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Lotilaner
View on Wikipediafrom Wikipedia
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| Clinical data | |
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| Trade names | Credelio, Xdemvy, others |
| Other names | TP-03 |
| AHFS/Drugs.com | Monograph |
| License data | |
| Routes of administration | By mouth, eye drops |
| Drug class | Antiparasitic |
| ATC code | |
| Legal status | |
| Legal status | |
| Identifiers | |
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| PubChem CID | |
| DrugBank | |
| ChemSpider | |
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| KEGG | |
| ChEBI | |
| ChEMBL | |
| CompTox Dashboard (EPA) | |
| Chemical and physical data | |
| Formula | C20H14Cl3F6N3O3S |
| Molar mass | 596.75 g·mol−1 |
| 3D model (JSmol) | |
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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).[1][7] It is used as an eye drop.[1]
It was approved for medical use in the United States in July 2023.[1][7][8][9] The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.[10]
Lotilaner is a member of the isoxazoline family of compounds.
Medical uses
[edit]Lotilaner is indicated for the treatment of Demodex blepharitis.[1] It had been first used in veterinary medicine against fleas and ticks, and later for Demodex mites.[11]
Veterinary uses
[edit]Lotilaner, sold under the brand name Credelio among others, is a veterinary medication used to control fleas and ticks in dogs and cats.[2][3][4][12] 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).[13] It is taken by mouth.[2][3]
Lotilaner in combination with milbemycin oxime is sold under the brand name Credelio Plus.[14] It is used in dogs to treat concurrent infestations with parasites living outside (ticks and/or fleas) and inside (worms) the animal's body.[14]
Lotilaner (brand Lotimax) is used for the treatment of flea, tick, and mite infestations in dogs, including treatment of demodicosis (caused by Demodex canis).[15]
Mechanism of action
[edit]Lotilaner paralyzes and kills parasites by interfering with the way that signals are passed between their nerve cells.[11]
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).[16]
Legal status
[edit]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.[5] The applicant for this veterinary medicinal product is Elanco GmbH.[5] Lotimax was approved for medical use in the European Union in April 2024.[15]
Research
[edit]Tarsus Pharmaceuticals has conducted phase II studies of lotilaner as a remedy to prevent tick bites in humans.[17][11]
References
[edit]- ^ a b c d e "Xdemvy- lotilaner ophthalmic solution solution/ drops". DailyMed. 26 July 2023. Retrieved 23 August 2023.
- ^ a b c "Credelio- lotilaner tablet, chewable". DailyMed. Archived from the original on 5 August 2021. Retrieved 4 August 2021.
- ^ a b c "Credelio- lotilaner tablet, chewable". DailyMed. Archived from the original on 5 August 2021. Retrieved 4 August 2021.
- ^ a b "Credelio EPAR". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 27 January 2022. Retrieved 4 August 2021.
- ^ a b c "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.
- ^ "Lotimax Product information". Union Register of veterinary medicinal products. 29 April 2024. Retrieved 29 August 2024.
- ^ a b "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.
- ^ "Xdemvy: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Archived from the original on 27 July 2023. Retrieved 5 August 2023.
- ^ "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.
- ^ 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.
- ^ a b c "A Pill That Kills Ticks Is a Promising New Weapon Against Lyme Disease". Wired. 15 March 2024. Retrieved 17 March 2024.
- ^ 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.
- ^ "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.
- ^ a b "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.
- ^ a b "Lotimax PI". Union Register of medicinal products. 29 April 2024. Retrieved 17 June 2024.
- ^ Prescribing Information for XDEMVY, Irvine, CA: Tarsus Pharmaceuticals, Inc., 2024
- ^ "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.
Lotilaner
View on Grokipediafrom Grokipedia
Lotilaner is an ectoparasiticide medication in the isoxazoline class, designed to target and eliminate infestations of external parasites such as fleas, ticks, and mites by acting as a non-competitive antagonist of GABA-gated chloride channels, leading to parasite paralysis and death without significantly affecting mammalian channels.[1] In human medicine, it is formulated as a 0.25% ophthalmic solution under the brand name Xdemvy for the topical treatment of Demodex blepharitis, an inflammatory eyelid condition caused by overpopulation of Demodex mites, with administration involving one drop in each eye twice daily for six weeks.[2] The U.S. Food and Drug Administration approved lotilaner for this indication on July 25, 2023, marking its transition from primarily veterinary applications to human use following clinical trials demonstrating rapid mite eradication within 24 hours and sustained efficacy over 42 days.[1]
Originally developed for veterinary purposes and first approved by the FDA in 2018 for dogs and 2019 for cats, lotilaner is widely used under the brand name Credelio as an oral chewable tablet to prevent flea infestations and control ticks, with monthly dosing recommended for animals over eight weeks old and meeting minimum weight thresholds.[3][4] It exhibits high efficacy against common tick species including Amblyomma americanum, Dermacentor variabilis, Ixodes scapularis, and Rhipicephalus sanguineus; as of October 2025, FDA label expansions for Credelio include explicit prevention of Lyme disease via killing of I. scapularis and protection against the Asian longhorned tick (Haemaphysalis longicornis).[3][5] It is used off-label for mite infestations in dogs, such as demodectic mange (Demodex spp.) and sarcoptic mange (Sarcoptes scabiei), with clinical studies demonstrating high efficacy (including >99.9% mite reduction and complete elimination in many cases), although it is not FDA-approved for mite treatment and there is no reliable evidence for efficacy against Cheyletiella mites; it may also be prescribed for ear mites in pets.[3][6][7][8] Pharmacokinetically in dogs, lotilaner achieves peak plasma concentrations within 2 hours post-administration, features extensive protein binding (>99.9%), and has an effective half-life of approximately 28 days, supporting its prolonged antiparasitic activity.[9]
Common adverse effects in human use include instillation site stinging or burning (affecting about 10% of patients), while veterinary applications may involve gastrointestinal upset such as vomiting or decreased appetite, with rare neurological signs like tremors in sensitive animals.[2] Precautions emphasize avoiding use in breeding, pregnant, or lactating animals without veterinary guidance, and regular monitoring is advised for both human and animal patients to assess treatment response and manage potential side effects.[3] As a member of the isoxazoline family, lotilaner represents an advancement in targeted parasite control, with ongoing research exploring its broader applications in ectoparasite management.[1]
Uses
Medical uses
Lotilaner ophthalmic solution 0.25% is indicated for the treatment of Demodex blepharitis in adults, a chronic inflammatory condition of the eyelids caused by infestation with Demodex mites (Demodex folliculorum and Demodex brevis), which contribute to the formation of collarettes (cylindrical dandruff-like deposits at the base of eyelashes) and elevated mite density on the lid margins.[2] The recommended dosing regimen consists of instilling one drop into each eye twice daily, approximately 12 hours apart, for 6 weeks using the provided dropper bottle.[2] Administration is topical and ocular, with patients advised to avoid touching the dropper tip to any surface to prevent contamination; if multiple topical ophthalmic medications are used, they should be administered at least 5 minutes apart.[2] Completing the full 6-week course is essential to achieve mite eradication and sustained reduction in collarettes and inflammation.[2] Efficacy was demonstrated in two randomized, double-masked, vehicle-controlled phase 3 clinical trials (Saturn-1 and Saturn-2) involving a total of 833 adults with Demodex blepharitis.[2] In Saturn-1 (n=421), 68% of lotilaner-treated patients achieved complete mite eradication (0 mites per lash) by day 43 compared to 17% in the vehicle group (p<0.0001), while collarette resolution (≤2 collarettes per upper lid) occurred in 44% versus 7% (p<0.0001).[2] In Saturn-2 (n=412), corresponding rates were 50% versus 14% for mite eradication (p<0.0001) and 55% versus 12% for collarette resolution (p<0.0001).[2] Lotilaner is suitable for adult patients with confirmed Demodex blepharitis, diagnosed via slit-lamp biomicroscopy showing at least 1 collarette per eyelid and an average mite density of ≥1.5 mites per lash (upper and lower eyelids combined) in each eye.[10][11]Veterinary uses
Lotilaner is approved for veterinary use in dogs and cats primarily for the prevention and treatment of flea infestations caused by Ctenocephalides felis, as well as tick control targeting species such as Ixodes scapularis (black-legged tick), Dermacentor variabilis (American dog tick), and others. Although not approved by the FDA for the treatment of mite infestations, lotilaner is used off-label in dogs for certain mite species.[12] In dogs, lotilaner has demonstrated high efficacy in the treatment of generalized demodicosis caused by Demodex spp. mites, with studies showing reduction of live mite counts to zero after three monthly doses in most cases.[13] It has also shown efficacy against sarcoptic mange caused by Sarcoptes scabiei, with clinical studies demonstrating complete mite elimination and resolution of clinical signs following monthly oral doses.[14] There is no reliable evidence supporting its efficacy against Cheyletiella mites in dogs. For cats, indications focus on flea and tick control, with a single oral dose providing protection for up to 30 days against adult fleas and specific ticks like I. scapularis.[15] The primary formulation is an oral chewable tablet, beef- or liver-flavored for palatability and administered monthly. For dogs, doses range from 56.25 mg for those weighing 4.4–6 lbs up to 900 mg for those over 100 lbs, ensuring a minimum of 20 mg/kg body weight, with combinations used for intermediate sizes.[16] In cats, tablets are dosed at 12 mg for 2–4 lbs and 48 mg for 4.1–17 lbs, with additional tablets for heavier cats to achieve 6–24 mg/kg.[17] Combination products expand protection: Credelio Plus pairs lotilaner with milbemycin oxime to address fleas, ticks, heartworm (Dirofilaria immitis), and intestinal nematodes in dogs. Credelio Quattro, approved by the FDA in October 2024, combines lotilaner with moxidectin, praziquantel, and pyrantel for comprehensive control of fleas, ticks, heartworm, roundworms, hookworms, and tapeworms in dogs. These formulations are given with or without food in dogs for flexibility, though cats should receive them with food to optimize absorption.[18] Lotilaner exhibits rapid onset of action, killing fleas within 4 hours in dogs and 6–12 hours in cats, with >98% reduction by 24 hours, and ticks within 48 hours. Field studies in client-owned dogs and cats show >99% efficacy in flea elimination after one dose, sustained monthly with geometric mean reductions exceeding 98% over 30 days. In tick-infested environments, it achieves 97–100% kill rates for key species, reducing transmission risks like Lyme disease. Dosing follows weight-based charts to ensure safety and efficacy across age groups, starting from 8 weeks in both species.[19][20]Pharmacology
Mechanism of action
Lotilaner is a member of the isoxazoline class of compounds, structurally related to other ectoparasiticides such as afoxolaner, and functions as a potent antiparasitic agent primarily through its action on invertebrate nervous systems.[21][1] It exerts its effects by selectively inhibiting γ-aminobutyric acid (GABA)-gated chloride channels (GABACls) and glutamate-gated chloride channels (GluCls) in the nervous systems of arthropods and mites. As a non-competitive antagonist, lotilaner binds to these channels in invertebrates, preventing the influx of chloride ions that normally hyperpolarizes neurons and inhibits excitatory signaling. This blockade disrupts normal nerve impulse transmission, resulting in hyperexcitation, paralysis, and rapid death of target parasites such as fleas, ticks, and mites. The physiological impact occurs within hours of exposure, with no significant effect on mammalian GABA receptors at therapeutic concentrations due to structural differences in channel composition.[21][2][22][23] The selectivity of lotilaner is attributed to its high affinity for invertebrate channels compared to mammalian counterparts, with IC50 values ranging from approximately 10-50 nM for arthropod GABACls (e.g., 23.8 nM in fruit fly and 36.8 nM in tick receptors) and exceeding 10 μM (>1000-fold higher) for canine or human GABAA receptors. This differential potency ensures efficacy against parasites while minimizing off-target effects in hosts. In systemic formulations for veterinary use, lotilaner provides contact kill against fleas and ticks upon biting, achieving substantial parasite mortality within 4-8 hours. In the ophthalmic formulation for ocular mites like Demodex, the compound penetrates eyelid tissues to target mites in hair follicles via the same channel inhibition mechanism.[21][24][25][22]Pharmacokinetics
Lotilaner exhibits distinct pharmacokinetic profiles depending on the route of administration and species, with rapid absorption in oral veterinary formulations and minimal systemic exposure following ophthalmic use in humans. In dogs and cats, oral administration leads to quick uptake from the gastrointestinal tract, while the topical ocular formulation in humans prioritizes local retention in eyelid tissues with limited plasma penetration. For the oral veterinary route in dogs, lotilaner is rapidly absorbed following ingestion, with median time to peak plasma concentration (Tmax) of 2 hours in fed animals (range: 1–24 hours) and 4 hours in fasted animals (range: 2–24 hours).[26] Bioavailability exceeds 80% when administered with food, compared to approximately 24% in fasted conditions, demonstrating a substantial food effect that enhances absorption by over threefold.[26] The volume of distribution at steady state (Vss) is approximately 6.45 L/kg, indicating extensive tissue distribution, and plasma protein binding is high (>99%).[26][2] In cats, absorption is similarly rapid, with Tmax of 4 hours (median) in fed animals and 2 hours in fasted ones, achieving nearly 100% bioavailability with food versus 8.4% without.[27] The Vss is about 5.37 L/kg, with comparable high protein binding.[27][2] In contrast, the ophthalmic formulation for human use results in minimal systemic absorption, with a maximum plasma concentration (Cmax) of approximately 0.6 ng/mL after a single dose, increasing to around 18 ng/mL after repeated dosing over 6 weeks due to accumulation.[2] The drug primarily localizes to ocular tissues, particularly the eyelid margin, where concentrations reach over 14,000 ng/mL post-dose in preclinical models, though human data emphasize low plasma levels and >99% protein binding.[2] Metabolism of lotilaner is minimal across species, with no significant biotransformation by cytochrome P450 enzymes, including CYP3A4; any metabolites formed are inactive.[2][27] Excretion occurs predominantly via feces (>90% of dose) in animals, with low urinary elimination (<1%).[27] Species-specific differences include higher clearance in dogs and cats, with elimination half-lives of 24–31 days in dogs and 28–34 days in cats following oral dosing, compared to an effective systemic half-life of 264 hours (11 days) in humans based on ophthalmic accumulation.[26][27][2] As detailed earlier, food intake substantially enhances oral bioavailability (over threefold in dogs and approximately twelvefold in cats), but monthly dosing regimens show no excessive accumulation due to the drug's long half-life aligning with treatment intervals.[26][27]Adverse effects
In humans
Lotilaner ophthalmic solution, used topically for Demodex blepharitis, is generally well-tolerated in humans, with most adverse reactions being mild and ocular in nature. The most common adverse reaction reported in phase 3 clinical trials (Saturn-1 and Saturn-2) was instillation site stinging and burning, occurring in 10% of treated patients (41 out of 415). Other notable ocular adverse reactions included chalazion or hordeolum in 1-2% of patients and punctate keratitis in 1% of patients.[29][2] Serious adverse events were rare and not attributed to lotilaner treatment; in the combined trials, 1.2% of patients experienced serious events such as diabetic retinopathy or gastrointestinal issues, but none were deemed treatment-related. No cases of hypersensitivity reactions or corneal abrasions directly linked to the drug were reported in these studies, and no systemic adverse effects were observed, consistent with the drug's low systemic absorption. Discontinuation due to adverse events occurred in only 1.4% of lotilaner-treated patients across the trials involving over 800 participants.[29][2] There are no absolute contraindications to lotilaner ophthalmic solution, though it should not be used in patients with known hypersensitivity to lotilaner or any excipients in the formulation. Safety and efficacy have not been established in pediatric patients under 18 years of age, and use is not recommended in this population due to limited data. For pregnant or lactating individuals, there are no adequate human studies; animal reproduction studies showed no adverse developmental effects at doses up to 100 times the human exposure, but caution is advised given the lack of clinical data, with potential benefits weighed against risks.[2][30] The overall safety profile remains favorable in long-term follow-up, with an extension study of the Saturn-1 trial (n=128 lotilaner-treated patients) showing no new safety signals up to 12 months post-treatment; only 0.8% reported a mild treatment-related ocular adverse event (blurred vision), and no serious ocular events occurred. Ocular adverse events in this period were reported in 10.9% of patients but were mostly unrelated to the drug. Drug interactions are minimal due to negligible systemic exposure, with no evidence of CYP450 enzyme induction or inhibition; other ophthalmic medications should be administered at least 5 minutes apart. Monitoring typically involves routine slit-lamp examinations to assess for ocular irritation, along with visual acuity and intraocular pressure checks, as performed in clinical trials.[31][2]In animals
In veterinary medicine, lotilaner, an isoxazoline-class ectoparasiticide administered orally, is generally well-tolerated in dogs and cats at recommended doses, but common adverse reactions include gastrointestinal disturbances such as vomiting and diarrhea, along with occasional lethargy. In dogs, common adverse reactions include vomiting, diarrhea, and lethargy, as reported in field studies (e.g., diarrhea in 1% of cases) and post-marketing surveillance, where vomiting is the most frequently reported event.[32][33] In cats, these reactions are less frequent, with vomiting reported in less than 5% and diarrhea in under 1%, often resolving without intervention.[34] Neurological signs, including tremors and ataxia, are rare and typically associated with overdoses exceeding five times the recommended dose (e.g., >100 mg/kg in dogs or >30 mg/kg in cats), occurring in fewer than 1% of cases overall.[35] Breed-specific risks warrant caution in dogs with the MDR1 gene mutation, such as Collies and related breeds (e.g., Australian Shepherds, Shetland Sheepdogs), where P-glycoprotein deficiency may increase susceptibility to isoxazolines; however, lotilaner demonstrates a lower risk profile compared to other class members, with safety confirmed up to five times the maximum dose in homozygous MDR1-mutant Collies following three monthly administrations.[36] Testing for the MDR1 mutation is recommended prior to use in at-risk breeds to mitigate potential neurological adverse events.[37] Contraindications include use in puppies and kittens under 8 weeks of age or weighing less than 2 kg for dogs and 0.9 kg for cats, as safety has not been established in these populations.[12][38] Lotilaner is not recommended for breeding, pregnant, or lactating animals due to unestablished safety, though Freedom of Information summaries from FDA approvals indicate no reproductive toxicity at three times the recommended dose in targeted safety studies.[9][12] Post-marketing surveillance through the FDA's Center for Veterinary Medicine (CVM) Adverse Drug Event database reveals rare serious events, such as rare reports of seizures in dogs through post-marketing surveillance, with neurologic reactions comprising a small proportion of submissions; most cases occur without MDR1 mutation.[35] In cats, post-approval reports are similarly infrequent, focusing on mild gastrointestinal issues rather than severe outcomes.[34] No teratogenic effects were observed in reproductive studies at up to three times the dose, supporting its profile in non-breeding animals.[38] For overdose management, immediate induction of emesis is advised if ingestion occurred within 2 hours, using 3% hydrogen peroxide (1-2 mL/kg orally, not exceeding 45 mL total) in conscious animals, followed by activated charcoal if appropriate.[37] Veterinary monitoring for 24-48 hours is essential to observe for neurological signs like tremors or ataxia, with supportive care including IV fluids and anticonvulsants if seizures occur; most overdoses resolve without long-term sequelae at doses up to five times therapeutic levels.[39]History
Development
Lotilaner, a member of the isoxazoline class of compounds, was initially developed by Novartis Animal Health in the early 2010s as part of efforts to create systemic ectoparasiticides for veterinary applications, targeting fleas and ticks in companion animals.[40] The compound was patented in 2013, marking a key advancement in isoxazoline chemistry for parasite control.[40] Following Elanco's acquisition of Novartis Animal Health in 2015, Elanco assumed responsibility for further development and commercialization.[41] Preclinical research focused on lotilaner's efficacy and safety profile, with in vitro studies demonstrating rapid killing of fleas (Ctenocephalides felis) and ticks (e.g., Ixodes scapularis, Dermacentor variabilis) within hours of exposure, outperforming several contemporary ectoparasiticides in speed of action.[19] Animal model studies in dogs and cats confirmed a wide safety margin, with no adverse effects observed at doses up to five times the therapeutic level over multiple administrations, supporting its suitability for monthly oral dosing.[42] Formulation efforts began with chewable oral tablets optimized for dogs, entering early clinical trials around 2015 to evaluate palatability and bioavailability in flea- and tick-infested models.[43] By 2018, the formulation was adapted for cats, incorporating flavor enhancements to improve acceptance while maintaining the active ingredient's systemic absorption for ectoparasite control.[23] In the 2020s, Elanco expanded the platform to combination products, integrating lotilaner with anthelmintics like moxidectin, praziquantel, and pyrantel for broader parasitic protection in canines.[44] In 2019, Elanco licensed lotilaner to Tarsus Pharmaceuticals for potential human ophthalmic uses, shifting focus to topical formulations for treating Demodex mite infestations on the ocular surface.[45] In May 2025, Elanco sold its royalty and milestone rights for lotilaner in human health to Blackstone for $295 million to accelerate debt paydown.[46] Tarsus conducted in vitro studies showing lotilaner's potent acaricidal activity against Demodex folliculorum, prompting the filing of an Investigational New Drug (IND) application with the FDA in July 2020.[29] This led to the initiation of Phase 1 ocular safety trials in healthy volunteers in 2021, assessing tolerability of the ophthalmic solution at various concentrations.[47] Key milestones include the 2013 patenting of the veterinary compound and the successful transition to human applications through the 2021 Phase 1 studies, which informed subsequent ophthalmic development.[40]Regulatory approvals
Lotilaner was first approved for veterinary use in dogs by the European Medicines Agency (EMA) in 2017 under the brand name Credelio for the treatment and prevention of flea and tick infestations.[48] The U.S. Food and Drug Administration (FDA) approved Credelio for the same indications in dogs in January 2018.[12] In September 2019, the FDA extended approval of Credelio to cats and kittens for the treatment and prevention of flea infestations.[49] The EMA granted approval for Credelio in cats in 2018.[50] Subsequent formulations expanded indications; for example, Credelio Plus (lotilaner combined with milbemycin oxime) received EMA approval in April 2021 for dogs to include prevention of heartworm disease and treatment of intestinal nematodes alongside flea and tick control.[51] In October 2024, the FDA approved Credelio Quattro (lotilaner combined with moxidectin, praziquantel, and pyrantel) for dogs, providing broad-spectrum protection against fleas, ticks, heartworms, and intestinal parasites in a single monthly dose.[44] For human use, the FDA approved lotilaner ophthalmic solution 0.25% (Xdemvy) on July 25, 2023, for the treatment of Demodex blepharitis, marking the first therapy specifically targeting this condition.[52] As of November 2025, lotilaner has not received approval from the EMA for human use.[53] Veterinary approvals for lotilaner occurred under the Animal Drug User Fee Act (ADUFA), which funds the FDA's review process and grants three years of market exclusivity for new animal drug applications to encourage innovation.[54] The human approval for Xdemvy benefited from priority review designation under the Prescription Drug User Fee Act (PDUFA), shortening the standard 10-month review timeline to six months for drugs addressing unmet medical needs.[55] By 2025, lotilaner formulations for veterinary use have been approved in the United States, the European Union, Australia, Canada, the United Kingdom, Japan, and numerous other countries.[56] In contrast, human approval remains limited to the U.S. market.[57] On October 24, 2025, the FDA issued an Emergency Use Authorization for Credelio to treat New World screwworm infestations in dogs.[58] In October 2025, the FDA approved labeling updates for Credelio and Credelio Quattro to expand protection against black-legged ticks (for Lyme disease prevention) and the emerging Asian longhorned tick species in dogs.[59]Society and culture
Legal status
Lotilaner is not classified as a controlled substance in the United States, as it does not appear on the Drug Enforcement Administration's list of scheduled substances.[60] For human use, the ophthalmic solution (0.25%) is available by prescription only in the United States, approved by the Food and Drug Administration (FDA) for the treatment of Demodex blepharitis, with no over-the-counter availability.[2][52] In veterinary medicine, lotilaner oral products are restricted to use by or on the order of a licensed veterinarian in both the United States and the European Union, where they are approved for flea and tick control in dogs and cats.[33][9] These products are regulated as new animal drugs under the FDA's 21 CFR Part 500 series, which governs animal drugs, feeds, and related products.[61][62] Internationally, lotilaner holds varying regulatory status, with approvals for veterinary use in regions including the European Union and select countries outside North America, while human formulations are primarily limited to the United States as of 2025.[48] It is not included on the World Health Organization's Model Lists of Essential Medicines.[63] Off-label use of lotilaner is permitted for veterinary purposes under the FDA's Animal Medicinal Drug Use Clarification Act (AMDUCA), allowing licensed veterinarians to prescribe it for unapproved species, indications, or conditions when no approved alternative exists, subject to restrictions such as avoiding promotion for extra-label uses and limitations on compounding for non-food animals.[64][65] However, use in prohibited species or for food-producing animals without adherence to withdrawal periods is restricted to prevent residues.[66] For the human formulation (Xdemvy), patent exclusivity extends until December 14, 2038, covering treatment of Demodex blepharitis via topical ocular administration.[67] Veterinary formulations face ongoing patent protections, with some combination products holding exclusivity until at least 2030, potentially delaying generic entry.[68]Brand names and marketing
Lotilaner is marketed for human use under the brand name Xdemvy by Tarsus Pharmaceuticals, which launched in the United States in August 2023 following FDA approval for treating Demodex blepharitis.[69] The product is available as a 0.25% ophthalmic solution, with a standard 6-week treatment course consisting of one drop per eye twice daily, and carries a list price of approximately $1,850 per prescription.[70] Tarsus employs direct-to-consumer marketing strategies for Xdemvy, including the "Mite Party" campaign launched in 2024 to educate patients on Demodex mite infestations and encourage consultations with eye care providers, alongside patient support programs like Tarsus Connect that offer copay assistance reducing out-of-pocket costs to as low as $30 for eligible patients.[71][72] In veterinary medicine, lotilaner is primarily branded as Credelio by Elanco Animal Health, available globally since 2018 for flea and tick control in dogs and cats.[18] Expanded formulations include Credelio for cats (authorized in the EU in 2020) and Credelio Quattro for dogs (approved in the US in October 2024 and launched in January 2025), which combine lotilaner with additional antiparasitic agents for broader spectrum protection.[59][73] Elanco markets Credelio products through veterinary channels, utilizing rebate programs to incentivize prescriptions and build loyalty among clinics and pet owners.[74] Xdemvy has demonstrated strong market uptake, with net product sales reaching $102.7 million in Q2 2025 and $119 million in Q3 2025, positioning it for annual sales exceeding $400 million in 2025 and analyst-projected peak sales of around $900 million by 2030.[75] In the veterinary segment, Credelio Quattro achieved blockbuster status with over $100 million in net sales within its first eight months of US launch in 2025, contributing to Elanco's pet health portfolio growth amid competition from products like Bravecto (fluralaner) and NexGard (afoxolaner).[56] Xdemvy is distributed through US pharmacies with options for home delivery and insurance navigation support.[76] Credelio products are available worldwide via veterinary clinics, with formulations tailored to regional parasite threats.[77]Research
Ongoing clinical trials
As of November 2025, several ongoing and recently completed clinical trials are investigating lotilaner for expanded human applications beyond its initial approval for Demodex blepharitis. These include studies on meibomian gland dysfunction (MGD), tick bite prevention, long-term safety, and pediatric safety, with a focus on ocular comorbidities registered on ClinicalTrials.gov.[78] A phase 2 trial (NCT05454956) evaluating lotilaner ophthalmic solution 0.25% for MGD compared twice-daily versus three-times-daily dosing, demonstrating improvements in meibomian gland expression and function; interim data from a related 12-week extension study reported approximately 86% enhancement in functioning meibomian glands, with 5-6 glands producing clear secretions among participants with coexisting Demodex blepharitis.[79][80] Similarly, the Ersa phase 2a trial (TP-03 formulation) confirmed statistically significant and clinically meaningful reductions in MGD signs, including meibum quality and gland structure, independent of dosing frequency.[81] For tick bite prevention, the phase 2 Carpo study (NCT05387083) assessed oral lotilaner (TP-05) in healthy adults, reporting 2024 results with 89% tick mortality after controlled infestations at day 30, supporting its potential as on-demand prophylaxis against Lyme disease transmission.[82][83] Long-term safety extension studies following Xdemvy approval, involving approximately 200 participants from pivotal trials, have monitored recurrence and adverse events up to 12 months post-treatment, revealing sustained collarette reductions with no new safety signals.[31][84] Overall, safety and efficacy in patients under 18 remain unestablished.[85] More than 10 active or recently completed studies are listed on ClinicalTrials.gov as of 2025, primarily targeting ocular comorbidities such as MGD, rosacea (e.g., NCT05838170), and contact lens compatibility (e.g., NCT06182358, completion July 2025).[78]Emerging applications
In veterinary medicine, lotilaner is being explored for expanded applications beyond companion animals, including emergency use against emerging parasitic threats. In October 2025, the U.S. Food and Drug Administration granted the first-ever emergency use authorization for Credelio (lotilaner) to treat New World screwworm infestations in dogs.[86] Additionally, Credelio Quattro, a combination formulation containing lotilaner, achieved blockbuster status in 2025 with over $100 million in net sales, marking it as one of the fastest-growing pet health products due to its broad-spectrum protection against fleas, ticks, heartworms, and intestinal parasites in dogs.[56] For human applications, lotilaner is under investigation for novel indications targeting mite-related conditions. Tarsus Pharmaceuticals is advancing TP-04, a topical ophthalmic gel formulation of lotilaner, into a Phase 2 clinical trial in the second half of 2025 for the treatment of ocular rosacea, an underserved condition lacking FDA-approved therapies, building on its established efficacy against Demodex mites.[87] Resistance surveillance is a key focus in lotilaner's ongoing use, with no confirmed cases of arthropod resistance reported as of 2025; studies continue to monitor mutations in GABA-gated chloride channels, as lotilaner shows no cross-resistance to common insecticides like dieldrin or fipronil.[21] Challenges include the potential for future arthropod resistance development, necessitating vigilant monitoring, and environmental impacts on non-target insects. Research from 2023 shows that lotilaner residues in treated animal carcasses pose low toxicity to beneficial arthropods, with no significant inhibition of decomposition processes, though prolonged exposure risks to aquatic insects warrant further study.[88]References
- https://pubmed.ncbi.nlm.nih.gov/39150371/