Propofol-lipuro 1 %

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PROPOFOL-LIPURO 1 % (PROPOFOL®-LIPURO 1 %)

Composition:

active substance: propofol;

1 ml of emulsion contains 10 mg of propofol;

1 ampoule (20 ml) contains 200 mg of propofol;

1 vial (50 ml) contains 500 mg of propofol;

1 vial (100 ml) contains 1000 mg of propofol;

excipients: soybean oil, medium-chain triglycerides, glycerol, egg yolk phospholipids for injection, sodium oleate, water for injection.

Pharmaceutical form. Emulsion for infusion.

Main physicochemical properties: white, milk-like "oil-in-water" emulsion, practically free from visible particles.

Pharmacotherapeutic group. General anesthetics. Propofol.

ATC code N01AX10.

Pharmacological Properties

Pharmacodynamics

Mechanism of action

After intravenous injection, the sedative effect of Propofol-Lipuro 1% begins rapidly. Depending on the rate of administration, the time to anesthesia induction ranges from 30 to
40 seconds. The duration of action after a single bolus injection is short due to rapid metabolism and elimination (4–6 minutes).

Pharmacodynamic properties

When following the recommended dosing regimen, clinically significant accumulation of propofol after repeated bolus injections or after infusion has not been observed.

Patients recover consciousness quickly.

Bradycardia and hypotension sometimes occur during anesthesia induction, likely due to insufficient vagolytic activity. Cardiovascular status usually normalizes during maintenance of anesthesia.

Children

Limited study data on propofol-based anesthesia duration in children suggest that safety and efficacy remain unchanged with anesthesia lasting up to 4 hours. Literature sources report prolonged procedures in children without changes in safety or efficacy.

Pharmacokinetics

Absorption

After intravenous administration, approximately 98% of propofol is bound to plasma proteins.

Distribution

After intravenous bolus injection, the initial blood concentration of propofol decreases rapidly due to fast distribution into various compartments (α-phase). The half-life during this phase is 2–4 minutes.

During the elimination phase, the decline in blood concentration is slower. The half-life during the β-phase ranges from 30 to 60 minutes. Subsequently, a third deep compartment appears, representing redistribution of propofol into poorly perfused tissues.

The central volume of distribution ranges from 0.2 to 0.79 L/kg body weight, and the steady-state volume of distribution ranges from 1.8 to 5.3 L/kg body weight.

Biotransformation

Propofol is primarily metabolized in the liver, forming propofol glucuronides and glucuronide and sulfate conjugates of the corresponding quinol. All metabolites are inactive.

Elimination

Propofol is rapidly eliminated from the body (total clearance is approximately 2 L/min). Clearance is achieved mainly through metabolic processes, predominantly in the liver, where it is blood flow-dependent.

Clearance is higher in pediatric patients compared to adults. Approximately 88% of the administered dose is excreted in urine as metabolites. Only 0.3% is excreted unchanged in urine.

Children

After intravenous administration of a single dose of 3 mg/kg, propofol clearance per kg body weight increases with age as follows: mean clearance is significantly lower in neonates under 1 month of age (n = 25) (20 mL/kg/min) compared to older children (n = 36, age range 4 months – 7 years). Additionally, in neonates, clearance shows high inter-individual variability (range 3.7–78 mL/kg/min). Due to these limited clinical data indicating significant variability, dosing recommendations cannot be provided for this patient group.

Mean propofol clearance in older children after a single bolus dose of 3 mg/kg was 37.5 mL/kg/min (4–24 months) (n = 8), 38.7 mL/kg/min (11–43 months) (n = 6), 48 mL/kg/min (1–3 years) (n = 12), 28.2 mL/kg/min (4–7 years) (n = 10), compared to 23.6 mL/kg/min in adults (n = 6).

Preclinical safety data

Published animal studies (including in primates), using doses that induce mild or moderate anesthesia, indicate that administration of anesthetics during periods of rapid brain growth or synaptogenesis leads to loss of developing brain cells, potentially resulting in long-term cognitive impairment. The clinical significance of these preclinical findings is unknown.

Published results from animal studies demonstrate that administration of anesthetic agents during periods of rapid brain growth or synaptogenesis causes widespread neuronal and oligodendrocyte cell loss in the developing brain, as well as morphological changes in synapses and neurogenesis. Based on comparisons across species, the risk of such changes is believed to correlate with exposure during the third trimester of pregnancy and the first several months of life, but may persist up to approximately 3 years of age in humans.

In neonatal primates, exposure to anesthesia for up to 3 hours under conditions producing light surgical anesthesia did not increase neuronal cell loss; however, anesthesia regimens lasting 5 hours or longer did lead to such increases. Data on effects in fetuses and neonates in rodents and primates indicate that neuronal and oligodendrocyte loss is associated with mild but long-lasting cognitive deficits in learning and memory. The clinical significance of these preclinical data is unknown; therefore, physicians should weigh the benefits of appropriate anesthesia in children under 3 years of age and in pregnant women requiring surgical intervention against the potential risks indicated by preclinical data.

Propofol is a medicinal product with extensive clinical experience. All necessary information for the prescribing physician is provided in the summary of product characteristics.

Clinical characteristics

Indications

For short-duration general anesthesia. The drug is administered intravenously for:

• induction and maintenance of general anesthesia in adults and children aged > 1 month;
• sedation of patients aged > 16 years who are undergoing mechanical ventilation in intensive care units (ICU);
• sedation during diagnostic and surgical procedures, either alone or in combination with local or general anesthetic agents, in adults and children aged > 1 month.

Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in the section "Composition".

Propofol-Lipuro 1% contains soybean oil and therefore must not be used in patients with hypersensitivity to peanuts or soy.

Propofol-Lipuro 1% must not be used for sedation of patients aged ≤ 16 years in intensive care units. Safety and efficacy in these age groups have not been established (see section "Special precautions").

Age under 1 month is always a contraindication.

Special safety measures

Patients with mitochondrial disorders should be treated with particular caution. Exacerbation of such disorders may occur during anesthesia, surgery, or ICU treatment. For these patients, maintenance of normothermia, carbohydrate supplementation, and adequate hydration are recommended. Early signs of mitochondrial disorder exacerbation and early signs of "propofol infusion syndrome" may be similar.

Propofol-Lipuro 1% does not contain antimicrobial preservatives and therefore does not prevent microbial growth.

After opening an ampoule or breaking the seal of a vial, the solution must be aseptically drawn into a sterile syringe or infusion system immediately. Infusion should be started without delay. Propofol and infusion equipment must be maintained under aseptic conditions throughout the entire infusion period. All infusion fluids added to propofol in the infusion system should be administered close to the cannula site.

Propofol-Lipuro 1% must not be used with microbial filter systems.

Propofol-Lipuro 1% and any syringe containing propofol are intended for single-patient, single-use only. According to established guidelines for other lipid emulsions, the duration of a single propofol infusion should not exceed 12 hours. After completion of the procedure or after 12 hours of infusion, whichever occurs first, the propofol container and infusion system must be discarded and replaced if necessary.

Special warnings regarding disposal and handling

Any unused medicinal product or waste materials must be disposed of in accordance with local requirements.

For single use only. Any remaining contents after first use must be discarded; see section "Dosage and administration".

Ampoules or vials should be shaken before use. If two layers are visible in the ampoule or vial after shaking, the medicinal product must not be used.

Propofol-Lipuro 1% may be mixed only with the following medicinal products: 50 mg/ml (5% w/v) glucose infusion solution, 9 mg/ml (0.9% w/v) sodium chloride infusion solution, or a mixture of 1.8 mg/ml sodium chloride (0.18% w/v) and 40 mg/ml glucose (4% w/v), as well as 1% lidocaine injection solution without preservatives (see section "Dosage and administration", "Infusion of diluted Propofol-Lipuro 1%").

Concomitant administration of Propofol-Lipuro 1% with 50 mg/ml (5% w/v) glucose infusion solution, 9 mg/ml (0.9% w/v) sodium chloride infusion solution, or a mixture of 1.8 mg/ml sodium chloride (0.18% w/v) and 40 mg/ml glucose (4% w/v) through a Y-connector as close as possible to the injection site is permitted.

Interaction with other medicinal products and other forms of interaction

Propofol has been used concomitantly with spinal and epidural anesthesia, as well as with commonly used premedication agents, neuromuscular blocking agents, inhalational agents, and analgesics; no pharmacological incompatibility has been observed. Lower doses of propofol may be required when general anesthesia or sedation is used as an adjunct to regional anesthetic techniques.

Concomitant use of other CNS depressants, such as premedication agents, inhalational agents, and analgesic drugs, may potentiate the sedative, anesthetic, and cardiorespiratory depressant effects of propofol.

Cases of pronounced hypotension have been observed when propofol was administered to patients taking rifampicin.

The hypotensive effect of Propofol-Lipuro 1% may be enhanced when used concomitantly with opioid analgesics. This effect may be more pronounced in elderly patients and when agents such as alfentanil are used for infusion.

A reduced requirement for propofol doses has been observed in patients taking valproates. When used concomitantly, consideration should be given to reducing the dose of propofol.

Reduced propofol dosage requirements have been observed in patients receiving midazolam. Concomitant use of propofol and midazolam may lead to enhanced sedation and respiratory depression. When used together, consideration should be given to reducing the dose of propofol.

Special precautions for use

Propofol must be administered by a qualified specialist in anaesthesiology (or, if necessary, by a physician experienced in managing patients in intensive care units).

Patients must be under continuous monitoring, and all necessary equipment for maintaining airway patency, artificial ventilation of the lungs, oxygen enrichment, and other resuscitation measures must be readily available at all times. Propofol must not be administered by the person performing the diagnostic or surgical procedure.

Cases of propofol abuse and propofol dependence have been reported, primarily among healthcare professionals.

As with other general anaesthetics, administration of propofol without ensuring airway patency may lead to respiratory complications with fatal outcome.

If propofol is used for sedation with preserved consciousness during surgical and diagnostic procedures, patients must be continuously monitored for early signs of hypotension, airway obstruction, and decreased blood oxygen saturation.

As with other sedative agents, involuntary patient movements may occur during administration of propofol for sedation during surgical procedures. During procedures requiring immobility, such movements may pose a danger to the patient.

Sufficient time must elapse before patient discharge to ensure complete recovery of physiological functions following propofol administration. Very rarely, use of propofol may be associated with postoperative loss of consciousness, which may be accompanied by increased muscle tone. This state may sometimes be preceded by a period of insomnia. Although this condition resolves spontaneously, appropriate care and assistance must be provided to any patient who loses consciousness.

Functional impairments caused by propofol are usually not evident more than 12 hours after administration. The effects of propofol, the nature of the procedure, the patient's age and condition should be taken into account when the physician provides patients with instructions regarding:

• the need for accompaniment when leaving the place where propofol was administered;
• the time required before resuming activities requiring skill or being potentially hazardous, e.g., driving a vehicle;
• the use of other substances that may have a sedative effect (e.g., benzodiazepines, opioids, alcohol).

As with other intravenous anaesthetics, propofol should be used with caution in patients with cardiac, respiratory, renal or hepatic impairment, hypovolemia, and in debilitated patients (see also section "Method of administration and dosage").

Propofol clearance is dependent on blood flow; therefore, concomitant therapy that reduces cardiac output will also reduce propofol clearance.

Propofol does not exhibit pronounced vagolytic activity; however, administration of this medicinal product has been associated with reports of bradycardia (sometimes profound) and asystole. Intravenous administration of anticholinergic medicinal products should be considered prior to induction or during maintenance of anaesthesia, especially in situations where increased vagal tone is possible, and when propofol is used concomitantly with other medicinal products that may cause bradycardia.

Particular caution should be exercised during bolus administration of the medicinal product during surgical procedures in patients with acute respiratory insufficiency or respiratory depression.

Concomitant use with medicinal products that depress the central nervous system, such as ethanol, general anaesthetics, and opioid analgesics, will lead to enhanced central nervous system depression. When Propofol-Lipuro 1% is used in combination with parenterally administered central nervous system depressants, severe depression of respiratory and cardiovascular function may occur. It is recommended to administer Propofol-Lipuro 1% after the analgesic has been given, and the dose should be carefully titrated according to clinical response (see section "Interaction with other medicinal products and other forms of interaction").

During induction of anaesthesia, dose-dependent hypotension and transient apnoea may occur, influenced by premedication and concomitant use of other medicinal products.

In individual cases, intravenous fluid administration and reduction of the infusion rate of Propofol-Lipuro 1% during the maintenance phase may be required to manage hypotension.

When Propofol-Lipuro 1% is used in patients with epilepsy, there is a risk of seizure development. The product should be administered with particular caution to patients with lipid metabolism disorders and other conditions requiring cautious use of lipid emulsions.

As with other intravenous anaesthetics and sedatives that depress the central nervous system, patients should be advised to avoid alcohol at least 8 hours before and for 8 hours after propofol administration.

As with other anaesthetic agents, disinhibition may occur during emergence from anaesthesia.

Patients with hypoproteinaemia may have an increased risk of adverse reactions due to a higher fraction of unbound propofol. A reduced dose is recommended for such patients (see also section "Method of administration and dosage").

Before repeated or prolonged (> 3 hours) use of propofol in young children (< 3 years of age) or in pregnant women, the benefit-risk ratio of the proposed procedure should be carefully considered, as neurotoxicity has been reported in preclinical studies (see section "Preclinical safety data").

This medicinal product contains less than 1 mmol (23 mg) of sodium per 100 ml, i.e., it is practically sodium-free.

Propofol-Lipuro 1% contains soybean oil. This medicinal product should not be administered to patients with known allergy to peanuts or soy.

Recommendations for use in intensive care units

The use of propofol emulsion for infusion for sedation of patients in intensive care units (ICU) has been associated with various metabolic disturbances and multi-organ failure that may lead to fatal outcome. Cases of a combination of the following adverse reactions have been reported: metabolic acidosis, rhabdomyolysis, hyperkalaemia, hepatomegaly, renal failure, hyperlipidaemia, cardiac arrhythmia, Brugada-type ECG (ST-segment elevation and coved T-wave), and rapidly progressive heart failure usually unresponsive to inotropic support. This combination of events is known as Propofol Infusion Syndrome and typically occurs in patients with severe head injuries and in children with respiratory infections who have received doses exceeding those recommended for adult sedation in the ICU.

Main risk factors for developing these events include: reduced tissue oxygen delivery; severe neurological injury and/or sepsis; use of high doses of one or more of the following medicinal products: vasoconstrictors, corticosteroids, inotropes, and/or propofol (usually at doses exceeding 4 mg/kg/hour for more than 48 hours).

Physicians prescribing propofol should be vigilant for these events in patients with the above-mentioned risk factors and must discontinue propofol administration immediately if the aforementioned signs appear. All sedatives and other medicinal products used in intensive care units should be titrated to maintain optimal tissue oxygen delivery and haemodynamic parameters. Patients with elevated intracranial pressure should receive appropriate treatment to maintain cerebral perfusion pressure. Doses exceeding 4 mg/kg/hour should be avoided if possible.

The product should be administered with particular caution to patients with lipid metabolism disorders and other conditions requiring cautious use of lipid emulsions.

Monitoring of blood lipid levels is recommended in patients considered to be at particular risk of fat overload. If monitoring indicates inadequate fat clearance, propofol administration should be adjusted accordingly. If the patient is simultaneously receiving other intravenous lipids, the amount of propofol should be reduced, taking into account the lipid content of the propofol formulation (1.0 ml of Propofol-Lipuro 1% contains 0.1 g of fat).

Use during pregnancy or breastfeeding

Pregnancy

The safety of propofol during pregnancy has not been established. Animal studies have demonstrated reproductive toxicity (see section "Preclinical safety data").

Propofol-Lipuro 1% should not be used in pregnant women except in cases of absolute necessity. Propofol crosses the placenta and may cause neonatal depression. However, Propofol-Lipuro 1% may be used for induction of abortion.

High doses (more than 2.5 mg/kg for induction or 6 mg/kg/hour for maintenance of anaesthesia) should be avoided.

Breastfeeding period

Studies in breastfeeding women have shown that small amounts of propofol are excreted in breast milk. Therefore, women should not breastfeed for 24 hours after propofol administration. Milk expressed during this period should be discarded.

Fertility

No data available.

Ability to affect reaction speed when driving or operating machinery

Patients should be warned that their ability to perform skilled tasks, such as driving vehicles or operating machinery, may be impaired for some time after administration of propofol.

Impairments caused by Propofol-Lipuro 1% are usually not evident more than 12 hours after administration (see section "Special precautions for use").

Method of Administration and Dosage

General Instructions

Propofol-Lipuro 1% must be administered only by anesthesiologists or intensive care physicians in hospitals or specially equipped day hospital units. Continuous monitoring of circulatory and respiratory parameters (e.g., using ECG, pulse oximetry) is required, and specialized equipment for maintaining airway patency, artificial ventilation of the lungs, and other resuscitation equipment must be readily available. For sedation during diagnostic and surgical procedures, Propofol-Lipuro 1% must not be administered by the same person performing the diagnostic or surgical procedure.

Analgesics are generally required in addition to Propofol-Lipuro 1%.

Dosage

Propofol-Lipuro 1% is administered intravenously. The dosage is determined individually by the physician according to the patient's response.

Induction of General Anesthesia

Adults

Induction of Anesthesia

For induction of anesthesia, Propofol-Lipuro 1% should be titrated (bolus injection or infusion of 20–40 mg propofol every 10 seconds) according to the patient's response until clinical signs of anesthesia appear. In most adult patients under 55 years of age, a dose of 1.5 to 2.5 mg/kg body weight is generally sufficient.

Patients aged 55 years and older, and patients classified as ASA class 3 and 4, especially those with impaired cardiac function, require a lower dose, and the total dose of Propofol-Lipuro 1% may be reduced to a minimum of 1 mg/kg body weight. These patients require a slower rate of administration (approximately 2 mL of the preparation, corresponding to 20 mg propofol, every 10 seconds).

Elderly Patients

Lower doses of the drug are required for induction of anesthesia in elderly patients.

Dosage reduction should take into account the patient's physical condition and age. The reduced dose should be administered at a slower rate and titrated according to clinical response.

Maintenance of Anesthesia

Anesthesia can be maintained by continuous infusion or repeated bolus injections of Propofol-Lipuro 1%. If repeated bolus injections are used, doses ranging from 25 mg (2.5 mL of Propofol-Lipuro 1%) to 50 mg (5 mL of Propofol-Lipuro 1%) may be administered according to clinical requirements. For maintenance of anesthesia by continuous infusion, the required dose is typically 4–12 mg/kg body weight/hour. The dose may be further reduced in elderly patients, patients with poor general condition, ASA class 3 and 4 patients, and patients with hypovolemia or hypoproteinemia, depending on the severity of the patient's condition and the anesthetic technique used.

Rapid bolus administration (single or repeated) should not be used in elderly patients, as it may lead to depression of cardiovascular and respiratory functions.

Children aged 1 month and older

Induction of Anesthesia

Propofol-Lipuro 1% is not recommended for induction of anesthesia in children under 1 month of age.

For induction of anesthesia in children, the dose of Propofol-Lipuro 1% should be slowly titrated according to the patient's response until clinical signs of anesthesia onset appear. The dose should be determined according to the patient's age and/or body weight.

For most patients aged 8 years and older, approximately 2.5 mg of propofol per 1 kg body weight is required for induction of anesthesia. Younger children, especially those aged 1 month to 3 years, may require higher doses (2.5–4 mg/kg body weight). A lower dose is recommended for children classified as ASA class 3 and 4.

Maintenance of Anesthesia

The drug is not recommended for maintenance of anesthesia in children under 1 month of age.

The required depth of anesthesia can be maintained by infusion or repeated bolus injections of Propofol-Lipuro 1%.

The required infusion rate varies significantly between patients, but a rate of 9 to 15 mg/kg/hour generally provides adequate anesthesia. Younger children, especially those aged 1 month to 3 years, may require higher doses within the recommended dose range.

Lower doses are recommended for ASA class 3 and 4 patients (see also section "Special Precautions").

Sedation of Patients Receiving Mechanical Ventilation in Intensive Care Units

For sedation during intensive care therapy, propofol is recommended to be administered by continuous infusion. The infusion rate is determined by the physician according to the required depth of sedation. In most patients, adequate sedation can be achieved with propofol doses of 0.3–4 mg/kg/hour (see also section "Special Precautions").

Propofol is not recommended for sedation of patients under 16 years of age in the intensive care unit (see section "Contraindications").

Administration of propofol using a TCI (Target Controlled Infusion) system is not recommended for sedation in the intensive care unit.

Elderly Patients

When Propofol-Lipuro 1% is used to achieve sedative effect, the infusion rate should also be reduced. Additional dose and infusion rate reduction will be necessary for ASA class 3 and 4 patients. Rapid bolus administration (single or repeated) should not be used in elderly patients, as it may lead to depression of cardiac and respiratory functions.

Sedation for Diagnostic and Surgical Procedures in Adults

For sedation during surgical and diagnostic procedures, dosage and infusion rate depend on individual clinical response. In most cases, induction of sedation requires 0.5–1 mg of propofol per 1 kg body weight over 1–5 minutes.

Maintenance of sedation is achieved by titrating the dose of Propofol-Lipuro 1% to achieve the desired level of sedation. The required dose for most patients is 1.5–4.5 mg/kg/hour. If rapid increase in depth of anesthesia is needed, an additional bolus injection of 10–20 mg propofol (1–2 mL of Propofol-Lipuro 1%) may be administered.

Patients over 55 years of age and ASA class 3 and 4 patients may require lower doses of Propofol-Lipuro 1%, and a reduction in infusion rate may also be necessary. Rapid bolus administration (single or repeated) should not be used in elderly patients, as it may lead to depression of cardiovascular and respiratory functions.

Sedation for Diagnostic and Surgical Procedures in Children Aged 1 Month and Older

Propofol-Lipuro 1% is not recommended for use in diagnostic and surgical procedures in children under 1 month of age.

For children aged 1 month and older, dosage and infusion rate should be adjusted according to the required depth of sedation and clinical response. In most children, induction of sedation can be achieved with a dose of 1–2 mg/kg body weight of Propofol-Lipuro 1%. Maintenance of sedation can be achieved by titrating the dose of Propofol-Lipuro 1% during infusion to achieve the desired depth of sedation. Most patients require a dose of Propofol-Lipuro 1% of 1.5–9.0 mg/kg/hour. The infusion may be supplemented with bolus doses up to 1 mg/kg body weight if a rapid increase in depth of sedation is required.

Dose reduction may be necessary for patients classified as ASA class 3 or 4.

Method and Duration of Administration

Route of Administration

Intravenous administration.

Propofol-Lipuro 1% is administered undiluted by injection or continuous infusion either undiluted or after dilution in 50 mg/mL (5% m/v) glucose solution, 9 mg/mL (0.9% m/v) sodium chloride solution, or a mixture of 1.8 mg/mL (0.18% m/v) sodium chloride solution and 40 mg/mL (4% m/v) glucose solution (see also section "Special Precautions").

Shake well before use.

Disinfect the ampoule neck or the surface of the bromobutyl rubber stopper of the vial with medical alcohol (using a spray or swab) before use. After use, all opened packages must be discarded.

Propofol-Lipuro 1% does not contain antimicrobial preservatives and supports microbial growth. Therefore, Propofol-Lipuro 1% must be aseptically drawn into a sterile syringe or infusion set immediately after opening the ampoule or vial. Administration should begin without delay. Aseptic conditions must be maintained throughout the administration period for both Propofol-Lipuro 1% and the infusion equipment.

Any medicinal products or fluids added to the ongoing infusion of Propofol-Lipuro 1% must be administered close to the cannula site. If infusion sets with filters are used, they must be lipid-permeable.

The contents of one ampoule or one vial of Propofol-Lipuro 1% and any syringe containing Propofol-Lipuro 1% are intended for single use in one patient only.

Infusion of Undiluted Propofol-Lipuro 1%

When administering Propofol-Lipuro 1% by continuous infusion, burettes, drop counters, syringe pumps, or volumetric infusion pumps should always be used to control the infusion rate.

As established for parenteral administration of all types of lipid emulsions, the duration of continuous infusion of Propofol-Lipuro 1% from one infusion system should not exceed 12 hours.

The infusion line and reservoir for Propofol-Lipuro 1% must be discarded and replaced no later than 12 hours after initiation. Any remaining portion of Propofol-Lipuro 1% after completion of administration must be discarded.

Infusion of Diluted Propofol-Lipuro 1%

For infusion of diluted Propofol-Lipuro 1%, burettes, drop counters, syringe pumps, or volumetric infusion pumps should always be used to control the infusion rate and prevent accidental uncontrolled infusion of large volumes of diluted Propofol-Lipuro 1%.

Maximum dilution should not exceed 1 part Propofol-Lipuro 1% to 4 parts of 50 mg/mL (5% m/v) glucose solution, 9 mg/mL (0.9% m/v) sodium chloride solution, or a mixture of 1.8 mg/mL (0.18% m/v) sodium chloride solution and 40 mg/mL (4% m/v) glucose solution (minimum concentration – 2 mg propofol/mL). The mixture should be prepared immediately before administration under aseptic conditions and used within 6 hours of preparation.

Propofol-Lipuro 1% does not exert analgesic effects; therefore, additional doses of analgesic agents are generally required in addition to Propofol-Lipuro 1%.

To reduce pain at the beginning of administration, Propofol-Lipuro 1% may be mixed with 1% lidocaine injection solution without preservatives (mix 20 parts Propofol-Lipuro 1% with 1 part 1% lidocaine injection solution) (see Table 1). Before administering neuromuscular blockers atracurium or mivacurium, the infusion line should be flushed after administration of Propofol-Lipuro 1%.

Table 1

Dilution of Propofol-Lipuro 1% and concomitant use with other medicinal products or infusion solutions (see also section "Special Precautions").

Target Controlled Infusion

Propofol can also be administered using a Target Controlled Infusion system. As different systems use different algorithms, dosage recommendations should be obtained from the operating instructions provided with the device.

Duration of administration

The maximum duration of administration of Propofol-Lipuro 1% is 7 days.

Children

Propofol is not recommended for use in neonates, as this patient group has not been sufficiently studied. Pharmacokinetic data (see section "Pharmacokinetics") indicate that clearance in neonates is substantially reduced and exhibits very high individual variability. Relative overdose may occur when doses recommended for older children are administered, which may lead to severe cardiovascular depression.

Propofol is contraindicated for sedation in intensive care unit settings in patients under 16 years of age, as the safety and efficacy of propofol for sedation in this age group have not been established (see section "Contraindications").

Overdose

Symptoms

Accidental overdose may result in depression of the cardiovascular and respiratory systems.

Treatment

Respiratory depression should be treated with artificial ventilation of the lungs and oxygen administration. In cases of cardiovascular depression, the patient's head should be lowered, and in severe cases, plasma expanders and pressor agents should be administered.

Adverse reactions

Induction and maintenance of anesthesia or sedation with propofol are generally uncomplicated, with minimal signs of excitation, although spontaneous movements may occur in some patients. The most frequently reported adverse reactions are pharmacologically predictable effects of anesthetics/sedative agents, such as hypotension. These reactions depend on the dose of propofol administered, as well as on the type of premedication and other concomitant medications. The nature, severity, and frequency of adverse events observed in patients receiving propofol may also be related to the patient's clinical condition and the type of surgical or therapeutic procedures being performed.

Adverse reaction table

(1) Severe bradycardia occurs rarely. There have been several reports of bradycardia progressing to asystole.

(2) In some cases, arterial hypotension may require intravenous infusions and reduction of the propofol infusion rate.

(3) Very rare cases of rhabdomyolysis have been reported with propofol administered at doses exceeding 4 mg/kg/hour for sedation in intensive care units.

(4) This can be minimized by administration into larger-diameter veins, such as forearm or antecubital veins. Local pain associated with Propofol-Lipuro 1% can also be reduced by co-administration of lidocaine.

(5) The combination of these events, known as "propofol infusion syndrome," may occur in critically ill patients, who often have multiple risk factors for developing these events—see section "Special warnings and precautions for use".

(6) ECG changes indicative of Brugada syndrome – ST-segment elevation and dome-shaped T waves on ECG.

(7) Rapidly progressive cardiac failure (in some cases fatal) in adults. Cardiac failure in these cases was usually unresponsive to inotropic supportive therapy.

(8) Propofol abuse and drug dependence, primarily among healthcare professionals.

(9) Frequency cannot be determined from available clinical trial data.

(10) Necrosis has been reported in cases of compromised tissue viability.

(11) Treatment is symptomatic and may include immobilization and, if possible, elevation of the affected limb, cooling, careful monitoring, and surgical consultation if necessary.

(12) After both long-term and short-term treatment, and in patients without major risk factors.

Reporting of suspected adverse reactions

Reporting of adverse reactions after medicinal product authorization is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life

2 years.

After first opening – use immediately.

After dilution – the solution must be used immediately.

Storage conditions

Store at temperatures not exceeding 25°C.

Do not freeze.

Keep out of reach of children.

Incompatibilities

This medicinal product must not be mixed with other medicinal products except those specified in the section "Special warnings and precautions for use".

Muscle relaxants, atracurium and mivacurium, must not be administered through the same intravenous line used for Propofol-Lipuro 1% without prior flushing of the line.

Packaging

Ampoules made of colorless type I glass containing 20 ml of emulsion. Packs of 5 ampoules in a cardboard box.

Vials made of colorless type II glass, stoppered with bromobutyl rubber closures, containing 50 ml or 100 ml of emulsion. Packs of 10 vials in a cardboard box.

Prescription status

Prescription only.

Manufacturer

B. Braun Melsungen AG / B. Braun Melsungen AG.

Manufacturer's address and location of operations

Carl-Braun-Strasse 1, 34212 Melsungen, Germany.

Mistelweg 2, 12357 Berlin, Germany.