DEXMEDETOMIDINE HYDROCHLORIDE injection, solution, concentrate DEXMEDETOMIDINE HYDROCHLORIDE injection, solution

Χώρα: Ηνωμένες Πολιτείες

Γλώσσα: Αγγλικά

Πηγή: NLM (National Library of Medicine)

Δραστική ουσία:

DEXMEDETOMIDINE HYDROCHLORIDE (UNII: 1018WH7F9I) (DEXMEDETOMIDINE - UNII:67VB76HONO)

Διαθέσιμο από:

ENDO USA, Inc.

INN (Διεθνής Όνομα):

DEXMEDETOMIDINE HYDROCHLORIDE

Σύνθεση:

DEXMEDETOMIDINE 100 ug in 1 mL

Οδός χορήγησης:

INTRAVENOUS

Τρόπος διάθεσης:

PRESCRIPTION DRUG

Θεραπευτικές ενδείξεις:

Dexmedetomidine hydrochloride injection is indicated for sedation of initially intubated and mechanically ventilated adult patients during treatment in an intensive care setting. Dexmedetomidine hydrochloride injection should be administered by continuous infusion not to exceed 24 hours. Dexmedetomidine hydrochloride 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 injection prior to extubation. Dexmedetomidine hydrochloride 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 PRECEDEX™ (dexmedetomidine hydrochloride) injection and PRECEDEX™ (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 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 0.2–0.7 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 PRECEDEX™ (dexmedetomidine hydrochloride) injection and PRECEDEX™ (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)]. P r o ce dural 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), 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)].

Περίληψη προϊόντος:

D exmedetomidine Injection, USP NDC 42023-146-25:  200 mcg/2 mL (100 mcg/mL) is clear and colorless, and available in 2 mL clear glass vials supplied in packages of twenty-five. The strength is based on the dexmedetomidine base. Vials are intended for single-dose only. Discard unused portion. Dexmedetomidine Hydrochloride in 0.9% Sodium Chloride Injection NDC 42023-186-20: 200 mcg/50 mL (4 mcg/mL) is clear and colorless, and available in 50 mL clear glass vials supplied in packages of twenty.    NDC 42023-187-10: 400 mcg/100 mL (4 mcg/mL) is clear and colorless, and available in 100 mL clear glass vials supplied in packages of ten.  The strength is based on the dexmedetomidine base.  Vials are intended for single-dose only.  Discard unused portion. Vial stoppers do not contain natural rubber latex. Store at 20° to 25°C (68° to 77°F) (See USP Controlled Room Temperature.) Do not use if product is discolored or if precipitate matter is present.

Καθεστώς αδειοδότησης:

Abbreviated New Drug Application

Αρχείο Π.Χ.Π.

DEXMEDETOMIDINE HYDROCHLORIDE- DEXMEDETOMIDINE
HYDROCHLORIDE INJECTION, SOLUTION, CONCENTRATE
DEXMEDETOMIDINE HYDROCHLORIDE- DEXMEDETOMIDINE
HYDROCHLORIDE INJECTION, SOLUTION
ENDO USA, INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
DEXMEDETOMIDINE
INJECTION SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
DEXMEDETOMIDINE
INJECTION.
DEXMEDETOMIDINE INJECTION, FOR INTRAVENOUS USE
DEXMEDETOMIDINE HYDROCHLORIDE IN SODIUM CHLORIDE INJECTION, FOR
INTRAVENOUS USE
INITIAL U.S. APPROVAL: 1999
RECENT MAJOR CHANGES
Dosage and Administration, Preparation of Solution (2.4) 08/2022
Warnings and Precautions, Hyperthermia or Pyrexia (5.7) 08/2022
INDICATIONS AND USAGE
Dexmedetomidine hydrochloride injection is a alpha -adrenergic
receptor agonist indicated for:
Sedation of initially intubated and mechanically ventilated adult
patients during treatment in an
intensive care setting. Administer dexmedetomidine hydrochloride
injection by continuous infusion not
to exceed 24 hours. (1.1)
Sedation of non-intubated adult patients prior to and/or during
surgical and other procedures. (1.2)
DOSAGE AND ADMINISTRATION
Individualize and titrate dexmedetomidine hydrochloride injection
dosing to desired clinical effect. (2.1)
Administer dexmedetomidine hydrochloride injection using a controlled
infusion device. (2.1)
Dilute the 200 mcg/2 mL (100 mcg/mL) vial contents in 0.9% sodium
chloride solution to achieve
required concentration (4 mcg/mL) prior to administration. (2.4)
The 200 mcg/50 mL and 400 mcg/100 mL single-dose vials do not require
further dilution prior to
administration. (2.4)
For Adult Intensive Care Unit Sedation: Initiate at one mcg/kg over 10
_minutes_, followed by a
maintenance infusion of 0.2 to 0.7 mcg/kg/_hour_. (2.2)
For Adult Procedural Sedation: Initiate at one mcg/kg over 10
_minutes_, followed by a maintenance
infusion initiated at 0.6 mcg/kg/_hour_ and titrated to achieve
desired clinical effect with doses ranging
from 0.2 to 1 mcg/