PRECEDEX

What it is

PRECEDEX (dexmedetomidine) is a relatively selective alpha 2-adrenoreceptor agonist with sedative pharmacologic properties. PRECEDEX dexmedetomidine (as hydrochloride) concentrated injection is a sterile, non-pyrogenic solution suitable for intravenous (IV) infusion. It is supplied as a clear, colourless, isotonic solution with a pH of 4.5–7.0, presented in 2 mL ampoule, 4 mL vial or 10 mL vial, and must be diluted prior to use.

Approved indications

— Sedation of initially intubated adult patients during treatment in an intensive care setting, with use by continuous infusion not to exceed 24 hours. — Sedation of non-intubated adult patients prior to and/or during surgical and other procedures.

Dosing overview

For ICU sedation in adult patients, PRECEDEX may be initiated with a loading infusion of 1 microgram/kg over 10 to 20 minutes if needed, with continuous infusion not exceeding 24 hours. Maintenance infusion generally requires 0.2 to 1 microgram/kg/hr, with 0.4 microgram/kg/hr recommended as initial maintenance, adjusted to achieve desired sedation level. For procedural sedation in non-intubated patients, PRECEDEX is generally initiated with a loading infusion of 1 microgram/kg over 10 to 20 minutes, followed by maintenance dosing generally initiated at 0.6 microgram/kg/hr and titrated to achieve desired effect with doses ranging from 0.2 to 1 microgram/kg/hr. Dose reduction should be considered in patients with impaired hepatic function and in patients over 65 years of age; for such patients, a loading dose of 0.5 microgram/kg over 10 minutes may be suitable.

Key safety warnings

Clinically significant events of bradycardia and sinus arrest have been associated with dexmedetomidine administration in young, healthy adult volunteers with high vagal tone. Decreased blood pressure and/or heart rate may occur with administration of PRECEDEX. Reports of hypotension and bradycardia have been associated with dexmedetomidine infusion, and some cases have resulted in fatalities. Elderly patients over 65 years of age, or diabetic patients, are more prone to hypotension with the administration of dexmedetomidine. Transient hypertension has been observed primarily during the loading infusion, associated with initial peripheral vasoconstrictive effects of dexmedetomidine and relatively higher plasma concentrations achieved during the loading infusion. If intervention is necessary, reduction of the loading infusion rate may be considered. Following the loading infusion, the central effects of dexmedetomidine dominate and the blood pressure usually decreases. Use of dexmedetomidine greater than 24 hours has been associated with an increased mortality in critically ill adult ICU patients 65 years of age and younger compared to usual care. Dexmedetomidine may induce hyperthermia that may be resistant to traditional cooling methods. PRECEDEX should be discontinued and hyperthermia should be managed with conventional medical measures.

Contraindications

PRECEDEX is contraindicated in patients with a known hypersensitivity to dexmedetomidine, or any of the excipients contained in PRECEDEX.

Key safety warnings (continued from cardiovascular risk)

Caution should be exercised when administering PRECEDEX to patients with advanced heart block and/or severe ventricular dysfunction. Dexmedetomidine lacks the anticonvulsant action of some other sedatives and so will not suppress underlying seizure activity.

Regulatory history

PRECEDEX was first approved on 14 November 2022. ARTG registrations for PRECEDEX include: ARTG 81323 (dexmedetomidine hydrochloride 200 micrograms/2mL injection vial, first listed 2002-04-04); ARTG 234023 (PRECEDEX READY TO USE 200 micrograms/50 mL, first listed 2015-12-09); ARTG 234024 (PRECEDEX READY TO USE 400 micrograms/100 mL, first listed 2015-12-09); and ARTG 234022 (PRECEDEX READY TO USE 80 micrograms/20 mL, first listed 2015-12-09).