Abametapir
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alara Ece Dagsali, M.D.
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Overview
Abametapir is a metalloproteinase inhibitor that is FDA approved for the treatment of 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. Common adverse reactions include *Erythema
- Rash
- Skin burning sensation
- Contact dermatitis
- Vomiting
- Eye irritation
- Hair color changes.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
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 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
DOSAGE 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.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Abametapir in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Abametapir in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Abametapir FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Abametapir in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Abametapir in pediatric patients.
Contraindications
None
Warnings
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.
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.
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.
Adverse Reactions
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.
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.
- For the calculation of the percentages, the denominators are the number of subjects who did not have the monitored local adverse reaction at baseline.
Postmarketing Experience
There is limited information regarding Abametapir Postmarketing Experience in the drug label.
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.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Abametapir in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Abametapir in women who are pregnant.
Labor and Delivery
There 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.
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.
Nursing Mothers
There is no FDA guidance on the use of Abametapir in women who are nursing.
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
Geriatic 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.
Gender
There is no FDA guidance on the use of Abametapir with respect to specific gender populations.
Race
There is no FDA guidance on the use of Abametapir with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Abametapir in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Abametapir in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Abametapir in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Abametapir in patients who are immunocompromised.
Administration and Monitoring
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.
Monitoring
There is limited information regarding Abametapir Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Abametapir and IV administrations.
Overdosage
If accidentally swallowed, advise patients to seek medical advice immediately and to call their local Poison Control Center at 1-800-222-1222.
Pharmacology
There is limited information regarding Abametapir Pharmacology in the drug label.
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.
Structure
There is limited information regarding Abametapir Structure in the drug label.
Pharmacodynamics
There is limited information regarding Abametapir Pharmacodynamics in the drug label.
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. 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.
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.
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. 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.
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
Nonclinical Toxicology
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/dayabametapir (50 times the MRHD based on Cmax comparisons).
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.
How Supplied
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.
Storage
Store upright at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F and 86°F)
Do not refrigerate or freeze.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
Advise the patient or caregiver to read the FDA-approved patient labeling.
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.
- 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.
Precautions with Alcohol
Alcohol-Abametapir interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
XEGLYZE
Look-Alike Drug Names
There is limited information regarding Abametapir Look-Alike Drug Names in the drug label.
Price
References
The contents of this FDA label are provided by the National Library of Medicine.