Dexmedetomidine

Registered South African indications:

• Intensive care unit sedation
  - Sedation of intubated and mechanically ventilated adult post-surgical patients during treatment in an intensive care setting
• Monitored anaesthesia care (MAC)/ Conscious sedation in a theatre or intensive care setting for
  - Minor surgical procedures under local anaesthesia
  - Fibreoptic intubation

Contraindications

South African recommendations

• Hypersensitivity to dexmedetomidine or to any of the excipients
• Patients with sepsis
• Unstable trauma patients
• Hypovolaemic patients
• Heart block
• Uncontrolled cardiac failure
• Imminent hepatic failure
• Uncontrolled hypotension
• Acute cerebrovascular conditions

Recommendations in other jurisdictions

• Hypersensitivity to the active substance or to any of the excipients listed
• Advanced heart block (grade 2 or 3) unless paced
• Uncontrolled hypotension
• Acute cerebrovascular conditions

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly
• Severe cardiovascular instability
• Bradycardia
• Hypotension
• Hypovolaemia
• Chronic hypotension
• Severe ventricular dysfunction
• Impaired peripheral autonomic activity 
• Ischaemic heart disease
• Severe cerebrovascular disease
• Myocardial ischaemia
• Cerebrovascular ischaemia
• Head injury 
• Post neurosurgery
• Abrupt withdrawal
• Malignant hyperthermia

Forms avail. in SA and covered in this monograph: inj, inf

Dosages below include:

• South African registered indications and dosages

South African registered indications and dosages

Dexmedetomidine should be administered only by health professionals skilled in the management of patients in the intensive care setting

Intensive care unit sedation
- Sedation of intubated and mechanically ventilated adult post-surgical patients during treatment in an intensive care setting

• IV: Loading dose: 1μg/kg, given over 10mins; Maintenance: Generally, 0.2-0.7μg/kg/hr, as an infusion; Can be adjusted to achieve desired clinical effect; Dosages as low as 0.05μg/kg/hr have been used in clinical studies

Dexmedetomidine dosage should be individualised and titrated to the desired clinical effect

Monitored anaesthesia care (MAC)/ Conscious sedation in a theatre or intensive care setting for
- Minor surgical procedures under local anaesthesia
- Fibreoptic intubation

• IV: Loading dose: 1μg/kg, given over 10mins; Maintenance for MAC: Initiated at 0.6μg/kg/hr, as an infusion; Titrate to achieve desired clinical effect with doses ranging from 0.2-1μg/kg/hr; Rate of the maintenance infusion should be adjusted to achieve the targeted level of sedation; For awake fibreoptic intubation (AFI): Fixed maintenance dose: 0.7μg/kg/hr, as an infusion should be used; For those undergoing less invasive procedure such as ophthalmic surgery: Loading infusion of 0.5μg/kg/hr, given over 10mins may be suitable; Dosage adjustment may be required when co-administered with other concomitant anaesthetics, sedatives, hypnotics or opioids

Continuous monitoring of vital signs is mandatory during infusion

In order to minimise undesirable pharmacologic side effects, bolus injections of dexmedetomidine should not be used

Dexmedetomidine should be administered by continuous intravenous infusion not to exceed 24 hours

Fluid supplementation should be administered prior to and during administration to ensure normovolaemia. There is no respiratory depression associated with the administration of dexmedetomidine. Patients are observed to be arousable and alert when stimulated, which is an expected component of dexmedetomidine sedation

Dexmedetomidine can be continuously infused in mechanically ventilated patients prior to extubation, during extubation and post extubation. It is not necessary to discontinue dexmedetomidine prior to extubtion

A controlled infusion device should be used to administer dexmedetomidine

Not established for use in children below 18 years

Pregnancy

• Caution
• There are no or limited amount of data from the use of dexmedetomidine in pregnant women. Studies in animals have shown reproductive toxicity. Dexmedetomidine should not be used during pregnancy unless the clinical condition of the woman requires treatment with dexmedetomidine

Breastfeeding

• Caution
• 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

Renal Impairment

• Caution; dose adjustment recommended
  ICU Sedation: A dose reduction for both the loading and maintenance infusions should be considered in patients with impaired renal function
  Since the majority of metabolites are excreted in the urine, dosage reductions may need to be considered for patients with renal impairment

Hepatic Impairment

• Caution; dose adjustment recommended
  ICU Sedation: A dose reduction for both the loading and maintenance infusions should be considered in patients with impaired hepatic function
  Dosage reductions may need to be considered for patients with hepatic impairment, as dexmedetomidine is metabolised primarily in the liver

Elderly

• Caution; dose adjustment recommended
  Since the elderly are more sensitive to the effects of dexmedetomidine dosage reductions may need to be considered
  ICU Sedation: A dose reduction for both the loading and maintenance infusions should be considered in patients over 65 years
  Conscious sedation: For patients over 65 years of age, a loading infusion of 0.5μg/kg/hr over 10mins may be suitable

Porphyria Information

• Possibly porphyrinogenic (PSP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Agitation
• Hallucination
• Thirst
• Withdrawal syndrome

Cardiovascular Disorders

• Hypertension
• Hypotension
• Bradycardia
• Myocardial ischaemia
• Myocardial infarction
• Tachycardia
• Decreased cardiac output
• First degree atrioventricular block

Respiratory Disorders

• Respiratory depression
• Dyspnoea
• Apnoea

Gastrointestinal Disorders

• Nausea and vomiting
• Dry mouth
• Abdominal distention

Endocrine and Metabolic Disorders

• Hyperglycaemia
• Hypoglycaemia
• Metabolic acidosis
• Hypoalbuminaemia

• Central nervous system depressants
• CYP2B6 substrates
• Beta blockers

• Cardiac monitoring
• Respiratory function

Dexmedetomidine is an alpha-2 agonist. It binds to presynaptic alpha-2 adrenoceptors, inhibits the release of norepinephrine, and therefore terminates the propagation of pain signals. Activation of postsynaptic alpha-2 adrenoceptors inhibits sympathetic activity, which decreases blood pressure and heart rate.

Injection (per ml) 100μg

• Demodinex (Mylan)
• Precedex (Pfizer) originator
• Precia (Lamar International)
• Sedalpha (Accord Healthcare)

Infusion (per ml) 100μg

• Demetev (Teva Pharmaceuticals)
• Dexisun (Ranbaxy Pharmaceuticals)