NDC 0078-0911 Xiidra
Lifitegrast Solution/ Drops Ophthalmic

Product Information

What is NDC 0078-0911?

The NDC code 0078-0911 is assigned by the FDA to the product Xiidra which is a human prescription drug product labeled by Novartis Pharmaceuticals Corporation. The generic name of Xiidra is lifitegrast. The product's dosage form is solution/ drops and is administered via ophthalmic form. The product is distributed in 2 packages with assigned NDC codes 0078-0911-12 12 pouch in 1 carton / 5 ampule in 1 pouch (0078-0911-05) / .2 ml in 1 ampule, 0078-0911-94 4 pouch in 1 carton / 5 ampule in 1 pouch (0078-0911-95) / .2 ml in 1 ampule. This page includes all the important details about this product, including active and inactive ingredients, pharmagologic classes, product uses and characteristics, UNII information, RxNorm crosswalk and the complete product label.

NDC Product Code0078-0911
Proprietary Name What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.
Xiidra
Non-Proprietary Name What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.
Lifitegrast
Product Type What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.
Human Prescription Drug
Dosage FormSolution/ Drops - A solution which is usually administered in a drop-wise fashion.
Administration Route(s) What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.
  • Ophthalmic - Administration to the external eye.
Product Labeler Information What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.
Novartis Pharmaceuticals Corporation
Labeler Code0078
FDA Application Number What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.
NDA208073
Marketing Category What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.
NDA - A product marketed under an approved New Drug Application.
Start Marketing Date What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.
07-11-2016
Listing Expiration Date What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.
12-31-2023
Exclude Flag What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA"s requests for correction to deficient or non-compliant submissions ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".
N
NDC Code Structure

What are the uses for Xiidra?


Product Packages

NDC Code 0078-0911-12

Package Description: 12 POUCH in 1 CARTON / 5 AMPULE in 1 POUCH (0078-0911-05) / .2 mL in 1 AMPULE

Price per Unit: $10.94713 per EA

NDC Code 0078-0911-94

Package Description: 4 POUCH in 1 CARTON / 5 AMPULE in 1 POUCH (0078-0911-95) / .2 mL in 1 AMPULE

Product Details

What are Xiidra Active Ingredients?

An active ingredient is the substance responsible for the medicinal effects of a product specified by the substance's molecular structure or if the molecular structure is not known, defined by an unambiguous definition that identifies the substance. Each active ingredient name is the preferred term of the UNII code submitted.

Xiidra Active Ingredients UNII Codes

NDC to RxNorm Crosswalk

What is RxNorm? RxNorm is a normalized naming system for generic and branded drugs that assigns unique concept identifier(s) known as RxCUIs to NDC products.The NDC to RxNorm Crosswalk for this produdct indicates multiple concept unique identifiers (RXCUIs) are associated with this product:

Xiidra Inactive Ingredients UNII Codes

The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

Pharmacologic Class(es)

A pharmacologic class is a group of drugs that share the same scientifically documented properties. The following is a list of the reported pharmacologic class(es) corresponding to the active ingredients of this product.

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Xiidra Product Label

FDA filings in the form of structured product labels are documents that include all published material associated whith this product. Product label information includes data like indications and usage generic names, contraindications, active ingredients, strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Label Table of Contents



1     Indications And Usage



Xiidra® (lifitegrast ophthalmic solution) 5% is indicated for the treatment of the signs and symptoms of dry eye disease (DED).


2     Dosage And Administration



Instill one drop of Xiidra twice daily (approximately 12 hours apart) into each eye using a single-use container. Discard the single-use container immediately after using in each eye.

Contact lenses should be removed prior to the administration of Xiidra and may be reinserted 15 minutes following administration.


3     Dosage Forms And Strengths



Ophthalmic solution containing lifitegrast 50 mg/mL (5%).


4     Contraindications



Xiidra is contraindicated in patients with known hypersensitivity to lifitegrast or to any of the other ingredients in the formulation [see Adverse Reactions (6.2)].


6     Adverse Reactions



The following serious adverse reactions are described elsewhere in the labeling:

  • Hypersensitivity [see Contraindications (4)]

6.1     Clinical Trials Experience



Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In five clinical trials of DED conducted with lifitegrast ophthalmic solution, 1401 patients received at least one dose of lifitegrast (1287 of which received lifitegrast 5%). The majority of patients (84%) had less than or equal to 3 months of treatment exposure. One hundred-seventy patients were exposed to lifitegrast for approximately 12 months. The majority of the treated patients were female (77%). The most common adverse reactions reported in 5%-25% of patients were instillation-site irritation, dysgeusia, and reduced visual acuity.

Other adverse reactions reported in 1%-5% of the patients were blurred vision, conjunctival hyperemia, eye irritation, headache, increased lacrimation, eye discharge, eye discomfort, eye pruritus, and sinusitis.


6.2     Postmarketing Experience



The following adverse reactions have been identified during post-approval use of Xiidra. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Rare serious cases of hypersensitivity, including anaphylactic reaction, bronchospasm, respiratory distress, pharyngeal edema, swollen tongue, urticaria, allergic conjunctivitis, dyspnea, angioedema, and allergic dermatitis have been reported. Eye swelling and rash have also been reported [see Contraindications (4)].


8.1     Pregnancy



Risk Summary

There are no available data on Xiidra use in pregnant women to inform any drug-associated risks. Intravenous (IV) administration of lifitegrast to pregnant rats, from premating through gestation day 17, did not produce teratogenicity at clinically relevant systemic exposures. Intravenous administration of lifitegrast to pregnant rabbits during organogenesis produced an increased incidence of omphalocele at the lowest dose tested, 3 mg/kg/day (400-fold the human plasma exposure at the recommended human ophthalmic dose [RHOD], based on the area under the curve [AUC] level). Since human systemic exposure to lifitegrast following ocular administration of Xiidra at the RHOD is low, the applicability of animal findings to the risk of Xiidra use in humans during pregnancy is unclear [see Clinical Pharmacology (12.3)].

Data

Animal Data

Lifitegrast administered daily by IV injection to rats, from premating through gestation day 17, caused an increase in mean pre-implantation loss and an increased incidence of several minor skeletal anomalies at 30 mg/kg/day, representing 5,400-fold the human plasma exposure at the RHOD of Xiidra, based on AUC. No teratogenicity was observed in the rat at 10 mg/kg/day (460-fold the human plasma exposure at the RHOD, based on AUC). In the rabbit, an increased incidence of omphalocele was observed at the lowest dose tested, 3 mg/kg/day (400-fold the human plasma exposure at the RHOD, based on AUC), when administered by IV injection daily from gestation days 7 through 19. A fetal no observed adverse effect level (NOAEL) was not identified in the rabbit.


8.2     Lactation



Risk Summary

There are no data on the presence of lifitegrast in human milk, the effects on the breastfed infant, or the effects on milk production. However, systemic exposure to lifitegrast from ocular administration is low [see Clinical Pharmacology (12.3)]. The developmental and health benefits of breastfeeding should be considered, along with the mother’s clinical need for Xiidra and any potential adverse effects on the breastfed child from Xiidra.


8.4     Pediatric Use



Safety and efficacy in pediatric patients below the age of 17 years have not been established.


8.5     Geriatric Use



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


11     Description



The chemical name for lifitegrast is (S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid. The molecular formula of lifitegrast is C29H24Cl2N2O7S and its molecular weight is 615.5 g/mol. The structural formula of lifitegrast is:

*Chiral center

Lifitegrast is a white to off-white powder, which is soluble in water.

Xiidra (lifitegrast ophthalmic solution) 5% is a lymphocyte function-associated antigen-1 (LFA-1) antagonist supplied as a sterile, clear, colorless to slightly brownish-yellow colored, isotonic solution of lifitegrast with a pH of 7.0-8.0, and an osmolality range of 200-330 mOsmol/kg.

Xiidra contains Active: lifitegrast 50 mg/mL; Inactives: sodium chloride, sodium phosphate dibasic anhydrous, sodium thiosulfate pentahydrate, and water for injection. Sodium hydroxide and/or hydrochloric acid (to adjust pH).


12.1     Mechanism Of Action



Lifitegrast binds to the integrin LFA-1, a cell surface protein found on leukocytes and blocks the interaction of LFA-1 with its cognate ligand intercellular adhesion molecule-1 (ICAM-1). ICAM-1 may be overexpressed in corneal and conjunctival tissues in DED. LFA-1/ICAM-1 interaction can contribute to the formation of an immunological synapse resulting in T-cell activation and migration to target tissues. In vitro studies demonstrated that lifitegrast may inhibit T-cell adhesion to ICAM-1 in a human T-cell line and may inhibit secretion of inflammatory cytokines in human peripheral blood mononuclear cells. The exact mechanism of action of lifitegrast in DED is not known.


12.3     Pharmacokinetics



In a subset of DED patients (n = 47) enrolled in a Phase 3 trial, the pre-dose (trough) plasma concentrations of lifitegrast were measured after 180 and 360 days of topical ocular dosing (one drop twice daily) with Xiidra (lifitegrast ophthalmic solution) 5%. A total of nine of the 47 patients (19%) had plasma lifitegrast trough concentrations above 0.5 ng/mL (the lower limit of assay quantitation). Trough plasma concentrations that could be quantitated ranged from 0.55 ng/mL to 3.74 ng/mL.


13.1     Carcinogenesis, Mutagenesis, Impairment Of Fertility



Carcinogenesis

Animal studies have not been conducted to determine the carcinogenic potential of lifitegrast.

Mutagenesis

Lifitegrast was not mutagenic in the in vitro Ames assay. Lifitegrast was not clastogenic in the in vivo mouse micronucleus assay. In an in vitro chromosomal aberration assay using mammalian cells (Chinese hamster ovary cells), lifitegrast was positive at the highest concentration tested, without metabolic activation.

Impairment of Fertility

Lifitegrast administered at IV doses of up to 30 mg/kg/day (5400-fold the human plasma exposure at the RHOD of lifitegrast ophthalmic solution, 5%) had no effect on fertility and reproductive performance in male and female-treated rats.


14     Clinical Studies



The safety and efficacy of lifitegrast for the treatment of DED were assessed in a total of 1181 patients (1067 of which received lifitegrast 5%) in four 12-week, randomized, multi-center, double-masked, vehicle-controlled studies. Patients were randomized to Xiidra or vehicle (placebo) in a 1:1 ratio and dosed twice a day. Use of artificial tears was not allowed during the studies. The mean age was 59 years (range, 19-97 years). The majority of patients were female (76%). Enrollment criteria included minimal signs (i.e., Corneal Fluorescein Staining and non-anesthetized Schirmer Tear Test) and symptoms (i.e., Eye Dryness Score (EDS) and Ocular Discomfort Score) severity scores at baseline.

Effects on Symptoms of Dry Eye Disease

Eye dryness score was rated by patients using a visual analogue scale (0 = no discomfort, 100 = maximal discomfort) at each study visit. The average baseline EDS was between 40 and 70. A larger reduction in EDS favoring Xiidra was observed in all studies at Day 42 and Day 84 (see Figure 1).

Figure 1: Mean Change (SD) From Baseline and Treatment Difference (Xiidra – Vehicle) in Eye Dryness Score in 12-Week Studies in Patients With Dry Eye Disease

[1] Based on analysis of covariance (ANCOVA) model adjusted for baseline value in Study 1, and ANCOVA model adjusted for baseline value and randomization stratification factors in Studies 2-4. All randomized and treated patients were included in the analysis and missing data were imputed using last-available data. In Study 1, one Xiidra-treated subject who did not have a baseline value was excluded from analysis.

Effects on Signs of Dry Eye Disease

Inferior fluorescein corneal staining score (ICSS) (0 = no staining, 1 = few/rare punctate lesions, 2 = discrete and countable lesions, 3 = lesions too numerous to count but not coalescent, 4 = coalescent) was recorded at each study visit. The average baseline ICSS was approximately 1.8 in Studies 1 and 2, and 2.4 in Studies 3 and 4. At Day 84, a larger reduction in ICSS favoring Xiidra was observed in three of the four studies (see Figure 2).

Figure 2: Mean Change (SD) From Baseline and Treatment Difference (Xiidra – Vehicle) in Inferior Corneal Staining Score in 12-Week Studies in Patients With Dry Eye Disease

[1] Based on ANCOVA model adjusted for baseline value in Study 1, and ANCOVA model adjusted for baseline value and randomization stratification factors in Studies 2-4. All randomized and treated patients were included in the analysis and missing data were imputed using last-available data. In Study 2, one vehicle-treated subject who did not have a study eye designated was excluded from analysis.


16     How Supplied/Storage And Handling



Xiidra (lifitegrast ophthalmic solution) 5% (50 mg/mL) is supplied in a foil pouch containing 5 low-density polyethylene 0.2 mL single-use containers.

Carton of 60 single-use containers          NDC 0078-0911-12

Storage:

Store at 20°C to 25°C (68°F to 77°F). Store single-use containers in the original foil pouch.


17     Patient Counseling Information



Advise patients to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

Handling the Single-use Container

Advise patients not to touch the tip of the single-use container to their eye or to any surface, in order to avoid eye injury or contamination of the solution.

Use With Contact Lenses

Advise patients that contact lenses should be removed prior to administration of Xiidra and can be reinserted 15 minutes after administration [see Dosage and Administration (2)].

Administration

Advise patients that the solution from one single-use container is to be used immediately after opening. It can be used to dose both eyes. The single-use container, including any remaining contents should be discarded immediately after administration [see Dosage and Administration (2)].

Storage Information

Instruct patients to store single-use containers in the original foil pouch until ready to use [see How Supplied/Storage and Handling (16)].

Distributed by:
Novartis Pharmaceuticals Corporation
One Health Plaza
East Hanover, NJ 07936

T2020-87


Principal Display Panel



NDC 0078-0911-12

Rx Only

60 Single-Use
Containers:
12 pouches x 5 single-use
containers (0.2 mL each)

xiidra®
(lifitegrast
ophthalmic solution) 5%

NOVARTIS


* Please review the disclaimer below.