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

fresenius kabi usa, llc - dexmedetomidine hydrochloride (unii: 1018wh7f9i) (dexmedetomidine - unii:67vb76hono) - dexmedetomidine hydrochloride in 0.9% sodium chloride is indicated for sedation of initially intubated and mechanically ventilated patients during treatment in an intensive care setting. dexmedetomidine hydrochloride in 0.9% sodium chloride should be administered by continuous infusion not to exceed 24 hours. dexmedetomidine hydrochloride in 0.9% sodium chloride has been continuously infused in mechanically ventilated patients prior to extubation, during extubation, and post-extubation. it is not necessary to discontinue dexmedetomidine hydrochloride in 0.9% sodium chloride prior to extubation. dexmedetomidine hydrochloride in 0.9% sodium chloride injection is indicated for sedation of non-intubated patients prior to and/or during surgical and other procedures. none. pregnancy category c there are no adequate and well-controlled studies of dexmedetomidine hydrochloride use in pregnant women. in an in vitro human placenta study, placental transfer of dexmedetomidine occurred. in a study in the pregnant rat, p

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

slayback pharma llc - dexmedetomidine hydrochloride (unii: 1018wh7f9i) (dexmedetomidine - unii:67vb76hono) - dexmedetomidine hydrochloride in 0.9% sodium chloride injection is indicated for sedation of initially intubated and mechanically ventilated patients during treatment in an intensive care setting. dexmedetomidine hydrochloride in 0.9% sodium chloride injection should be administered by continuous infusion not to exceed 24 hours. dexmedetomidine hydrochloride in 0.9% sodium chloride injection has been continuously infused in mechanically ventilated patients prior to extubation, during extubation, and post-extubation. it is not necessary to discontinue dexmedetomidine hydrochloride in 0.9% sodium chloride injection prior to extubation. dexmedetomidine hydrochloride in 0.9% sodium chloride injection is indicated for sedation of non-intubated patients prior to and/or during surgical and other procedures. none pregnancy category c there are no adequate and well-controlled studies of dexmedetomidine hydrochloride in 0.9% sodium chloride injection use in pregnant women. in an in vitro human placenta study, placent

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

baxter healthcare company - dexmedetomidine hydrochloride (unii: 1018wh7f9i) (dexmedetomidine - unii:67vb76hono) - dexmedetomidine hydrochloride in 0.9% sodium chloride injection is indicated for sedation of initially intubated and mechanically ventilated adult patients during treatment in an intensive care setting. dexmedetomidine hydrochloride in 0.9% sodium chloride injection should be administered by continuous infusion not to exceed 24 hours. dexmedetomidine hydrochloride in 0.9% sodium chloride injection has been continuously infused in mechanically ventilated adult patients prior to extubation, during extubation, and post-extubation. it is not necessary to discontinue dexmedetomidine hydrochloride in 0.9% sodium chloride injection prior to extubation. dexmedetomidine hydrochloride in 0.9% sodium chloride injection is indicated for sedation of non-intubated adult patients prior to and/or during surgical and other procedures. pediatric use information is approved for hospira inc.’s precedextm (dexmedetomidine hydrochloride) injection and precedextm (dexmedetomidine hydrochloride) in sodium chloride injection. however, due to hospira inc.’s marketing exclusivity rights, this drug product is not labeled with that information. none. risk summary available data from published randomized controlled trials and case reports over several decades of use with intravenously administered dexmedetomidine during pregnancy have not identified a drug-associated risk of major birth defects and miscarriage; however, the reported exposures occurred after the first trimester. most of the available data are based on studies with exposures that occurred at the time of caesarean section delivery, and these studies have not identified an adverse effect on maternal outcomes or infant apgar scores. available data indicate that dexmedetomidine crosses the placenta. in animal reproduction studies, fetal toxicity that lower fetal viability and reduced live fetuses occurred with subcutaneous administration of dexmedetomidine to pregnant rats during organogenesis at doses 1.8 times the maximum recommended human dose (mrhd) of 17.8 mcg/kg/day. developmental toxicity (low pup weights and adult offspring weights, decreased f1 grip strength, increased early implantation loss and decreased viability of second-generation offspring) occurred when pregnant rats were subcutaneously administered dexmedetomidine at doses less than the clinical dose from late pregnancy through lactation and weaning (see data) . the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. data animal data increased post-implantation losses and reduced live fetuses in the presence of maternal toxicity (i.e. decreased body weight) were noted in a rat embryo-fetal development study in which pregnant dams were administered subcutaneous doses of dexmedetomidine 200 mcg/kg/day (equivalent to 1.8 times the intravenous mrhd of 17.8 mcg/kg/day based on body surface area [bsa]) during the period of organogenesis (gestation day [gd] 6 to 15). no malformations were reported. no malformations or embryo-fetal toxicity were noted in a rabbit embryo-fetal development study in which pregnant does were administered dexmedetomidine intravenously at doses of up to 96 mcg/kg/day (approximately half the human exposure at the mrhd based on auc) during the period of organogenesis (gd 6 to 18). reduced pup and adult offspring birth weights, and grip strength were reported in a rat developmental toxicology study in which pregnant females were administered dexmedetomidine subcutaneously at doses of 8 mcg/kg/day (0.07 times the mrhd based on bsa) during late pregnancy through lactation and weaning (gd 16 to postnatal day [pnd] 25). decreased viability of second generation offspring and an increase in early implantation loss along with delayed motor development occurred in the 32 mcg/kg/day group (equivalent to less than the clinical dose based on bsa) when first generation offspring were allowed to mate. this study limited dosing to hard palate closure (gd 15 to 18) through weaning instead of dosing from implantation (gd 6 to 7) to weaning (pnd 21). in a study in the pregnant rat, placental transfer of dexmedetomidine was observed when radiolabeled dexmedetomidine was administered subcutaneously. risk summary available published literature reports the presence of dexmedetomidine in human milk following intravenous administration (see data) . there is no information regarding the effects of dexmedetomidine on the breastfed infant or the effects on milk production. advise women to monitor the breastfed infant for irritability. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for dexmedetomidine hydrochloride in 0.9% sodium chloride injection and any potential adverse effects on the breastfed infant from dexmedetomidine hydrochloride in 0.9% sodium chloride injection or from the underlying condition. data in two published clinical studies, a total of 14 women were given intravenous dexmedetomidine 6 mcg/kg/hour for 10 minutes after delivery followed by continuous infusion of 0.2–0.7 mcg/kg/hour. breast milk and maternal blood samples were collected at 0, 6, 12, and 24 hours after discontinuation of dexmedetomidine. plasma and milk dexmedetomidine concentrations were detectable up to 6 hours in most subjects, up to 12 hours in one subject and undetectable in all at 24 hours. the milk-to-plasma ratio from single paired maternal milk and plasma concentrations at each time point ranged from 0.53 to 0.95. the relative infant dose was estimated to range from 0.02 to 0.098%. sedation for non-invasive procedures the safety and effectiveness of dexmedetomidine hydrochloride in 0.9% sodium chloride injection have not been established in pediatric patients less than 1 month of age. pediatric use information is approved for hospira inc.’s precedextm (dexmedetomidine hydrochloride) injection and precedextm (dexmedetomidine hydrochloride) in sodium chloride injection. however, due to hospira inc.’s marketing exclusivity rights, this drug product is not labeled with that information. icu sedation the safety and efficacy of dexmedetomidine hydrochloride in 0.9% sodium chloride injection have not been established in pediatric patients for icu sedation. one assessor-blinded trial in pediatric patients and two open label studies in neonates were conducted to assess efficacy for icu sedation. these studies did not meet their primary efficacy endpoints and the safety data submitted were insufficient to fully characterize the safety profile of dexmedetomidine hydrochloride in 0.9% sodium chloride injection for these patient populations. intensive care unit sedation a total of 729 patients in the clinical studies were 65 years of age and over. a total of 200 patients were 75 years of age and over. in patients greater than 65 years of age, a higher incidence of bradycardia and hypotension was observed following administration of dexmedetomidine hydrochloride in 0.9% sodium chloride injection [see warnings and precautions (5.2) ]. therefore, a dose reduction may be considered in patients over 65 years of age [see dosage and administration (2.2, 2.3 ), clinical pharmacology (12.3) ]. procedural sedation a total of 131 patients in the clinical studies were 65 years of age and over. a total of 47 patients were 75 years of age and over. hypotension occurred in a higher incidence in dexmedetomidine hydrochloride in 0.9% sodium chloride injection-treated patients 65 years or older (72%) and 75 years or older (74%) as compared to patients <65 years (47%). a reduced loading dose of 0.5 mcg/kg given over 10 minutes is recommended and a reduction in the maintenance infusion should be considered for patients greater than 65 years of age. since dexmedetomidine hydrochloride in 0.9% sodium chloride injection clearance decreases with increasing severity of hepatic impairment, dose reduction should be considered in patients with impaired hepatic function [see dosage and administration (2.2 , 2.3), clinical pharmacology (12.3) ]. dexmedetomidine hydrochloride in 0.9% sodium chloride injection (dexmedetomidine hydrochloride) is not a controlled substance. the dependence potential of dexmedetomidine hydrochloride in 0.9% sodium chloride injection has not been studied in humans. however, since studies in rodents and primates have demonstrated that dexmedetomidine hydrochloride in 0.9% sodium chloride injection exhibits pharmacologic actions similar to those of clonidine, it is possible that dexmedetomidine hydrochloride in 0.9% sodium chloride injection may produce a clonidine-like withdrawal syndrome upon abrupt discontinuation [see warnings and precautions (5.5) ].

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

baxter healthcare corporation - dexmedetomidine hydrochloride (unii: 1018wh7f9i) (dexmedetomidine - unii:67vb76hono) - dexmedetomidine hydrochloride in 0.9% sodium chloride injection is indicated for sedation of initially intubated and mechanically ventilated adult patients during treatment in an intensive care setting. dexmedetomidine hydrochloride in 0.9% sodium chloride injection should be administered by continuous infusion not to exceed 24 hours. dexmedetomidine hydrochloride in 0.9% sodium chloride injection has been continuously infused in mechanically ventilated adult patients prior to extubation, during extubation, and post-extubation. it is not necessary to discontinue dexmedetomidine hydrochloride in 0.9% sodium chloride injection prior to extubation. dexmedetomidine hydrochloride in 0.9% sodium chloride injection is indicated for sedation of non-intubated adult patients prior to and/or during surgical and other procedures. pediatric use information is approved for hospira inc.’s precedextm (dexmedetomidine hydrochloride) injection and precedextm (dexmedetomidine hydrochloride) in sodium chloride injection. however, due to hospira inc.’s marketing exclusivity rights, this drug product is not labeled with that information. none. risk summary available data from published randomized controlled trials and case reports over several decades of use with intravenously administered dexmedetomidine during pregnancy have not identified a drug-associated risk of major birth defects and miscarriage; however, the reported exposures occurred after the first trimester. most of the available data are based on studies with exposures that occurred at the time of caesarean section delivery, and these studies have not identified an adverse effect on maternal outcomes or infant apgar scores. available data indicate that dexmedetomidine crosses the placenta. in animal reproduction studies, fetal toxicity that lower fetal viability and reduced live fetuses occurred with subcutaneous administration of dexmedetomidine to pregnant rats during organogenesis at doses 1.8 times the maximum recommended human dose (mrhd) of 17.8 mcg/kg/day. developmental toxicity (low pup weights and adult offspring weights, decreased f1 grip strength, increased early implantation loss and decreased viability of second-generation offspring) occurred when pregnant rats were subcutaneously administered dexmedetomidine at doses less than the clinical dose from late pregnancy through lactation and weaning (see data). the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. data animal data increased post-implantation losses and reduced live fetuses in the presence of maternal toxicity (i.e. decreased body weight) were noted in a rat embryo-fetal development study in which pregnant dams were administered subcutaneous doses of dexmedetomidine 200 mcg/kg/day (equivalent to 1.8 times the intravenous mrhd of 17.8 mcg/kg/day based on body surface area [bsa]) during the period of organogenesis (gestation day [gd] 6 to 15). no malformations were reported. no malformations or embryo-fetal toxicity were noted in a rabbit embryo-fetal development study in which pregnant does were administered dexmedetomidine intravenously at doses of up to 96 mcg/kg/day (approximately half the human exposure at the mrhd based on auc) during the period of organogenesis (gd 6 to 18). reduced pup and adult offspring birth weights, and grip strength were reported in a rat developmental toxicology study in which pregnant females were administered dexmedetomidine subcutaneously at doses of 8 mcg/kg/day (0.07 times the mrhd based on bsa) during late pregnancy through lactation and weaning (gd 16 to postnatal day [pnd] 25). decreased viability of second generation offspring and an increase in early implantation loss along with delayed motor development occurred in the 32 mcg/kg/day group (equivalent to less than the clinical dose based on bsa) when first generation offspring were allowed to mate. this study limited dosing to hard palate closure (gd 15 to 18) through weaning instead of dosing from implantation (gd 6 to 7) to weaning (pnd 21). in a study in the pregnant rat, placental transfer of dexmedetomidine was observed when radiolabeled dexmedetomidine was administered subcutaneously. risk summary available published literature reports the presence of dexmedetomidine in human milk following intravenous administration (see data) . there is no information regarding the effects of dexmedetomidine on the breastfed infant or the effects on milk production. advise women to monitor the breastfed infant for irritability. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for dexmedetomidine hydrochloride in 0.9% sodium chloride injection and any potential adverse effects on the breastfed infant from dexmedetomidine hydrochloride in 0.9% sodium chloride injection or from the underlying condition. data in two published clinical studies, a total of 14 women were given intravenous dexmedetomidine 6 mcg/kg/hour for 10 minutes after delivery followed by continuous infusion of 0.2–0.7 mcg/kg/hour. breast milk and maternal blood samples were collected at 0, 6, 12, and 24 hours after discontinuation of dexmedetomidine. plasma and milk dexmedetomidine concentrations were detectable up to 6 hours in most subjects, up to 12 hours in one subject and undetectable in all at 24 hours. the milk-to-plasma ratio from single paired maternal milk and plasma concentrations at each time point ranged from 0.53 to 0.95. the relative infant dose was estimated to range from 0.02 to 0.098%. sedation for non-invasive procedures the safety and effectiveness of dexmedetomidine hydrochloride in 0.9% sodium chloride injection have not been established in pediatric patients less than 1 month of age. pediatric use information is approved for hospira inc.’s precedextm (dexmedetomidine hydrochloride) injection and precedextm (dexmedetomidine hydrochloride) in sodium chloride injection. however, due to hospira inc.’s marketing exclusivity rights, this drug product is not labeled with that information. icu sedation the safety and efficacy of dexmedetomidine hydrochloride in 0.9% sodium chloride injection have not been established in pediatric patients for icu sedation. one assessor-blinded trial in pediatric patients and two open label studies in neonates were conducted to assess efficacy for icu sedation. these studies did not meet their primary efficacy endpoints and the safety data submitted were insufficient to fully characterize the safety profile of dexmedetomidine hydrochloride in 0.9% sodium chloride injection for these patient populations. intensive care unit sedation a total of 729 patients in the clinical studies were 65 years of age and over. a total of 200 patients were 75 years of age and over. in patients greater than 65 years of age, a higher incidence of bradycardia and hypotension was observed following administration of dexmedetomidine hydrochloride in 0.9% sodium chloride injection [see warnings and precautions (5.2) ]. therefore, a dose reduction may be considered in patients over 65 years of age [see dosage and administration (2.2 , 2.3), clinical pharmacology (12.3) ]. procedural sedation a total of 131 patients in the clinical studies were 65 years of age and over. a total of 47 patients were 75 years of age and over. hypotension occurred in a higher incidence in dexmedetomidine hydrochloride in 0.9% sodium chloride injection-treated patients 65 years or older (72%) and 75 years or older (74%) as compared to patients <65 years (47%). a reduced loading dose of 0.5 mcg/kg given over 10 minutes is recommended and a reduction in the maintenance infusion should be considered for patients greater than 65 years of age. since dexmedetomidine hydrochloride in 0.9% sodium chloride injection clearance decreases with increasing severity of hepatic impairment, dose reduction should be considered in patients with impaired hepatic function [see dosage and administration (2.2, 2.3) , clinical pharmacology (12.3) ]. dexmedetomidine hydrochloride in 0.9% sodium chloride injection (dexmedetomidine hydrochloride) is not a controlled substance. the dependence potential of dexmedetomidine hydrochloride in 0.9% sodium chloride injection has not been studied in humans. however, since studies in rodents and primates have demonstrated that dexmedetomidine hydrochloride in 0.9% sodium chloride injection exhibits pharmacologic actions similar to those of clonidine, it is possible that dexmedetomidine hydrochloride in 0.9% sodium chloride injection may produce a clonidine-like withdrawal syndrome upon abrupt discontinuation [see warnings and precautions (5.5) ].

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

amneal pharmaceuticals llc - dexmedetomidine hydrochloride (unii: 1018wh7f9i) (dexmedetomidine - unii:67vb76hono) - dexmedetomidine hydrochloride in 0.9% sodium chloride injection is indicated for sedation of initially intubated and mechanically ventilated adult patients during treatment in an intensive care setting. dexmedetomidine hydrochloride in 0.9% sodium chloride injection should be administered by continuous infusion not to exceed 24 hours. dexmedetomidine hydrochloride in 0.9% sodium chloride injection has been continuously infused in mechanically ventilated adult patients prior to extubation, during extubation, and post-extubation. it is not necessary to discontinue dexmedetomidine hydrochloride in 0.9% sodium chloride injection prior to extubation. dexmedetomidine hydrochloride in 0.9% sodium chloride injection is indicated for sedation of non-intubated adult patients prior to and/or during surgical and other procedures. pediatric use information is approved for hospira inc.’s precedextm (dexmedetomidine hydrochloride) in sodium chloride injection. however, due to hospira inc.’s marketing exclusivity rights, this drug product is not labeled with that information. none. risk summary available data from published randomized controlled trials and case reports over several decades of use with intravenously administered dexmedetomidine during pregnancy have not identified a drug-associated risk of major birth defects and miscarriage; however, the reported exposures occurred after the first trimester. most of the available data are based on studies with exposures that occurred at the time of caesarean section delivery, and these studies have not identified an adverse effect on maternal outcomes or infant apgar scores. available data indicate that dexmedetomidine crosses the placenta. in animal reproduction studies, fetal toxicity that lower fetal viability and reduced live fetuses occurred with subcutaneous administration of dexmedetomidine to pregnant rats during organogenesis at doses 1.8 times the maximum recommended human dose (mrhd) of 17.8 mcg/kg/day. developmental toxicity (low pup weights and adult offspring weights, decreased f1 grip strength, increased early implantation loss and decreased viability of second-generation offspring) occurred when pregnant rats were subcutaneously administered dexmedetomidine at doses less than the clinical dose from late pregnancy through lactation and weaning (see data) . the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. 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. data animal data increased post-implantation losses and reduced live fetuses in the presence of maternal toxicity (i.e. decreased body weight) were noted in a rat embryo-fetal development study in which pregnant dams were administered subcutaneous doses of dexmedetomidine 200 mcg/kg/day (equivalent to 1.8 times the intravenous mrhd of 17.8 mcg/kg/day based on body surface area [bsa]) during the period of organogenesis (gestation day [gd] 6 to 15). no malformations were reported. no malformations or embryo-fetal toxicity were noted in a rabbit embryo-fetal development study in which pregnant does were administered dexmedetomidine intravenously at doses of up to 96 mcg/kg/day (approximately half the human exposure at the mrhd based on auc) during the period of organogenesis (gd 6 to 18). reduced pup and adult offspring birth weights, and grip strength were reported in a rat developmental toxicology study in which pregnant females were administered dexmedetomidine subcutaneously at doses of 8 mcg/kg/day (0.07 times the mrhd based on bsa) during late pregnancy through lactation and weaning (gd 16 to postnatal day [pnd] 25). decreased viability of second generation offspring and an increase in early implantation loss along with delayed motor development occurred in the 32 mcg/kg/day group (equivalent to less than the clinical dose based on bsa) when first generation offspring were allowed to mate. this study limited dosing to hard palate closure (gd 15 to 18) through weaning instead of dosing from implantation (gd 6 to 7) to weaning (pnd 21). in a study in the pregnant rat, placental transfer of dexmedetomidine was observed when radiolabeled dexmedetomidine was administered subcutaneously. risk summary available published literature reports the presence of dexmedetomidine in human milk following intravenous administration (see data) . there is no information regarding the effects of dexmedetomidine on the breastfed infant or the effects on milk production. advise women to monitor the breastfed infant for irritability. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for dexmedetomidine hydrochloride and any potential adverse effects on the breastfed infant from dexmedetomidine hydrochloride or from the underlying condition. data in two published clinical studies, a total of 14 women were given intravenous dexmedetomidine 6 mcg/kg/hour for 10 minutes after delivery followed by continuous infusion of 0.2 to 0.7 mcg/kg/hour. breast milk and maternal blood samples were collected at 0, 6, 12, and 24 hours after discontinuation of dexmedetomidine. plasma and milk dexmedetomidine concentrations were detectable up to 6 hours in most subjects, up to 12 hours in one subject and undetectable in all at 24 hours. the milk-to-plasma ratio from single paired maternal milk and plasma concentrations at each time point ranged from 0.53 to 0.95. the relative infant dose was estimated to range from 0.02% to 0.098%. sedation for non-invasive procedures the safety and effectiveness of dexmedetomidine hydrochloride have not been established in pediatric patients less than 1 month of age. pediatric use information is approved for hospira inc.’s precedextm (dexmedetomidine hydrochloride) in sodium chloride injection. however, due to hospira inc.’s marketing exclusivity rights, this drug product is not labeled with that information. icu sedation the safety and efficacy of dexmedetomidine hydrochloride have not been established in pediatric patients for icu sedation. one assessor-blinded trial in pediatric patients and two open label studies in neonates were conducted to assess efficacy for icu sedation. these studies did not meet their primary efficacy endpoints and the safety data submitted were insufficient to fully characterize the safety profile of dexmedetomidine hydrochloride for these patient populations. intensive care unit sedation a total of 729 patients in the clinical studies were 65 years of age and over. a total of 200 patients were 75 years of age and over. in patients greater than 65 years of age, a higher incidence of bradycardia and hypotension was observed following administration of dexmedetomidine hydrochloride [see warnings and precautions (5.2)] . therefore, a dose reduction may be considered in patients over 65 years of age [see dosage and administration (2.2 , 2.3), clinical pharmacology (12.3)] . procedural sedation a total of 131 patients in the clinical studies were 65 years of age and over. a total of 47 patients were 75 years of age and over. hypotension occurred in a higher incidence in dexmedetomidine hydrochloride-treated patients 65 years or older (72%) and 75 years or older (74%) as compared to patients < 65 years (47%). a reduced loading dose of 0.5 mcg/kg given over 10 minutes is recommended and a reduction in the maintenance infusion should be considered for patients greater than 65 years of age. since dexmedetomidine hydrochloride clearance decreases with increasing severity of hepatic impairment, dose reduction should be considered in patients with impaired hepatic function [see dosage and administration (2.2 , 2.3), clinical pharmacology (12.3)] . dexmedetomidine hydrochloride is not a controlled substance. the dependence potential of dexmedetomidine hydrochloride has not been studied in humans. however, since studies in rodents and primates have demonstrated that dexmedetomidine hydrochloride exhibits pharmacologic actions similar to those of clonidine, it is possible that dexmedetomidine hydrochloride may produce a clonidine-like withdrawal syndrome upon abrupt discontinuation [see warnings and precautions (5.5)] .

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

baxter healthcare corporation - dexmedetomidine hydrochloride (unii: 1018wh7f9i) (dexmedetomidine - unii:67vb76hono) - dexmedetomidine hydrochloride in 0.9% sodium chloride injection is indicated for sedation of initially intubated and mechanically ventilated adult patients during treatment in an intensive care setting. dexmedetomidine hydrochloride in 0.9% sodium chloride injection should be administered by continuous infusion not to exceed 24 hours. dexmedetomidine hydrochloride in 0.9% sodium chloride injection has been continuously infused in mechanically ventilated adult patients prior to extubation, during extubation, and post-extubation. it is not necessary to discontinue dexmedetomidine hydrochloride in 0.9% sodium chloride injection prior to extubation. dexmedetomidine hydrochloride in 0.9% sodium chloride injection is indicated for sedation of non-intubated adult patients prior to and/or during surgical and other procedures. pediatric use information is approved for hospira inc.’s precedextm (dexmedetomidine hydrochloride) injection and precedextm (dexmedetomidine hydrochloride) in sodium chloride injection. however, due to hospira inc.’s marketing exclusivity rights, this drug product is not labeled with that information. none. risk summary available data from published randomized controlled trials and case reports over several decades of use with intravenously administered dexmedetomidine during pregnancy have not identified a drug-associated risk of major birth defects and miscarriage; however, the reported exposures occurred after the first trimester. most of the available data are based on studies with exposures that occurred at the time of caesarean section delivery, and these studies have not identified an adverse effect on maternal outcomes or infant apgar scores. available data indicate that dexmedetomidine crosses the placenta. in animal reproduction studies, fetal toxicity that lower fetal viability and reduced live fetuses occurred with subcutaneous administration of dexmedetomidine to pregnant rats during organogenesis at doses 1.8 times the maximum recommended human dose (mrhd) of 17.8 mcg/kg/day. developmental toxicity (low pup weights and adult offspring weights, decreased f1 grip strength, increased early implantation loss and decreased viability of second-generation offspring) occurred when pregnant rats were subcutaneously administered dexmedetomidine at doses less than the clinical dose from late pregnancy through lactation and weaning (see data) . the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. data animal data increased post-implantation losses and reduced live fetuses in the presence of maternal toxicity (i.e. decreased body weight) were noted in a rat embryo-fetal development study in which pregnant dams were administered subcutaneous doses of dexmedetomidine 200 mcg/kg/day (equivalent to 1.8 times the intravenous mrhd of 17.8 mcg/kg/day based on body surface area [bsa]) during the period of organogenesis (gestation day [gd] 6 to 15). no malformations were reported. no malformations or embryo-fetal toxicity were noted in a rabbit embryo-fetal development study in which pregnant does were administered dexmedetomidine intravenously at doses of up to 96 mcg/kg/day (approximately half the human exposure at the mrhd based on auc) during the period of organogenesis (gd 6 to 18). reduced pup and adult offspring birth weights, and grip strength were reported in a rat developmental toxicology study in which pregnant females were administered dexmedetomidine subcutaneously at doses of 8 mcg/kg/day (0.07 times the mrhd based on bsa) during late pregnancy through lactation and weaning (gd 16 to postnatal day [pnd] 25). decreased viability of second generation offspring and an increase in early implantation loss along with delayed motor development occurred in the 32 mcg/kg/day group (equivalent to less than the clinical dose based on bsa) when first generation offspring were allowed to mate. this study limited dosing to hard palate closure (gd 15 to 18) through weaning instead of dosing from implantation (gd 6 to 7) to weaning (pnd 21). in a study in the pregnant rat, placental transfer of dexmedetomidine was observed when radiolabeled dexmedetomidine was administered subcutaneously. risk summary available published literature reports the presence of dexmedetomidine in human milk following intravenous administration (see data) . there is no information regarding the effects of dexmedetomidine on the breastfed infant or the effects on milk production. advise women to monitor the breastfed infant for irritability. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for dexmedetomidine hydrochloride in 0.9% sodium chloride injection and any potential adverse effects on the breastfed infant from dexmedetomidine hydrochloride in 0.9% sodium chloride injection or from the underlying condition. data in two published clinical studies, a total of 14 women were given intravenous dexmedetomidine 6 mcg/kg/hour for 10 minutes after delivery followed by continuous infusion of 0.2–0.7 mcg/kg/hour. breast milk and maternal blood samples were collected at 0, 6, 12, and 24 hours after discontinuation of dexmedetomidine. plasma and milk dexmedetomidine concentrations were detectable up to 6 hours in most subjects, up to 12 hours in one subject and undetectable in all at 24 hours. the milk-to-plasma ratio from single paired maternal milk and plasma concentrations at each time point ranged from 0.53 to 0.95. the relative infant dose was estimated to range from 0.02 to 0.098%. sedation for non-invasive procedures the safety and effectiveness of dexmedetomidine hydrochloride in 0.9% sodium chloride injection have not been established in pediatric patients less than 1 month of age. pediatric use information is approved for hospira inc.’s precedextm (dexmedetomidine hydrochloride) injection and precedextm (dexmedetomidine hydrochloride) in sodium chloride injection. however, due to hospira inc.’s marketing exclusivity rights, this drug product is not labeled with that information. icu sedation the safety and efficacy of dexmedetomidine hydrochloride in 0.9% sodium chloride injection have not been established in pediatric patients for icu sedation. one assessor-blinded trial in pediatric patients and two open label studies in neonates were conducted to assess efficacy for icu sedation. these studies did not meet their primary efficacy endpoints and the safety data submitted were insufficient to fully characterize the safety profile of dexmedetomidine hydrochloride in 0.9% sodium chloride injection for these patient populations. intensive care unit sedation a total of 729 patients in the clinical studies were 65 years of age and over. a total of 200 patients were 75 years of age and over. in patients greater than 65 years of age, a higher incidence of bradycardia and hypotension was observed following administration of dexmedetomidine hydrochloride in 0.9% sodium chloride injection [see warnings and precautions (5.2) ]. therefore, a dose reduction may be considered in patients over 65 years of age [see dosage and administration (2.2, 2.3), clinical pharmacology (12.3) ]. procedural sedation a total of 131 patients in the clinical studies were 65 years of age and over. a total of 47 patients were 75 years of age and over. hypotension occurred in a higher incidence in dexmedetomidine hydrochloride in 0.9% sodium chloride injection-treated patients 65 years or older (72%) and 75 years or older (74%) as compared to patients <65 years (47%). a reduced loading dose of 0.5 mcg/kg given over 10 minutes is recommended and a reduction in the maintenance infusion should be considered for patients greater than 65 years of age. since dexmedetomidine hydrochloride in 0.9% sodium chloride injection clearance decreases with increasing severity of hepatic impairment, dose reduction should be considered in patients with impaired hepatic function [see dosage and administration (2.2, 2.3), clinical pharmacology (12.3) ]. dexmedetomidine hydrochloride in 0.9% sodium chloride injection (dexmedetomidine hydrochloride) is not a controlled substance. the dependence potential of dexmedetomidine hydrochloride in 0.9% sodium chloride injection has not been studied in humans. however, since studies in rodents and primates have demonstrated that dexmedetomidine hydrochloride in 0.9% sodium chloride injection exhibits pharmacologic actions similar to those of clonidine, it is possible that dexmedetomidine hydrochloride in 0.9% sodium chloride injection may produce a clonidine-like withdrawal syndrome upon abrupt discontinuation [see warnings and precautions (5.5) ].

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

dr.reddy's laboratories inc - dexmedetomidine hydrochloride (unii: 1018wh7f9i) (dexmedetomidine - unii:67vb76hono) - dexmedetomidine hydrochloride in 0.9% sodium chloride injection is indicated for sedation of initially intubated and mechanically ventilated patients during treatment in an intensive care setting. dexmedetomidine hydrochloride in 0.9% sodium chloride injection should be administered by continuous infusion not to exceed 24 hours. dexmedetomidine hydrochloride in 0.9% sodium chloride injection has been continuously infused in mechanically ventilated patients prior to extubation, during extubation, and post-extubation. it is not necessary to discontinue dexmedetomidine hydrochloride in 0.9% sodium chloride injection prior to extubation. dexmedetomidine hydrochloride in 0.9% sodium chloride injection is indicated for sedation of non-intubated patients prior to and/or during surgical and other procedures. none. pregnancy category c there are no adequate and well-controlled studies of dexmedetomidine hydrochloride in 0.9% sodium chloride injection use in pregnant women. in an in vitro human placenta study, placenta

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

tagi pharma, inc. - dexmedetomidine hydrochloride (unii: 1018wh7f9i) (dexmedetomidine - unii:67vb76hono) - dexmedetomidine hcl in 0.9% sodium chloride injection is indicated for sedation of initially intubated and mechanically ventilated patients during treatment in an intensive care setting. dexmedetomidine hcl in 0.9% sodium chloride injection should be administered by continuous infusion not to exceed 24 hours. dexmedetomidine hcl in 0.9% sodium chloride injection has been continuously infused in mechanically ventilated patients prior to extubation, during extubation, and post-extubation. it is not necessary to discontinue dexmedetomidine hcl in 0.9% sodium chloride injection prior to extubation. dexmedetomidine hcl in 0.9% sodium chloride injection is indicated for sedation of non-intubated patients prior to and/or during surgical and other procedures. none. pregnancy category c there are no adequate and well-controlled studies of dexmedetomidine hcl in 0.9% sodium chloride injection use in pregnant women. in an in vitro human placenta study, placental transfer of dexmedetomidine occurred. in a study in the p

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

piramal critical care inc - dexmedetomidine hydrochloride (unii: 1018wh7f9i) (dexmedetomidine - unii:67vb76hono) - dexmedetomidine hydrochloride in 0.9% sodium chloride injection is indicated for sedation of initially intubated and mechanically ventilated patients during treatment in an intensive care setting. dexmedetomidine hydrochloride in 0.9% sodium chloride injection should be administered by continuous infusion not to exceed 24 hours.  dexmedetomidine hydrochloride in 0.9% sodium chloride injection has been continuously infused in mechanically ventilated patients prior to extubation, during extubation, and post-extubation. it is not necessary to discontinue dexmedetomidine hydrochloride in 0.9% sodium chloride injection prior to extubation. dexmedetomidine hydrochloride in 0.9% sodium chloride injection is indicated for sedation of non-intubated patients prior to and/or during surgical and other procedures. none. pregnancy category c there are no adequate and well-controlled studies of dexmedetomidine hydrochloride in 0.9% sodium chloride injection use in pregnant women. in an in vitro human placenta study, placental transfer of dexmedetomidine occurred. in a study in the pregnant rat, placental transfer of dexmedetomidine was observed when radiolabeled dexmedetomidine was administered subcutaneously. thus, fetal exposure should be expected in humans, and dexmedetomidine hydrochloride in 0.9% sodium chloride injection should be used during pregnancy only if the potential benefits justify the potential risk to the fetus. teratogenic effects were not observed in rats following subcutaneous administration of dexmedetomidine during the period of fetal organogenesis (from gestation day 5 to 16) with doses up to 200 mcg/kg (representing a dose approximately equal to the maximum recommended human intravenous dose based on body surface area) or in rabbits following intravenous administration of dexmedetomidine during the period of fetal organogenesis (from gestation day 6 to 18) with doses up to 96 mcg/kg (representing approximately half the human exposure at the maximum recommended dose based on plasma area under the time-curve comparison). however, fetal toxicity, as evidenced by increased post-implantation losses and reduced live pups, was observed in rats at a subcutaneous dose of 200 mcg/kg. the no-effect dose in rats was 20 mcg/kg (representing a dose less than the maximum recommended human intravenous dose based on a body surface area comparison). in another reproductive toxicity study when dexmedetomidine was administered subcutaneously to pregnant rats at 8 and 32 mcg/kg (representing a dose less than the maximum recommended human intravenous dose based on a body surface area comparison) from gestation day 16 through weaning, lower offspring weights were observed. additionally, when offspring of the 32 mcg/kg group were allowed to mate, elevated fetal and embryocidal toxicity and delayed motor development was observed in second generation offspring. the safety of dexmedetomidine hydrochloride in 0.9% sodium chloride injection during labor and delivery has not been studied. it is not known whether dexmedetomidine is excreted in human milk. radio-labeled dexmedetomidine administered subcutaneously to lactating female rats was excreted in milk. because many drugs are excreted in human milk, caution should be exercised when dexmedetomidine hydrochloride in 0.9% sodium chloride injection is administered to a nursing woman. safety and efficacy have not been established for procedural or icu sedation in pediatric patients. one assessor-blinded trial in pediatric patients and two open label studies in neonates were conducted to assess efficacy for icu sedation. these studies did not meet their primary efficacy endpoints and the safety data submitted were insufficient to fully characterize the safety profile of dexmedetomidine hydrochloride in 0.9% sodium chloride injection for this patient population. the use of dexmedetomidine hydrochloride in 0.9% sodium chloride injection for procedural sedation in pediatric patients has not been evaluated. intensive care unit sedation a total of 729 patients in the clinical studies were 65 years of age and over. a total of 200 patients were 75 years of age and over. in patients greater than 65 years of age, a higher incidence of bradycardia and hypotension was observed following administration of dexmedetomidine hydrochloride in 0.9% sodium chloride injection [ see warnings and precautions (5.2) ]. therefore, a dose reduction may be considered in patients over 65 years of age [ see  dosage and administration (2.2,2.3) and clinical pharmacology (12.3) ] . procedural sedation a total of 131 patients in the clinical studies were 65 years of age and over. a total of 47 patients were 75 years of age and over. hypotension occurred in a higher incidence in dexmedetomidine-treated patients 65 years or older (72%) and 75 years or older (74%) as compared to patients <65 years (47%). a reduced loading dose of 0.5 mcg/kg given over 10 minutes is recommended and a reduction in the maintenance infusion should be considered for patients greater than 65 years of age. since dexmedetomidine clearance decreases with increasing severity of hepatic impairment, dose reduction should be considered in patients with impaired hepatic function [ see dosage and administration (2.2, 2.3) and clinical pharmacology (12.3) ]. dexmedetomidine hydrochloride is not a controlled substance. the dependence potential of dexmedetomidine hydrochloride in 0.9% sodium chloride injection has not been studied in humans. however, since studies in rodents and primates have demonstrated that dexmedetomidine exhibits pharmacologic actions similar to those of clonidine, it is possible that dexmedetomidine hydrochloride in 0.9% sodium chloride injection may produce a clonidine-like withdrawal syndrome upon abrupt discontinuation [ see warnings and precautions (5.5) ].

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

amneal pharmaceuticals llc - dexmedetomidine hydrochloride (unii: 1018wh7f9i) (dexmedetomidine - unii:67vb76hono) - dexmedetomidine hydrochloride in 0.9% sodium chloride injection is indicated for sedation of initially intubated and mechanically ventilated adult patients during treatment in an intensive care setting. dexmedetomidine hydrochloride in 0.9% sodium chloride injection should be administered by continuous infusion not to exceed 24 hours. dexmedetomidine hydrochloride in 0.9% sodium chloride injection has been continuously infused in mechanically ventilated adult patients prior to extubation, during extubation, and post-extubation. it is not necessary to discontinue dexmedetomidine hydrochloride in 0.9% sodium chloride injection prior to extubation. dexmedetomidine hydrochloride in 0.9% sodium chloride injection is indicated for sedation of non-intubated adult patients prior to and/or during surgical and other procedures. pediatric use information is approved for hospira inc.’s precedextm (dexmedetomidine hydrochloride) in sodium chloride injection. however, due to hospira inc.’s marketing exclusivity rights, this drug product is not labeled with that information. none. risk summary available data from published randomized controlled trials and case reports over several decades of use with intravenously administered dexmedetomidine during pregnancy have not identified a drug-associated risk of major birth defects and miscarriage; however, the reported exposures occurred after the first trimester. most of the available data are based on studies with exposures that occurred at the time of caesarean section delivery and these studies have not identified an adverse effect on maternal outcomes or infant apgar scores. available data indicate that dexmedetomidine crosses the placenta. in animal reproduction studies, fetal toxicity that lower fetal viability and reduced live fetuses occurred with subcutaneous administration of dexmedetomidine to pregnant rats during organogenesis at doses 1.8 times the maximum recommended human dose (mrhd) of 17.8 mcg/kg/day. developmental toxicity (low pup weights and adult offspring weights, decreased f1 grip strength, increased early implantation loss and decreased viability of second-generation offspring) occurred when pregnant rats were subcutaneously administered dexmedetomidine at doses less than the clinical dose from late pregnancy through lactation and weaning (see data) . the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. 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. data animal data increased post-implantation losses and reduced live fetuses in the presence of maternal toxicity (i.e. decreased body weight) were noted in a rat embryo-fetal development study in which pregnant dams were administered subcutaneous doses of dexmedetomidine 200 mcg/kg/day (equivalent to 1.8 times the intravenous mrhd of 17.8 mcg/kg/day based on body surface area [bsa]) during the period of organogenesis (gestation day [gd] 6 to 15). no malformations were reported. no malformations or embryo-fetal toxicity were noted in a rabbit embryo-fetal development study in which pregnant does were administered dexmedetomidine intravenously at doses of up to 96 mcg/kg/day (approximately half the human exposure at the mrhd based on auc) during the period of organogenesis (gd 6 to 18). reduced pup and adult offspring birth weights, and grip strength were reported in a rat developmental toxicology study in which pregnant females were administered dexmedetomidine subcutaneously at doses of 8 mcg/kg/day (0.07 times the mrhd based on bsa) during late pregnancy through lactation and weaning (gd 16 to postnatal day [pnd] 25). decreased viability of second generation offspring and an increase in early implantation loss along with delayed motor development occurred in the 32 mcg/kg/day group (equivalent to less than the clinical dose based on bsa) when first generation offspring were allowed to mate. this study limited dosing to hard palate closure (gd 15 to 18) through weaning instead of dosing from implantation (gd 6 to 7) to weaning (pnd 21). in a study in the pregnant rat, placental transfer of dexmedetomidine was observed when radiolabeled dexmedetomidine was administered subcutaneously. risk summary available published literature reports the presence of dexmedetomidine in human milk following intravenous administration (see data) . there is no information regarding the effects of dexmedetomidine on the breastfed infant or the effects on milk production. advise women to monitor the breastfed infant for irritability. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for dexmedetomidine hydrochloride and any potential adverse effects on the breastfed infant from dexmedetomidine hydrochloride or from the underlying condition. data in two published clinical studies, a total of 14 women were given intravenous dexmedetomidine 6 mcg/kg/hour for 10 minutes after delivery followed by continuous infusion of 0.2 to 0.7 mcg/kg/hour. breast milk and maternal blood samples were collected at 0, 6, 12, and 24 hours after discontinuation of dexmedetomidine. plasma and milk dexmedetomidine  concentrations were detectable up to 6 hours in most subjects, up to 12 hours in one subject and undetectable in all at 24 hours. the milk-to-plasma ratio from single paired maternal milk and plasma concentrations at each time point ranged from 0.53 to 0.95. the relative infant dose was estimated to range from 0.02% to 0.098%. sedation for non-invasive procedures the safety and effectiveness of dexmedetomidine hydrochloride have not been established in pediatric patients less than 1 month of age. pediatric use information is approved for hospira inc.’s precedextm (dexmedetomidine hydrochloride) in sodium chloride injection. however, due to hospira inc.’s marketing exclusivity rights, this drug product is not labeled with that information. icu sedation the safety and efficacy of dexmedetomidine hydrochloride have not been established in pediatric patients for icu sedation. one assessor-blinded trial in pediatric patients and two open label studies in neonates were conducted to assess efficacy for icu sedation. these studies did not meet their primary efficacy endpoints and the safety data submitted were insufficient to fully characterize the safety profile of dexmedetomidine hydrochloride for these patient populations. intensive care unit sedation a total of 729 patients in the clinical studies were 65 years of age and over. a total of 200 patients were 75 years of age and over. in patients greater than 65 years of age, a higher incidence of bradycardia and hypotension was observed following administration of dexmedetomidine hydrochloride [see warnings and precautions (5.2)] . therefore, a dose reduction may be considered in patients over 65 years of age [see dosage and administration (2.2, 2.3), clinical pharmacology (12.3)]. procedural sedation a total of 131 patients in the clinical studies were 65 years of age and over. a total of 47 patients were 75 years of age and over. hypotension occurred in a higher incidence in dexmedetomidine hydrochloride-treated patients 65 years or older (72%) and 75 years or older (74%) as compared to patients < 65 years (47%). a reduced loading dose of 0.5 mcg/kg given over 10 minutes is recommended and a reduction in the maintenance infusion should be considered for patients greater than 65 years of age. since dexmedetomidine hydrochloride clearance decreases with increasing severity of hepatic impairment, dose reduction should be considered in patients with impaired hepatic function [see dosage and administration (2.2, 2.3), clinical pharmacology (12.3)] . dexmedetomidine hydrochloride is not a controlled substance. the dependence potential of dexmedetomidine hydrochloride has not been studied in humans. however, since studies in rodents and primates have demonstrated that dexmedetomidine hydrochloride exhibits pharmacologic actions similar to those of clonidine, it is possible that dexmedetomidine hydrochloride may produce a clonidine-like withdrawal syndrome upon abrupt discontinuation [see warnings and precautions (5.5)] .