DEXMEDETOMIDINE HYDROCHLORIDE- dexmedetomidine hydrochloride in sodium chloride injection

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

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

Available from:

Amneal Pharmaceuticals LLC

Administration route:

INTRAVENOUS

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

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)] .

Product summary:

Dexmedetomidine Hydrochloride in 0.9% Sodium Chloride Injection is clear, colorless solution and is supplied as 200 mcg/50 mL (4 mcg/mL) and 400 mcg/100 mL (4 mcg/mL) strengths. It is available as follows: Concentration Unit of Sale Unit of Use 200 mcg/50 mL (4 mcg/mL) NDC 70121-1711-9 Carton of 24 Single-Dose flexible container NDC 70121-1711-1 50 mL Single-Dose flexible container in overwrap (aluminium pouch) NDC 70121-1711-2 Carton of 15 Single-Dose flexible container 400 mcg/100 mL (4 mcg/mL) NDC 70121-1712-3 Carton of 12 Single-Dose flexible container NDC 70121-1712-1 100 mL Single-Dose flexible container in overwrap (aluminium pouch) NDC 70121-1712-2 Carton of 10 Single-Dose flexible container Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Do not freeze. Do not use if product is discolored or if precipitate matter is present. Flexible containers are intended for single-dose only. Discard unused portion.

Authorization status:

Abbreviated New Drug Application

Summary of Product characteristics

DEXMEDETOMIDINE HYDROCHLORIDE- DEXMEDETOMIDINE HYDROCHLORIDE IN
SODIUM CHLORIDE INJECTION
AMNEAL PHARMACEUTICALS LLC
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
DEXMEDETOMIDINE
HYDROCHLORIDE IN 0.9% SODIUM CHLORIDE INJECTION SAFELY AND
EFFECTIVELY. SEE FULL
PRESCRIBING INFORMATION FOR DEXMEDETOMIDINE HYDROCHLORIDE IN 0.9%
SODIUM
CHLORIDE INJECTION.
DEXMEDETOMIDINE HYDROCHLORIDE IN 0.9% SODIUM CHLORIDE INJECTION, FOR
INTRAVENOUS USE
INITIAL U.S. APPROVAL: 1999
INDICATIONS AND USAGE
Dexmedetomidine hydrochloride 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 in
0.9% sodium chloride 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 in 0.9% sodium
chloride injection dosing to
desired clinical effect. (2.1)
Administer dexmedetomidine hydrochloride in 0.9% sodium chloride
injection using a controlled infusion
device. (2.1)
The 200 mcg/50 mL and 400 mcg/100 mL single-dose flexible container 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/kg/_hour_. (2.2)
Alternative Doses: Recommended for patients over 65 years of age and
awake fiberoptic intubation
patients. (2.2)
DOSAGE FORMS AND STRENGTHS
Dexmedetomidine hydrochloride in 0.9% sodium chloride injection, 200
mcg/50 mL (4 mcg/mL) in a
single-dose flexible c