Dexdor · 4.3 Contraindications · 1

HOS-095984 · has-adverse-reaction-information · PDF-Seite 7

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. 7 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. 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), not known (cannot be estimated from the available data). Table 1. Adverse reactions Endocrine disorders Not known: Diabetes insipidus 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 General disorders and administration site conditions Common: Withdrawal syndrome, hyperther

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HOS-095980 · has-contraindication-information · PDF-Seite 4

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.

HOS-095979 · has-indication-information · PDF-Seite 2

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.

HOS-095982 · has-interaction-information · PDF-Seite 6

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. 6 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. 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.

HOS-095983 · has-pregnancy-information · PDF-Seite 7

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). Dexdor should not be used during pregnancy unless the clinical condition of the woman requires treatment with dexmedetomidine. Breastfeeding 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 breastfeeding 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.

HOS-095981 · has-warning-information · PDF-Seite 4

Monitoring Dexdor 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 Dexdor 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 Dexdor 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 Dexdor 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. 4 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. Dexdor 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. Dexdor is not recommended for patient controlled sedation. Adequate data is not available. When Dexdor 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 obse

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