Lotilaner

Lotilaner
Clinical data
Trade namesCredelio, Xdemvy, others
Other namesTP-03
AHFS/Drugs.comMonograph
License data
Routes of
administration		By mouth, eye drops
Drug classAntiparasitic
ATC code
Legal status
Legal status
Identifiers
  • 3-Methyl-N-[2-oxo-2-(2,2,2-trifluoroethylamino)ethyl]-5-[(5S)-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4H-1,2-oxazol-3-yl]thiophene-2-carboxamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC20H14Cl3F6N3O3S
Molar mass596.75 g·mol−1
3D model (JSmol)
  • Cc1cc(C2=NO[C@@](c3cc(Cl)c(Cl)c(Cl)c3)(C(F)(F)F)C2)sc1C(=O)NCC(=O)NCC(F)(F)F
  • InChI=1S/C20H14Cl3F6N3O3S/c1-8-2-13(36-16(8)17(34)30-6-14(33)31-7-19(24,25)26)12-5-18(35-32-12,20(27,28)29)9-3-10(21)15(23)11(22)4-9/h2-4H,5-7H2,1H3,(H,30,34)(H,31,33)/t18-/m0/s1
  • Key:HDKWFBCPLKNOCK-SFHVURJKSA-N

Lotilaner, sold under the brand name Xdemvy, is an ectoparasiticide (anti-parasitic) medication used for the treatment of blepharitis (inflammation of the eyelid) caused by infestation by Demodex (tiny mites). It is used as an eye drop.

It was approved for medical use in the United States in July 2023. The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.

Lotilaner is a member of the isoxazoline family of compounds.

Medical uses

Lotilaner is indicated for the treatment of Demodex blepharitis. It had been first used in veterinary medicine against fleas and ticks, and later for Demodex mites.

Veterinary uses

Lotilaner, sold under the brand name Credelio among others, is a veterinary medication used to control fleas and ticks in dogs and cats. It is indicated for the treatment and prevention of flea infestations (Ctenocephalides felis) and for the treatment and control of tick infestations including lone star tick (Amblyomma americanum), American dog tick (Dermacentor variabilis), black-legged tick (Ixodes scapularis), and brown dog tick (Rhipicephalus sanguineus). It is taken by mouth.

Lotilaner in combination with milbemycin oxime is sold under the brand name Credelio Plus. It is used in dogs to treat concurrent infestations with parasites living outside (ticks and/or fleas) and inside (worms) the animal's body.

Lotilaner (brand Lotimax) is used for the treatment of flea, tick, and mite infestations in dogs, including treatment of demodicosis (caused by Demodex canis).

Mechanism of action

Lotilaner paralyzes and kills parasites by interfering with the way that signals are passed between their nerve cells.

Lotilaner is a gamma-aminobutyric acid (GABA)-gated chloride channel inhibitor selective for arthropods. Inhibition of these GABA chloride channels causes a paralytic action in the target organism leading to its death. Lotilaner is not an inhibitor of mammalian GABA mediated chloride channels when tested at up to 30 μM (18 μg/mL) in vitro (approximately 1100 times the RHOD).

In March 2024, the Committee for Veterinary Medicinal Products (CVMP) of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the veterinary medicinal product Lotimax, Chewable tablet, intended for use in dogs. The applicant for this veterinary medicinal product is Elanco GmbH. Lotimax was approved for medical use in the European Union in April 2024.

Research

Tarsus Pharmaceuticals has conducted phase II studies of lotilaner as a remedy to prevent tick bites in humans.

References

  1. 1 2 3 4 5 "Xdemvy- lotilaner ophthalmic solution solution/ drops". DailyMed. 26 July 2023. Retrieved 23 August 2023.
  2. 1 2 3 "Credelio- lotilaner tablet, chewable". DailyMed. Archived from the original on 5 August 2021. Retrieved 4 August 2021.
  3. 1 2 3 "Credelio- lotilaner tablet, chewable". DailyMed. Archived from the original on 5 August 2021. Retrieved 4 August 2021.
  4. 1 2 "Credelio EPAR". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 27 January 2022. Retrieved 4 August 2021.
  5. 1 2 3 "Lotimax EPAR". European Medicines Agency. 13 March 2024. Retrieved 20 March 2024. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  6. ↑ "Lotimax Product information". Union Register of veterinary medicinal products. 29 April 2024. Retrieved 29 August 2024.
  7. 1 2 "Novel Drug Approvals for 2023". U.S. Food and Drug Administration (FDA). 25 July 2023. Archived from the original on 21 January 2023. Retrieved 5 August 2023.
  8. ↑ "Xdemvy: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Archived from the original on 27 July 2023. Retrieved 5 August 2023.
  9. ↑ "FDA Approves Xdemvy (lotilaner ophthalmic solution) 0.25% for the treatment of Demodex blepharitis" (Press release). Tarsus Pharmaceuticals. 25 July 2023. Retrieved 5 August 2023 – via GlobeNewswire.
  10. ↑ New Drug Therapy Approvals 2023. U.S. Food and Drug Administration (FDA) (Report). January 2024. Archived from the original (PDF) on 10 January 2024. Retrieved 9 January 2024.
  11. 1 2 3 "A Pill That Kills Ticks Is a Promising New Weapon Against Lyme Disease". Wired. 15 March 2024. Retrieved 17 March 2024.
  12. ↑ Kuntz EA, Kammanadiminti S (November 2017). "Safety evaluation of lotilaner in dogs after oral administration as flavoured chewable tablets (Credelio)". Parasites & Vectors. 10 (1): 538. doi:10.1186/s13071-017-2468-y. PMC 5664904. PMID 29089043.
  13. ↑ "Freedom Of Information Summary, Supplemental New Animal Drug Application, NADA 141-494, Credelio, Lotilaner, Chewable Tablets, Dogs". 3 September 2019. Archived from the original on 18 May 2022. Retrieved 1 December 2019.
  14. 1 2 "Credelio Plus EPAR". European Medicines Agency. 19 February 2021. Archived from the original on 7 December 2022. Retrieved 4 August 2021. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  15. 1 2 "Lotimax PI". Union Register of medicinal products. 29 April 2024. Retrieved 17 June 2024.
  16. ↑ Prescribing Information for XDEMVY, Irvine, CA: Tarsus Pharmaceuticals, Inc., 2024
  17. ↑ "Tarsus Announces Positive Topline Results from Carpo, a Phase 2a Proof-of-Concept "Tick-Kill" Trial Evaluating TP-05 (lotilaner) for the Prevention of Lyme Disease (press release)". Tarsus Pharmaceuticals. 22 February 2024. Archived from the original on 17 March 2024. Retrieved 17 March 2024.