Dexdor

Specific remedy Dexdor (international non-proprietary name - Dexmedetomidine) is a concentrated preparation for the manufacture of an infusion solution, required for intravenous anesthesia. Dexdor is considered a sedative means of medical use.

[1]

Indications Dexdor

Dexdor is used as a sedative in people over 18 years of age who are being treated in intensive care units.

The recommended depth of sedation should not exceed the awakening due to a response to verbal stimulation, which is typical for the range from zero to -3 points according to the Richmond Agitation and Sedation Scale (RASS).

[2]

Release form

Dexdor is a concentrated substance for the manufacture of an infusion solution, with the active ingredient dexmedetomidine g / x.

As auxiliary components in the preparation are sodium chloride and injection water.

Concentrate has the form of a transparent-colorless liquid. It is released in transparent ampoules of 2 ml, or in transparent glass bottles of 4 ml and 10 ml.

Cardboard packaging can contain 5 or 25 ampoules, or 1 bottle of medication.

Dexdor can be prescribed and applied only by a doctor in a hospital, so you can buy the drug in a pharmacy only if you have a prescription medication.

[3], [4], [5]

Pharmacodynamics

Active ingredient Dexdor is a selective agonist of alpha2-adrenergic receptors, which has a large number of pharmaceutical effects.

Dexmedetomidine has a sympatholytic property, which is manifested by a decrease in the release of noradrenaline by sympathetic neuronal endings.

The sedative property is explained by a decrease in excitability in the bluish spot, with the predominance of noradrenergic nerve cells located in the brain stem.

In addition, Dexdor has an analgesic effect and can influence the reduction of dosage of anesthetics and analgesics. The properties associated with the cardiovascular system depend on the administered dose of the drug:

• with a small introduction, it is possible to observe predominantly central effects that lead to bradycardia and hypotension;
• with a higher amount of the drug, a predominantly vasoconstrictive effect is observed, which provokes the development of general vascular resistance and an increase in blood pressure (the bradycardia only increases).

Depression of respiratory function with the introduction of Dexdor does not occur.

[6],

Pharmacokinetics

The kinetic properties of Dexdor were investigated by a single short infusion of healthy individuals and prolonged infusion of patients in the intensive care unit.

Distribution of the drug is a two-chamber method. In the first group of persons, the distribution stage was rapid: the half-distribution time was 6 minutes.

The average index of the terminal half-life was approximately 1.35-3.68 hours. The average equilibrium distribution index was approximately from 90 to 151 liters per kg. The clearance in plasma was from 35.7 to 51.1 liters per hour.

The average weight of patients at the above indications was equal to 69 kg.

Estimated parametric kinetic range:

• the term half-life is one and a half hours;
• equilibrium distribution ~ 93 L;
• clearance rates ~ 43 liters per kilogram.

There is no cumulation in infusion administration for a period of up to 2 weeks.

The binding of the active ingredient with plasma proteins is about 94%.

The quality of binding with proteins is considered constant in the concentration gap of 0.85-85 ng per ml.

Active ingredient Dexdor can bind to serum albumin and alpha-1-acid glycoprotein.

The metabolism of the drug occurs in the liver and consists of direct n-glucuronation, n-methylation and cytochrome P450-mediated oxidation.

The main products of metabolism are considered to be a pair of isomeric n-glucuronides.

After intravenous infusion of the labeled drug 9 days later, about 95% of the label was detected in the urinary fluid and about 4% in the feces.

The main metabolic products in the urinary fluid are isomeric n-glucuronides (34%) and o-glucuronide (14.5%). Metabolism products of a secondary nature can range from 1.11 to 7.66% of the dosage.

Up to 1% of the unchanged active ingredient, Dexdor was found in the urinary fluid. Approximately 28% of metabolic products in urinary fluid are recognized as secondary: their character is not established.

Information on the kinetic properties of Dexdor, used in childhood, is relatively small. The half-life period, presumably, is equated to the adult indices. The clearance in the plasma in children up to 2 months of age can presumably be underestimated.

Dosing and administration

Dexdor can only be used by qualified specialists with adequate knowledge in the relevant direction.

Intubated patients are transferred to Dexdor with an initial infusion rate of 0.7 μg per kg per hour, with a further change in dosage in the corridor of 0.2-1.4 μg per kg per hour, taking into account the patient's reaction. For initially malnourished weak patients, the initial rate is often reduced.

Dexdor is considered a strong medicine - its introduction is carried out for not minutes, and hours. Usually one hour of infusion is not enough to achieve the necessary quality of sedation.

Do not use a more than limiting dosage of 1.4 mcg per kg per hour. If the required sedation has not been achieved, then the patient must be transferred to another sedative.

There is no information on the continued use of Dexdor - more than 2 weeks.

For the elderly, dosage adjustment is not necessary.

Destination Dexdor in childhood was practically not studied.

 Dexdor is bred in 5% of r-dextrose, r-re Ringer, saline or mannitol. For breeding, the following scheme is usually used:

• 2 ml of concentrated medperate - 48 ml of infusion solution - 50 ml of total volume;
• 4 ml of concentrated medication - 96 ml of infusion solution - 100 ml of total administered volume;
• 10 ml of concentrate - 240 ml of infusion solution - 250 ml of total volume;
• 20 ml of concentrated medication - 480 ml of infusion solution - 500 ml of total administered volume.

The prepared liquid is well mixed, its homogeneity and color are evaluated.

The unused solution is not to be stored and must be disposed of.

[11], [12],

Use Dexdor during pregnancy

There is no reliable information about the use of the drug Deksdor during pregnancy.

When testing animals, a reproductive toxic effect of the drug was found, but the degree of toxicity to the human body is not defined. For this reason, medical specialists advise to avoid the appointment of Dexdor during the period of bearing the child, except when this is vital.

Studies have shown that Dexdor and its active ingredient enter the breast milk of animals. Therefore, a certain degree of risk for children who are breastfed can not be ruled out. If there is a need to use Dexdor in a woman breast-feeding, it is recommended to stop breastfeeding.

Contraindications

Dexdor is not used for patients:

• with the likelihood of developing hypersensitivity reactions;
• with the existing atrioventricular blockade of the second-third degree (if there is no IVR);
• with uncontrolled hypotension;
• with acute cerebrovascular disorders;
• under the age of 18;
• during pregnancy and breastfeeding.

[7], [8], [9], [10]

Side effects Dexdor

The most common side effects when Dexdor is administered are fluctuations in blood pressure and bradycardia. However, in some cases, other, less frequent, undesirable manifestations were described:

• hypo- and hyperglycemia;
• signs of metabolic acidosis;
• strong emotional agitation (agitation);
• hallucinations;
• increased heart activity;
• myocardial damage;
• reduction of cardiac ejection;
• difficulty breathing;
• attacks of nausea and vomiting, thirst;
• flatulence;
• delirium;
• fever.

Overdose

Specialists reported several cases of overdose with the drug Dexdor. According to available information, the infusion rate in patients was 60 μg per kg of body weight per hour for 36 minutes, or 30 μg per kg of body weight per hour for 15 minutes (in a 20-month-old infant and adult patient, respectively).

In most cases, signs of an overdose were bradycardia, hypotension, deep sedation, excessive drowsiness and cardiac arrest.

If you suspect a greater amount of the drug, dexdorum infusion should be reduced or stopped. If necessary, provide resuscitation assistance.

It is worth noting that at the moment no case of death of the patient from an overdose of Dexdor has been registered.

[13], [14], [15]

Interactions with other drugs

Dexdor interactions with other medications have been studied in adult patients.

The combination of Dexdor with anesthetics, sedatives, barbiturates and narcotic drugs can cause an increase in their effect. A similar study was performed with infusion of isoflurane, midazolam, propofol, alfentanil. Taking into account the received data, it is possible to adjust the dosages of Dexdor.

Microsomal hepatic studies were conducted to study the ability of the active ingredient Dexdor to inhibit cytochrome P450, including the isozyme CYP2B6. In vitro studies have indicated the likelihood of drug interaction Dexdor with substrates in vivo.

It is possible that the active ingredient can induce the preparation of isozymes CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP3A4.

People who are treated with drugs that lower blood pressure or provoke a bradycardia (for example, beta-blockers), it is necessary to pay attention to the possible enhancement of these effects.

[16], [17], [18]

Storage conditions

Dexdor is kept in the temperature range from + 8 ° C to + 25 ° C, in a room with limited access for children.

The diluted infusion solution is retained only in the refrigerator with a temperature of + 2 ° C to + 8 ° C.

[19]

Shelf life

Ampoules and bottles with the drug Dexdor can be stored for up to 3 years.

The diluted drug is stored for no more than a day, provided that the storage conditions described above are observed.

[20], [21]