XDEMVY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for XDEMVY (XDEMVY).
XDEMVY (lotilaner ophthalmic solution) is a gamma-aminobutyric acid (GABA)-gated chloride channel antagonist. It inhibits the GABA-gated chloride channels in Demodex mites, leading to paralysis and death of the mites.
| Metabolism | Lotilaner is metabolized via cytochrome P450 (CYP) enzymes, primarily CYP3A4, and to a lesser extent CYP2C9 and CYP2C19. |
| Excretion | Primary renal excretion as unchanged drug and metabolites; ~70% in urine. Biliary/fecal excretion accounts for ~25%. |
| Half-life | Terminal elimination half-life of approximately 4-6 hours; clinically, steady-state is reached within 24-36 hours. |
| Protein binding | Approximately 90% bound to serum albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is 0.35 L/kg, indicating limited extravascular distribution. |
| Bioavailability | Oral bioavailability is approximately 85%; food may delay absorption but does not affect extent. |
| Onset of Action | Orally administered; onset of clinical effect occurs within 30-60 minutes. |
| Duration of Action | Duration of action is approximately 4-8 hours, based on pharmacodynamic response and dosing interval. |
| Molecular Weight | 498.5 |
1 drop in each eye once daily in the evening for 6 weeks.
| Dosage form | SOLUTION/DROPS |
| Renal impairment | No dosage adjustment is recommended for patients with renal impairment. |
| Liver impairment | No dosage adjustment is recommended for patients with hepatic impairment. |
| Pediatric use | Safety and efficacy have not been established in pediatric patients. |
| Geriatric use | No dosage adjustment is recommended based on age; clinical studies included patients ≥65 years, and no overall differences in safety or efficacy were observed. |
| 1st trimester | No adequate human data; animal studies show no risk at clinically relevant doses. Use only if clearly needed. |
| 2nd trimester | No adequate human data; animal studies show no risk. Consider benefit vs. risk. |
| 3rd trimester | No adequate human data; animal studies show no risk. Consider benefit vs. risk. |
Clinical note
Comprehensive clinical and safety monograph for XDEMVY (XDEMVY).
| Placental transfer | Unknown; molecular weight suggests potential transfer, but low systemic absorption limits exposure. |
| Breastfeeding | No data on presence in human milk; due to low systemic absorption, risk to infant likely low. Use with caution. |
| Lactation Rating |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to lotilaner or any excipient
| Precautions | Contains preservative benzalkonium chloride, which may cause eye irritation and is adsorbable by soft contact lenses. Patients should remove contact lenses prior to administration and wait at least 15 minutes before reinserting., Use with caution in patients with known hypersensitivity to any component of the product., Not for injection. For topical ophthalmic use only. |
| Food/Dietary | No clinically significant food interactions reported. |
| Clinical Pearls |
Loading safety data…
| L3 (Moderately Safe) |
| Teratogenic Risk | No adequate and well-controlled studies in pregnant women. In animal reproduction studies, no teratogenic effects were observed at exposures up to 5 times the human exposure at the recommended ophthalmic dose. Risk cannot be ruled out; use only if potential benefit justifies potential risk to fetus. |
| Fetal Monitoring | No specific monitoring required beyond routine prenatal care. |
| Fertility Effects | No fertility studies conducted; based on mechanism of action (peripheral vasoconstrictor), no anticipated impact on fertility. |
| XDEMVY (lotilaner ophthalmic solution) 0.25% is the first FDA-approved treatment for Demodex blepharitis. Administer one drop in each affected eye twice daily (approximately 12 hours apart) for 6 weeks. Shake well before use. Contact lenses should be removed prior to instillation and may be reinserted 15 minutes after dosing. Avoid touching the dropper tip to any surface to prevent contamination. |
| Patient Advice | Use exactly as prescribed: one drop in each eye twice daily for 6 weeks. · Shake the bottle well before each use. · Remove contact lenses before applying and wait at least 15 minutes before reinserting. · Do not touch the dropper tip to your eye or any surface to avoid contamination. · If you miss a dose, apply as soon as you remember, but if it is close to the next dose, skip the missed dose and resume normal schedule. · Common side effects may include temporary stinging or blurred vision after application. |