city 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.

with warm water. (2) 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. (2)

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 reactions xeglyze n=349 subjects (%) vehicle n=350 subjects (%) erythema 14 (4.0) 6 (2) rash 11 (3.2) 8 (2.3) skin burning sensation 9 (2.6) 0 (0.0) contact dermatitis 6 (1.7) 4 (1.1) vomiting 6 (1.7) 2 (0.6) eye irritation 4 (1.2) 2 (0.6) hair color changes 3 (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 reactions xeglyze subjects (%)* vehicle subjects (%)* scalp erythema/edema 11 (3.2) 5 (1.4) scalp pruritus 2 (1.4) 1 (0.7) eye irritation 6 (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.

espectively. data animal data systemic 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 c max 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 c max 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 c max comparisons). 8.2 labor and delivery 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. 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.

systemic 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 c max 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 c max 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 c max comparisons).

d 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) ].

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 t max of 0.57 to 1.54 hours. table 3 abametapir pharmacokinetic parameters in subjects with head lice infestation study age group n c max (ng/ml) mean (%cv) auc 0-8h (ng*h/ml) mean (%cv) b 6 months to <1 year 1 418 1057 c 5 228 (50%) 688 (43%) b 1 year to <2 years 3 209 (62%) 446 (65%) c 8 147 (49%) 406 (37%) b 2 years to <3 years 6 206 (66%) 633 (57%) c 8 160 (48%) 602 (51%) b 3 years to 17 years 12 121 (60%) 330 (49%) c 7 52 (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 c max 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 ) ]. 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 c max and auc 0-72h 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 [ see drug interactions (7) ].

ble 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 t max of 0.57 to 1.54 hours. table 3 abametapir pharmacokinetic parameters in subjects with head lice infestation study age group n c max (ng/ml) mean (%cv) auc 0-8h (ng*h/ml) mean (%cv) b 6 months to <1 year 1 418 1057 c 5 228 (50%) 688 (43%) b 1 year to <2 years 3 209 (62%) 446 (65%) c 8 147 (49%) 406 (37%) b 2 years to <3 years 6 206 (66%) 633 (57%) c 8 160 (48%) 602 (51%) b 3 years to 17 years 12 121 (60%) 330 (49%) c 7 52 (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 c max 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 ) ]. 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 c max and auc 0-72h 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 [ see drug interactions (7) ].

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 treatment trial 1 trial 2 xeglyze (n=53) vehicle (n=55) xeglyze (n=55) vehicle (n=53) treatment success 43 (81.1%) 28 (50.9%) 45 (81.8%) 25 (47.2%)

s.a. issued: 01 / 2022

es into your breast milk. how should i use xeglyze? see the “instructions for use” for detailed information about the right way to apply xeglyze. use xeglyze exactly as your healthcare provider tells you to use it. your healthcare provider will prescribe the treatment that is right for you. do not change your treatment without talking to your healthcare provider. use xeglyze on dry hair. completely cover all of your hair and scalp with xeglyze. children will need an adult to apply xeglyze for them. do not swallow xeglyze. if swallowed, call your poison control center at 1-800-222-1222. do not get xeglyze into your eyes. if xeglyze gets in your eye, gently flush with water. wash your hands after you apply xeglyze. you may shampoo your hair any time after the treatment. when you complete your dose of xeglyze, do not use xeglyze again. throw away any unused xeglyze. do not flush xeglyze down sink or toilet. what are the possible side effects of xeglyze? the most common side effects of xeglyze include: redness of the skin or scalp rash burning sensation of the skin skin irritation vomiting eye irritation itchy scalp changes in your hair color tell your healthcare provider if you have any side effect that bothers you or that does not go away. these are not all the possible side effects of xeglyze. for more information, ask your healthcare provider or pharmacist. call your doctor for medical advice about side effects. you may report side effects to the fda at 1-800-fda-1088. how should i store xeglyze? 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) [see usp controlled room temperature]. do not refrigerate or freeze xeglyze. discard (throw away) any unused product. keep xeglyze and all medicines out of reach of children. general information about the safe and effective use of xeglyze medicines are sometimes prescribed for purposes other than those listed in a patient information leaflet. do not use xeglyze for a condition for which it was not prescribed. do not give xeglyze to other people, even if they have the same symptoms you have. it may harm them. you can also ask your pharmacist or healthcare provider for information about xeglyze that is written for health professionals. what are the ingredients in xeglyze? active ingredient: abametapir inactive ingredients: benzyl alcohol 2.0%, butylated hydroxytoluene, carbomer homopolymer type c, light mineral oil, polysorbate 20, trolamine and water. manufactured by groupe parima, inc., for dr. reddy’s laboratories, s.a. elisabethenanlage 11, 4051 basel, switzerland xeglyze is a registered trademark of dr. reddy’s laboratories, s.a. distributed by dr. reddy’s laboratories, inc., 107 college road east, princeton, nj 08540. this patient information has been approved by the u.s. food and drug administration issued: 01/2022