United States - English - NLM (National Library of Medicine)

merck sharp & dohme llc - sugammadex sodium (unii: erj6x2mxv7) (sugammadex - unii:361lpm2t56) - sugammadex 100 mg in 1 ml - bridion® is indicated for the reversal of neuromuscular blockade induced by rocuronium bromide and vecuronium bromide in adults and pediatric patients aged 2 years and older undergoing surgery. bridion is contraindicated in patients with known hypersensitivity to sugammadex or any of its components. hypersensitivity reactions that occurred varied from isolated skin reactions to serious systemic reactions (i.e., anaphylaxis, anaphylactic shock) and have occurred in patients with no prior exposure to sugammadex [see warnings and precautions (5.1), adverse reactions (6)] . risk summary there are no clinical trial data on bridion use in pregnant women to inform any drug-associated risks. the available data from the pharmacovigilance safety database and published literature on bridion use in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. in animal reproduction studies, there was no evidence of malformations following daily intravenous administration of sugammadex to rats and rabbits during organogenesis at exposures of up to 6 and 8 times, respectively, the maximum recommended human dose (mrhd) of 16 mg/kg. however, there was an increase in the incidence of incomplete ossification of the sternebra and reduced fetal body weights in the rabbit study at 8 times the mrhd, which is a dose level in which maternal toxicity was also observed. in a pre- and postnatal development study, sugammadex treatment resulted in an increase in early postnatal loss, which correlated with maternal behavior (increased incidence of pup cannibalism), at exposures equivalent to the mrhd and higher (see data) . the background risk of major birth defects and miscarriage for the indicated population are unknown. however, the background risk in the u.s. general population of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies. data animal data in an embryofetal development study in rats, pregnant animals received daily intravenous administration of sugammadex at 0, 20, 100, and 500 mg/kg (0.2, 1, and 6 times the mrhd of 16 mg/kg/day, respectively, based on auc comparison) during organogenesis (gestational days 6-17). no treatment-related maternal and embryofetal changes were observed. in another embryofetal development study, pregnant new zealand white rabbits received daily intravenous administration of sugammadex at 0, 20, 65, 200 mg/kg (0.6, 2, and 8 times the mrhd, respectively, based on auc comparison) during organogenesis (gestational days 6-18). fetal body weight decreases (10 and 14%, respectively) were observed in the offspring at maternal doses of 65 mg/kg and 200 mg/kg. in addition, incomplete ossification of sternebra, and unossified 1st metacarpal were noted at a maternal dose of 200 mg/kg/day. maternal toxicity was also observed at 200 mg/kg. considering the observed effects of sugammadex on bone [see nonclinical toxicology (13.2)] , it is possible that these findings may be attributable to drug. there was no evidence of malformations at any dose. in a prenatal and postnatal development study, pregnant rats were administered sugammadex intravenously at 0, 30, 120, and 500 mg/kg (0.3, 1, and 6 times the mrhd, respectively, based on auc comparison) from gestational day (gd) 6 to postnatal day (pnd) 21 (corresponding to the beginning of organogenesis through parturition and subsequent pup weaning). postnatal loss during pnd 1-4 was noted across control litters and treated litters from dams receiving sugammadex as a result of pup cannibalization by dams. overall incidence of affected litters was 2, 1, 4, and 3 litters, respectively, at 0, 30, 120, or 500 mg/kg/day. the reason for the increased cannibalization is not known. an effect of sugammadex on steroidal hormones and/or pheromones cannot be ruled out. in addition, there were no drug-related effects on parturition in rats during evaluations for prenatal or postnatal development. risk summary no data are available regarding the presence of sugammadex in human milk, the effects of sugammadex on the breast fed infant, or the effects of sugammadex on milk production. however, sugammadex is present in rat milk (see data) . the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for bridion and any potential adverse effects on the breastfed infant from bridion or from the underlying maternal condition. data in a milk excretion study in rat dams following single intravenous dose of 20 mg/kg sugammadex on postnatal day 9, the maximum drug level was achieved at about 30 minutes after dosing with a ratio of milk to plasma level approximately 1:1. the oral exposure via milk did not induce effects on survival, body weight and physical or the behavioral developmental parameters monitored in rats in the prenatal and postnatal development studies [see use in specific populations (8.1)] . contraception upon administration of bridion, the efficacy of hormonal contraceptives may be reduced for up to 7 days. advise female patients of reproductive potential using hormonal contraceptives to use an additional, non-hormonal contraceptive for the next 7 days following bridion administration [see drug interactions (7.3)] . the safety and effectiveness of bridion for reversal of neuromuscular blockade induced by rocuronium bromide or vecuronium bromide have been established in pediatric patients aged 2 years and older. use of bridion in these age groups is supported by evidence from an adequate and well-controlled study of bridion [see clinical pharmacology (12.3) and clinical studies (14.1)]. in pediatric patients aged 2 years and older, the safety profile is generally consistent with that observed in adults [see adverse reactions (6.1)] . safety and effectiveness in patients younger than 2 years of age have not been established. juvenile animal studies in a bone deposition study, sugammadex concentrations were significantly higher in juvenile rats compared to adult rats (13% vs. 3% of the administered dose, respectively) following a single intravenous (iv) dose at 30 mg/kg (0.3 times the mrhd based on adult auc comparison). in a juvenile animal bone toxicity study, 7-day old rats were dosed intravenously once daily for 28 days with 0, 30, 120, and 500 mg/kg sugammadex (approximately 0.1, 0.6, and 3 times the mrhd, respectively, by adult auc comparison). sugammadex at 120 and 500 mg/kg decreased ulna and femur bone lengths by approximately 3%, which did not recover after an 8-week treatment-free period. reversible whitish discoloration and disturbance of enamel formation were also observed in the incisors at these dose levels. in molars, this effect was only observed at 500 mg/kg. the no-observed-effect-level (noel) was 30 mg/kg. in a second juvenile animal bone toxicity study, 7-day old rats were dosed once weekly for 8 weeks with 0, 7.5, 30, and 120 mg/kg (up to 1.2 times the mrhd of 16 mg/kg based on adult auc comparison). no adverse effects on bone or teeth were noted. bridion has been administered in a dedicated clinical study to a total 102 geriatric patients that compared the time to recovery from neuromuscular blockade induced by rocuronium (0.6 mg/kg) following administration of 2 mg/kg bridion given at the reappearance of t2 in 65-74 year-olds (n=62) and ≥75 year-olds (n=40) compared with 18-64 year-olds (n=48). the median time to recovery of the tof (t4 /t1 ) ratio to 0.9 in 18-64 year-olds was 2.2 minutes; in 65-74 year-olds it was 2.5 minutes, and in ≥75 year-olds it was 3.6 minutes. for time to recovery from neuromuscular blockade induced by rocuronium following administration of 4 mg/kg bridion given at 1-2 ptcs, results across clinical trials revealed a median recovery of 2.5 minutes for geriatric patients (≥65 years, n=63) versus 2.0 minutes, for adults aged 18-64 years (n=359). hence no dose adjustment is necessary in geriatric patients with normal organ function [see dosage and administration (2.2)] . this drug is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see use in specific populations (8.6), clinical pharmacology (12.3)] . this drug is known to be substantially excreted by the kidney. effect of mild or moderate renal impairment (creatinine clearance ≥30 and ≤80 ml/min) on sugammadex pk and pd was obtained from a study in elderly patients [see use in specific populations (8.5)] . although clearance of drug decreased in elderly subjects with mild and moderate renal impairment, there was no significant difference in the ability of sugammadex to reverse the pharmacodynamic effect of rocuronium. hence, no dosage adjustment is necessary for mild and moderate renal impairment. bridion is not recommended for use in patients with severe renal impairment (creatinine clearance <30 ml/min) due to insufficient safety information combined with the prolonged and increased overall exposure in these patients [see warnings and precautions (5.11), clinical pharmacology (12.3)] . bridion is not metabolized nor excreted by the liver; therefore, dedicated trials in patients with hepatic impairment have not been conducted. exercise caution when administering bridion to patients with hepatic impairment accompanied by coagulopathy or severe edema [see warnings and precautions (5.10, 5.14)] . one trial of 76 patients who were diagnosed with or have a history of cardiac disease (e.g., patients with ischemic heart disease, chronic heart failure, or arrhythmia) of primarily nyha (new york heart association) class ii investigated time to recovery from neuromuscular blockade induced by rocuronium 0.6 mg/kg following administration of 2 mg/kg or 4 mg/kg bridion given at the reappearance of t2 . the trial showed that the median time to recovery of the t4 /t1 ratio to 0.9 was 1.7 minutes and 1.3 minutes, respectively, in the 2 mg/kg and 4 mg/kg bridion dose groups. this is similar to the median values observed in the other trials; therefore, no dosage adjustment is necessary [see dosage and administration (2.2)] . one trial of 77 patients who were diagnosed with or have a history of pulmonary complications investigated the time to recovery from neuromuscular blockade induced by rocuronium (0.6 mg/kg) following administration of 2 mg/kg or 4 mg/kg bridion given at the first signs of recovery (reappearance of t2 ). the trial showed that for these patients the median time to recovery of the t4 /t1 ratio to 0.9 was 2.1 minutes after a dose of 2 mg/kg bridion and 1.9 minutes after a dose of 4 mg/kg bridion. this is similar to the median values observed in the other trials; therefore, no dosage adjustment is necessary. [see dosage and administration (2.2), adverse reactions (6.1).] a trial of 188 obese patients, with a body mass index ≥40 kg/m2 , investigated the time to recovery from moderate or deep neuromuscular blockade induced by rocuronium or vecuronium. patients received 2 mg/kg or 4 mg/kg bridion, as appropriate for level of block, dosed according to either actual body weight (abw) or ideal body weight (ibw) in random, double-blinded fashion. pooled across depth of block and neuromuscular blocking agent, the median time to recover to a train-of-four (tof) ratio ≥0.9 in patients dosed by abw (1.8 minutes) was statistically significantly faster compared to patients dosed by ibw (3.3 minutes). the adverse reaction profile was generally similar to the profile in adult patients in pooled phase 1 to 3 studies [see adverse reactions (6.1)] . no dosage adjustment is necessary [see dosage and administration (2.2)] . one trial of 331 patients who were assessed as asa class 3 or 4 investigated the incidence of treatment-emergent arrhythmias (sinus bradycardia, sinus tachycardia, or other cardiac arrhythmias) after administration of sugammadex. in patients receiving sugammadex (2 mg/kg, 4 mg/kg, or 16 mg/kg), the number (%) of patients with treatment-emergent sinus bradycardia (up to 35 minutes post-administration of sugammadex) was 1/105 (1.0%) in the 2 mg/kg sugammadex treatment group, 2/107 (1.9%) in the 4 mg/kg sugammadex treatment group, and 5/68 (7.4%) in the 16 mg/kg sugammadex treatment group, compared to 4/51 (7.8%) in the neostigmine (50 µg/kg up to 5 mg maximum dose) + glycopyrrolate (10 µg/kg up to 1 mg maximum dose) treatment group. the number of patients with treatment-emergent sinus tachycardia (up to 35 minutes post-administration of sugammadex) was 7/105 (6.7%) in the 2 mg/kg sugammadex treatment group, 10/107 (9.3%) in the 4 mg/kg sugammadex treatment group, and 6/68 (8.8%) in the 16 mg/kg sugammadex treatment group, compared to 11/51 (21.6%) in the neostigmine + glycopyrrolate treatment group. the number of other treatment-emergent arrhythmias (up to 35 minutes post administration of sugammadex) was 1/105 (1.0%) in the 2 mg/kg sugammadex treatment group, 0/107 (0%) in the 4 mg/kg sugammadex treatment group, and 1/68 (1.5%) in the 16 mg/kg sugammadex treatment group, compared to 1/51 (2.0%) in the neostigmine + glycopyrrolate treatment group. the adverse reaction profiles in asa class 3 and 4 patients were generally similar to those in adult patients in pooled phase 1 to 3 studies; therefore, no dosage adjustment is necessary [see dosage and administration (2.1), adverse reactions (6.1)] .

Belgium - English - AFMPS (Agence Fédérale des Médicaments et des Produits de Santé)

sandoz sa-nv - sugammadex sodium 108,8 mg/ml - eq. sugammadex 100 mg/ml - solution for injection - 100 mg/ml - sugammadex sodium 108.8 mg/ml - sugammadex

Belgium - English - AFMPS (Agence Fédérale des Médicaments et des Produits de Santé)

sandoz sa-nv - sugammadex sodium 108,8 mg/ml - eq. sugammadex 100 mg/ml - solution for injection - 100 mg/ml - sugammadex sodium 108.8 mg/ml - sugammadex

Belgium - English - AFMPS (Agence Fédérale des Médicaments et des Produits de Santé)

reddy holding gmbh - sugammadex sodium 108,8 mg/ml - eq. sugammadex 100 mg/ml - solution for injection - 100 mg/ml - sugammadex sodium 108.8 mg/ml - sugammadex

Belgium - English - AFMPS (Agence Fédérale des Médicaments et des Produits de Santé)

reddy holding gmbh - sugammadex sodium 108,8 mg/ml - eq. sugammadex 100 mg/ml - solution for injection - 100 mg/ml - sugammadex sodium 108.8 mg/ml - sugammadex

Belgium - English - AFMPS (Agence Fédérale des Médicaments et des Produits de Santé)

teva b.v. - sugammadex sodium 108,8 mg/ml - eq. sugammadex 100 mg/ml - solution for injection - 100 mg/ml - sugammadex sodium 108.8 mg/ml - sugammadex

Belgium - English - AFMPS (Agence Fédérale des Médicaments et des Produits de Santé)

teva b.v. - sugammadex sodium 108,8 mg/ml - eq. sugammadex 100 mg/ml - solution for injection - 100 mg/ml - sugammadex sodium 108.8 mg/ml - sugammadex

Australia - English - Department of Health (Therapeutic Goods Administration)

dr reddys laboratories australia pty ltd - sugammadex sodium, quantity: 544 mg (equivalent: sugammadex, qty 500 mg) - injection, solution - excipient ingredients: water for injections; hydrochloric acid; sodium hydroxide - reversal of neuromuscular blockade induced by rocuronium or vecuronium in patients 2 years of age and older.

Australia - English - Department of Health (Therapeutic Goods Administration)

dr reddys laboratories australia pty ltd - sugammadex sodium, quantity: 217.6 mg (equivalent: sugammadex, qty 200 mg) - injection, solution - excipient ingredients: water for injections; sodium hydroxide; hydrochloric acid - reversal of neuromuscular blockade induced by rocuronium or vecuronium in patients 2 years of age and older.

Ireland - English - HPRA (Health Products Regulatory Authority)

reddy holding gmbh - sugammadex - solution for injection - sugammadex