Dexmedetomidine Accord

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Dexmedetomidine Accord 100 micrograms/ml concentrate for solution for infusion  
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each 1 ml of concentrate contains dexmedetomidine hydrochloride equivalent to 100.0  micrograms 
dexmedetomidine.  
 
Each 2 ml vial contains 200 micrograms of dexmedetomidine. 
Each 4 ml vial contains 400 micrograms of dexmedetomidine. 
Each 10 ml vial contains 1000 micrograms of dexmedetomidine. 
 
The concentration of the final solution after dilution should be either 4 micrograms/ml or 8 
micrograms/ml.  
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Concentrate for solution for infusion (sterile concentrate).  
 
The concentrate is a clear, colourless solution, pH 4.5 – 7.0  
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
 For sedation of adult ICU (Intensive Care Unit) patients requiring a sedation level not deeper than 
arousal in response to verbal stimulation (corresponding to Richmond Agitation-Sedation Scale 
(RASS) 0 to -3). 
 
 For sedation of non-intubated adult patients prior to and/or during diagnostic or surgical procedures 
requiring sedation, i.e. procedural/awake sedation. 
 
4.2 Posology and method of administration 
 
For sedation of adult ICU (Intensive Care Unit) patients requiring a sedation level not deeper 
than arousal in response to verbal stimulation (corresponding to Richmond Agitation-Sedation 
Scale (RASS) 0 to -3). 
 
For hospital use only. Dexmedetomidine Accord should be administered by healthcare professionals 
skilled in the management of patients requiring intensive care. 
 
Posology 
 
Patients already intubated and sedated may switch to dexmedetomidine with an initial infusion rate of 
0.7 micrograms/kg/h which may then be adjusted stepwise within the dose range 0.2 to 
1.4 micrograms/kg/h in order to achieve the desired level of sedation, depending on the patient’s 
response. A lower starting infusion rate should be considered for frail patients. Dexmedetomidine is 
very potent and the infusion rate is given per hour. After dose adjustment, a new steady state sedation 
level may not be reached for up to one hour. 

Maximum dose 



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The maximum dose of 1.4 micrograms/kg/h should not be exceeded. Patients failing to achieve an 
adequate level of sedation with the maximum dose of dexmedetomidine should be switched to an 
alternative sedative agent. 
 
Use of a loading dose of Dexmedetomidine Accord in ICU sedation is not recommended and is 
associated with increased adverse reactions. Propofol or midazolam may be administered if needed 
until clinical effects of dexmedetomidine are established.  
 
Duration 
 
There is no experience in the use of dexmedetomidine for more than 14 days. The use of 
dexmedetomidine for longer than this period should be regularly reassessed.  
 
For sedation of non-intubated adult patients prior to and/or during diagnostic or surgical 
procedures requiring sedation, i.e. procedural/awake sedation. 
 
Dexmedetomidine Accord should be administered only by health care professionals skilled in the 
anaesthetic management of patients in the operating room or during diagnostic procedures. When 
Dexmedetomidine Accord is administered for conscious sedation, patients should be continuously 
monitored by persons not involved in the conduct of the diagnostic or surgical procedure. Patients 
should be monitored continuously for early signs of hypotension, hypertension, bradycardia, 
respiratory depression, airway obstruction, apnoea, dyspnoea and/or oxygen desaturation (see section 
4.8).  
 
Supplemental oxygen should be immediately available and provided when indicated. The oxygen 
saturation should be monitored by pulse oximetry. 
 
Dexmedetomidine Accord is given as a loading infusion followed by maintenance infusion. 
Depending on the procedure concomitant local anaesthesia or analgesia may be needed in order to 
achieve the desired clinical effect. Additional analgesia or sedatives (e.g. opioids, midazolam, or 
propofol) are recommended in case of painful procedures or if increased depth of sedation is 
necessary. The pharmacokinetic distribution half –life of dexmedetomidine has been estimated to be 
around 6 min, which can be taken into consideration, together with the effects of other administered 
medications, when assessing the appropriate time needed for titration to desired clinical effect of  
dexmedetomidine. 
 
Initiation of Procedural Sedation: 
 
- A loading infusion of 1.0 microgram/kg over 10 minutes. For less invasive procedures such as 

ophthalmic surgery, a loading infusion of 0.5 micrograms/kg given over 10 minutes may be 
suitable. 
 

Maintenance of Procedural Sedation: 
 
- The maintenance infusion is generally initiated at 0.6-0.7 microgram/kg/hour and titrated to 

achieve desired clinical effect with doses ranging from 0.2 to 1 microgram/kg/hour. The rate of 
the maintenance infusion should be adjusted to achieve the targeted level of sedation. 

 
Special populations 
 
Elderly  
 
No dose adjustment is normally required for elderly patients (see section 5.2). Elderly patients appear 
to have an increased risk for hypotension (see section 4.4) but the limited data available from 
procedural sedation do not suggest a clear dose dependency.  



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Renal impairment  
 
No dose adjustment is required for patients with renal impairment. 
 
Hepatic impairment  
 
Dexmedetomidine is metabolised in the liver and should be used with caution in patients with hepatic 
impairment. A reduced maintenance dose may be considered (see sections 4.4 and 5.2). 
 
Paediatric population  
 
The safety and efficacy of dexmedetomidine in children aged 0 to 18 years have not been established. 
Currently available data are described in sections 4.8, 5.1 and 5.2 but no recommendation on a 
posology can be made. 
 
Method of administration  
 
Dexmedetomidine Accord must be administered only as a diluted intravenous infusion using a 
controlled infusion device. For instructions on dilution of the medicinal product before administration, 
see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
Advanced heart block (grade 2 or 3) unless paced. 
 
Uncontrolled hypotension. 
 
Acute cerebrovascular conditions. 
 
4.4 Special warnings and precautions for use 
 
Monitoring 
 
Dexmedetomidine Accord is intended for use in an intensive care setting, operating room and during 
diagnostic procedures. The use in other environments is not recommended. All patients should have 
continuous cardiac monitoring during Dexmedetomidine Accord infusion. Respiration should be 
monitored in non-intubated patients due to the risk of respiratory depression and in some case apnoea 
(see section 4.8). 
 
The time to recovery after the use of dexmedetomidine was reported to be approximately one hour. 
When used in an outpatient setting close monitoring should continue for at least one hour (or longer 
based on the patient condition), with medical supervision continued for at least one further hour to 
ensure the safety of the patient. 
 
General precautions 
 
Dexmedetomidine Accord should not be given as a bolus dose and in the ICU a loading dose is not 
recommended. Users should therefore be ready to use an alternative sedative for acute control of 
agitation or during procedures, especially during the first few hours of treatment. During procedural 
sedation a small bolus of another sedative may be used if a rapid increase in sedation level is required. 
Some patients receiving dexmedetomidine have been observed to be arousable and alert when 
stimulated. This alone should not be considered as evidence of lack of efficacy in the absence of other 
clinical signs and symptoms.  



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Dexmedetomidine normally does not cause deep sedation and patients may be easily roused. 
Dexmedetomidine is therefore not suitable in patients who will not tolerate this profile of effects, for 
example those requiring continuous deep sedation. 
 
Dexmedetomidine Accord should not be used as a general anaesthetic induction agent for intubation or 
to provide sedation during muscle relaxant use. 
 
Dexmedetomidine lacks the anticonvulsant action of some other sedatives and so will not suppress 
underlying seizure activity. 
 
Care should be taken if combining dexmedetomidine with other substances with sedative or 
cardiovascular actions as additive effects may occur. 
 
Dexmedetomidine Accord is not recommended for patient controlled sedation. Adequate data is not 
available. 
 
When Dexmedetomidine Accord is used in an outpatient setting patients should normally be 
discharged into the care of a suitable third party. Patients should be advised to refrain from driving or 
other hazardous tasks and where possible to avoid the use of other agents that may sedate (e.g, 
benzodiazepines, opioids, alcohol) for a suitable period of time based on observed effects of 
dexmedetomidine, the procedure, concomitant medications, the age and the condition of the patient. 
 
Caution should be exercised when administering dexmedetomidine to elderly patients. Elderly patients 
over 65 years of age may be more prone to hypotension with the administration of dexmedetomidine, 
including a loading dose, for procedures. A dose reduction should be considered. Please refer to 
section 4.2. 
 
Cardio-vascular effects and precautions 
 
Dexmedetomidine reduces heart rate and blood pressure through central sympatholysis but at higher 
concentrations causes peripheral vasoconstriction leading to hypertension (see section 5.1). 
Dexmedetomidine is therefore not suitable in patients with severe cardiovascular instability.  
 
Caution should be exercised when administering dexmedetomidine to patients with pre-existing 
bradycardia. Data on the effects of dexmedetomidine in patients with heart rate <60 are very limited 
and particular care should be taken with such patients. Bradycardia does not normally require 
treatment, but has commonly responded to anti-cholinergic medicine or dose reduction where needed. 
Patients with high physical fitness and slow resting heart rate may be particularly sensitive to 
bradycardic effects of alpha-2 receptor agonists and cases of transient sinus arrest have been reported. 
Also cases of cardiac arrest, often preceded by bradycardia or atrioventricular block, have been 
reported (see section 4.8). 
 
The hypotensive effects of dexmedetomidine may be of greater significance in those patients with pre-
existing hypotension (especially if not responsive to vasopressors), hypovolaemia, chronic 
hypotension or reduced functional reserve such as patients with severe ventricular dysfunction and the 
elderly and special care is warranted in these cases (see section 4.3). Hypotension does not normally 
require specific treatment but, where needed, users should be ready to intervene with dose reduction, 
fluids and/or vasoconstrictors . 
 
Patients with impaired peripheral autonomic activity (e.g. due to spinal cord injury) may have more 
pronounced haemodynamic changes after starting dexmedetomidine and so should be treated with 
care. 
 
Transient hypertension has been observed primarily during the loading dose in association with the 
peripheral vasoconstrictive effects of dexmedetomidine and a loading dose is not recommended in 



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ICU sedation. Treatment of hypertension has generally not been necessary but decreasing the 
continuous infusion rate may be advisable. 
 
Local vasoconstriction at higher concentration may be of greater significance in patients with 
ischaemic heart disease or severe cerebrovascular disease who should be monitored closely. Dose 
reduction or discontinuation should be considered in a patient developing signs of myocardial or 
cerebral ischaemia. 
 
Caution is advised when administering dexmedetomidine together with spinal or epidural anaesthesia 
due to possible increased risk of hypotension or bradycardia.  
 
Patients with hepatic impairment 
 
Care should be taken in severe hepatic impairment as excessive dosing may increase the risk of 
adverse reactions, over-sedation or prolonged effect as a result of reduced dexmedetomidine clearance. 
 
Patients with neurological disorders 
 
Experience of dexmedetomidine in severe neurological disorders such as head injury and after 
neurosurgery is limited and it should be used with caution here, especially if deep sedation is required. 
Dexmedetomidine may reduce cerebral blood flow and intracranial pressure and this should be 
considered when selecting therapy. 
 
Other 
 
Alpha-2 agonists have rarely been associated with withdrawal reactions when stopped abruptly after 
prolonged use. This possibility should be considered if the patient develops agitation and hypertension 
shortly after stopping dexmedetomidine. 
 
Dexmedetomidine may induce hyperthermia that may be resistant to traditional cooling methods. 
Dexmedetomidine treatment should be discontinued in the event of a sustained unexplained fever and 
is not recommended for use in malignant hyperthermia-sensitive patients. 
 
Dexmedetomidine Accord contains less than 1 mmol sodium (23 mg) per ml. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Interaction studies have only been performed in adults. 
 
Co-administration of dexmedetomidine with anaesthetics, sedatives, hypnotics, and opioids is likely to 
lead to an enhancement of effects, including sedative, anaesthetic and cardiorespiratory effects. 
Specific studies have confirmed enhanced effects with isoflurane, propofol, alfentanil, and midazolam.  
 
No pharmacokinetic interactions between dexmedetomidine and isoflurane, propofol, alfentanil and 
midazolam have been demonstrated. However, due to possible pharmacodynamic interactions, when 
co-administered with dexmedetomidine, a reduction in dosage of dexmedetomidine or the concomitant 
anaesthetic, sedative, hypnotic or opioid may be required. 
 
Inhibition of CYP enzymes including CYP2B6 by dexmedetomidine has been studied in human liver 
microsome incubations. In vitro study suggests that interaction potential in vivo exists between 
dexmedetomidine and substrates with dominant CYP2B6 metabolism. 
 
Induction of dexmedetomidine in vitro was observed on CYP1A2, CYP2B6, CYP2C8, CYP2C9 and 
CYP3A4, and induction in vivo cannot be excluded. The clinical significance is unknown. 
 



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The possibility of enhanced hypotensive and bradycardic effects should be considered in patients 
receiving other medicinal products causing these effects, for example beta blockers, although 
additional effects in an interaction study with esmolol were modest. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no or limited amount of data from the use of dexmedetomidine in pregnant women.  
 
Studies in animals have shown reproductive toxicity (see section 5.3). Dexmedetomidine Accord 
should not be used during pregnancy unless the clinical condition of the woman requires treatment 
with dexmedetomidine.  
 
Breast-feeding 
 
Dexmedetomidine is excreted in human milk, however levels will be below the limit of detection by 
24 hours following treatment discontinuation. A risk to infants cannot be excluded. A decision must be 
made whether to discontinue breast-feeding or to discontinue dexmedetomidine therapy taking into 
account the benefit of breastfeeding for the child and the benefit of therapy for the woman. 
 
Fertility 
 
In the rat fertility study, dexmedetomidine had no effect on male or female fertility. No human data on 
fertility are available. 
 
4.7 Effects on ability to drive and use machines 
 
Patients should be advised to refrain from driving or other hazardous tasks for a suitable period of time 
after receiving Dexmedetomidine Accord for procedural sedation. 
 
4.8 Undesirable effects  
 
Summary of the safety profile 
 
Sedation of adult ICU (Intensive Care Unit) patients 
The most frequently reported adverse reactions with dexmedetomidine in ICU setting are hypotension, 
hypertension and bradycardia, occurring in approximately 25%, 15% and 13% of patients respectively.  
Hypotension and bradycardia were also the most frequent dexmedetomidine-related serious adverse 
reactions occurring in 1.7% and 0.9% of randomised Intensive Care Unit (ICU) patients respectively. 
 
Procedural/awake sedation  
The most frequently reported adverse reactions with dexmedetomidine in procedural sedation are 
listed below (the protocols of phase III studies contained pre-defined thresholds for reporting changes 
in blood pressure, respiratory rate and heart rate as AEs). 
- Hypotension (55 % in dexmedetomidine-group vs. 30 % in placebo-group receiving rescue 

midazolam and fentanyl) 
- Respiratory depression ( 38 % in dexmedetomidine-group vs. 35 % in placebo-group receiving 

rescue midazolam and fentanyl) 
- Bradycardia (14 % in dexmedetomidine-group vs. 4 % in placebo-group receiving rescue 

midazolam and fentanyl) 
  
Tabulated list of adverse reactions 
 
The adverse reactions listed in Table 1 have been accumulated from pooled data of clinical trials in 
intensive care. 



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Adverse reactions are ranked under headings of frequency, the most frequent first, using the following 
convention: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare 
(≥1/10,000 to <1/1,000), very rare (<1/10,000).  
 
Table 1. Adverse reactions 
 
Metabolism and nutrition disorders 
Common: Hyperglycaemia, hypoglycaemia 
Uncommon: Metabolic acidosis, hypoalbuminaemia 
 
Psychiatric disorders 
Common: Agitation 
Uncommon: Hallucination 
 
Cardiac disorders 
Very common: Bradycardia1,2 
Common: Myocardial ischaemia or infarction, tachycardia 
Uncommon: Atrioventricular block1, cardiac output decreased, cardiac arrest1 
 
Vascular disorders: 
Very common: Hypotension1,2, hypertension1,2 
 
Respiratory, thoracic and mediastinal disorders 
Very common: Respiratory depression2,3 
Uncommon: Dyspnoea, apnoea 
 
Gastrointestinal disorders 
Common: Nausea2, vomiting, dry mouth2 
Uncommon: Abdominal distension  
 
Renal and urinary disorders 
Not known: Polyuria 
 
General disorders and administration site conditions 
Common: Withdrawal syndrome, hyperthermia 
Uncommon:  Drug ineffective, thirst 
 
1 See section on Description of selected adverse reactions 
2 Adverse reaction observed also in procedural sedation studies 
3 Incidence ‘common’ in ICU sedation studies 
 
Description of selected adverse reactions  
 
Clinically significant hypotension or bradycardia should be treated as described in section 4.4. 
 
In relatively healthy non-ICU subjects treated with dexmedetomidine, bradycardia has occasionally 
led to sinus arrest or pause. The symptoms responded to leg raising and anticholinergics such as 
atropine or glycopyrrolate. In isolated cases bradycardia has progressed to periods of asystole in 
patients with pre-existing bradycardia. Also cases of cardiac arrest, often preceded by bradycardia or 
atrioventricular block, have been reported. 
 
Hypertension has been associated with the use of a loading dose and this reaction can be reduced by 
avoiding such a loading dose or reducing the infusion rate or size of the loading dose. 
 



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Paediatric population 
 
Children > 1 month post-natal, predominantly post-operative, have been evaluated for treatment up to 
24 hours in the ICU and demonstrated a similar safety profile as in adults. Data in new-born infants 
(28 – 44 weeks gestation) is very limited and restricted to maintenance doses ≤ 0.2 mcg/kg/h. A single 
case of hypothermic bradycardia in a neonate has been reported in the literature. 
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.  
 
4.9 Overdose 
 
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, oversedation, respiratory depression and cardiac arrest.  
 
Management 
 
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.  
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Psycholeptics, other hypnotics and sedatives, ATC code: N05CM18 
 
Dexmedetomidine is a selective alpha-2 receptor agonist with a broad range of pharmacological 
properties. It has a sympatholytic effect through decrease of the release of noradrenaline in 
sympathetic nerve endings. The sedative effects are mediated through decreased firing of locus 
coeruleus, the predominant noradrenergic nucleus, situated in the brainstem. Dexmedetomidine has 
analgesic and anaesthetic/analgesic-sparing effects. The cardiovascular effects depend on the dose; 
with lower infusion rates the central effects dominate leading to decrease in heart rate and blood 
pressure. With higher doses, peripheral vasoconstricting effects prevail leading to an increase in 
systemic vascular resistance and blood pressure, while the bradycardic effect is further emphasised. 
Dexmedetomidine is relatively free from respiratory depressive effects when given as monotherapy to 
healthy subjects.  
 
Sedation of adult ICU (Intensive Care Unit) patients 
 
In placebo controlled trials in a post-operative ICU population previously intubated and sedated with 
midazolam or propofol, dexmedetomidine  significantly reduced the requirement for both rescue 
sedative (midazolam or propofol) and opioids during sedation for up to 24 hours. Most 

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dexmedetomidine patients required no additional sedative treatment. Patients could be successfully 
extubated without stopping the dexmedetomidine infusion. Studies from outside the ICU have 
confirmed that dexmedetomidine  can be administered safely to patients without endotracheal 
intubation provided adequate monitoring is in place.  
 
Dexmedetomidine was similar to midazolam (Ratio 1.07; 95% CI 0.971, 1.176) and propofol (Ratio 
1.00; 95% CI 0.922, 1.075) on the time in target sedation range in a predominently medical population 
requiring prolonged light to moderate sedation (RASS 0 to -3) in the ICU for up to 14 days, reduced 
the duration of mechanical ventilation compared to midazolam and reduced the time to extubation 
compared to midazolam and propofol. Compared to both propofol and midazolam, patients were more 
easily roused, more cooperative and better able to communicate whether or not they had pain. 
Dexmedetomidine treated patients had more frequent hypotension and bradycardia but less tachycardia 
than those receiving midazolam and more frequent tachycardia but similar hypotension to propofol-
treated patients. Delirium measured by the CAM-ICU scale was reduced in a study compared to 
midazolam and delirium-related adverse events were lower on dexmedetomidine compared to 
propofol. Those patients who withdrew due to insufficient sedation were switched to either propofol or 
midazolam. The risk of insufficient sedation was increased in patients who were difficult to sedate 
with standard care immediately prior to switching. 
 
Evidence of paediatric efficacy was seen in a dose-controlled ICU study in a largely post-operative 
population aged 1 month to ≤ 17 years. Approximately 50% of patients treated with dexmedetomidine 
did not require rescue addition of midazolam during a median treatment period of 20.3 hours, not 
exceeding 24 hours. Data on treatment for > 24 hours is not available. Data in new-born infants (28 – 
44 weeks gestation) is very limited and restricted to low doses (≤ 0.2 mcg/kg/h) (see sections 5.2 and 
4.4). New-born infants may be particularly sensitive to the bradycardic effects of Dexmedetomidine 
Accord  in the presence of hypothermia and in conditions of heart rate-dependent cardiac output.  
 
In double blind comparator controlled ICU studies the incidence of cortisol suppression in patients 
treated with dexmedetomidine (n=778) was 0.5% compared with 0% in patients treated with either 
midazolam (n=338) or propofol (n=275). The event was reported as mild in 1 and moderate in 3 cases. 
 
Procedural/awake sedation 
 
The safety and efficacy of dexmedetomidine for sedation of non-intubated patients prior to and/or 
during surgical and diagnostic procedures was evaluated in two randomised, double-blind, placebo-
controlled multicentre clinical trials. 
 

 Study 1 randomised patients undergoing elective surgeries/procedures under monitored 
anaesthesia care and local/regional anaesthesia to receive a loading infusion of 
dexmedetomidine either 1 µg/kg (n=129) or 0.5 µg/kg (n=134), or placebo (normal saline; 
n=63) given over 10 minutes and followed by a maintenance infusion started at 0.6 µg/kg/h. 
The maintenance infusion of study drug could be titrated from 0.2 µg/kg/h to 1 µg/kg/h. The 
proportion of patients that achieved the targeted sedation level (Observer’s Assessment of 
Alertness/Sedation Scale ≤4) without need for rescue midazolam was 54% of the patients 
receiving dexmedetomidine 1 µg/kg and 40% of the patients receiving dexmedetomidine 0.5 
µg/kg compared to 3% of patients receiving the placebo.The risk difference in proportion of 
subjects randomised to dexmedetomidine 1 μg/kg group and dexmedetomidine 0.5 μg/kg 
group not requiring rescue midazolam was 48% (95% CI: 37 % - 57%) and 40% (95% CI: 
28% - 48%), respectively compared placebo. The median (range) midazolam rescue dose was 
1.5 (0.5-7.0) mg in the dexmedetomidine1.0 µg/kg group, 2.0 (0.5-8.0) mg in the 
dexmedetomidine 0.5 µg/kg group, and 4.0 (0.5-14.0) mg in the placebo group. The 
difference in means in dose of rescue midazolam in dexmedetomidine 1 μg/kg and 
dexmedetomidine 0.5 μg/kg group compared to placebo was -3.1 mg (95% CI: -3.8 - -2.5) 
and -2.7 mg (95% CI: -3.3 - -2.1), respectively favouring dexmedetomidine.The median time 
to first rescue dose was 114 minutes in the dexmedetomidine 1.0 µg/kg group, 40 minutes in 
the dexmedetomidine 0.5 µg/kg group, and 20 minutes in the placebo group.   



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 Study 2 randomised patients undergoing awake fibreoptic intubation under topical anaesthesia 
to receive a loading infusion of dexmedetomidine 1 µg/kg (n=55) or placebo (normal saline) 
(n=50) given over 10 minutes and followed by a fixed maintenance infusion of 0.7 µg/kg/h. 
To maintain a Ramsay Sedation Scale ≥2 53% of the patients receiving dexmedetomidine did 
not require midazoloam rescue vs. 14% of patients receiving placebo. The risk difference in 
proportion of subjects randomised to dexmedetomidine not requiring rescue midazolam was 
43% (95% CI: 23 % - 57%) compared placebo. The mean midazolam rescue dose was 1.1 
mg in the dexmedetomidine group, and 2.8 mg in the placebo group. The difference in means 
in dose of rescue midazolam was -1.8 mg (95% CI: -2.7 - -0.86) favouring dexmedetomidine. 

 
5.2 Pharmacokinetic properties 
 
The pharmacokinetics of dexmedetomidine has been assessed following short term IV administration 
in healthy volunteers and long term infusion in ICU population.  
 
Distribution 
 
Dexmedetomidine exhibits a two-compartment disposition model. In healthy volunteers it exhibits a 
rapid distribution phase with a central estimate of the distribution half-life (t1/2α) of about 6 minutes. 
The mean estimate of the terminal elimination half-life (t1/2) is approximately 1.9 to 2.5 h (min 1.35, 
max 3.68 h) and the mean estimate of the steady-state volume of distribution (Vss) is approximately 
1.16 to 2.16 l/kg (90 to 151 litres). Plasma clearance (Cl) has a mean estimated value of 0.46 to 
0.73 l/h/kg (35.7 to 51.1 l/h). The mean body weight associated with these Vss and Cl estimates was 
69 kg. Plasma pharmacokinetics of dexmedetomidine is similar in the ICU population following 
infusion >24 h. The estimated pharmacokinetic parameters are: t1/2 approximately 1.5 hours, Vss 
approximately 93 litres and Cl approximately 43 l/h. The pharmacokinetics of dexmedetomidine is 
linear in the dosing range from 0.2 to 1.4 µg/kg/h and it does not accumulate in treatments lasting up 
to 14 days. Dexmedetomidine is 94% bound to plasma proteins. Plasma protein binding is constant 
over the concentration range of 0.85 to 85 ng/ml. Dexmedetomidine binds to both human serum 
albumin and Alpha-1-acid glycoprotein with serum albumin as the major binding protein of 
dexmedetomidine in plasma.  
 
Biotransformation and Elimination 
 
Dexmedetomidine is eliminated by extensive metabolism in the liver. There are three types of initial 
metabolic reactions; direct N-glucuronidation, direct N-methylation and cytochrome P450 catalysed 
oxidation. The most abundant circulating dexmedetomidine metabolites are two isomeric N-
glucuronides. Metabolite H-1, N-methyl 3-hydroxymethyl dexmedetomidine O-glucuronide, is also a 
major circulating product of dexmedetomidine biotransformation. Cytochrome P-450 catalyses the 
formation of two minor circulating metabolites, 3-hydroxymethyl dexmedetomidine produced by 
hydroxylation at the 3-methyl group of dexmedetomidine and H-3 produced by oxidation in the 
imidazole ring. Available data suggest that the formation of the oxidised metabolites is mediated by 
several CYP forms (CYP2A6, CYP1A2, CYP2E1, CYP2D6 and CYP2C19). These metabolites have 
negligible pharmacological activity.  
 
Following IV administration of radiolabeled dexmedetomidine an average 95% of radioactivity was 
recovered in the urine and 4% in the faeces after nine days. The major urinary metabolites are the two 
isomeric N-glucuronides, which together accounted for approximately 34% of the dose and N-methyl 
3-hydroxymethyl dexmedetomidine O-glucuronide that accounted for 14.51% of the dose. The minor 
metabolites dexmedetomidine carboxylic acid, 3-hydroxymethyl dexmedetomidine and its O-
glucuronide individually comprised 1.11 to 7.66% of the dose. Less than 1% of unchanged parent drug 
was recovered in the urine. Approximately 28% of the urinary metabolites are unidentified minor 
metabolites.  
 
Special Populations 
 
No major pharmacokinetic differences have been observed based on gender or age. 



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Dexmedetomidine plasma protein binding is decreased in subjects with hepatic impairment compared 
with healthy subjects. The mean percentage of unbound dexmedetomidine in plasma ranged from 
8.5% in healthy subjects to 17.9% in subjects with severe hepatic impairment. Subjects with varying 
degrees of hepatic impairment (Child-Pugh Class A, B, or C) had decreased hepatic clearance of 
dexmedetomidine and prolonged plasma elimination t1/2. The mean plasma clearance values of 
unbound dexmedetomidine for subjects with mild, moderate, and severe hepatic impairment were 
59%, 51% and 32% of those observed in the normal healthy subjects, respectively. The mean t1/2 for 
the subjects with mild, moderate or severe hepatic impairment was prolonged to 3.9, 5.4, and 
7.4 hours, respectively. Although dexmedetomidine is administered to effect, it may be necessary to 
consider initial/maintenance dose reduction in patients with hepatic impairment depending on the 
degree of impairment and the response. 
 
The pharmacokinetics of dexmedetomidine in subjects with severe renal impairment (creatinine 
clearance <30 ml/min) is not altered relative to healthy subjects.  
 
Data in new-born infants (28 - 44 weeks gestation) to children 17 years of age are limited. 
Dexmedetomidine half life in children (1 months to 17 years) appears similar to that seen in adults, but 
in new-born infants (under 1 month) it appears higher. In the age groups 1 months to 6 years, body 
weight-adjusted plasma clearance appeared higher but decreased in older children. Body weight-
adjusted plasma clearance in new-born infants (under 1 month) appeared lower (0.9 l/h/kg) than in the 
older groups due to immaturity. The available data is summarised in the following table; 
 
  Mean (95% CI) 

Age N Cl (l/h/kg) t1/2 (h) 

Under 1 month 28 0.93 (0.76, 1.14) 
4.47 

(3.81, 5.25) 

1 to < 6 months 14 1.21 (0.99, 1.48) 
2.05 

(1.59, 2.65) 

6 to < 12 months 15 1.11 (0.94, 1.31) 
2.01 

(1.81, 2.22) 

12 to < 24 months 13 1.06 (0.87, 1.29) 
1.97 

(1.62, 2.39) 

2 to < 6 years 26 
1.11 

(1.00, 1.23) 
1.75 

(1.57, 1.96) 

6 to < 17 years 28 0.80 
(0.69, 0.92) 

2.03 
(1.78, 2.31) 

 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, single and repeated dose toxicity and genotoxicity.  
 
In the reproductive toxicity studies, dexmedetomidine had no effect on male or female fertility in the 
rat, and no teratogenic effects were observed in the rat or rabbit. In the rabbit study intravenous 
administration of the maximum dose, 96 µg/kg/day, produced exposures that are similar to those 
observed clinically. In the rat, subcutaneous administration at the maximum dose, 200 µg/kg/day, 
caused an increase in embryofetal death and reduced the fetal body weight. These effects were 
associated with clear maternal toxicity. Reduced fetal body weight was noted also in the rat fertility 
study at dose 18 µg/kg/day and was accompanied with delayed ossification at dose 54 µg/kg/day. The 
observed exposure levels in the rat are below the clinical exposure range.  
 
 
6. PHARMACEUTICAL PARTICULARS 
 



13 
 

6.1 List of excipients 
 
Sodium chloride 
Water for injections 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
Compatibility studies have shown potential for adsorption of dexmedetomidine to some types of 
natural rubber. Although dexmedetomidine is dosed to effect, it is advisable to use components with 
synthetic or coated natural rubber gaskets. 
 
6.3 Shelf life 
 
2 years 
 
After dilution 
Chemical and physical in-use stability has been demonstrated for 72 hours at 25°C and 2° to 8°C. 
From a microbiological point of view, the product should be used immediately. If not used 
immediately, in-use storage times and conditions prior to the use are the responsibility of the user and 
would not normally be longer than 24 hours at 2° to 8°C, unless dilution has taken place in controlled 
and validated aseptic conditions. 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special temperature storage conditions. Keep the vials in 
the outer carton in order to protect from light. 
 
For storage conditions after dilution of the medicinal product, see section 6.3 
 
6.5 Nature and contents of container  
 
2, 6 or 10 ml Type I glass vials (with filling volumes of 2, 4 and 10 ml), rubber stopper and aluminium 
flip off white seal (for 2ml and 4 ml) and red seal (for 10ml). 
 
Pack sizes 
1 x 2 ml vial 
4 x 2 ml vials 
5 x 2 ml vials 
25 x 2 ml vials 
1 x 4 ml vial 
4 x 4 ml vials 
5 x 4 ml vials 
1 x 10 ml vial 
4 x 10 ml vials 
5 x 10 ml vials 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Vials are intended for single patient use only. 
 
Preparation of solution 
 



14 
 

Dexmedetomidine Accord can be diluted in glucose 50 mg/ml (5%), Ringers, mannitol or sodium 
chloride 9 mg/ml (0.9%) solution for injection to achieve the required concentration of either 
4 micrograms/ml or 8 micrograms/ml prior to administration. Please see below in tabulated form the 
volumes needed to prepare the infusion.   
 
In case the required concentration is 4 micrograms/ml: 
 

Volume of 
Dexmedetomidine Accord 

100 micrograms/ml 
concentrate for solution for 

infusion 

Volume of diluent  Total volume of infusion 

2 ml 48 ml 50 ml 

4 ml 96 ml 100 ml 

10 ml 240 ml 250 ml 

20 ml 480 ml 500 ml 
 
In case the required concentration is 8 micrograms/ml: 
 

Volume of 
Dexmedetomidine Accord 

100 micrograms/ml 
concentrate for solution for 

infusion 

Volume of diluent  Total volume of infusion 

4 ml 46 ml 50 ml 

8 ml 92 ml 100 ml 

20 ml 230 ml 250 ml 

40 ml 460 ml 500 ml 
 
The solution should be shaken gently to mix well.  
 
Dexmedetomidine Accord should be inspected visually for particulate matter and discoloration prior to 
administration.  
 
Dexmedetomidine Accord has been shown to be compatible when administered with the following 
intravenous fluids and medicinal products: 
 
Lactated Ringers, 5% glucose solution, sodium chloride 9 mg/ml (0.9%) solution for injection, 
mannitol 200 mg/ml (20%), thiopental sodium, etomidate, vecuronium bromide, pancuronium 
bromide, succinylcholine, atracurium besylate, mivacurium chloride, rocuronium bromide, 
glycopyrrolate bromide, phenylephrine HCl, atropine sulfate, dopamine, noradrenaline, dobutamine, 
midazolam, morphine sulfate, fentanyl citrate, and a plasma-substitute.  
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Accord Healthcare S.L.U.  
World Trade Center,  



15 
 

Moll de Barcelona, s/n,  
Edifici Est 6ª planta,  
08039 Barcelona, Spain 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
200 micrograms/2 ml 
EU/1/19/1418/001-004 
 
400 micrograms/4 ml 
EU/1/19/1418/005-007 
 
1000 micrograms/10 ml 
EU/1/19/1418/008-010 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 13th February 2020 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this product is available on the website of the European Medicines Agency 
http://www.ema.europa.eu 

http://www.ema.europa.eu/


16 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH 
RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 

  C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

 



17 
 

A. MANUFACTURER (S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturers responsible for batch release 
 

Accord Healthcare Limited 
Sage House  
319, Pinner Road 
North Harrow 
Middlesex HA1 4HF 
United Kingdom 
 
Accord Healthcare Polska Sp.z.o.o. 
Ul. Lutomierska 50,  
95-200, Pabianice, Poland 
 
Laboratori Fundació Dau 
C/ C, 12-14 Pol. Ind. 
Zona Franca, Barcelona, 08040, Spain 
 
Accord Healthcare B.V. 
Winthontlaan 200, 3526KV Utrecht 
Netherlands 

 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic safety update reports  
The requirements for submission of periodic safety update reports  for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT   
 

- Risk Management Plan (RMP) 
 
The MAHshall perform the required pharmacovigilance activities and interventions detailed in 
the agreed RMP presented in Module 1.8.2 of the marketing authorisation and any agreed 
subsequent updates of the RMP.  
 
An updated RMP should be submitted: 
 

• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 



18 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



19 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 
 



20 
 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Dexmedetomidine Accord 100 micrograms/ml concentrate for solution for infusion 
dexmedetomidine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each ml of concentrate contains dexmedetomidine hydrochloride equivalent to 100.0 micrograms 
dexmedetomidine. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains sodium chloride,water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Concentrate for solution for infusion 
 
 
1 x 2 ml vial 
4 x 2 ml vials 
5 x 2 ml vials 
25 x 2 ml vials 
1 x 4 ml vial 
4 x 4 ml vials 
5 x 4 ml vials 
1 x 10 ml vial 
4 x 10 ml vials 
5 x 10 ml vials 
 
200 micrograms/2 ml  
400 micrograms/4 ml 
1000 micrograms/10 ml 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Read the package leaflet before use. 
Intravenous use after dilution. 
Use immediately after dilution. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 



21 
 

 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Keep the vials in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Accord Healthcare S.L.U.  
World Trade Center,  
Moll de Barcelona, s/n,  
Edifici Est 6ª planta,  
08039 Barcelona, Spain 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
200 micrograms/2 ml 
EU/1/19/1418/001-004 
 
400 micrograms/4 ml 
EU/1/19/1418/005-007 
 
1000 micrograms/10 ml 
EU/1/19/1418/008-010 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 



22 
 

Justification for not including Braille accepted 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC :{number}  
SN :{number}  
NN :{number}  



23 
 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIALS 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION 
 
Dexmedetomidine Accord 100 micrograms/ml sterile concentrate 
dexmedetomidine 
Intravenous use (IV) 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
200 mcg/ 2 ml 
400 mcg/ 4 ml 
1000 mcg/ 10 ml 
 
 
6. OTHER 



24 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



25 
 

 
Package leaflet: Information for the user 

 
Dexmedetomidine Accord 100 micrograms/ml concentrate for solution for infusion 

dexmedetomidine 
 
Read all of this leaflet carefully before you are given this medicine because it contains important 

information for you. 
 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or nurse. 
- If you get any side effects, talk to your doctor. This includes any possible side effects not listed 

in this leaflet. See section 4. 
 
What is in this leaflet: 
1. What Dexmedetomidine Accord is and what it is used for 
2. What you need to know before you are given Dexmedetomidine Accord 
3. How to use Dexmedetomidine Accord 
4. Possible side effects 
5.  How to store Dexmedetomidine Accord 
6. Contents of the pack and other information 
 
 
1. What Dexmedetomidine Accord is and what it is used for 
 
Dexmedetomidine Accord contains an active substance called dexmedetomidine which belongs to a 
medicine group called sedatives. It is used to provide sedation (a state of calm, drowsiness or sleep) 
for adult patients in hospital intensive care settings or awake sedation during different diagnostic or 
surgical procedures.   
 
 
2. What you need to know before you are given Dexmedetomidine Accord 
 
You must not be given Dexmedetomidine Accord 
 
- if you are allergic to dexmedetomidine or any of the other ingredients of this medicine (listed in 

section 6).  
- if you have some disorders of heart rhythm (heart block grade 2 or 3). 
- if you have very low blood pressure which does not respond to treatment. 
- if you have recently had a stroke or other serious condition affecting blood supply to the brain. 
 
Warnings and precautions 
 
Before you have this medicine, tell your doctor or nurse if any of the following apply as 
Dexmedetomidine Accord should be used cautiously: 
 
- if you have an abnormally slow heart rate (either due to illness or high levels of physical fitness) 

as it may increase the risk for cardiac arrest 
- if you have low blood pressure 
- if you have low blood volume, for example after bleeding 
- if you have certain heart disorders  
- if you are elderly 
- if you have a neurological disorder (for instance head or spinal cord injury or stroke) 
- if you have severe liver problems 
- if you have ever developed a serious fever after some medicines, especially anaesthetics 
 
Other medicines and Dexmedetomidine Accord 



26 
 

 
Tell your doctor or nurse if you are taking, have recently taken or might take any other medicines. 
 
The following medicines may enhance the effect of Dexmedetomidine Accord:  
- medicines that help you sleep or cause sedation (e.g. midazolam, propofol) 
- strong pain medicines (e.g. opioids such as morphine, codeine) 
- anaesthetic medicines (e.g. sevoflurane, isoflurane) 
 
If you are using medicines which lower your blood pressure and heart rate, co-administration with 
Dexmedetomidine Accord may enhance this effect. Dexmedetomidine Accord should not be used with 
medicines that cause temporary paralysis. 
 
Pregnancy and breast-feeding 
 
Dexmedetomidine Accord should not be used during pregnancy or breast-feeding unless clearly 
necessary.  
Ask your doctor for advice before having this medicine  
 
Driving and using machines 
 
 Dexmedetomidine Accord has major impact on the ability to drive and use machines. After you have 
been given Dexmedetomidine Accord you must not drive, operate machinery, or work in dangerous 
situations until the effects are completely gone. Ask your doctor when you can start doing these 
activities again and when you can go back to this kind of work.  
 
Excipients 
 
Dexmedetomidine Accord contains less than 1 mmol sodium (23 mg) per ml, that is to say essentially 
‘sodium-free’. 
 
 
3. How to use Dexmedetomidine Accord 
 
Hospital intensive care 
Dexmedetomidine Accord is administered to you by a doctor or nurse in hospital intensive care.  
 
Procedural sedation/awake sedation 
Dexmedetomidine Accord is administered to you by a doctor or a nurse prior to and/or during 
diagnostic or surgical procedures requiring sedation, i.e. procedural/awake sedation.  
 
Your doctor will decide on a suitable dose for you. The amount of Dexmedetomidine Accord depends 
on your age, size, general condition of health, the level of sedation needed and how you respond to the 
medicine. Your doctor may change your dose if needed and will monitor your heart and blood 
pressure during the treatment.  
 
Dexmedetomidine Accord is diluted and it is given to you as an infusion (drip) into your veins. 
 
After sedation/wake-up 
 
- The doctor will keep you under medical supervision for some hours after the sedation to make 

sure that you feel well. 
- You should not go home unaccompanied. 
- Medicines to help you sleep, cause sedation or strong painkillers may not be appropriate for 

some time after you have been given Dexmedetomidine Accord. Talk to your doctor about the 
use of these medicines and about the use of alcohol.  



27 
 

 
If you have been given more Dexmedetomidine Accord than you should 
 
If you are given too much Dexmedetomidine Accord, your blood pressure may go up or down, your 
heartbeat may slow down, you may breathe more slowly and you may feel more drowsy. Your doctor 
will know how to treat you based on your condition.  
 
If you have any further questions on the use of this medicine, ask your doctor. 
 
 
4.  Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Very common (affects more than 1 user in 10)  
- slow heart rate 
- low or high blood pressure 
- change in breathing pattern or stopping breathing. 
 
Common (affects 1 to 10 users in 100) 
- chest pain or heart attack 
- fast heart rate 
- low or high blood sugar 
- nausea, vomiting or dry mouth 
- restlessness  
- high temperature 
- symptoms after stopping the medicine. 
 
Uncommon (affects 1 to 10 users in 1,000) 
- reduced heart function, cardiac arrest 
- swelling of the stomach 
- thirst 
- a condition where there is too much acid in the body 
- low albumin level in blood 
- shortness of breath 
- hallucinations 
- the medicine is not effective enough. 
 
Not known (frequency cannot be estimated from the available data)    
- increased need to pass urine. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not 
listed in this leaflet. You can also report side effects directly via the national reporting system listed in 
Appendix V. By reporting side effects you can help provide more information on the safety of this 
medicine. 
 
 
5. How to store  Dexmedetomidine Accord 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the label and carton after EXP. 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


28 
 

This medicine does not require any special temperature storage conditions. Keep the vials in the outer 
carton in order to protect from light. 
 
After dilution 
Chemical and physical in-use stability has been demonstrated for 72 hours at 25°C and 2° to 8°C. 
 
From a microbiological point of view, the product should be used immediately. If not used 
immediately, in-use storage times and conditions prior to the use are the responsibility of the user and 
would not normally be longer than 24 hours at 2° to 8°C, unless dilution has taken place in controlled 
and validated aseptic conditions. 
 
Do not use this medicine if you notice discoloration or visible particles. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Dexmedetomidine Accord contains  
 
- The active substance is dexmedetomidine. Each ml of concentrate contains dexmedetomidine 

hydrochloride equivalent to 100.0 micrograms dexmedetomidine. 
- The other ingredients are sodium chloride and water for injections. 
 
Each 2 ml vial contains 200 micrograms of dexmedetomidine (as hydrochloride). 
Each 4 ml vial contains 400 micrograms of dexmedetomidine (as hydrochloride). 
Each 10 ml vial contains 1000 micrograms of dexmedetomidine (as hydrochloride). 
 
The concentration of the final solution after dilution should be either 4 micrograms/ml or 
8 micrograms/ml. 
 
What Dexmedetomidine Accord looks like and contents of the pack 
 
Concentrate for solution for infusion (sterile concentrate).  
The concentrate is a clear, colourless solution. 
 
Containers 
2, 6 or 10 ml glass vials 
 
Pack sizes 
1 x 2 ml vial 
4 x 2 ml vials 
5 x 2 ml vials 
25 x 2 ml vials 
1 x 4 ml vial 
4 x 4 ml vials 
5 x 4 ml vials 
1 x 10 ml vial 
4 x 10 ml vials 
5 x 10 ml vials 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
 



29 
 

Marketing Authorisation Holder: 
Accord Healthcare S.L.U.  
World Trade Center,  
Moll de Barcelona, s/n,  
Edifici Est 6ª planta,  
08039 Barcelona, Spain 
 
Manufacturer: 
Accord Healthcare Limited,  
Sage House, 319 Pinner Road, North Harrow,  
Middlesex, HA1 4HF,  
United Kingdom 
 
Or 
Accord Healthcare Polska Sp.z o.o. 
ul. Lutomierska 50,  
95-200 Pabianice 
Poland 
 
Or 
Laboratori Fundació Dau 
C/ C, 12-14 Pol. Ind. 
Zona Franca, Barcelona, 08040,  
Spain 
 
Or 
Accord Healthcare B.V. 
Winthontlaan 200, 3526KV Utrecht 
Netherlands 
 
This leaflet was last revised in {MM/YYYY}. 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

http://www.ema.europa.eu/


30 
 

 
-------------------------------------------------------------------------------------------------------------- 
 
The following information is intended for healthcare professionals only: 
 
Dexmedetomidine Accord 100 micrograms/ml concentrate for solution for infusion 
 
Method of administration  

Dexmedetomidine Accord should be administered by healthcare professionals skilled in the 
management of patients requiring intensive care or in the anaesthetic management of patients in the 
operating room. It must be administered only as a diluted intravenous infusion using a controlled 
infusion device 
 
Preparation of solution 
 
Dexmedetomidine Accord can be diluted in glucose 50 mg/ml (5%), Ringers, mannitol or sodium 
chloride 9 mg/ml (0.9%) solution for injection to achieve the required concentration of either 4 
micrograms/ml or 8 micrograms/ml prior to administration. Please see below in tabulated form the 
volumes needed to prepare the infusion.  
 
In the case the required concentration is 4 micrograms/ml: 
 

Volume of 
 Dexmedetomidine 

Accord 
100 micrograms/ml 

concentrate for solution for 
infusion 

Volume of diluent  Total volume of infusion 

2 ml 48 ml 50 ml 

4 ml 96 ml 100 ml 

10 ml 240 ml 250 ml 

20 ml 480 ml 500 ml 
 
In the case the required concentration is 8 micrograms/ml: 
 

Volume of 
 Dexmedetomidine 

Accord 100 micrograms/ml 
concentrate for solution for 

infusion 

Volume of diluent  Total volume of infusion 

4 ml 46 ml 50 ml 

8 ml 92 ml 100 ml 

20 ml 230 ml 250 ml 

40 ml 460 ml 500 ml 
 
The solution should be shaken gently to mix well. 
 
Dexmedetomidine Accord should be inspected visually for particulate matter and discoloration prior to 
administration.  
 



31 
 

Dexmedetomidine Accord has been shown to be compatible when administered with the following 
intravenous fluids and medicinal products: 
 
Lactated Ringers, 5% glucose solution, sodium chloride 9 mg/ml (0.9%) solution for injection, 
mannitol 200 mg/ml (20%), thiopental sodium, etomidate, vecuronium bromide, pancuronium 
bromide, succinylcholine, atracurium besylate, mivacurium chloride, rocuronium bromide, 
glycopyrrolate bromide, phenylephrine HCl, atropine sulfate, dopamine, noradrenaline, dobutamine, 
midazolam, morphine sulfate, fentanyl citrate, and a plasma-substitute. 
 
Compatibility studies have shown potential for adsorption of dexmedetomidine to some types of 
natural rubber. Although dexmedetomidine is dosed to effect, it is advisable to use components with 
synthetic or coated natural rubber gaskets.  
 
Shelf life 
 
Chemical and physical in-use stability has been demonstrated for  72 hours at 25°C and 2° to 8°C. 
  
 
From a microbiological point of view, the product should be used immediately. If not used 
immediately, in-use storage times and conditions prior to the use are the responsibility of the user and 
would not normally be longer than 24 hours at 2° to 8°C, unless dilution has taken place in controlled 
and validated aseptic conditions. 



32 
 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER (S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET