Dexmedetomidine hydrochloride Injection, Concentrate

Procedural Sedation

Dexmedetomidine hydrochloride injection is indicated for sedation of non-intubated patients prior to and/or during surgical and other procedures.

Dexmedetomidine hydrochloride injection is a sterile, nonpyrogenic solution suitable for intravenous infusion following dilution. Dexmedetomidine hydrochloride is the S-enantiomer of medetomidine and is chemically described as (+)-4-(S)-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole monohydrochloride. Dexmedetomidine hydrochloride has a molecular weight of 236.7 and the empirical formula is C13H16N2•HCl and the structural formula is:

Dexmedetomidine hydrochloride is a white or almost white powder that is freely soluble in water and has a pKa of 7.1. Its partition coefficient in-octanol: water at pH 7.4 is 2.89.

Dexmedetomidine hydrochloride injection is supplied as a clear, colorless, isotonic solution with a pH of 4.5 to 7.0. Each mL contains 118 mcg of dexmedetomidine hydrochloride equivalent to 100 mcg (0.1 mg) of dexmedetomidine and 9 mg of sodium chloride in water and is to be used after dilution. The solution is preservative-free and contains no additives or chemical stabilizers.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Animal carcinogenicity studies have not been performed with dexmedetomidine.

Dexmedetomidine was not mutagenic in vitro, in either the bacterial reverse mutation assay ( E. coli and Salmonella typhimurium) or the mammalian cell forward mutation assay (mouse lymphoma). Dexmedetomidine was clastogenic in the in vitro human lymphocyte chromosome aberration test with, but not without, rat S9 metabolic activation. In contrast, dexmedetomidine was not clastogenic in the in vitro human lymphocyte chromosome aberration test with or without human S9 metabolic activation. Although dexmedetomidine was clastogenic in an in vivo mouse micronucleus test in NMRI mice, there was no evidence of clastogenicity in CD-1 mice.

Fertility in male or female rats was not affected after daily subcutaneous injections of dexmedetomidine at doses up to 54 mcg/kg (less than the maximum recommended human intravenous dose on a mcg/m 2 basis) administered from 10 weeks prior to mating in males, and 3 weeks prior to mating and during mating in females.

Animal Pharmacology and/or Toxicology

There were no differences in the adrenocorticotropic hormone (ACTH)-stimulated cortisol response in dogs following a single dose of dexmedetomidine compared to saline control. However, after continuous subcutaneous infusions of dexmedetomidine at 3 mcg/kg/hr and 10 mcg/kg/hr for one week in dogs (exposures estimated to be within the clinical range), the ACTH-stimulated cortisol response was diminished by approximately 27% and 40%, respectively, compared to saline-treated control animals indicating a dose-dependent adrenal suppression.

Dexmedetomidine hydrochloride injection

Dexmedetomidine hydrochloride injection, 200 mcg/2 mL (100 mcg/mL) is available in 2 mL clear glass vials. The strength is based on the dexmedetomidine base. Vials are intended for single use only. 25 Single-dose fliptop vials are packaged in one carton.

Store at 25°C (77°F), excursions permitted between 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature.]
Discard unused portion.
Sterile, Nonpyrogenic, Preservative-free.
The container closure is not made with natural rubber latex.

Dexmedetomidine hydrochloride injection is indicated for short-term intravenous sedation. Dosage must be individualized and titrated to the desired clinical effect. Blood pressure, heart rate and oxygen levels will be monitored both continuously during the infusion of dexmedetomidine hydrochloride injection and as clinically appropriate after discontinuation.

• When dexmedetomidine hydrochloride injection is infused for more than 6 hours, patients should be informed to report nervousness, agitation, and headaches that may occur for up to 48 hours.
• Additionally, patients should be informed to report symptoms that may occur within 48 hours after the administration of dexmedetomidine hydrochloride injection such as: weakness, confusion, excessive sweating, weight loss, abdominal pain, salt cravings, diarrhea, constipation, dizziness or light-headedness.

Manufactured by:

Jiangsu Hengrui Medicine Co., Ltd.
Lianyungang, Jiangsu 222047, China

Distributed by:
eVenus Pharmaceutical Laboratories, Inc.
506 Carnegie Center, Suite 100,
Princeton, NJ 08540 USA

Revised: August 2017

Rev. 03