Lotilaner for Demodex Blepharitis: The Journey from Veterinary Use to Human Medicine

In 2023, Xdemvy® (0.25% lotilaner ophthalmic solution) was approved by the U.S. FDA for treating Demodex blepharitis in humans. This article reviews lotilaner's history, physicochemical properties, pharmacokinetics, pharmacology, clinical outcomes, and other indications for which it is being evaluated clinically. Furthermore, the article discusses Demodex blepharitis, alternative treatments used in the clinic to ameliorate its symptoms, and other drugs in development. Prior to its approval in humans, lotilaner found extensive application in treating parasitic infections in cats and dogs. Lotilaner was previously approved in 2017 as an oral veterinary medicine (Credelio®) for canines to treat demodicosis, other mite infections, and tick infections. Lotilaner belongs to the isoxazoline class of drugs and is a potent arthropod-selective gamma-aminobutyric acid-gated chloride ion channel inhibitor. Like several other drugs in the isoxazoline class, lotilaner has a long plasma half-life and high plasma protein binding of about 99.9%. When used as indicated, lotilaner treats infested Demodex blepharitis in 42 days, with its antiparasitic action starting within 24 h. Furthermore, lotilaner is also being evaluated for its efficacy in other conditions such as Lyme disease and dry eye disease. Other products evaluated for treating Demodex blepharitis include ivermectin eye ointment, ivermectin-metronidazole gel, permethrin cream, terpinen-4-ol wipes, and hypochlorous acid spray. Along with these, azithromycin eye drop, azithromycin/loteprednol eye drop, and other treatments are being evaluated for treating blepharitis. Other drugs from the isoxazoline drug class including afoxolaner, sarolaner, and fluralaner, could also be potentially explored for human use.