BRIEF SUMMARY

LOTILANER (July 2023)

Indication-  To treat Demodex blepharitis 

Dosage-    Instill one drop of XDEMVY in each eye twice daily (approximately 12 hours apart) for 6 weeks. 

CI     None.

Pat inform-If  patients  develops an intercurrent ocular condition, or  any ocular reactions, particularly conjunctivitis and eyelid reactions, they should immediately seek their physician’s advice concerning the continued use

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U.S. FDA APPROVED DRUGS SURING 2023                                     

Serial No 29

Name of the Drug-    XDEMVY

Active Ingredient -   Lotillaner

Pharmacological Classification- To treat Demodex blepharitis                                                                           

                                                                                                                                            Date of Approval-          7/25/23       

HIGHLIGHTS OF PRESCRIBING INFORMATION-

These highlights do not include all the information needed to use XDEMVY safely and effectively.

See full prescribing information for XDEMVY. XDEMVY™ (lotilaner ophthalmic solution) 0.25%, for topical ophthalmic use.

Initial U.S. Approval: 2023

INDICATIONS AND USAGE-

 XDEMVY is an ectoparasiticide (anti-parasitic) indicated for the treatment of Demodex blepharitis.

DOSAGE FORMS AND STRENGTHS--------------- Ophthalmic solution containing lotilaner 0.25%.

CONTRAINDICATIONS-

None.

ADVERSE REACTIONS-------------------------- The most common adverse reaction was instillation site stinging and burning (10%). (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Tarsus Pharmaceuticals at 1-888-421-4002 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

DOSAGE AND ADMINISTRATION

 Instill one drop of XDEMVY in each eye twice daily (approximately 12 hours apart) for 6 weeks. 

PATIENT COUNSELING INFORMATION-

Handling the Container-

Instruct patients to avoid allowing the tip of the dispensing container to contact the eye, surrounding structures, fingers, or any other surface in order to minimize contamination of the solution.

Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions.

When to Seek Physician Advice-

Advise patients that if they develop an intercurrent ocular condition (e.g., trauma or infection), have ocular surgery, or develop any ocular reactions, particularly conjunctivitis and eyelid reactions, they should immediately seek their physician’s advice concerning the continued use of XDEMVY.

Use with Contact Lenses-

Advise patients that XDEMVY contains potassium sorbate, which may discolor soft contact lenses.

Contact lenses should be removed prior to instillation of XDEMVY and may be reinserted 15 minutes following its administration.

Use with Other Ophthalmic Drugs -

Advise patients that if more than one topical ophthalmic drug is being used, the drugs should be administered at least 5 minutes between applications.

Missed Dose

Advise patients that if one dose is missed, treatment should continue with the next dose. XDEMVY and/or methods of use thereof may be covered by one or more of the patents listed at www.tarsusrx.com/patents

XDEMVY is a trademark of Tarsus Pharmaceuticals, Inc. Manufactured for: Tarsus Pharmaceuticals, Inc., Irvine, CA 92618

CLINICAL PHARMACOLOGY

1 Mechanism of Action -

Lotilaner is a gamma-aminobutyric acid (GABA)-gated chloride channel inhibitor selective for mites. Inhibition of these GABA chloride channels causes a paralytic action in the target organism leading to its death.

2. Pharmacokinetics-

The systemic pharmacokinetic profile after topical ocular administration was evaluated in healthy volunteers after single and repeat dose administration. The systemic exposure was evaluated in patients at the end of 6 weeks of treatment

Absorption -                                                                                                                 Maximum lotilaner concentration was observed 2 hours after a single ocular administration on Day 1 and 1 hour after the last drug administration on Day 42. In healthy subjects, the peak concentration (Cmax) and total exposure (AUC0-12) of lotilaner in whole blood increased after 42 days of repeated ocular administration from 0.596 to 17.8 ng/mL and from 5.75 to 149 hr•ng/mL for Cmax and AUC0-12 respectively.

The effective half-life of lotilaner, which is based on the accumulation ratio over the dosing interval of 12 hours, was 264 hours (11 days). In patients with Demodex blepharitis (n=138) who received XDEMVY twice daily for 42 days, the mean (range) systemic exposure at the end of treatment was 12.0 ng/mL (0.4-46.1 ng/mL).

Distribution-                                                                                                                  Lotilaner plasma protein binding is high (> 99.9%) in human plasma. The partitioning of lotilaner to human blood cells is approximately 10% (range 0-20%).

Elimination-                                                                                                                        The effective half-life in healthy subjects, which is based on the accumulation ratio over the dosing interval of 12 hours, is 264 hours (11 days). Metabolism Lotilaner is not metabolized by CYP enzymes.

USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary

There are no available data on XDEMVY use in pregnant women to inform any drug associated risk; however, systemic exposure to lotilaner from ocular administration is low [see Clinical Pharmacology (12.3)].

In animal reproduction studies, lotilaner did not produce malformations at clinically relevant doses.

2 Lactation Risk Summary

There are no data on the presence of XDEMVY in human milk, the effects on the breastfed infant, or the effects on milk production.

However, systemic exposure to lotilaner following 6 weeks of topical ocular administration is low and is >99% plasma U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov Reference ID: 5214344 NDA 217603 Page: 7 protein bound [see Clinical Pharmacology (12.3)], thus it is not known whether measurable levels of lotilaner would be present in maternal milk following topical ocular administration.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for XDEMVY and any potential adverse effects on the breast-fed child from XDEMVY.

3. Pediatric Use-

Safety and effectiveness in pediatric patients below the age of 18 years have not been established.

4.Geriatric Use-

No overall differences in safety or effectiveness have been observed between elderly and other adult patients.