.DRUG INTERACTIONS-(summary)

 For 2 weeks after XEGLYZE application, avoid taking drugs that are substrates of CYP3A4, CYP2B6 or CYP1A2. Otherwise, avoid use of XEGLYZE. 

INTERACTIONS(details)-

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..

US FDA APPROVED DRUG DURING 2020

Sr. NO  29

Name of the Drug -     XEGLYZE

Active Ingredient -      Abametapir

Pharmocological Classification-  To treat Head Lice

 Date of Approval        July 2020

 ( Ref FDA Approved List)

HIGHLIGHTS OF PRESCRIBING INFORMATION-

These highlights do not include all the information needed to use                         XEGLYZETM safely and effectively.                                                                              See full prescribing information for XEGLYZE. XEGLYZE (abametapir) lotion, for topical use

Initial U.S. Approval: 2020

 INDICATIONS AND USAGE-                                                                                        XEGLYZE is a pediculicide 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 towels

• Wash personal care items such as combs, brushes and hair clips in hot water

• Use a fine-tooth comb or special nit comb to remove dead lice and nits

ADVERSE REACTIONS

 Most common adverse reactions (incidence of = 1%) were erythema, rash, skin burning sensation, contact dermatitis, vomiting, eye irritation, pruritus, and hair color changes.

CONTRAINDICATIONS-

 None.

 WARNINGS AND PRECAUTIONS-

 • Risk of Neonatal Benzyl Alcohol Toxicity: Systemic exposure to benzyl alcohol has been associated with serious adverse reactions and death in neonates and low birth-weight infants.

Safety and effectiveness in pediatric patients below the age of 6 months have not been established. Use is not recommended in pediatric patients under 6 months of age because of the potential for increased systemic absorption.

 • Risk of Benzyl Alcohol Toxicity from Accidental Ingestion: Administer only under direct supervision of an adult.

DOSAGE AND ADMINISTRATION

• For topical use only. Not for oral, ophthalmic, or intravaginal use.

 • Shake well before use.

 • Apply XEGLYZE to dry hair in an amount sufficient (up to the full content of one bottle) to thoroughly coat the hair and scalp. Avoid contact with eyes.

 • Massage XEGLYZE into the scalp and throughout the hair; leave on the hair and scalp for 10 minutes and then rinse off with warm water

 • Treatment with XEGLYZE involves a single application. Discard any unused product. Do not flush contents down sink or toilet.

DOSAGE FORMS AND STRENGTHS-

Lotion: 0.74% [weight by weight]. 

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 and Use in Specific Populations 

. • Avoid contact with eye

• 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.

Manufactured by Groupe Parima Inc., for Dr. Reddy’s Laboratories, S.A. Elisabethenanlage 11, 4051 Basel, Switzerland Distributed by Dr. Reddy’s Laboratories Inc., 107 College Road East, Princeton, NJ 08540

XEGLYZETM is a registered trademark of Dr. Reddy’s Laboratories, S.A.  

CLINICAL PHARMACOLOGY

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.

2. Pharmacokinetics-                                                                                            Absorption-                                                                                                                        The 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.

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.. 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. 

Distribution-                                                                                                               Abametapir 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.

Elimination-                                                                                                           Metabolism -Abametapir 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.

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.

Excretion-                                                                                                                   Excretion of abametapir and its human metabolites was not examined in patients.

Drug Interaction Studies-                                                                                                In 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 ].

 USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary

There are no available data on XEGLYZE use in pregnant women to evaluate for a drugassociated 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

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.

2. Lactation Risk Summary-

No 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.

4. Pediatric Use-                                                                                                         The safety and effectiveness of XEGLYZE have been established in pediatric patients 6 months of age and older.

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.

Because of the risk of accidental ingestion, XEGLYZE should be administered to pediatric patients only under direct adult supervision.

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.

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