Dexdor

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DEXDOR (DEXDOR)

Composition:

Active substance: dexmedetomidine hydrochloride;

1 ml contains dexmedetomidine hydrochloride 118 mcg, equivalent to 100 mcg of dexmedetomidine;

Excipients: sodium chloride, water for injections.

Pharmaceutical form. Concentrate for solution for infusion.

Main physicochemical characteristics: clear, colorless solution.

Pharmacotherapeutic group. Psycholeptics. Other hypnotics and sedatives.
ATC code N05CM18.

Pharmacological Properties

Pharmacodynamics

Dexmedetomidine is a highly selective alpha-2 receptor agonist with a broad spectrum of pharmacological properties. It exerts a strong sympatholytic effect by reducing the release of norepinephrine from sympathetic nerve endings. Sedative effects are mediated by decreased activation of the locus coeruleus, the primary noradrenergic nucleus located in the brainstem. Due to its action on this area, dexmedetomidine produces sedation (similar to natural sleep without rapid eye movement), enabling sedative effects while allowing the patient to remain in an awake and responsive state. Dexmedetomidine has anesthetic and moderate analgesic properties; analgesic effects have been demonstrated in patients with chronic lower back pain. Effects on the cardiovascular system are dose-dependent; at lower infusion rates, central effects predominate, resulting in decreased heart rate and arterial blood pressure. At higher doses, peripheral vasoconstrictive effects prevail, leading to increased systemic vascular resistance and arterial blood pressure, while the bradycardic effect becomes more pronounced. Dexmedetomidine has virtually no respiratory depressant effects.

Sedation in hospital settings (in intensive care, anesthesia, and resuscitation units)

Evidence of efficacy in the pediatric population was obtained from a placebo-controlled ICU study in a large postoperative population aged 1 month to ≤17 years. Approximately 50% of patients receiving dexmedetomidine did not require additional midazolam during a treatment period averaging 20.3 hours and not exceeding 24 hours. Data on treatment durations longer than 24 hours are unavailable. Data in neonates (28–44 weeks of gestation) are limited and relate to the use of low doses (≤0.2 mcg/kg/hr). Neonates may be particularly sensitive to bradycardic effects of DEXDOR under conditions of hypothermia and when heart rate depends on cardiac output.

Procedural Sedation

The safety and efficacy of dexmedetomidine for sedation of non-intubated patients before and/or during surgical and diagnostic procedures were evaluated in two randomized, double-blind, placebo-controlled, multicenter clinical trials.

In Study 1, patients undergoing planned surgical procedures under monitored anesthesia care and local/regional anesthesia were randomized to receive a loading infusion of dexmedetomidine at 1 mcg/kg (n = 129) or 0.5 mcg/kg (n = 134), or placebo (normal saline; n = 63) over 10 minutes, followed by a maintenance infusion initiated at 0.6 mcg/kg/hr.

The maintenance infusion dose of the investigational drug was titrated from 0.2 mcg/kg/hr to 1 mcg/kg/hr. The proportion of patients achieving the target sedation level (≤4 on the Sedation and Activity Score scale) without requiring rescue midazolam was 54% in the 1 mcg/kg dexmedetomidine group and 40% in the 0.5 mcg/kg group, compared to 3% in the placebo group. The risk difference in the proportion of patients randomized to the 1 mcg/kg and 0.5 mcg/kg dexmedetomidine groups who did not require rescue midazolam therapy was 48% (95% CI: 37–57%) and 40% (95% CI: 28–48%), respectively, compared to placebo. The median (range) rescue midazolam dose was 1.5 (0.5–7.0) mg in the 1.0 mcg/kg dexmedetomidine group, 2.0 (0.5–8.0) mg in the 0.5 mcg/kg dexmedetomidine group, and 4.0 (0.5–14.0) mg in the placebo group. The difference in mean rescue midazolam dose in the 1 mcg/kg and 0.5 mcg/kg dexmedetomidine groups compared to placebo was -3.1 mg (95% CI: -3.8 to -2.5) and -2.7 mg (95% CI: -3.3 to -2.1), respectively, in favor of dexmedetomidine. The median time to first rescue dose administration was 114 minutes in the 1.0 mcg/kg dexmedetomidine group, 40 minutes in the 0.5 mcg/kg group, and 20 minutes in the placebo group.

In Study 2, patients undergoing awake fiberoptic intubation under local anesthesia were randomized to receive a 10-minute loading infusion of dexmedetomidine at 1 mcg/kg (n = 55) or placebo (normal saline) (n = 50), followed by a fixed maintenance infusion at 0.7 mcg/kg/hr. To maintain a sedation level >2 on the Ramsay Sedation Scale, 53% of patients receiving dexmedetomidine did not require rescue midazolam therapy compared to 14% in the placebo group. The risk difference in the proportion of patients randomized to the dexmedetomidine group who did not require rescue midazolam therapy was 43% (95% CI: 23–57%) compared to placebo. The mean rescue midazolam dose was 1.1 mg in the dexmedetomidine group and 2.8 mg in the placebo group. The difference in mean rescue midazolam dose was -1.8 mg (95% CI: -2.7 to -0.86) in favor of dexmedetomidine.

Pharmacokinetics

The pharmacokinetics of dexmedetomidine were evaluated after short-term intravenous administration in healthy volunteers and after prolonged infusion in ICU patients. Dexmedetomidine exhibits a two-compartment distribution model. In healthy volunteers, it shows a rapid distribution phase with an estimated central distribution half-life (t_1/2α) of approximately 6 minutes. The estimated terminal elimination half-life (t_1/2) is approximately 2.1 (±0.43) hours, and the estimated steady-state volume of distribution (V_ss) is approximately 91 (±25.5) liters. The estimated plasma clearance (Cl) is approximately 39 (±9.9) L/hr. The mean body weight associated with these V_ss and Cl estimates was 69 kg. Plasma pharmacokinetics of dexmedetomidine are similar in ICU patients after infusions lasting >24 hours. Estimated pharmacokinetic parameters are: t_1/2 – approximately 1.5 hours, V_ss – approximately 93 liters, and Cl – approximately 43 L/hr. Dexmedetomidine pharmacokinetics are linear within the dose range of 0.2–1.4 mcg/kg/hr and do not accumulate during treatment periods up to 14 days. Dexmedetomidine is 94% protein-bound in plasma. Protein binding is constant across concentrations of 0.85–85 ng/mL. Dexmedetomidine binds to human serum albumin and alpha-1-acid glycoprotein, with serum albumin being the primary binding protein in plasma.

Dexmedetomidine is extensively metabolized in the liver. There are three initial metabolic pathways: direct N-glucuronidation, direct N-methylation, and oxidation catalyzed by cytochrome P450. The major circulating metabolites of dexmedetomidine are two isomeric N-glucuronides, one formed by oxidation of the imidazole ring, and the other resulting from sequential processes: N-methylation, hydroxylation of the methyl group, and O-glucuronidation. Available data indicate that the formation of oxidized metabolites is mediated by CYP enzymes (CYP2A6, CYP1A2, CYP2E1, CYP2D6, and CYP2C19). These metabolites have minimal pharmacological activity.

After intravenous administration of radiolabeled dexmedetomidine, approximately 95% of radioactivity was recovered in urine and 4% in feces over nine days. The primary urinary metabolites are two isomeric N-glucuronides, accounting for approximately 34% of the dose, and the N-methylated O-glucuronide, accounting for 14.51% of the dose. Minor metabolites, including carboxylic acid, 3-hydroxy, and O-glucuronide metabolites, individually account for 1.11–7.66% of the dose. Less than 1% of unchanged parent drug was found in urine. Approximately 28% of metabolites detected in urine are unidentified polar metabolites.

No significant pharmacokinetic differences were observed based on patient sex or age.

Dexmedetomidine plasma protein binding is reduced in individuals with hepatic impairment compared to healthy volunteers. The mean percentage of unbound dexmedetomidine in plasma increased from 8.5% in healthy volunteers to 17.9% in patients with severe hepatic impairment. Subjects with varying degrees of hepatic impairment (Child-Pugh classes A, B, or C) showed reduced hepatic clearance of dexmedetomidine and prolonged plasma elimination half-life (t_1/2). Mean clearance values in patients with mild, moderate, and severe hepatic impairment were 74%, 64%, and 53% of that in healthy volunteers, respectively. Mean t_1/2 in patients with mild, moderate, and severe hepatic impairment was prolonged to 3.9, 5.4, and 7.4 hours, respectively. Although dexmedetomidine is dosed to effect, consideration should be given to reducing the initial/maintenance dose in patients with hepatic impairment depending on the degree of impairment and clinical response.

The pharmacokinetics of dexmedetomidine in patients with severe renal impairment (creatinine clearance <30 mL/min) are unchanged.

Data on use in pediatric patients—from neonates (born at 28 to 44 weeks of gestation) to 17 years—are limited. The elimination half-life of dexmedetomidine in children (aged 1 month to 17 years) is likely comparable to that in adults, but is higher in neonates (born at 28 to 44 weeks of gestation) and decreases with age. In age groups from 1 month to 6 years, body weight-adjusted plasma clearance is higher but decreases with increasing age. Due to immaturity, plasma clearance in neonates (up to 1 month of age) may be lower (0.9 L/hr/kg) than in older age groups.

Clinical characteristics.

Indications.

For sedation in hospital settings (in intensive care, anesthesiology and resuscitation departments) of patients requiring a level of sedation no deeper than awakening in response to verbal stimulation.

For sedation of patients during diagnostic or surgical procedures requiring sedation/procedural sedation.

Contraindications.

Hypersensitivity to dexmedetomidine or to any of the excipients of the medicinal product.

Second- or third-degree atrioventricular block (in the absence of an artificial pacemaker).

Uncontrolled arterial hypotension.

Acute cerebrovascular pathology.

Interaction with other medicinal products and other forms of interaction.

Studies on interaction with other medicinal products have been conducted only in adults.

Concomitant administration of dexmedetomidine with anesthetics, sedatives, hypnotics, and opioids may lead to potentiation of their effects, as confirmed in studies with isoflurane, propofol, alfentanil, and midazolam.

No pharmacokinetic interactions between dexmedetomidine and isoflurane, propofol, alfentanil, and midazolam were observed. However, due to possible pharmacodynamic interactions, when these agents are used in combination with dexmedetomidine, dosage reduction of dexmedetomidine or the concomitant anesthetic, sedative, hypnotic, or opioid may be necessary.

The ability of dexmedetomidine to inhibit cytochrome P450, including the CYP2B6 isoenzyme, was studied in human liver microsomes. According to in vitro studies, there is a potential for interaction between dexmedetomidine and substrates (primarily of the CYP2B6 isoenzyme) in vivo.

Induction of CYP1A2, CYP2B6, CYP2C8, CYP2C9, and CYP3A4 isoenzymes by dexmedetomidine was observed in vitro, therefore such interactions in vivo cannot be excluded.

Potential enhancement of hypotensive and bradycardic effects should be considered in patients receiving other medicinal products causing such effects, e.g., β-adrenoblockers (although additional effects in an interaction study using esmolol were moderate).

Special precautions for use.

Dexdor is intended for use in hospital settings (in intensive care units, anesthesia and resuscitation departments), operating rooms, and during diagnostic procedures; its use in other settings is not recommended.

During Dexdor infusion, cardiac function must be continuously monitored in all patients. In non-intubated patients, respiratory function should be monitored due to the risk of respiratory depression and, in some cases, the development of apnea.

Recovery time after administration of dexmedetomidine is approximately one hour. When used in outpatient settings, careful monitoring should continue for at least one hour (or longer, depending on the patient's condition); medical supervision should continue for an additional hour to ensure patient safety.

General warnings

Dexdor must not be administered as a bolus injection, and loading doses are not recommended in intensive care units. Therefore, users should be prepared to use an alternative sedative agent to immediately control agitation or during procedures, especially during the first few hours of treatment. For procedural sedation, a small bolus dose of another sedative may be used if rapid increase in the level of sedation is required.

In some patients receiving Dexdor, mild arousal has been observed, with rapid return to consciousness upon stimulation. In the absence of other clinical symptoms, this sign alone should not be considered as evidence of inadequate drug efficacy.

Dexmedetomidine typically does not cause deep sedation, allowing patients to be easily aroused. Therefore, dexmedetomidine is not suitable for patients requiring continuous deep sedation.

Dexdor must not be used as a general anesthetic for intubation induction or for providing sedation when muscle relaxants are used.

Dexdor is unlikely to suppress seizure activity and therefore should not be used as monotherapy in status epilepticus.

Caution should be exercised when using dexmedetomidine concomitantly with medicinal products that have sedative effects or affect the cardiovascular system, due to the potential for additive effects.

Dexdor is not recommended for patient-controlled sedation. If Dexdor is used in outpatient settings, patient discharge should only occur under supervision by a third party. Patients should be advised to refrain from driving or operating machinery and from performing other potentially hazardous tasks. If possible, they should also avoid using other sedative agents (e.g., benzodiazepines, opioids, alcohol) for a certain period of time, depending on the observed effects of dexmedetomidine, the procedure performed, concomitant medications, age, and patient condition.

Caution should be exercised when using dexmedetomidine in elderly patients. Patients over 65 years of age may be more susceptible to hypotension when receiving dexmedetomidine, including during administration of a loading dose and during procedures. Dose reduction should be considered (see section "Dosage and administration").

Effects on heart and blood vessels; warnings

Dexdor reduces heart rate and blood pressure (central sympatholytic effect), but at higher concentrations causes peripheral vasoconstriction, leading to increased blood pressure. Therefore, Dexdor is not suitable for patients with severe cardiovascular diseases.

Caution should be exercised when administering dexmedetomidine to patients with concomitant bradycardia. Data on the effects of the drug in patients with heart rates < 60 bpm are limited; such patients require enhanced monitoring. Bradycardia usually does not require treatment but can generally be effectively managed with anticholinergic agents (e.g., atropine) and dose reduction. Athletes with low resting heart rates may be particularly sensitive to the negative chronotropic effects of alpha-2 receptor agonists; cases of sinus arrest have been reported. Cases of cardiac arrest, often preceded by bradycardia or atrioventricular block, have also been reported.

In patients with concomitant arterial hypotension (especially refractory to vasopressors), including chronic hypotension, hypovolemia, or reduced functional reserve (e.g., patients with severe ventricular dysfunction and elderly patients), the hypotensive effect of Dexdor may be more pronounced, requiring special care. Reduction in blood pressure usually does not require specific interventions, but readiness to reduce the dose, administer volume expanders, and/or vasopressors should be maintained.

Hemodynamic effects after Dexdor administration may be more pronounced in patients with peripheral autonomic nervous system dysfunction (e.g., due to spinal cord injury), requiring special patient monitoring.

Transient increases in blood pressure with concomitant peripheral vasoconstrictive effects have been observed during administration of a loading dose of dexmedetomidine; therefore, loading doses for sedation in hospital settings (in intensive care, anesthesia, and resuscitation units) are not recommended. Treatment of elevated blood pressure is usually not required, but consideration should be given to reducing the infusion rate.

Central vasoconstriction at high concentrations may be more significant in patients with ischemic heart disease or severe cerebrovascular diseases; such patients require careful monitoring. In patients with signs of myocardial or cerebral ischemia, consideration should be given to reducing the dose or discontinuing the drug.

Caution should be exercised when administering dexmedetomidine together with spinal or epidural anesthesia due to the potential increased risk of hypotension and bradycardia.

Patients with hepatic impairment

Caution should be exercised in patients with severe hepatic insufficiency, as reduced clearance of dexmedetomidine may lead to accumulation and increased risk of adverse reactions and excessive sedation.

Patients with neurological disorders

Experience with the use of Dexdor in severe neurological conditions such as head trauma and the postoperative period after neurosurgical procedures is limited; therefore, it should be used with caution in such conditions, especially when deep sedation is required. When selecting therapy, it should be considered that Dexdor reduces cerebral blood flow and intracranial pressure.

Other warnings

After prolonged use of alpha-2 receptor agonists, withdrawal syndrome has rarely occurred upon abrupt discontinuation. Agitation and elevated blood pressure immediately after stopping dexmedetomidine should raise suspicion of such a condition.

Dexmedetomidine may cause hyperthermia, which may be resistant to conventional cooling methods. Administration of dexmedetomidine should be discontinued if persistent fever of unknown origin develops. Dexmedetomidine is not recommended for patients prone to malignant hyperthermia.

Dexdor contains less than 1 mmol of sodium (23 mg) per 1 ml.

Cases of non-diabetic diabetes insipidus have been reported in association with dexmedetomidine use. If polyuria develops, dexmedetomidine administration should be discontinued, and serum sodium and urine osmolality should be checked.

Use during pregnancy or breastfeeding.

Pregnancy. Data on the use of dexmedetomidine in pregnant women are lacking or limited. Reproductive toxicity has been observed in animal studies. Dexdor should not be used during pregnancy unless the woman's clinical condition requires treatment with dexmedetomidine.

Breastfeeding period. Dexmedetomidine is excreted in human breast milk, but its levels fall below the limit of detection within 24 hours after discontinuation of the drug. Risk to the infant cannot be excluded. The decision to discontinue breastfeeding or to discontinue dexmedetomidine therapy should be made considering the benefits of breastfeeding for the infant and the benefits of dexmedetomidine therapy for the mother.

Fertility. Fertility studies in rats did not reveal any effect of dexmedetomidine on male or female fertility. Data on effects on human fertility are lacking.

Ability to affect reaction speed when driving or operating machinery.

Patients are advised to refrain from driving or operating machinery or performing other potentially hazardous tasks for a certain period after administration of Dexdor for procedural sedation.

Method of Administration and Dosage

For sedation in hospital settings (in intensive care, anesthesia, and resuscitation units) of patients requiring a level of sedation no deeper than awakening in response to verbal stimulation.

For hospital use only.

Dosage for Adults

Patients who have already been intubated and are under sedation may be switched to Dexdor at an initial infusion rate of 0.7 mcg/kg/hr, which may be gradually adjusted within the dose range of 0.2–1.4 mcg/kg/hr to achieve the desired level of sedation. For debilitated patients, consideration should be given to using the lowest initial infusion rate. It should be noted that dexmedetomidine is a very potent agent; therefore, infusion rates are specified per hour. After dose adjustment, up to 1 hour may be required to achieve a stable level of sedation.

The maximum dose of 1.4 mcg/kg/hr must not be exceeded. Patients who fail to achieve adequate sedation at the maximum dose of Dexdor should be switched to an alternative sedative agent.

The use of a loading dose of Dexdor for sedation is not recommended, as it is associated with an increased incidence of adverse effects. If necessary, propofol or midazolam may be used until the clinical effect of dexmedetomidine is achieved.

The duration of treatment depends on the need for sedation. There is no experience with the use of Dexdor for periods longer than 14 days. When treatment exceeds 14 days, the patient's condition must be regularly evaluated.

For sedation of patients during diagnostic or surgical procedures requiring sedation/procedural sedation.

Dexdor must be administered only by healthcare professionals qualified in anesthesia management for patients in operating rooms or during diagnostic procedures. When Dexdor is administered for sedation with preserved consciousness, patients must be continuously monitored by personnel not involved in performing the diagnostic or surgical procedure. Continuous monitoring is required to detect early signs of hypotension, hypertension, bradycardia, respiratory depression, airway obstruction, apnea, dyspnea, and/or oxygen desaturation (see section "Adverse Reactions").

Availability of supplemental oxygen must be ensured and administered promptly if indicated. Oxygen saturation should be monitored using pulse oximetry.

Dexdor is administered as a loading infusion followed by a maintenance infusion. Depending on the procedure, concomitant local anesthesia or analgesia may be required to achieve the desired clinical effect. Additional analgesics or sedatives (e.g., opioids, midazolam, or propofol) are recommended when performing painful procedures or when deeper sedation is needed. The pharmacokinetic distribution half-life of Dexdor is approximately 6 minutes, which, along with the effects of other administered drugs, should be considered when estimating the appropriate time required to titrate to the desired clinical effect of Dexdor.

Initiation of Procedural Sedation

Loading infusion: 1.0 mcg/kg over 10 minutes. For less invasive procedures, such as ophthalmologic surgeries, a loading infusion of 0.5 mcg/kg over 10 minutes may be used.

Maintenance of Procedural Sedation

Maintenance infusion is generally initiated at 0.6–0.7 mcg/kg/hr and titrated to achieve the desired clinical effect within the dose range of 0.2 to 1 mcg/kg/hr. The maintenance infusion rate should be adjusted until the target level of sedation is achieved.

Elderly Patients. Dose adjustment is generally not required in elderly patients (see section "Pharmacokinetics"). However, elderly patients may have an increased risk of developing hypotension (see section "Special Warnings and Precautions**"**), although limited available data on procedural sedation do not clearly indicate a dose-dependent relationship.

Renal Impairment. Dose adjustment is generally not required in patients with renal impairment.

Hepatic Impairment. Dexdor is metabolized in the liver and should therefore be used with caution in patients with hepatic impairment. Consideration should be given to using a reduced maintenance dose.

Method of Administration

Dexdor must be administered by personnel experienced in managing patients requiring intensive care. The drug should be used only as a diluted intravenous infusion using a controlled infusion device.

Ampoules and vials are intended for individual use in a single patient only.

Preparation of Solution

Prior to administration, Dexdor may be diluted with 5% dextrose solution, Ringer's solution, mannitol, or 0.9% sodium chloride solution to achieve the desired concentration of 4 mcg/mL or 8 mcg/mL. The table below provides the volumes required to prepare the infusion.

To achieve a concentration of 4 mcg/mL:

To achieve a concentration of 8 mcg/mL:

Shake carefully to mix the solution well.

Parenteral preparations should be inspected visually for the presence of foreign particles and discoloration prior to administration.

Dexdor is compatible with the following intravenous fluids and drugs: Ringer's lactate solution, 5 % glucose solution, 0.9 % sodium chloride solution, 20 % mannitol, sodium thiopental, etomidate, vecuronium bromide, pancuronium bromide, succinylcholine, atracurium besylate, mivacurium chloride, rocuronium bromide, glycopyrronium bromide, phenylephrine hydrochloride, atropine sulfate, dopamine, noradrenaline, dobutamine, midazolam, morphine sulfate, fentanyl citrate, and plasma substitute (Haemaccel®).

Children. The safety and efficacy of Dexdor in children (aged 0 to 18 years) have not been established. Data on use in children are provided in the sections “Pharmacological properties” and “Adverse reactions**”**, but dosage recommendations cannot be given.

Overdose.

Several cases of dexmedetomidine overdose have been reported in clinical and post-marketing studies. Infusion rates of dexmedetomidine reported in these cases reached 60 mcg/kg/hr for 36 minutes and 30 mcg/kg/hr for 15 minutes in a 20-month-old child and an adult, respectively. The most commonly reported adverse reactions associated with overdose include bradycardia, arterial hypotension, arterial hypertension, excessive sedation, respiratory depression, and cardiac arrest.

In case of overdose with clinical symptoms, infusion of Dexdor should be reduced or discontinued. Cardiovascular effects are predominantly expected and should be treated according to clinical indications. At high concentrations, arterial hypertension may be more pronounced than arterial hypotension. In clinical studies, cases of sinus node arrest resolved spontaneously or responded to treatment with atropine or glycopyrronium. In isolated cases of severe overdose leading to cardiac arrest, resuscitation measures were required.

Adverse Reactions

Sedation of adult patients in the intensive care unit.

The most commonly reported adverse reactions during administration of Dexdor in the intensive care unit setting are arterial hypotension, arterial hypertension, and bradycardia, occurring in approximately 25%, 15%, and 13% of patients, respectively. Arterial hypotension and bradycardia were also the most frequent serious adverse reactions related to Dexdor, occurring in 1.7% and 0.9% of randomized intensive care, anesthesia, and resuscitation patients, respectively.

Procedural sedation.

The most commonly reported adverse reactions during administration of dexmedetomidine for procedural sedation are listed below (Phase III study protocols included predefined threshold levels for changes in blood pressure, respiratory rate, and heart rate considered as adverse effects):

• Hypotension (55% in the dexmedetomidine group compared to 30% in the placebo group receiving rescue therapy with midazolam and fentanyl);
• Respiratory depression (38% in the dexmedetomidine group compared to 35% in the placebo group receiving rescue therapy with midazolam and fentanyl);
• Bradycardia (14% in the dexmedetomidine group compared to 4% in the placebo group receiving rescue therapy with midazolam and fentanyl).

The frequency of adverse reactions is classified as follows: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10000, < 1/1000); very rare (< 1/10000); frequency not known (cannot be estimated from available data).

Endocrine disorders

Frequency not known: Diabetes insipidus.

Metabolism and nutrition disorders

Common: Hyperglycemia, hypoglycemia.

Uncommon: Metabolic acidosis, hypoalbuminemia.

Psychiatric disorders

Common: Agitation.

Uncommon: Hallucinations.

Cardiac disorders

Very common: Bradycardia^1,2.

Common: Myocardial ischemia or infarction, tachycardia.

Uncommon: Atrioventricular block, decreased cardiac output, cardiac arrest.

Vascular disorders

Very common: Hypotension^1,2, hypertension^1,2.

Respiratory system disorders

Very common: Respiratory depression^2,3.

Uncommon: Dyspnea, apnea.

Gastrointestinal disorders

Common: Nausea², vomiting, dry mouth².

Uncommon: Abdominal distension.

General disorders and administration site conditions

Common: Withdrawal syndrome, hyperthermia.

Uncommon: Ineffectiveness of the drug, thirst.

¹ Description of individual adverse reactions.

² Adverse reaction also observed in procedural sedation studies.

³ Frequency "common" in intensive care unit setting studies.

In relatively healthy volunteers not in the intensive care unit, administration of Dexdor occasionally led to sinus node suppression or sinus pause due to bradycardia. Symptoms resolved after leg elevation and administration of anticholinergic agents such as atropine or glycopyrrolate. In isolated cases, bradycardia progressed to periods of asystole in patients with prior history of bradycardia.

Cases of cardiac arrest have also been reported, often preceded by bradycardia or atrioventricular block.

Arterial hypertension has been associated with the administration of a loading dose. This reaction can be minimized by avoiding a loading dose, reducing the infusion rate, or decreasing the loading dose.

Pediatric population. In patients aged 1 month and older, predominantly postoperative, in intensive care units, and with administration duration up to 24 hours, the drug demonstrates a safety profile similar to that in adults. Data in neonates (born at 28 to 44 weeks of gestation) are limited and restricted to maintenance doses ≤ 0.2 mcg/kg/hour. One case of hypothermic bradycardia in a neonate has been reported in the literature.

Shelf life. 3 years.

Physical and chemical stability has been demonstrated for 24 hours at 25°C.

From a microbiological standpoint, this medicinal product should be used immediately. If not used immediately, the duration and conditions of storage during use are the responsibility of the user and should not normally exceed 24 hours at a temperature of 2 to 8°C, except in cases where dilution is performed under controlled and validated aseptic conditions.

Storage conditions.

Store at a temperature not exceeding 25°C. Keep out of the reach of children.
Keep ampoules or vials in the outer carton to protect from light.

Incompatibilities.

Use only the diluents specified in the section "Instructions for use and dosage."

Packaging.

2 ml in an ampoule; packs of 5 or 25 ampoules in a cardboard box.

4 ml or 10 ml in a vial; packs of 4 vials in a cardboard box.

Prescription category. Prescription only.

Manufacturer.

Orion Corporation / Orion Corporation.

Manufacturer's address and place of business.

Orionintie 1, 02200 Espoo, Finland / Orionintie 1, 02200 Espoo, Finland.