NDC 43598-921 Xeglyze

Abametapir

NDC Product Code 43598-921

NDC 43598-921-11

Package Description: 1 BOTTLE in 1 CARTON > 200 g in 1 BOTTLE

NDC Product Information

Xeglyze with NDC 43598-921 is a a human prescription drug product labeled by Dr. Reddy¿s Laboratories, Inc.. The generic name of Xeglyze is abametapir. The product's dosage form is lotion and is administered via topical form.

Labeler Name: Dr. Reddy¿s Laboratories, Inc.

Dosage Form: Lotion - An emulsion, liquid1 dosage form. This dosage form is generally for external application to the skin.2

Product Type: Human Prescription Drug 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.

Xeglyze Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • ABAMETAPIR .74 g/100g

Inactive Ingredient(s)

About the Inactive Ingredient(s)
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.

  • WATER (UNII: 059QF0KO0R)
  • POLYSORBATE 20 (UNII: 7T1F30V5YH)
  • CARBOMER 980 (UNII: 4Q93RCW27E)
  • TROLAMINE (UNII: 9O3K93S3TK)
  • BUTYLATED HYDROXYTOLUENE (UNII: 1P9D0Z171K)
  • BENZYL ALCOHOL (UNII: LKG8494WBH)
  • LIGHT MINERAL OIL (UNII: N6K5787QVP)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Topical - Administration to a particular spot on the outer surface of the body. The E2B term TRANSMAMMARY is a subset of the term TOPICAL.

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Dr. Reddy¿s Laboratories, Inc.
Labeler Code: 43598
FDA Application Number: NDA206966 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.

Marketing Category: NDA - A product marketed under an approved New Drug Application. 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.

Start Marketing Date: 01-29-2021 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2021 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.

Exclude Flag: N 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. Values = ‘Y’ or ‘N’.

* Please review the disclaimer below.

Xeglyze Product Label Images

Xeglyze Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1 Indications And Usage

  • XEGLYZE is indicated for the topical treatment of head lice infestation in patients 6 months of age and older. XEGLYZE should be used in the context of an overall lice management program:Wash (with hot water) or dry-clean all recently worn clothing, hats, used bedding and towelsWash personal care items such as combs, brushes, and hair clips in hot waterUse a fine-tooth comb or special nit comb to remove dead lice and nits

2 Dosage And Administration

For topical use only. XEGLYZE is not for oral, ophthalmic, or intravaginal use. Treatment with XEGLYZE involves a single application.Shake well before use. Apply XEGLYZE to dry hair in an amount (up to the full content of one bottle) sufficient to thoroughly coat the hair and scalp. Massage XEGLYZE into the scalp and throughout the hair. Avoid contact with eyes. Leave on the hair and scalp for 10 minutes and then rinse off with warm water. Wash hands after application. Hair may be shampooed any time after the treatment. Discard any unused product. Do not flush contents down sink or toilet.

3 Dosage Forms And Strengths

Lotion, 0.74% [weight by weight], a viscous white to off-white oil in water emulsion, containing abametapir.

4 Contraindications

None.

5.1 Risk Of Neonatal Benzyl Alcohol Toxicity

XEGLYZE contains benzyl alcohol. Systemic exposure to benzyl alcohol has been associated with serious and fatal adverse reactions including “gasping syndrome” in neonates and low birth weight infants. The “gasping syndrome” is characterized by central nervous system depression, metabolic acidosis, and gasping respirations. The minimum amount of benzyl alcohol at which toxicity may occur is not known. Premature and low-birth weight infants may be more likely to develop toxicity [see Use in Specific Populations (8.4)].The safety and effectiveness of XEGLYZE have not been established in pediatric patients below the age of 6 months. Use is not recommended in pediatric patients under 6 months of age because of the potential for increased systemic absorption.

5.2 Risk Of Benzyl Alcohol Toxicity From Accidental Ingestion

In order to prevent accidental ingestion in pediatric patients, XEGLYZE should only be administered under direct supervision of an adult.Ingestion of benzyl alcohol in large quantities may result in gastrointestinal (nausea, vomiting, diarrhea) and central nervous system (headache, ataxia, convulsions, coma) adverse reactions. Serious adverse reactions may include respiratory depression and death. If accidentally swallowed, advise the patient or the caregiver to call their Poison Control Center at 1-800-222-1222.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug, and may not reflect the rates observed in practice. The data described below reflect exposure to a single 10-minute treatment of XEGLYZE in 349 subjects (6 months of age and older) with head lice infestation in randomized, double-blind, vehicle-controlled trials (Trials 1 and 2). Of these subjects, 21 were 6 months to 4 years of age, 166 subjects were 4 to 12 years of age, 57 subjects were 12 to 18 years of age, and 105 subjects were 18 years of age or older. Table 1 provides adverse reactions that occurred in at least 1% of subjects in the XEGLYZE group and at a greater frequency than in the vehicle group.Table 1: Adverse Reactions Occurring in ≥ 1% of the XEGLYZE Group and at a Greater Frequency than in the Vehicle Group (Trials 1 and 2) Adverse ReactionsXEGLYZE N=349 Subjects (%)Vehicle N=350 Subjects (%) Erythema14 (4.0) 6 (2) Rash11 (3.2) 8 (2.3) Skin burning sensation9 (2.6) 0 (0.0) Contact dermatitis 6 (1.7) 4 (1.1) Vomiting6 (1.7) 2 (0.6) Eye irritation4 (1.2)2 (0.6) Hair color changes3 (1)0 (0.0)During the trials, subjects were monitored for new onset of scalp erythema/edema, scalp pruritus, and eye irritation. The number and percentage of subjects who developed these local adverse reactions after treatment are presented in Table 2.Table 2: Monitored Local Adverse Reactions with New Onset on Day 1 Post Treatment (Trials 1 and 2)Adverse ReactionsXEGLYZE Subjects (%)* Vehicle Subjects (%)*Scalp Erythema/Edema11 (3.2)5 (1.4)Scalp Pruritus2 (1.4)1 (0.7)Eye Irritation6 (1.7)5 (1.4) *For the calculation of the percentages, the denominators are the number of subjects who did not have the monitored local adverse reaction at baseline.

7 Drug Interactions

In vitro studies suggest there is a potential for inhibition of cytochrome P450 (CYP) 3A4, 2B6 and 1A2 enzymes following a single application of XEGLYZE. Use of XEGLYZE with drugs that are substrates of these enzymes may lead to increased systemic concentrations of the interacting drugs. Avoid administration of drugs that are substrates of CYP3A4, CYP2B6, or CYP1A2 within 2 weeks after application of XEGLYZE. If this is not feasible, avoid use of XEGLYZE [see Clinical Pharmacology (12.3)].

Other

Risk SummaryThere are no available data on XEGLYZE use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In embryofetal development studies conducted with oral administration of abametapir during organogenesis, no evidence of fetal harm or malformations, independent of maternal toxicity were observed in pregnant rats and rabbits at doses that produced exposures up to 50 times and equivalent to the maximum recommended human dose (MRHD) in rats and rabbits, respectively. The highest dose evaluated in rabbits was limited due to maternal toxicity associated with the vehicle used in the study (see Data).The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

DataAnimal DataSystemic embryofetal development studies were performed in rats and rabbits. Oral doses of 10, 25 and 75 mg/kg/day abametapir were administered during the period of organogenesis (gestational days 6 – 17) to pregnant rats. In the presence of maternal toxicity, embryofetal toxicity (lower fetal body weights and delayed ossification) was noted at 75 mg/kg/day. No treatment related effects on malformations were noted at 75 mg/kg/day (50 times the MRHD based on Cmax comparisons). Oral doses of 4, 16 and 40 mg/kg/day abametapir were administered during the period of organogenesis (gestational days 6 – 19) to pregnant rabbits. No treatment related effects on embryofetal toxicity or malformations were noted at 40 mg/kg/day (~1 time the MRHD based on Cmax comparisons). Maternal toxicity related to the vehicle limited the maximum dose in pregnant rabbits. In a perinatal and postnatal development study in rats, oral doses of 10, 25 and 75 mg/kg/day were administered from the beginning of organogenesis (gestational day 6) through the end of lactation (lactation day 20). In the presence of maternal toxicity, embryofetal lethality, and decreased fetal body weight gain were noted at 75 mg/kg/day. No treatment related effects on postnatal development were noted at 75 mg/kg/day (47 times the MRHD based on Cmax comparisons).

Risk SummaryNo data are available regarding the presence of abametapir in human milk or the effects of abametapir on the breastfed infant or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for XEGLYZE and any potential adverse effects on the breastfed child from XEGLYZE or from the underlying maternal condition.

8.4 Pediatric Use

The safety and effectiveness of XEGLYZE have been established in pediatric patients 6 months of age and older [see Clinical Pharmacology (12) and Clinical Studies (14)].The safety and effectiveness of XEGLYZE have not been established in pediatric patients below the age of 6 months. XEGLYZE is not recommended in pediatric patients under 6 months of age because of the potential for increased systemic absorption due to a high ratio of skin surface to body mass and the potential for an immature skin barrier.XEGLYZE contains benzyl alcohol. Benzyl alcohol has been associated with serious adverse reactions and death in neonates and low birth-weight infants. The “gasping syndrome” (characterized by central nervous system depression, metabolic acidosis, gasping respirations, and high levels of benzyl alcohol and its metabolites found in the blood and urine) has been associated with intravenously administered benzyl alcohol dosages >99 mg/kg/day in neonates and low birthweight infants. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. The minimum amount of benzyl alcohol at which toxicity may occur is not known. Premature and low-birthweight infants, as well as patients receiving high dosages, may be more likely to develop toxicity [see Warnings and Precautions (5.1)].Because of the risk of accidental ingestion, XEGLYZE should be administered to pediatric patients only under direct adult supervision [see Warnings and Precautions (5.2)].

8.5 Geriatric Use

Clinical studies of XEGLYZE did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger subjects.

10 Overdosage

If accidentally swallowed, advise patients to seek medical advice immediately and to call their local Poison Control Center at 1-800-222-1222.

11 Description

The active pharmacological ingredient in XEGLYZE (abametapir) Lotion is the pediculicide, abametapir, which is a dipyridyl compound. The chemical name of abametapir is 5,5'-dimethyl-2,2'-bipyridinyl.The structural formula is:The empirical formula is C12H12N2 and the molecular weight is 184.24. XEGLYZE is a white to off-white oil in water emulsion, containing 0.74% [weight by weight] of abametapir, intended for topical administration. XEGLYZE contains the following inactive ingredients: benzyl alcohol, butylated hydroxytoluene, carbomer 980, light mineral oil, polysorbate 20, trolamine and water.

12.1 Mechanism Of Action

Abametapir (5,5’-dimethyl 2,2’-bipyridinyl) is a metalloproteinase inhibitor. Metalloproteinases have a role in physiological processes critical to egg development and survival of lice.

12.3 Pharmacokinetics

AbsorptionThe pharmacokinetics of XEGLYZE were evaluated in 3 trials, Trials A, B, and C. Each trial enrolled lice infested subjects who received a single 10-minute application of XEGLYZE. Pharmacokinetic samplings were carried out to 72 hours post-dose in adults and 8 hours post-dose in pediatric subjects in all trials. Trial A evaluated pharmacokinetics in 6 adult and 12 pediatric subjects 3 to 12 years of age. The mean (%CV) abametapir plasma maximum concentration (Cmax) and area under the concentration time curve from 0 to 8 hours post-dose (AUC0-8h) in the adult group were 41 (66%) ng/mL and 121 (50%) ng*h/mL, respectively. The mean (%CV) Cmax and AUC0-8h in the pediatric group were 73 (57%) ng/mL and 264 (62%) ng*h/mL, respectively. The mean (%CV) terminal half-life in adults was 21 (11%) hours.Trials B and C evaluated pharmacokinetics in 50 pediatric subjects 6 months to 17 years old. The pharmacokinetic results for plasma abametapir are shown in Table 3. Even though the values varied between the 2 trials, abametapir exposure increased as the age of the subject decreased. Abametapir absorption was rapid with a median Tmax of 0.57 to 1.54 hours.Table 3 Abametapir Pharmacokinetic Parameters in Subjects with Head Lice InfestationStudyAge GroupnCmax (ng/mL)Mean (%CV) AUC0-8h(ng*h/mL) Mean (%CV)B6 months to <1 year14181057C5228 (50%)688 (43%)B1 year to <2 years3209 (62%)446 (65%)C8147 (49%)406 (37%)B2 years to <3 years6206 (66%)633 (57%)C8160 (48%)602 (51%)B12121 (60%)330 (49%)C3 years to 17 years752 (45%)194 (39%)Serum concentration of benzyl alcohol, an excipient in the formulation of XEGLYZE, was assessed in Trials B and C. Benzyl alcohol in serum was measurable (limit of quantitation = 0.5 µg/mL) in 7 subjects out of 39 evaluable subjects. The Cmax of benzyl alcohol in these 7 subjects ranged from 0.52 to 3.57 µg/mL [see Warnings and Precautions (5) and Use in Specific Populations (8.4)]. DistributionAbametapir and its primary human metabolite, abametapir carboxyl, are highly bound to proteins in plasma. Abametapir is 91.3 – 92.3% bound to plasma proteins, and abametapir carboxyl is 96.0% – 97.5% bound to plasma proteins. EliminationMetabolismAbametapir is extensively metabolized, primarily by the cytochrome P450 enzyme CYP1A2 to a mono-hydroxylated metabolite (abametapir hydroxyl) and further to a mono-carboxylated metabolite (abametapir carboxyl).  Abametapir carboxyl is cleared slowly from the systemic circulation resulting in plasma concentration higher than that of abametapir. Based on data in adults in Trial A above, where sampling was carried out to 72 hours, the ratios of Cmax and AUC0-72h between abametapir carboxyl and abametapir were about 30 and 250, respectively. The elimination half-life of abametapir carboxyl has not been well characterized but is estimated to be approximately (mean ± SD) 71 ± 40 hours or longer in adults. ExcretionExcretion of abametapir and its human metabolites was not examined in patients. Drug Interaction StudiesIn vitro studies suggest that there is a potential for inhibition of cytochrome P450 3A4, 2B6, and 1A2 enzymes following application of XEGLYZE due to high and prolonged systemic exposure of the metabolite abametapir carboxyl [see Drug Interactions (7)].

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

Long-term studies in animals have not been conducted to evaluate the carcinogenic potential of XEGLYZE or abametapir.Abametapir was not mutagenic or clastogenic based on the results of two in vitro genotoxicity tests (Ames test and human lymphocyte chromosomal aberration assay) and one in vivo genotoxicity test (rat micronucleus assay).  No effects on fertility have been observed in rats following repeated oral doses of up to 75 mg/kg/day abametapir (50 times the MRHD based on Cmax comparisons).

14 Clinical Studies

Two identical multi-center, randomized, double-blind, vehicle-controlled trials (Trials 1 and 2) were conducted in 704 subjects 6 months of age and older with head lice infestation. All subjects received a single application of either XEGLYZE or vehicle control. For the evaluation of efficacy, the youngest subject from each household was considered to be the index subject of the household (N=216). Other enrolled infested household members received the same treatment as the youngest subject and were evaluated for all efficacy and safety parameters. Index subjects ranged from 6 months to 49 years of age (mean 7 years), and approximately 85% of the index subjects were female, and 95% of the index subjects were Caucasian.Efficacy was assessed as the proportion of index subjects who were treated with a single 10-minute application and were free of live lice at all follow-up visits on Days 1, 7, and 14. Subjects with live lice at any time up to the final evaluation were considered treatment failures. Table 4 presents the proportion of subjects who were free of live lice at all visits Day 1 through Day 14 in Trials 1 and 2. Table 4: Proportion of Index Subjects Free of Live Lice at All visits Days 1 Through 14 After TreatmentTrial 1Trial 2XEGLYZE (N=53)Vehicle (N=55)XEGLYZE (N=55)Vehicle (N=53)Treatment Success43 (81.1%)28 (50.9%)45 (81.8%)25 (47.2%)

16 How Supplied/Storage And Handling

XEGLYZE is a white to off-white oil in water emulsion containing 0.74% [weight by weight] abametapir and supplied in a polyvinyl chloride (PVC) safety-coated single-use round amber glass bottle affixed with a polypropylene child resistant cap (NDC # 43598-921-11) featuring a tri-foil inner liner. The container is filled to a nominal 200 g (approximately 7 oz. or 210 mL) of the lotion. Store upright at room temperature, 20°C to 25°C (68°F to 77°F), with allowable excursions between 15°C and 30°C (59°F and 86°F). Do not refrigerate or freeze.

17 Patient Counseling Information

  • Advise the patient or caregiver to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Inform the patient and caregiver of the following instructions:Do not ingest XEGLYZE.Keep out of reach of children. Use on children should be under the direct supervision of an adult because of the risk of benzyl alcohol toxicity [see Warnings and Precautions (5) and Use in Specific Populations (8.4)].Avoid contact with eyes.Wash hands after application.Hair may be shampooed any time after the treatment. Treatment with XEGLYZE involves a single application. Do not re-treat.Discard any unused portion. Do not flush contents down sink or toilet.

* Please review the disclaimer below.