ECCLADEX Concentrated solution for intravenous infusion Ref.[115322] Active ingredients: Dexmedetomidine

Posology

NOTE: ECCLADEX should be administered only by healthcare providers skilled in the management of patients in the intensive care setting. Continuous monitoring of vital signs, in particular blood pressure, heart rate and oxygen saturation is mandatory during infusion of ECCLADEX. In order to minimise undesirable pharmacologic side effects, bolus injections of ECCLADEX should not be used.

Clinically significant events of bradycardia and sinus arrest have been associated with dexmedetomidine hydrochloride administration in young healthy volunteers with high vagal tone, or with different routes of administration including rapid intravenous or bolus administration of dexmedetomidine hydrochloride.

Fluid supplementation should be administered prior to and during administration of ECCLADEX to ensure normovolaemia. ECCLADEX has been administered to patients requiring mechanical ventilation as well as to patients breathing spontaneously after extubation. There is no respiratory depression associated with the administration of ECCLADEX.

Patients receiving ECCLADEX have been observed to be arousable and alert when stimulated. This is an expected component of dexmedetomidine sedation and should not be considered as evidence of lack of efficacy in the absence of other clinical signs and symptoms. ECCLADEX has been continuously infused in mechanically ventilated patients prior to extubation, during extubation, and post extubation. It is not necessary to discontinue dexmedetomidine prior to extubation.

Adults

ICU Sedation

ECCLADEX dosage should be individualised and titrated to the desired clinical effect.

Initiation:

For adult patients, it is recommended to initiate ECCLADEX with a loading dose of 1,0 (one) microgram/kg over ten minutes.

Maintenance of ICU sedation:

Adult patients will generally require a maintenance infusion in the range of 0,2 to 0,7 microgram/kg/hr. The rate of the maintenance infusion can be adjusted in order to achieve the desired clinical effect. Dosages as low as 0,05 micrograms/kg/hr have been used in clinical studies.

A dose reduction for both the loading and maintenance infusions should be considered in patients with impaired hepatic or renal function and in patients over 65 years of age (see sections 4.3, 4.4 and 5.2).

Conscious Sedation

Monitored anaesthesia care (MAC) with an adequate nerve block and awake fibreoptic intubation (AFI) ECCLADEX dosing should be individualised and titrated to the desired clinical effect.

Initiation:

For adult patients, ECCLADEX is generally initiated with a loading infusion of 1 (one) mcg/kg over 10 minutes.

For patients over 65 years of age or those undergoing less invasive procedures such as ophthalmic surgery, aloading infusion of 0,5 mcg/kg over 10 minutes may be suitable.

Maintenance of Conscious Sedation:

MAC: Following the load, maintenance dosing of ECCLADEX should generally be initiated at 0,6 mcg/kg/hr and titrated to achieve desired clinical effect with doses ranging from 0,2 to 1 mcg/kg/hr for all procedures. The rate of the maintenance infusion should be adjusted to achieve the targeted level of sedation.

AFI: Following the load in awake fibreoptic intubation, a fixed maintenance dose of 0,7 mcg/kg/hr should be used.

Dosage Adjustment

Due to possible pharmacodynamic interactions a reduction in dosage of ECCLADEX or other concomitant anaesthetics, sedatives, hypnotics or opioids may be required when co-administered (see section 4.5).

Special populations

Elderly population

Since the elderly are more sensitive to the effects of ECCLADEX dosage reductions may need to be considered (see section 4.4).

Renal impairment

Since the majority of metabolites are excreted in the urine, dosage reductions may need to be considered for patients with renal impairment.

Hepatic impairment

Dosage reductions may need to be considered for patients with hepatic impairment, as ECCLADEX is metabolized primarily in the liver.

Paediatric population

Safety and efficacy of ECCLADEX has not been studied in children and adolescents and is therefore not recommended for patients under 18 years of age.

Method of administration

A controlled infusion device should be used to administer ECCLADEX. ECCLADEX should be administered by continuous intravenous infusion not to exceed 24 hours.

For instructions on preparation of the solution refer to section 6.6.

Parenteral products should be inspected visually for particulate matter and discolouration prior to administration.

Vials are intended for single patient use only.

Symptoms

Several cases of dexmedetomidine overdose have been reported both in the clinical trial and the post-marketing data.

The reported highest infusion rates of dexmedetomidine in these cases have reached up to 60 μg/kg/h for 36 minutes and 30 μg/kg/h for 15 minutes in a 20-month-old child and in an adult, respectively. The most common adverse reactions reported in conjunction with overdose include bradycardia, hypotension, hypertension, over sedation, respiratory depression and cardiac arrest. First-degree AV block and second-degree heart block may occur.

Treatment

In cases of overdose with clinical symptoms, dexmedetomidine infusion should be reduced or stopped. Expected effects are primarily cardiovascular and should be treated as clinically indicated (see section 4.4). At high concentration hypertension may be more prominent than hypotension. In clinical studies, cases of sinus arrest reversed spontaneously or responded to treatment with atropine and glycopyrrolate. Resuscitation was required in isolated cases of severe overdose resulting in cardiac arrest.

36 months.

Store at or below 25°C in original container. Protect from light. For storage of sterile products that have been opened, diluted or reconstituted, a cross-reference should be made to section 6.

ECCLADEX is packed in 5 x 2 ml glass ampoules in an outer carton.

ECCLADEX is packed in 4 x 4 ml glass vials closed with a fluoropolymer coated bromobutyl rubber stopper, secured with an aluminium over seal with a white plastic lid and packed in an outer carton.

ECCLADEX is packed in 4 x 10 ml glass vials closed with a fluoropolymer coated bromobutyl rubber stopper, secured with an aluminium over seal with a white plastic lid and packed in an outer carton.

Not all packs or pack sizes may be marketed.

Preparation of Solution

Strict aseptic technique must always be maintained during handling of ECCLADEX infusion. Preparation of infusion solutions is the same, whether for the loading dose or for the maintenance dose.

To prepare the infusion, withdraw 2 ml of ECCLADEX concentrate and add to 48 ml of 0,9% sodium chloride solution to total 50 ml. Shake gently to mix well.

After dilution, ECCLADEX is intended for immediate use and should be discarded after 24 hours.

Parenteral medicines should be inspected visually for particulate matter and discolouration prior to administration.

Ampoules/vials are intended for single patient use only.

ECCLADEX has been shown to be compatible when administered with the following intravenous fluids and medicines: Lactated Ringers, 5% Dextrose in Water, 0,9% Sodium Chloride in Water, 20% Mannitol, thiopental sodium, etomidate, vecuronium bromide, pancuronium bromide, succinylcholine, atracurium besylate, mivacurium chloride, glycopyrrolate bromide, phenylephrine HCI, atropine sulphate, midazolam, morphine sulphate, fentanyl citrate and a plasma-substitute (i.e. Haemacel).

Compatibility studies have shown potential for adsorption of ECCLADEX to some types of natural rubber. Although ECCLADEX is dosed to effect, it is advisable to use components with synthetic or coated natural rubber gaskets.