.9) at Day 28 | Day 0 -- 28 18.1 mean; 5.1 SD 324.6 mean; 68.5 SD 9.3 days mean; 1 – 21 days On Day 28: 10.5 mean; 2.9 SD |
| cmax | Moxidectin 33.5 mcg/L mean (SD 6.1) after third monthly dose | Third dose interval (Days 60-88); AUC 596.4 mcg·day/L (SD 91.8); Tmax 4.6 days mean (8 hrs – 28 days); 18.8 mcg/L at Day 88; steady state expected within 4-5 monthly applications | Day 60 -- 88 33.5 mean; 6.1 SD 596.4 mean; 91.8 SD 4.6 days mean; 8 hrs – 28 days On Day 88: 18.8 mean; 4.1 SD |
| other | Moxidectin 1.3 mcg/L mean (SD 0.7) 16 weeks after the third dose | Non-GLP follow-up in 8 of the 10 dogs (6.3 mcg/L at 8 weeks, 2.7 at 12 weeks) | 16 weeks 1.3 mean; 0.7 SD |
Target-animal safety
dose multiples 1X, 3X, 5X; duration Once every 14 days for 6 topical applications (Days 0-70) in 7-week-old Beagle puppies; necropsy Days 84-85 (GLP Study #150.872); animals 48.
Animals: 48 Beagle puppies (6 females and 6 males per treatment group), 7 weeks of age and weighing between 2.6 and 5.7 pounds at initial treatment
| Finding | Quote |
|---|---|
| Occasional vomiting in treated puppies (1X: 1, 3X: 2, 5X: 1) | Clinical Observations: Vomiting was reported in one puppy from the 1X group (Day 57), in two puppies from the 3X group (Days 1 and 79), and in one puppy from the 5X group (Day 1). |
| More puppies with increased direct bilirubin (within normal range) in treated groups | Although all individual bilirubin values were within the normal range, the number of puppies with increases in direct bilirubin was higher in the treated groups: 1/11 puppies in the control group, 8/12 puppies in the 1X group, 6/12 puppies in the 3X group, and 6/12 puppies in the 5X group. |
| Considered safe in seven-week-old puppies; transient rapid, difficult respiration in one 5X puppy | Conclusions: Imidacloprid + moxidectin is safe following topical administration to seven-week-old Beagle puppies. |
| Single 10X topical dose: application-site discomfort, vomiting, decreased weight gain, increased direct bilirubin, APTT, RBC and hemoglobin (Study #150.874) | Conclusions: A single topical administration of imidacloprid + moxidectin topical solution at 10X the recommended dose was associated with behavioral signs of application site discomfort, vomiting, decreased weight gain, and increased direct bilirubin, activated partial thromboplastin, RBC counts, and hemoglobin. |
| No clinical abnormalities in ivermectin-sensitive Collies at 3X and 5X topical doses (Study #150.876) | Conclusions: Topical application of imidacloprid + moxidectin was not associated with clinical abnormalities in ivermectin-sensitive Collies at 3 or 5 times the recommended dose. |
| Oral ingestion of the 1X volume caused vomiting and avermectin toxicity signs in Beagles (Study #150.875) | Conclusions: Oral administration of imidacloprid + moxidectin to adult Beagles caused vomiting and signs of avermectin toxicity (ataxia, muscle tremors, and mydriasis). |
| Oral 40% of minimum label dose caused severe moxidectin toxicity (coma) in 4/5 ivermectin-sensitive Collies (Study #150.877) | However, following oral administration of 0.04 mL/kg on Day 28, 4 of the 5 Collies developed signs of severe moxidectin toxicity. |
Effectiveness
Laboratory heartworm prevention/non-interference study (Report #75490): purpose-bred Beagles inoculated with 50 D. immitis L3 and treated once topically 45 days post-infection with imidacloprid + moxidectin, moxidectin alone, or imidacloprid alone (control); necropsy Day 119; n = 24 (8 per group); primary endpoint: Geometric mean adult heartworm counts at necropsy vs control; result: Imidacloprid + moxidectin and moxidectin alone: 0 heartworms (100% effective); imidacloprid-only control geometric mean 37.6 heartworms; imidacloprid did not interfere with moxidectin
Animals: 24 purpose bred Beagles (12 females and 12 males) 5 to 7 months of age, between 19.7 and 28.9 pounds, 8 dogs per treatment group
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Pruritus | 19 dogs (14.8%) | 7 dogs (10.3%) | Pruritus 19 dogs (14.8%) 7 dogs (10.3%) |
| Residue at application site | 9 dogs (7.0%) | 5 dogs (7.4%) | Residue 9 dogs (7.0%) 5 dogs (7.4%) |
| Medicinal odor | 5 dogs (3.9%) | None observed | Medicinal Odor 5 dogs (3.9%) None observed |
| Lethargy | 1 dog (0.8%) | 1 dog (1.5%) | Lethargy 1 dog (0.8%) 1 dog (1.5%) |
| Inappetence | 1 dog (0.8%) | 1 dog (1.5%) | Inappetence 1 dog (0.8%) 1 dog (1.5%) |
| Hyperactivity | 1 dog (0.8%) | None observed | Hyperactivity 1 dog (0.8%) None observed |
Extraction notes: Very large summary (many laboratory studies); the record captures the 45-day heartworm study as the pivotal effectiveness example. Other effectiveness results: heartworm 100% at 33-34 days post-infection incl. after bathing/swimming (Reports #75459, #75484); fleas 99.0-100% to Day 35 (Study #150.902) and 95.1-100% (Study #151.038); adult T. canis 96.2% and 100%; T. leonina 100% (natural) and 97.0% (induced); A. caninum 100% (two studies); U. stenocephala 100% (two studies); T. vulpis 97.2%; immature-stage studies not extracted. PK entries come from the serum PK study in the target animal safety section (Study #141.329, 10 adult Beagles), quoted as flattened table rows (column order given in conditions). Adverse reactions are owner-recorded observations from the clinical field safety study (Study #151.252; 128 Advantage Multi vs 68 active control REVOLUTION/selamectin dogs). Batch plan species flag was 'unknown'; summary states Species/Class: Dogs.
Barrier® for dogs NADA 200-718, Original approval, February 07, 2022; sponsor Aurora Pharmaceutical, Inc.; species: Dogs; foi_id 11988; FDA PDF
Indication
Prevention of heartworm disease (Dirofilaria immitis) and treatment of circulating D. immitis microfilariae in heartworm-positive dogs; kills adult fleas / treatment of flea infestations (Ctenocephalides felis); treatment and control of sarcoptic mange (Sarcoptes scabiei var. canis); treatment and control of hookworms (Ancylostoma caninum, Uncinaria stenocephala), roundworms (Toxocara canis, Toxascaris leonina) and whipworm (Trichuris vulpis).
Dose regimen
minimum 10 mg/kg imidacloprid and 2.5 mg/kg moxidectin (4.5 mg/lb and 1.1 mg/lb); entire tube matched to body-weight band, Topical, once a month
The recommended minimum dose is 4.5 mg/lb (10 mg/kg) imidacloprid and 1.1 mg/lb (2.5 mg/kg) moxidectin, once a month, by topical administration.
Effectiveness
No study: generic ANADA granted a biowaiver (waiver of in vivo bioequivalence) based on formulation characteristics; relies on the RLNAD Advantage Multi for Dogs (NADA 141-251); result: Biowaiver granted; effectiveness and target animal safety rest on the RLNAD
Based on the formulation characteristics of the generic product, Aurora Pharmaceutical, Inc., was granted a biowaiver for the generic product Barrier™ for dogs (imidacloprid + moxidectin) Topical Solution.
Extraction notes: Generic ANADA with biowaiver; no PK, target animal safety, effectiveness or adverse reaction data (effectiveness field records the biowaiver only). Intestinal-parasite stage table in the indication was flattened by PDF extraction; indication text paraphrases it.
Midamox® for Dogs NADA 200-716, Original approval, January 28, 2022; sponsor Norbrook Laboratories, Ltd.; species: Dogs; foi_id 11967; FDA PDF
Indication
Prevention of heartworm disease (Dirofilaria immitis) and treatment of circulating D. immitis microfilariae in heartworm-positive dogs; kills adult fleas / treatment of flea infestations (Ctenocephalides felis); treatment and control of sarcoptic mange (Sarcoptes scabiei var. canis); treatment and control of hookworms (Ancylostoma caninum, Uncinaria stenocephala), roundworms (Toxocara canis, Toxascaris leonina) and whipworm (Trichuris vulpis).
Dose regimen
minimum 10 mg/kg imidacloprid and 2.5 mg/kg moxidectin (4.5 mg/lb and 1.1 mg/lb); entire tube matched to body-weight band, Topical, once a month
The recommended minimum dose is 4.5 mg/lb (10 mg/kg) imidacloprid and 1.1 mg/lb (2.5 mg/kg) moxidectin, once a month, by topical administration.
Effectiveness
No study: generic ANADA granted a biowaiver (waiver of in vivo bioequivalence) based on formulation characteristics; relies on the RLNAD Advantage Multi for Dogs (NADA 141-251); result: Biowaiver granted; effectiveness and target animal safety rest on the RLNAD
Based on the formulation characteristics of the generic product, Norbrook Laboratories, Ltd., was granted a biowaiver for the generic product Midamox™ for Dogs (imidacloprid + moxidectin) topical solution.
Extraction notes: Generic ANADA with biowaiver; no PK, target animal safety, effectiveness or adverse reaction data (effectiveness field records the biowaiver only). Intestinal-parasite stage table in the indication was flattened by PDF extraction; indication text paraphrases it.
PARASEDGE® Multi for Dogs NADA 200-700, Original approval, June 10, 2021; sponsor Virbac AH, Inc.; species: Dogs; foi_id 11585; FDA PDF
Indication
Prevention of heartworm disease (Dirofilaria immitis) and treatment of circulating D. immitis microfilariae in heartworm-positive dogs; kills adult fleas / treatment of flea infestations (Ctenocephalides felis); treatment and control of sarcoptic mange (Sarcoptes scabiei var. canis); treatment and control of hookworms (Ancylostoma caninum, Uncinaria stenocephala), roundworms (Toxocara canis, Toxascaris leonina) and whipworm (Trichuris vulpis).
Dose regimen
minimum 10 mg/kg imidacloprid and 2.5 mg/kg moxidectin (4.5 mg/lb and 1.1 mg/lb); entire tube matched to body-weight band, Topical, once a month
The recommended minimum dose is 4.5 mg/lb. (10 mg/kg) imidacloprid and 1.1 mg/lb. (2.5 mg/kg) moxidectin, once a month, by topical administration.
Effectiveness
No study: generic ANADA granted a biowaiver (waiver of in vivo bioequivalence) based on formulation characteristics; relies on the RLNAD Advantage Multi for Dogs (NADA 141-251); result: Biowaiver granted; effectiveness and target animal safety rest on the RLNAD
Based on the formulation characteristics of the generic product Chanelle Pharmaceuticals Manufacturing Ltd., was granted a biowaiver for the generic product PARASEDGE™ Multi for Dogs (imidacloprid + moxidectin) Topical Solution
Extraction notes: Generic ANADA with biowaiver; no PK, target animal safety, effectiveness or adverse reaction data (effectiveness field records the biowaiver only). Sponsor in the summary is Chanelle Pharmaceuticals Manufacturing Ltd. (catalogue lists Virbac AH, Inc.). This is a CORRECTED FOI summary: the Appendix records a November 17, 2021 correction to How Supplied (three, not six, tubes per package) and to the indication wording.
Advantage Multi™ for Dogs NADA 141-251, Supplemental approval, October 24, 2013; sponsor Elanco US Inc.; species: Dog; foi_id 804; FDA PDF
Indication
Supplement adds treatment of Dirofilaria immitis circulating microfilariae in heartworm-positive dogs and treatment and control of sarcoptic mange (Sarcoptes scabiei var. canis) to the existing heartworm prevention, flea and intestinal nematode indications.
Dose regimen
Minimum 10 mg/kg imidacloprid + 2.5 mg/kg moxidectin (4.5 mg/lb + 1.1 mg/lb), Topical, Once a month, Unchanged by the supplement; microfilariae and sarcoptic mange studies used two treatments 28 days apart at 0.1 mL/kg
The recommended minimum dose is 4.5 mg/lb (10 mg/kg) imidacloprid and 1.1 mg/lb (2.5 mg/kg) moxidectin, once a month, by topical administration.
Target-animal safety
dose multiples 1X; duration Field safety study (Study 152.260): two label-dose applications on Days 0 and 28, alone or with melarsomine dihydrochloride on Days -14, 14 and 15; observation to Day 42; animals 214.
214 purebred or mixed breed (110 male and 104 female) dogs, 6 months to 12 years of age, weighing 3.0 to 139.7 lbs.
| Finding | Quote |
|---|---|
| Three deaths from pulmonary embolism in dogs also receiving melarsomine adulticide | Three dogs treated with 10% imidacloprid + 2.5% moxidectin topical solution in a dosing regimen with melarsomine dihydrochloride died of pulmonary embolism from dead and dying heartworms. |
| Two dogs given Advantage Multi alone hospitalized after first treatment (coughing, vomiting, dyspnea) | Following the first treatment with 10% imidacloprid + 2.5% moxidectin topical solution only, two dogs experienced adverse reactions (coughing, vomiting, and dyspnea) that required hospitalization. |
| Considered well tolerated in heartworm-positive dogs alone or with melarsomine | The 10% imidacloprid + 2.5% moxidectin topical solution was well- tolerated when administered to heartworm -positive dogs, alone or when used in a dosing regimen with melarsomine dihydrochloride adulticide treatment. |
Effectiveness
Multi-site clinical field study in naturally heartworm-positive, microfilaremic dogs (Study 152.260; 6 sites): 0.1 mL/kg topically on Days 0 and 28, alone or with melarsomine; modified Knott's counts to Day 42; n = 181 (effectiveness evaluation); primary endpoint: Percent reduction of circulating microfilariae on Study Day 42 (>90%) with significant pre- vs post-treatment difference; result: Geometric mean microfilariae 4480.9 pre-treatment to 32.5 (Day 28) and 21.8 (Day 42); effectiveness 99.3% and 99.5% (p<0.0001); >90% at five of six sites (one site 73.3%)
A total of 181 dogs were evaluated for effectiveness. Each dog was antigen and microfilaria positive for D. immitis prior to Study Day -14. The post-treatment circulating microfilaria counts on Study Day 28 and 42 were significantly reduced compared to the pre-treatment counts (p < 0.0001) with effectiveness of 99.3% on Study Day 28, and 99.5% on Study Day 42.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Cough | 24 (22.6%) | 25 (23.1%) | Cough 24 (22.6%) 25 (23.1%) |
| Lethargy | 14 (13.2%) | 42 (38.9%) | Lethargy 14 (13.2%) 42 (38.9%) |
| Vomiting | 11 (10.4%) | 18 (16.7%) | Vomiting 11 (10.4%) 18 (16.7%) |
| Diarrhea, including hemorrhagic | 10 (9.4%) | 22 (20.4%) | Diarrhea, including hemorrhagic 10 (9.4%) 22 (20.4%) |
| Inappetance | 7 (6.6%) | 19 (17.6%) | Inappetance 7 (6.6%) 19 (17.6%) |
| Death | 0 | 3 (2.8%) | Death 0 3 (2.8%) |
Extraction notes: Supplemental approval; CVM required no new margin-of-safety study (refers to the 2006 original). Species/Class recorded as 'Dog' exactly as stated. The target_animal_safety entry is the clinical field safety study, not a dose-multiple study. IMPORTANT: in adverse_reactions the 'control' column is NOT a negative control; it is the group given Advantage Multi plus melarsomine dihydrochloride (n=108) versus Advantage Multi alone (n=106) in 'treated' (Table 4). Laboratory microfilariae studies (152.222 induced, 20 Beagles; 152.224 natural, 22 dogs) showed 99.9-100% reduction on Days 28/42. Sarcoptic mange: laboratory study 93.4% (single dose, Day 28) and 100% (two doses, Day 56); field study (62 evaluable dogs vs selamectin) 98.7% and 99.5% reduction in live mites.
Reproduce: foi_structured_search(query="Imidacloprid, Moxidectin") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).