Isoxazolines for Treatment of Demodicosis

In the literature

Zhou X, Hohman A, Hsu WH. Review of extralabel use of isoxazolines for treatment of demodicosis in dogs and cats. J Am Vet Med Assoc. 2020;256(12):1342-1346.

The Research …

Demodex canis, the most common Demodex species leading to canine demodicosis, is a normal part of the skin microbiota but can proliferate secondary to immunocompromise.^1,2 Demodicosis is characterized by time of onset (juvenile vs adult) and areas affected (localized vs generalized). Localized demodicosis is generally self-limiting, whereas generalized demodicosis can be difficult to treat.

Topical amitraz, the only FDA-approved drug for the treatment of demodicosis in the United States, has been considered the standard for decades. Treatment requires intense topical therapy and carries risk for severe adverse effects. Topical moxidectin formulations are labeled for demodicosis treatment in other countries but not in the United States. Additional treatments include ivermectin, moxidectin, doramectin, lime sulfur, milbemycin oxime, and isoxazolines.^3-5 Many treatments have a high risk for adverse effects, and some can be cost-prohibitive.

This article reviewed the use of isoxazolines in the treatment of demodicosis in dogs and cats, as well as the safety of orally administered formulations of these drugs.

Isoxazolines are FDA-approved for use against fleas and ticks. Oral canine formulations include afoxolaner, sarolaner, fluralaner, and lotilaner.⁶ Topical fluralaner is available for use in dogs and cats.⁷ Field trials and reports have demonstrated successful treatment of generalized demodicosis using isoxazolines^8-14:

• Oral fluralaner has been shown to decrease the number of mites identified on scrapings by 100% at day 56.⁸ Topically administered fluralaner had similar efficacy.⁹ Another field study demonstrated parasitological cure in dogs with juvenile and generalized demodicosis within 2 to 4 months.¹⁰

• Both oral afoxolaner and lotilaner have been shown to reduce mite numbers by ≈99.9% on day 56 and 100% on day 84.^11,12 

• Sarolaner has been shown to reduce mite numbers by 99.8% within 29 days with no live mites detected thereafter; the control treatment had a lower efficacy with a longer duration of treatment.¹³ A multicenter study found mite counts decreased by 100% by day 150 following monthly administration of sarolaner as compared with the control that resulted in 82.2% reduction at 6 months.¹⁴

No large studies have been performed to investigate efficacy of isoxazoline treatment of feline demodicosis, although reports describe elimination of D gatoi and D cati after a single dose of oral fluralaner.^15,16

Oral fluralaner, afoxolaner, and sarolaner have all been assessed for safety in 8-week-old puppies receiving ≤5 times the maximum dose^17,18; no major adverse effects or impact on growth have been associated with treatment.^19,20 In one study, oral sarolaner at ≤5 times the maximum dose was administered to adult beagles, with no adverse effects noted.¹⁹ In another study, oral lotilaner was administered to 112 cats, with no adverse effects documented.²⁰ Oral fluralaner in breeding dogs has not been shown to have significant impact on reproductive performance or semen quality when administered at 3 times the maximum dose from breeding until weaning.⁷

Many historical treatments for demodicosis cannot be used in dogs with the multidrug sensitivity gene (MDR1 gene, also known as ABCB1 gene) mutation.²¹ Isoxazolines have the potential to cause neurologic excitation in vertebrates by blocking γ-aminobutyric acid-gated chloride channels. Fluralaner has been evaluated in dogs homozygous for the MDR1 mutation, and only minor clinical findings not associated with treatment have been observed.²² One report described neurologic signs observed in some dogs when given sarolaner doses higher than recommended.²³ One clinical report noted transient neurologic abnormalities in a young dog after administration of fluralaner at the recommended dose.²³ The FDA has reported adverse neurologic reactions across the isoxazoline class but has stated this class is effective and safe for most animals.²⁴

… The Takeaways

Key pearls to put into practice:

• Isoxazolines are not currently labeled for the treatment of demodicosis in the United States, but studies and clinical reports support their clinical use.

• Isoxazolines appear to be well-tolerated in most dogs, with minimal adverse effects; however, neurologic adverse effects have been reported.

• Findings suggest that fluralaner is well-tolerated in dogs with the MDR1 mutation.