In 2014, a new class of parasiticides was introduced to the Canadian small animal health market. Isoxazoline drugs include afoxolaner, fluralaner, lotilaner, and sarolaner. A plethora of oral and topical spot-on products are now commercially available and contain either a single isoxazoline or an isoxazoline in combination with 1 or 2 other active ingredient(s). There are geographical differences in the availability and licensure of these drugs. Therefore, one must judiciously consider regional prescribing recommendations. Isoxazolines currently available for use in dogs in Canada are listed in Table 1.
Table 1.
Isoxazolines currently available for use in dogs in Canada.
| Product name (market year) | Manufacturer | Route | Isoxazoline | Macrocyclic lactone | Other | Label use | Extra-label use |
|---|---|---|---|---|---|---|---|
| Bravecto (2014) | Merck/Intervet | Oral | Fluralaner | N/A | N/A | F,T | D,S,L |
| Bravecto topical solution (2018) | Merck/Intervet | Topical | Fluralaner | N/A | N/A | F,T | D,S,L |
| Bravecto one (2021) | Merck/Intervet | Oral | Fluralaner | N/A | N/A | F,T | D,S,L |
| Credelio (2019) | Elanco | Oral | Lotilaner | N/A | N/A | F,T | D,S |
| Credelio plus (2022) | Elanco | Oral | Lotilaner | Milbemycin oxime | N/A | F,T,R,HT | D,S |
| NexGard (2014) | Boehringer Ingelheim | Oral | Afoxolaner | N/A | N/A | F,T,D | S |
| NexGard spectra (2019) | Boehringer Ingelheim | Oral | Afoxolaner | Milbemycin oxime | N/A | F,T,D,HK,R,W,HT | S |
| Simparica (2016) | Zoetis | Oral | Sarolaner | N/A | N/A | F,T | D,S,L |
| Simparica trio (2020) | Zoetis | Oral | Sarolaner | Moxidectin | Pyrantel | F,T,H,K,R,HT | D,S,L |
D — Demodicosis; F — Fleas; HK — Hookworm; HT — Heartworm; L — Lice infestation; R — Roundworm; S — Sarcoptic mange (scabies); T — Ticks; W — Whipworm.
N/A — Not available.
Isoxazolines have had impressive results in controlling canine demodicosis (Figure 1 A, B), sarcoptic mange (scabies) and lice infestation. This article reviews the clinical use (both label and extra label) of isoxazolines in Canada for cutaneous parasites affecting dogs.
Figure 1.
Juvenile demodicosis in a 6-month-old intact male Australian shepherd. Note the facial lesions on initial presentation, including alopecia, erythema, and crusts. Before (Day 0; A) and after (Day 44; B) treatment with a single dose of oral fluralaner.
Canine demodicosis
Demodicosis is a common skin disease caused by proliferation of Demodex mites. The efficacy of isoxazolines was evaluated in 697 dogs enrolled in 20 studies.
Oral afoxolaner
The efficacy of oral afoxolaner was evaluated in 253 dogs enrolled in 7 studies (1–7). Details are summarized in Table 2.
Table 2.
Canine demodicosis — Afoxolaner studies.
| Reference/year | Treatment protocol and outcome |
|---|---|
| (1) 2016 | Controlled study — 8 dogs 3 doses, 14 d apart and a fourth dose 28 d later 100% mite-free at Day 84 No adverse effects Another 8 dogs were treated with a spot-on containing imidacloprid and moxidectin (same intervals) Afoxolaner performed better than the spot-on |
| (2) 2016 | Case series — 4 dogs 3 doses, 28 d apart 100% mite-free at Day 56 Adverse effects not recorded |
| (3) 2017 | Unpublished case series — 102 dogs Treated every 2 to 4 wk 100% mite-free at Day 90 Adverse effects not recorded |
| (4) 2018 | Case series — 6 dogs 1, 2 or 3 doses; 21, 28, 35 or 42 d apart 100% mite-free at Day 77 No adverse effects |
| (5) 2018 | Case series — 15 dogs Treated with the combination of afoxolanermilbemycin oxime 3 doses, 28 d apart 99.9% mite reduction at Day 84 No adverse effects |
| (6) 2018 | Case series — 50 dogs Treated with afoxolaner (31 dogs) or the combination of afoxolaner-milbemycin oxime (19 dogs) 3 doses, 28 d apart 98% mite reduction at Day 84 Adverse effect: vomiting (1 dog) |
| (7) 2019 | Case series — 68 dogs Treated with the combination of afoxolanermilbemycin oxime Single dose 82.4% mite reduction at Day 28 Adverse effects not recorded |
Oral/topical fluralaner
The efficacy of oral or topical fluralaner was evaluated in 373 dogs enrolled in 10 studies (8–17). Details are summarized in Table 3.
Table 3.
Canine demodicosis — Fluralaner studies.
| Reference/year | Treatment protocol and outcome |
|---|---|
| (8) 2015 | Controlled study — 8 dogs Single oral dose 100% mite-free at Day 56 No adverse effects Another 8 dogs were treated with a spot-on containing imidacloprid and moxidectin (3 doses, 28 d apart) Oral fluralaner performed better than the spot-on |
| (9) 2015 | Case series — 163 dogs Single oral dose 100% mite-free at Day 60 No adverse effects |
| (10) 2016 | Case series — 4 dogs 2 oral doses, 60 d apart 98% mite reduction at Day 90 Adverse effects not recorded |
| (11) 2017 | Case report — 1 dog with Demodex injai Single oral dose 100% mite-free at Day 49 Adverse effects not recorded |
| (12) 2018 | Case report — 1 dog with hyperadrenocorticism and hypothyroidism Single oral dose 100% mite-free at Day 60 Diffuse nonpruritic erythematous papules on trunk 3 d after administration (resolved spontaneously within a few days) |
| (13) 2018 | Case series — 67 dogs 1 to 3 oral doses, 84 d apart 100% mite-free at Day 90 No adverse effects |
| (14) 2019 | Case series — 20 dogs Single oral dose 100% mite-free at Day 56 No adverse effects |
| (15) 2019 | Controlled study — 8 dogs Single topical spot-on dose 100% mite-free at Day 84 No adverse effects Another 8 dogs were treated with a spot-on containing imidacloprid and moxidectin (at weekly to monthly intervals over 84 d) Topical spot-on fluralaner performed better than the imidacloprid/moxidectin spot-on |
| (16) 2020 | Controlled study — 100 dogs Single oral or topical spot-on dose 100% mite-free at Day 84 (oral) 98% mite-free at Day 84 (topical spot-on) No adverse effects Another 24 dogs were treated with a spot-on containing imidacloprid and moxidectin (at weekly to monthly intervals over 84 d) Oral and topical spot-on fluralaner performed better than the imidacloprid/moxidectin spot-on |
| (17) 2021 | Case report — 1 dog with localized demodicosis Single oral dose 100% mite-free at Day 56 |
Oral lotilaner
The efficacy of oral lotilaner was evaluated in 1 case series (18). Ten dogs were treated orally 3 times, 28 d apart. All dogs were mite-free at Day 70. There were no adverse effects.
Oral sarolaner
The efficacy of oral sarolaner was evaluated in 2 controlled studies. In the first study (19), 8 dogs were treated 3 times, 30 d apart. All dogs were mite-free at Day 44. There were no adverse effects. Another 8 dogs were treated with a weekly spot-on containing imidacloprid and moxidectin. Sarolaner performed better than the spot-on. The second non-inferiority study (20) compared the same 2 products. Fifty-three dogs were treated 30 d apart. All dogs were mite-free at Day 150. Another 28 dogs were treated weekly or monthly with the imidacloprid-moxidectin spot-on. There were no adverse effects with oral sarolaner. Once again, sarolaner performed better than the spot-on.
Canine sarcoptic mange (scabies)
Canine sarcoptic mange (scabies) is a pruritic and contagious skin disease caused by the mite Sarcoptes scabiei var. canis. The efficacy of isoxazolines was evaluated in 464 dogs enrolled in 9 studies.
Oral afoxolaner
The efficacy of oral afoxolaner was evaluated in 1 controlled study (21). Ten dogs were treated twice, 28 d apart. All dogs were mite-free at Day 28. The efficacy of oral afoxolaner or the combination of afoxolaner-milbemycin oxime was evaluated in 2 case series (22,23). In the first study, 65 dogs were treated twice, 30 d apart; 99.7 to 100% of the dogs were mite-free at Day 60. In the second study, 142 dogs were treated with a single dose. All dogs were mite-free at Day 56. There were no adverse effects in these studies.
Oral/topical fluralaner
The efficacy of oral or topical fluralaner was evaluated in 1 controlled study (24). Nine dogs were treated with a single oral dose and 11 dogs were treated with a single topical spot-on dose. All dogs were mite-free at Day 28. There were no adverse effects. The efficacy of oral fluralaner was evaluated in 1 case series (25). Seventeen dogs were treated with a single oral dose. All dogs were mite-free at Day 14. Adverse effects were not recorded.
The efficacy of oral or topical fluralaner was evaluated in 1 case series (26). Fifty-four dogs were treated with a single oral dose and 46 dogs were treated with a single topical spot-on dose. All dogs were mite-free at Day 56. There were no adverse effects.
Lastly, the efficacy of a single dose of oral fluralaner was evaluated in 1 case report of crusted — Norwegian-like-scabies (27). The dog was mite-free at Day 30.
Oral lotilaner
The efficacy of oral lotilaner was evaluated in 1 case series (28). Eight dogs were treated orally 3 times, 30 d apart. All dogs were mite-free at Day 30. There were no adverse effects.
Oral sarolaner
The efficacy of oral sarolaner was evaluated in a placebo-controlled laboratory study and in a controlled field study (29). Forty-four dogs were enrolled in the laboratory study. Twenty-two dogs were treated with oral sarolaner, whereas another 22 dogs received a placebo tablet on 2 occasions, 30 d apart. All sarolaner-treated dogs were mite-free at Day 30. Seventy-nine dogs were enrolled in the field study. Fifty-three dogs were treated with oral sarolaner, whereas another 26 dogs were treated with a spot-on containing imidacloprid and moxidectin, twice, 30 d apart. All sarolaner-treated dogs were mite-free at Day 60. Oral sarolaner was noninferior to topically applied imidacloprid/moxidectin. There were no adverse effects in either study.
The efficacy of oral sarolaner was evaluated in 1 case series (26). Twenty-six dogs were treated twice, 28 d apart. All dogs were mite-free at Day 56. There were no adverse effects.
Canine lice infestation
The efficacy of oral fluralaner was evaluated in 1 controlled study (30). Fourteen dogs with a sucking lice infestation caused by Linognathus setosus were treated with a single dose. All dogs were lice-free at Day 28. Another 10 dogs were treated once with a spot-on containing permethrin. There were no adverse effects. Fluralaner performed better than the spot-on.
The efficacy of a single oral dose of sarolaner was evaluated in 1 dog with a biting louse infestation caused by Heterodoxus spiniger (31). The dog was lice-free at Day 28. There were no adverse effects.
What is the recommend dosage and number of doses?
The number of recommended doses, based on a review of the available scientific literature, is summarized in Table 4. It is recommended to use the labelled dosage for flea and tick prevention/control/treatment, and to conform to the minimum age and body weight requirements. Due to reduced drug bio-availability in the fasted state, fluralaner and lotilaner should be administered with food, whereas for afoxolaner and sarolaner plasma concentrations are the same, regardless of whether the drug is given with or without food.
Table 4.
Number of recommended doses of isoxazolines (use either a single isoxazoline product or a combination product).
| Disease | Number of doses |
|---|---|
| Canine demodicosis | 1 oral or topical dose of fluralaner 3 monthly oral doses of afoxolaner or lotilaner or sarolaner |
| Canine sarcoptic mange (scabies) | 1 oral or topical dose of fluralaner 1 oral dose of afoxolaner 2 monthly oral doses of lotilaner or sarolaner |
| Canine lice infestation | 1 oral or topical dose of fluralaner 1 oral dose of sarolaner |
What are the potential side effects of isoxazolines?
Isoxazolines have potential side effects (including vomiting, diarrhea, anorexia, lethargy, and seizures). They should only be used in suitable patients (i.e., use with caution in dogs with a history of seizures or neurological disorders), and under veterinary supervision.
Conclusion
The recent introduction of isoxazolines in veterinary medicine has resulted in effective and safe treatment of canine demodicosis, sarcoptic mange (scabies) or lice infestations, with low frequency of administration.
Footnotes
Use of this article is limited to a single copy for personal study. Anyone interested in obtaining reprints should contact the CVMA office (hbroughton@cvma-acmv.org) for additional copies or permission to use this material elsewhere.
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