Dexmedetomidine (Dexdomitor) is a sedative drug that provides semi-arousable and cooperative sedation without the risk of respiratory depression.

Dexmedetomidine (Dexdomitor) Uses:

• Intensive care unit sedation:
  • Patients who are mechanically ventilated and first intubated are sedated in an intensive care setting.
• Procedural sedation:
  • Procedural sedation before and/or during awake fiberoptic intubation; sedation before and/or during surgical or other procedures of non-intubated patients
• Use: Off-Label: Adult
  • Sedation during awake craniotomy
  • Treatment of shivering

Dexmedetomidine (Dexdomitor) Dose in Adults

Note:

• Errors have occurred due to misinterpretation of dosing information.
• Maintenance dose expressed as mcg/kg/hour.
• Individualized and titrated to the desired clinical effect.
• At adequate doses, dexmedetomidine does not provide adequate and reliable loss of memory (when necessary); therefore,
• use of additional agents with amnestic properties (eg, benzodiazepines) may be required.

Dexmedetomidine (Dexdomitor) Dose in the ICU sedation:

• IV: Initial:
  • Loading infusion  of 1 mcg/kg over 10 minutes, followed by a maintenance infusion  of 0.2 to 0.7 mcg/kg/hour;
  • adjust the rate to the desired level of sedation;
  • titration no more frequently than every 30 minutes may decrease the incidence of hypotension.

Note:

• Loading infusion:
  • The loading dose may be omitted if the patient is either being converted from another sedative and the patient is adequately sedated or there are concerns for hemodynamic compromise.
• Maintenance infusion:
  • Dosing ranges from 0.2 to 1.5 mcg/kg/hour have been observed during randomized controlled clinical trials.
  • Although infusion rates as high as 2.5 mcg/kg/hour have been used, it is suggested that doses of >1.5 mcg/kg/hour do not add to clinical efficacy.
  • The manufacturer recommends the duration of infusion should not exceed 24 hours;
  • however, randomized clinical trials have demonstrated efficacy and safety comparable to lorazepam and midazolam with longer-term infusions of up to 5 days.

Dexmedetomidine (Dexdomitor) Dose in the Procedural sedation:

• IV: Initial:
  • Loading infusion of 1 mcg/kg (or 0.5 mcg/kg for less invasive procedures such as ophthalmic) over 10 minutes,
  • followed by a maintenance infusion of 0.6 mcg/kg/hour, titrate to get desired effect; usual range: 0.2 to 1 mcg/kg/hour
• Fiberoptic intubation (awake):
  • IV: Initial:
    • Loading infusion of 1 mcg/kg over 10 minutes,
    • followed by a maintenance infusion of 0.7 mcg/kg/hour til endotracheal tube is secured.

dexmedetomidine (Dexdomitor) Dose in the treatment of Craniotomy in awake patients:

• IV: Initial:
  • Loading infusion of 0.5 to 1 mcg/kg over 10 to 20 minutes,
  • followed by a maintenance infusion of 0.5 mcg/kg/hour, titrated to the desired effect.
  • The usual range: 0.1 to 0.7 mcg/kg/hour.

Dexmedetomidine (Dexdomitor) Dose in Childrens

Note:

• Errors have occurred due to misinterpretation of adequate dosing information.
• Maintenance dose expressed as mcg/kg/hour. Individualize and titrate to the desired clinical effect.
• At adequate doses, dexmedetomidine does not provide adequate and reliable loss of memory (when necessary); therefore, the use of additional agents with amnestic properties (eg, benzodiazepines) may be necessary.

Dexmedetomidine (Dexdomitor) Dose in the ICU sedation:

• Loading dose (Optional):
  • IV: 0.5 to 1 mcg/kg/dose over 10 minutes time.
  • use of loading dose is dependent upon concomitant sedation agents and patient’s current and desired level of sedation
• Maintenance dose:
  • Continuous IV infusion:
    • Initial: 0.2 to 0.5 mcg/kg/hour;
    • adjust the dose to the desired level of sedation.
    • Dosing based on multiple retrospective studies, case reports, and a few prospective studies.
    • Most reported increasing by 0.1 to 0.3 mcg/kg/hour as needed.
    • Reported maintenance dose variable, the usual reported range was 0.4 to 0.7 mcg/kg/hour.
    • In general, infants may require higher maintenance infusion rates than either neonates or older children.
    • Maximum reported doses varied; most utilized doses <1 mcg/kg/hour; however, doses as high as 2.5 mcg/kg/hour in intubated patients have been described.
    • Although the manufacturer recommends a duration of infusion should not exceed 24 hours, most studies reported use beyond this time period; most patients received infusion for ≤72 hours; however, one patient received dexmedetomidine for 103 days.
    • Prolonged infusions should not be abruptly discontinued and are generally tapered over several days to prevent withdrawal symptoms.

Dexmedetomidine (Dexdomitor) Dose in the treatment of Sedation/ anesthesia in noninvasive procedures:

• Loading dose:
  • Infants, Children, and Adolescents:
    • IV: 0.5 to 2 mcg/kg/dose over 10 minutes; maybe repeated if sedation is not adequate.
• Maintenance dose:
  • Infants, Children, and Adolescents:
    • Continuous IV infusion:
      • 0.5 to 1 mcg/kg/hour.
      • Dosing based on multiple retrospective and prospective studies in over 800 pediatric patients receiving dexmedetomidine (± other sedatives) for noninvasive procedures (eg, EEG, MRI, PET scan).

Dexmedetomidine (Dexdomitor) Dose as a pre-anesthetic (for Sedation):

• Children and Adolescents (very limited data available in patients >9 years):
  • Intranasal: 1 to 2 mcg/kg as a single dose 30 to 60 minutes prior to induction of anesthesia.
  • Higher-end doses (2 mcg/kg) are suggested for older children (≥ 5 years) and adolescents.

Pregnancy Risk Factor C

• Some studies on animal reproduction have shown adverse effects.
• Dexmedetomidine should cross the placenta.
• It is not known if it can be used during pregnancy.

Use Dexdomitor while breastfeeding

• It is unknown if dexmedetomidine excreted in breastmilk.
• The manufacturer claims that while deciding whether to quit or continue nursing during therapy, the risks to the baby, the benefits to the baby, and the benefits to the mother must all be taken into consideration.

Dexdomitor Dose in Kidney Disease:

• The drug maker's labeling does not include any dosage adjustments.
• However, the pharmacokinetics of patients with severe renal impairment (CrCl 30mL/minute) were not significantly different.

Dexdomitor Dose in Liver disease:

• The manufacturer's labeling does not contain any specific dosage adjustments. However, you can consider a dose decrease.
• Based on the degree of impairment, clearance can be reduced to varying degrees.

Common Side Effects of dexmedetomidine (Dexdomitor):

• Cardiovascular:
  • Hypotension
  • Bradycardia
  • Systolic hypertension
  • Tachycardia
  • Hypertension Hypertension
• Central nervous system:
  • Agitation
• Gastrointestinal:
  • Constipation
  • Nausea
• Respiratory:
  • Respiratory depression

Less Common Side Effects of Dexdomitor (dexmedetomidine):

• Cardiovascular:
  • Atrial Fibrillation
  • Peripheral Edema
  • Hypovolemia
  • Edema
• Central Nervous System:
  • Anxiety
• Endocrine & Metabolic:
  • Hypokalemia
  • Hyperglycemia
  • Hypoglycemia
  • Increased Thirst
  • Hypocalcemia
  • Hypomagnesemia
• Gastrointestinal:
  • Xerostomia
• Genitourinary:
  • Oliguria
• Hematologic & Oncologic:
  • Anemia
• Renal:
  • Acute Renal Failure
  • Decreased Urine Output
• Respiratory:
  • Respiratory Failure
  • Adult Respiratory Distress Syndrome
  • Pleural Effusion
  • Wheezing
• Miscellaneous:
  • Fever
  • Withdrawal Syndrome

Contraindications to dexmedetomidine (Dexdomitor):

• Hypersensitivity to dexmedetomidine and any component of the formulation

Warnings and precautions for Dexdomitor

• Cardiovascular effects
  • Rapid IV administration (eg, Bolus administration) and when administered to patients with high vagal tone have been linked to episodes of hypotension, bradycardia, and sinus arrest.
  • A loading dose can be used to sedate patients in the ICU.
  • Hypotension can be reduced by maintaining infusions that are titrated no more often than once every 30 minutes.
  • Medical intervention may be required if the infusion is stopped or decreased, increased IV fluid administration rate, use of pressor agent, elevation of the lower extremities, and/or increasing the rate at which the IV fluid is administered.
  • Low concentrations of CVP, PAOP and PVR may reduce mean arterial pressure (MAP), but other hemodynamic parameters, such as pulmonary artery obstruction pressure [PAOP], can be affected. However, higher concentrations (>1.9ng/mL) will cause MAP, CVP and PAOP to increase.
• Hypertension transient:
  • This effect was primarily seen during loading dose administration.
  • The majority of treatment is unnecessary. However, it may be necessary to reduce the infusion rate.
• Cardiovascular disease
  • Patients with severe ventricular dysfunction, heart block, bradycardia, hypovolemia or chronic hypertension should be cautious.
  • According to the American Heart Association's scientific statement, dexmedetomidine may be an agent that can exacerbate myocardial dysfunction.
• Diabetes:
  • Patients with diabetes mellitus should be cautious; the risk of cardiovascular adverse events, such as hypotension and bradycardia may be greater.
• Hepatic impairment
  • Patients with hepatic impairment should be cautious; dosage reductions are recommended.

Dexmedetomidine: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Gradual level of sedation
• Heart rate
• Breathing
• rhythm
• Blood pressure
• Pain control

Notice: Dexmedetomidine causes minimal breathing depression, inhibits salivation and is analgesic sparing.

• ICU patients with critical illnesses who are mechanically ventilated:
  • In accordance with the score system, you can modify sedation (Richmond Agitation-Sedation Scale[RASS] or Sedation-Agitation Scale[SAS]).

How to administer dexmedetomidine (Dexdomitor)?

• Use a controlled infusion device to administer the medication.
• It is recommended to use administration components with natural rubber gaskets coated or synthetic.
• Do not give loading doses for more than 10 minutes. It may be extended to 20 minutes to reduce vasoconstrictive effects.
• When ICU sedation is being performed, titration should be limited to once every 30 minutes. This may decrease the chance of hypotension.

Mechanism of action of dexmedetomidine (Dexdomitor):

• a specific alpha-adrenoceptor antagonist with sedative and anaesthetic effects.
• The generation of norepinephrine is hypothesised to be inhibited as a result of alpha-adrenoceptors in the brainstem activating G protein receptors.
• High doses or quick IV administration can activate peripheral alpha-adrenoceptors.
• This causes vasoconstriction.

The onset of action:

• IV loading dose: 5 to 10 minutes
• Intranasal: 45 to 60 minutes, maybe faster in pediatric patients when administered via an atomizing device.

Peak effect:

• IV loading dose: 15 to 30 minutes
• Intranasal: 90 to 105 minutes.

Duration (dose-dependent):

• 60 to 120 minutes

Bioavailability:

• Intranasal: Variable: Median: 65% (range: 35% to 93%)

Protein binding:

• ~94%

Metabolism:

• Hepatic via N-glucuronidation, N-methylation, and CYP2A6

Half-life elimination:

• Preterm Neonates (28 to <36 weeks GA): Terminal: 7.6 hours (range: 3 to 9.1 hours).
• Term Neonates (36 to ≤44 weeks GA): Terminal: Median: 3.2 hours (range: 1 to 9.4 hours).
• Infants and Children <2 years: Terminal: Median: 2.3 hours (range: 1.5 to 3.3 hours).
• Children 2 to 11 years: Terminal: Median: 1.6 hours (range: 1.2 to 2.3 hours).
• Adults:
  • Distribution: ~6 minutes;
  • Terminal: ~up to 3 hours (Venn 2002);
  • significantly prolonged in patients with severe hepatic impairment.

Time to peak serum concentration:

• Intranasal: Median: 38 minutes (range: 15 to 60 minutes).

Excretion:

• Urine (95%);
• feces (4%)

Clearance:

• Note:
  • Clearance following cardiac surgery was reduced by 27% in pediatric patients aged 1 week to 14 years.
  • Preterm Neonates (28 to <36 weeks GA): 0.3 L/hour/kg (0.2 to 0.4 L/hour/kg).
  • Term Neonates (36 to ≤44 weeks GA): 0.9 L/hour/kg (0.2 to 1.5 L/hour/kg)
  • Infants and Children <2 years: Median: 1 L/hour/kg (0.85 to 1.66 L/hour/kg).
  • Children 2 to 11 years: Median: 1 L/hour/kg (0.56 to 1.35 L/hour/kg).
  • Adults: ~39 L/hour; Hepatic impairment (Child-Pugh class A, B, or C):
    • Mean clearance values were 74%, 64%, and 53% respectively, of those observed in healthy adults

International Brands of dexmedetomidine:

• Precedex
• Cepedex
• Demesynt
• Demsynt
• Detomax IV
• Dexdomitor
• Dexdor
• Dexem
• Meproxidina
• Precedex
• Sedadex

Dexmedetomidine Brand Names in Pakistan:

No Brands Available in Pakistan.