Propofol pharmunion

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PROPOFOL FARMYUNION

Composition:

Active substance: propofol;

1 ml of emulsion contains: propofol 10 mg;

Excipients: soybean oil, egg lecithin, glycerol, sodium hydroxide, water for injections.

Pharmaceutical form. Emulsion for infusion.

Main physicochemical properties: white or almost white emulsion; free from foreign particles; no signs of phase separation.

Pharmacotherapeutic group. Agents for general anesthesia. ATC code N01AX10.

Pharmacological properties.

Pharmacodynamics.

Mechanism of action

Propofol (2,6-diisopropylphenol) is a short-acting agent for general anesthesia with a rapid onset of action, occurring within approximately 30 seconds. Recovery from anesthesia is usually rapid. The mechanism of action of propofol, as with all general anesthetic agents, is not fully understood. However, it is believed that propofol exerts its sedative and anesthetic effects by positively modulating the inhibitory function of the neurotransmitter gamma-aminobutyric acid (GABA) through facilitation of its interaction with ligand-gated GABAA receptors.

Pharmacodynamic properties

Generally, when propofol 1% is used for induction and maintenance of anesthesia, a reduction in mean arterial pressure and minor changes in heart rate are observed. However, hemodynamic parameters usually remain relatively stable during the maintenance phase of anesthesia, and the incidence of adverse hemodynamic reactions is low.

Although respiratory depression may occur after administration of propofol 1%, such reactions are qualitatively similar to those observed with other intravenous anesthetic agents and are easily managed under clinical conditions.

Propofol reduces cerebral blood flow, intracranial pressure, and cerebral metabolism. The reduction in intracranial pressure is more pronounced in patients with elevated baseline intracranial pressure.

Clinical safety and efficacy

Recovery from anesthesia is typically rapid and characterized by quick restoration of cognitive functions, with a low incidence of headache, postoperative nausea, and vomiting.

Overall, postoperative nausea and vomiting occur less frequently with propofol 1% compared to inhalational anesthetic agents. This may be related to the reduced emetogenic potential of propofol.

Propofol 1% does not suppress adrenal cortical hormone synthesis at clinically relevant concentrations.

Pediatric population

Limited study data on anesthesia using propofol in children indicate maintained safety and efficacy with anesthesia duration up to 4 hours. According to published data, the medicinal product can be used in children undergoing prolonged procedures without changes in safety or efficacy.

Pharmacokinetics.

Absorption

When propofol 1% is administered for maintenance of anesthesia, blood concentrations asymptotically approach a steady state at a given infusion rate.

Distribution

Propofol is widely distributed and rapidly eliminated from the body (total clearance is 1.5–2.0 L/min).

Elimination

The decline in propofol concentrations after a bolus dose or at the end of infusion can be described by an open three-compartment model, with a very rapid distribution phase (distribution half-life of 2–4 minutes), a rapid elimination phase (elimination half-life of 30–60 minutes), and a slower terminal phase reflecting redistribution of propofol from poorly perfused tissues.

Clearance is achieved via metabolic processes, primarily in the liver, where it is blood flow-dependent, resulting in the formation of inactive conjugates of propofol and the corresponding quinol, which are excreted in urine.

Following intravenous administration of a single 3 mg/kg dose, propofol clearance per kg of body weight increases with age: mean clearance is significantly lower in neonates aged <1 month (n = 25) (20 mL/kg/min) compared to older children (n = 36, age range 4 months – 7 years). Furthermore, in neonates, this parameter showed considerable interpatient variability (range 3.7–78 mL/kg/min). Due to these limited clinical data indicating substantial 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).

Linearity

When propofol 1% is administered within the recommended infusion rate range, the pharmacokinetics of the drug are linear.

Preclinical safety data.

Published animal studies (including in primates), using doses producing mild to moderate anesthesia, indicate that administration of anesthetics during periods of rapid brain growth or synaptogenesis leads to degeneration of developing brain cells, potentially resulting in long-term cognitive deficits. The clinical relevance 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 leads to widespread neuronal and oligodendrocyte cell loss in the developing brain, as well as alterations in synaptic morphology and neurogenesis.

Based on comparisons across species, it has been established that the risk of such changes correlates with exposure during the third trimester of pregnancy and the first few months of life, but may persist up to approximately 3 years of age in humans. In neonatal primates, anesthesia exposure of up to 3 hours under conditions of light surgical anesthesia did not increase neuronal cell loss; however, regimens of anesthesia lasting 5 hours or longer were associated with increased neuronal cell loss.

Data on effects in fetuses and neonates from rodent and primate studies suggest that neuronal and oligodendrocyte cell loss is associated with mild but persistent 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 surgery 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-term general anesthesia, the medicinal product is administered intravenously for:

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

Contraindications.

Hypersensitivity to the active substance or to any of the excipients.

Children under 1 month of age (for induction and maintenance of general anesthesia).

Propofol Farmunion contains soybean oil and is not intended for use in patients with hypersensitivity to peanuts or soy.

Propofol Farmunion should not be used for sedation in patients aged ≤ 16 years in intensive care units (see section "Special precautions for use").

Interaction with other medicinal products and other forms of interaction.

Propofol 1% has been used in combination with agents for spinal and epidural anesthesia, as well as with drugs commonly used for premedication, neuromuscular blockers, inhalational anesthetics, and analgesics—no cases of pharmacological incompatibility have been observed. When general anesthesia or sedation is combined with local anesthetics, lower doses of Propofol Farmunion may be required. Cases of marked hypotension have been observed when propofol was used for anesthesia induction in patients receiving rifampicin.

Concomitant use with other central nervous system depressants, such as premedication agents, inhalational anesthetics, and analgesics, may enhance the sedative and analgesic effects, as well as the depressant effects of Propofol Farmunion on cardiovascular and respiratory function (see section "Special precautions for use").

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

Reduced propofol dosage requirements have been observed in patients receiving valproate.

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 administration of propofol and midazolam may lead to enhanced sedation and respiratory depression. When used concomitantly, consideration should be given to reducing the dose of propofol.

Special precautions for use.

Propofol Farmunion must be administered by a specialist experienced in anaesthesia (or, if necessary, by a physician experienced in intensive care unit practice).

Continuous monitoring of the patient's condition is required. Equipment for maintaining airway patency, artificial ventilation of the lungs, oxygen delivery, and other resuscitation measures must be readily available and ready for immediate use. Propofol Farmunion must not be administered by the same individual who is performing the diagnostic or surgical procedure.

Cases of abuse and development of drug dependence on propofol have been reported, primarily among healthcare professionals. As with other drugs used for general anaesthesia, administration of Propofol Farmunion without respiratory support may lead to life-threatening respiratory complications.

When administering Propofol Farmunion for sedation without loss of consciousness during surgical or diagnostic procedures, continuous monitoring of the patient for early signs of hypotension, airway obstruction, and decreased oxygen saturation is essential.

As with other central nervous system (CNS) depressants, administration of Propofol Farmunion for sedation during surgical procedures may result in involuntary movements in the patient. Such movements may pose a risk to the patient during procedures requiring immobilization.

Sufficient time should elapse before discharge to ensure complete recovery of physiological functions following administration of Propofol Farmunion. Very rarely, use of Propofol Farmunion may be associated with postoperative loss of consciousness, which may be accompanied by increased muscle tone. This condition may be preceded by a period of insomnia. Although this condition resolves spontaneously, appropriate supportive care should be provided to unconscious patients.

Functional disturbances caused by administration of Propofol Farmunion usually resolve within 12 hours. The effects of Propofol Farmunion, the nature of the procedure performed, concomitant medication use, age, and patient status should be considered when advising on:

• the advisability of leaving the healthcare facility accompanied by another person;
• the time interval before resuming activities involving complex or hazardous tasks, such as driving vehicles;
• use of other medications that may depress the central nervous system (e.g., benzodiazepines, opioids, ethyl alcohol).

As with other intravenous anaesthetic agents, Propofol Farmunion should be used with caution in patients with impaired cardiac, respiratory, renal, or hepatic function, as well as in hypovolemic or debilitated patients. The clearance of Propofol Farmunion depends on blood circulation; therefore, concomitant administration of drugs that reduce cardiac output will lead to decreased clearance of Propofol Farmunion.

Propofol Farmunion does not have pronounced vagolytic activity; however, administration of this drug has been associated with cases of bradycardia (in some cases profound) and asystole. Consideration should be given to intravenous administration of an anticholinergic agent prior to induction or during maintenance of anaesthesia, especially if vagal tone predominance is anticipated or when Propofol Farmunion is used concomitantly with other drugs that may cause bradycardia.

As with other intravenous anaesthetics and CNS depressants, patients should be advised to avoid alcohol consumption before and for at least 8 hours after administration of propofol.

Particular caution is required during bolus administration of the drug during surgical procedures in patients with acute respiratory insufficiency or respiratory depression.

Concomitant use with CNS depressants, such as ethyl alcohol, general anaesthetics, and narcotic analgesics, will potentiate CNS depression. When Propofol Farmunion is used in combination with parenterally administered CNS depressants, severe depression of respiratory and cardiovascular function may occur. It is recommended to administer Propofol Farmunion after administration of an analgesic, 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, depending on the dose, premedication, and concomitant use of other drugs.

In individual cases, treatment of hypotension may require intravenous fluid administration and reduction of the infusion rate of Propofol Farmunion during maintenance of anaesthesia.

There is a risk of seizure occurrence when administering Propofol Farmunion to patients with epilepsy.

Appropriate management should be provided for patients with lipid metabolism disorders and conditions where lipid emulsions should be used with caution (see section "Method of administration and dosage").

Use during electroconvulsive therapy is not recommended.

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

Before repeated or prolonged (>3 hours) use of propofol in children under 3 years of age or in pregnant women, the benefits and risks of the procedure should be carefully weighed, as neurotoxicity has been reported in preclinical studies.

Recommendations for use in intensive care unit (ICU) patients

Use of propofol emulsion for infusion for sedation in ICU patients has been associated with various metabolic disturbances and multi-organ failure that may lead to fatal outcomes. Cases have been reported of a combination of the following adverse effects: metabolic acidosis, rhabdomyolysis, hyperkalemia, hepatomegaly, renal failure, hyperlipidemia, cardiac arrhythmia, Brugada-type ECG (ST-segment elevation and convex T-wave), and rapidly progressive heart failure, usually unresponsive to inotropic support therapy. This combination of effects is known as propofol infusion syndrome and is typically observed in patients with severe head trauma and in children with respiratory infections who have received doses exceeding the recommended levels, as well as in adults receiving sedation in intensive care units.

Main risk factors for development of these effects include: reduced tissue oxygen delivery; severe neurological injury and/or sepsis; administration of high doses of one or more of the following drugs: vasoconstrictors, steroids, inotropes, and/or Propofol Farmunion (usually at doses exceeding 4 mg/kg/hour with infusion duration longer than 48 hours).

Healthcare professionals should be prepared for the possible occurrence of these effects in patients with the above-mentioned risk factors and must discontinue Propofol Farmunion immediately upon development of the described signs. Doses of all CNS depressants and other drugs used in intensive care should be titrated to ensure adequate oxygen delivery and maintenance of hemodynamic parameters. Patients with elevated intracranial pressure should receive appropriate treatment aimed at maintaining adequate cerebral perfusion pressure during these therapeutic changes.

It is advisable not to exceed a dose of 4 mg/kg/hour.

Appropriate management should be provided for patients with lipid metabolism disorders and other conditions where lipid emulsions should be used with caution.

Monitoring of blood lipid concentrations is recommended when administering propofol to patients at particular risk of fat overload. If monitoring results indicate impaired fat clearance, propofol infusion should be adjusted accordingly. If other lipid-containing intravenous fluids are administered concomitantly, the dose should be reduced to account for the amount of fat delivered via propofol infusion; 1 mL of Propofol Farmunion contains approximately 0.1 g of fat.

Propofol Farmunion contains sodium hydroxide. This should be taken into account when treating patients on a sodium-restricted diet.

Additional precautions

Patients with mitochondrial disorders should be treated with caution. Exacerbation of the disease may occur during anaesthesia, surgical procedures, and other interventions in ICU. In such patients, normothermia should be maintained, and adequate carbohydrate and fluid supply should be ensured. Early signs of exacerbation of mitochondrial disorders and propofol infusion syndrome may be similar.

The medicinal product Propofol Farmunion should be drawn into a sterile syringe or infusion system under aseptic conditions immediately after opening the ampoule. Administration should begin immediately thereafter. All operations involving Propofol Farmunion and infusion equipment should be performed under aseptic conditions during infusion. Any infusion solutions should be added to the infusion line containing Propofol Farmunion immediately before the administration site. Propofol Farmunion should not be used in systems with microbial filters.

Propofol Farmunion and syringes containing this medicinal product are intended for single use in one patient only. According to accepted guidelines for use of other lipid emulsions, a single propofol infusion should not last longer than 12 hours. At the end of the procedure or after 12 hours, whichever comes first, the container with propofol and the infusion line should be discarded and replaced with new ones.

The contents of the primary packaging should be shaken before use.

Any unused volume of the medicinal product after administration should be discarded.

Propofol Farmunion should not be mixed with injection or infusion solutions prior to administration, except with 5% dextrose solution or lidocaine injection solution (see "Method of administration and dosage").

Use during pregnancy or breastfeeding.

Pregnancy

The safety of Propofol Farmunion during pregnancy has not been established. Animal studies have demonstrated reproductive toxicity. Propofol Farmunion should not be used in pregnant women except in cases of absolute necessity. However, Propofol Farmunion may be used for induction of abortion.

Labour

Propofol Farmunion crosses the placental barrier and may cause depression in newborns. This medicinal product should not be used for anaesthesia during labour except in cases of absolute necessity.

Breastfeeding

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

Ability to affect reaction speed when driving vehicles or operating machinery.

Propofol Farmunion has a moderate influence on the ability to drive vehicles and operate machinery. Patients should be warned that performance of complex tasks, such as driving vehicles or operating automated systems, may be impaired for some time after general anaesthesia.

Functional disturbances caused by administration of Propofol Farmunion usually resolve within 12 hours (see section "Special precautions for use").

Administration and Dosage

Dosing

Induction of General Anesthesia

Adults

Regardless of whether premedication has been administered, the dose of Propofol Farmunion should be titrated (administered to adult patients as a bolus injection or infusion of approximately 4 mL (40 mg) every 10 seconds), taking into account the clinical response until signs of anesthesia appear. For most adult patients under 55 years of age, the dose ranges from 1.5–2.5 mg/kg. The required total dose can be reduced by decreasing the rate of administration [from 2 to 5 mL/min (20 to 50 mg/min)]. Patients over 55 years of age generally require lower doses to achieve general anesthesia. For patients classified as ASA (American Society of Anesthesiologists) class 3 or 4, the drug should be administered at a slower rate (approximately 2 mL (20 mg) every 10 seconds).

Elderly Patients

Elderly patients require lower doses of the drug for induction of anesthesia.

When reducing the dose, the patient’s health status and age should be taken into account. The reduced dose should be administered more slowly and titrated according to clinical response.

Children

Propofol Farmunion is not recommended for induction of general anesthesia in children under 1 month of age.

For induction of anesthesia in children aged 1 month and older, Propofol Farmunion should be administered slowly until clinical signs of anesthesia appear. The dose should be adjusted according to age and/or body weight. For most children aged 8 years and older, approximately 2.5 mg/kg body weight is required for induction of general 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 patients classified as ASA class 3 or 4 (see section "Special Considerations").

Maintenance of General Anesthesia

Adults

Anesthesia can be maintained by continuous infusion or repeated bolus injections of Propofol Farmunion to sustain the appropriate depth of anesthesia. Recovery from anesthesia is usually rapid; therefore, it is important to continue administering Propofol Farmunion until the end of the procedure.

Continuous Infusion

The required infusion rate varies significantly among individual patients, but generally, a rate within the range of 4–12 mg/kg/hour maintains adequate depth of anesthesia.

Repeated Bolus Injections

With repeated bolus injections, incrementally increasing doses from 25 mg (2.5 mL) to 50 mg (5 mL) should be administered according to clinical need.

Elderly Patients

In elderly patients, the infusion rate or target concentration should also be reduced to maintain anesthesia. Additional dose and infusion rate reduction is required for patients classified as ASA class 3 or 4. 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

Propofol Farmunion is not recommended for maintenance of general anesthesia in children under 1 month of age.

In children aged 1 month and older, anesthesia can be maintained by infusion or repeated bolus injections to sustain the appropriate depth of anesthesia. The required infusion rate varies significantly among individual patients, but a rate within the range of 9–15 mg/kg/hour generally maintains adequate depth of anesthesia.

Younger children, particularly those aged 1 month to 3 years, may require higher doses within the recommended range compared to older children. The dose should be individually adjusted, and the adequacy of anesthesia should be carefully monitored.

Lower doses are recommended for patients classified as ASA class 3 or 4 (see also section "Special Considerations").

Sedation in Intensive Care Unit (ICU) Patients

Adults

For sedation during intensive care, Propofol Farmunion is recommended to be administered via continuous infusion. The infusion rate should depend on the desired depth of sedation. In most patients, adequate sedation can be achieved with Propofol Farmunion administered at a dose of 0.3–4.0 mg/kg/hour. It is recommended that the upper limit of the infusion rate should not exceed 4 mg/kg/hour. Propofol Farmunion should not be used for sedation in patients aged ≤16 years in the intensive care unit.

Propofol Farmunion can be diluted with 5% dextrose solution (see Table 1 below).

Lipid levels in blood should be monitored when administering the drug to patients at particular risk of elevated lipid levels. The administration should be adjusted accordingly if monitoring indicates impaired lipid clearance. If other intravenous lipid-containing solutions are administered simultaneously, the dose should be reduced, taking into account the amount of fat delivered via propofol infusion. 1 mL of Propofol Farmunion contains approximately 0.1 g of fat.

If sedation duration exceeds 3 days, lipid concentration monitoring should be performed in all patients.

Elderly Patients

When Propofol Farmunion is used to achieve sedation, the infusion rate should also be reduced. Additional dose and infusion rate reduction is required for patients classified as ASA class 3 or 4. 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

Propofol Farmunion should not be used for sedation in children under 16 years of age who are undergoing mechanical ventilation in the intensive care unit.

Sedation for Surgical and Diagnostic Procedures

Adults

For sedation during surgical and diagnostic procedures, the drug administration rate should be individually adjusted and titrated according to clinical response.

In most patients, sedation is achieved by administering 0.5–1.0 mg/kg over 1–5 minutes.

Maintenance of sedation can be achieved by titrating the infusion rate to the desired depth of sedation. For most patients, an infusion rate of 1.5–4.5 mg/kg/hour is sufficient. Bolus doses of 10–20 mg may be administered if rapid onset of deep sedation is required. Patients classified as ASA class 3 or 4 may require reduced doses and infusion rates.

Elderly Patients

When the drug is used for sedation, the infusion rate or target concentration should also be reduced. Additional dose and infusion rate reduction is required for patients classified as ASA class 3 or 4. 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

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

In children aged 1 month and older, doses and administration rates should be selected according to the desired depth of sedation and clinical response. In most children, sedation can be induced by administering 1–2 mg/kg body weight. Maintenance of sedation can be achieved by titrating Propofol Farmunion doses during infusion to achieve the desired depth of sedation. Most patients require a dose 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 sedation depth is required.

Patients classified as ASA class 3 or 4 may require dose reduction.

Administration Method

The ampoule should be shaken before use.

The medicinal product does not contain preservatives; therefore, aseptic conditions must be maintained.

One ampoule is intended for use in a single patient only.

Any unused portion of the medicinal product after administration must be discarded.

Propofol Farmunion has no analgesic activity; therefore, concomitant administration of analgesic agents is generally required.

For infusion, Propofol Farmunion can be used undiluted, using glass containers, plastic syringes, or pre-filled syringes, or diluted only with 5% dextrose solution (for intravenous infusion) in PVC infusion bags or glass infusion bottles. Dilution, with a ratio not exceeding 1 to 5 (2 mg propofol per 1 mL), should be performed under aseptic conditions immediately before administration. The diluted emulsion should be used within 6 hours after dilution.

It is recommended that when using diluted Propofol Farmunion, the volume of 5% dextrose solution removed from the infusion bag during dilution should be fully replaced with Propofol Farmunion emulsion (see Table 1 below).

The diluted preparation can be administered using various infusion control techniques, but using only an infusion set does not fully prevent accidental uncontrolled infusion of large volumes of diluted drug. The infusion line must always include burettes, drop counters, or infusion pumps. The risk of uncontrolled infusion should always be considered when calculating the maximum volume of drug in the burette.

When using the undiluted medicinal product for maintenance of anesthesia, it is recommended to always use equipment such as a syringe pump or volumetric infusion pump to control the infusion rate.

Propofol Farmunion can be administered through a Y-connector placed near the injection site during infusion of the following solutions:

• 5% dextrose solution for intravenous infusion;
• 0.9% sodium chloride solution for intravenous infusion;
• 4% dextrose with 0.18% sodium chloride solution for intravenous infusion.

The pre-filled glass syringe has lower plunger resistance compared to a plastic disposable syringe and is easier to initiate. Therefore, when manually administering the drug using a pre-filled syringe, the infusion system between the syringe and the patient must not be left unattended without medical supervision.

When using a pre-filled syringe with a syringe pump, compatibility between the syringe and the pump must be ensured. In particular, the pump design must prevent siphoning and have an occlusion alarm at a pressure not exceeding 1000 mmHg. If a programmable or equivalent pump allowing the use of various syringes is used, only the "B-D" 50/60 mL "PLASTIPAK" mode should be selected when using a pre-filled syringe.

Propofol Farmunion can be pre-mixed with alfenatnil for injection containing 500 mcg/mL alfenatnil in volume ratios from 20:1 to 50:1. Mixtures should be prepared under aseptic conditions and used within 6 hours after preparation.

To reduce pain at the start of administration, the drug can be mixed with 0.5% or 1% lidocaine injection solution without preservatives (see Table 1 below). In such cases, skin sensitivity testing to lidocaine should be performed beforehand.

Target-Controlled Infusion (TCI)

Propofol Farmunion can be administered using a target-controlled infusion (TCI) system, but such systems are limited to using only 20 mL plastic syringes. Their use is restricted to induction and maintenance of general anesthesia in adults and is not recommended for sedation in intensive care units (ICU) or for sedation during surgical or diagnostic procedures.

Propofol Farmunion can be administered using TCI with appropriate software. Users should familiarize themselves with the instructions for using the infusion pump and guidelines for administering Propofol Farmunion with TCI. This system allows the anesthesiologist to achieve and control the desired induction rate and depth of anesthesia by adjusting and modifying the (predicted) plasma concentration and/or local concentration of propofol.

Different operating principles of various infusion pumps should be considered. Since the initial propofol concentration in patients' blood is zero, a lower initial target concentration may be necessary for patients who have previously received propofol when using TCI. Immediate resumption of TCI after pump shutdown is also not recommended.

Target propofol concentration recommendations are provided below. Due to variability in pharmacokinetic and pharmacodynamic characteristics among different patients, the target propofol concentration for patients with or without premedication should be adjusted according to patient response to achieve the appropriate depth of anesthesia.

Induction and Maintenance of General Anesthesia

Adult patients under 55 years of age: anesthesia is typically induced with a target propofol concentration in the range of 4–8 mcg/mL. An initial target concentration of 4 mcg/mL is recommended for patients who have received premedication, while an initial target concentration of 6 mcg/mL is recommended for those who have not. Induction time at these target levels is typically 60–120 seconds. Higher target values provide faster induction of anesthesia but may be associated with more pronounced depression of cardiovascular and respiratory functions.

Patients aged 55 years or older or classified as ASA class 3 or 4: a lower initial target concentration is required. The target concentration can then be increased in steps of 0.5–1.0 mcg/mL at 1-minute intervals to ensure gradual induction of anesthesia.

Maintenance of anesthesia: additional analgesia is usually required. The extent of reduction in target concentration for anesthesia maintenance depends on the amount of concomitant analgesics administered. A target propofol concentration in the range of 3–6 mcg/mL usually provides satisfactory anesthesia maintenance.

Predicted propofol concentration at awakening is typically 1.0–2.0 mcg/mL and depends on the amount of analgesics administered during maintenance anesthesia.

Sedation of patients in intensive care units: TCI use is not recommended in these cases.

Propofol Farmunion Dilution and Concomitant Use with Other Medicinal Products or Infusion Solutions (see also section "Special Considerations").

Table 1

* If lidocaine is used for dilution of the medicinal product, the safety information regarding lidocaine should be taken into account.

Children.

The medicinal product is not recommended for use in neonates, as its use in this patient group has not been fully investigated. Pharmacokinetic data indicate that drug clearance is significantly reduced and highly variable among neonates. Administration of doses recommended for older children may lead to relative overdose and development of severe cardiovascular depression.

Propofol should not be used for sedation in patients under 16 years of age in intensive care units, as the safety and efficacy of propofol for sedation in this age group are unknown (see section "Contraindications").

Overdose.

Accidental overdose is highly likely to result in depression of cardiovascular and respiratory function. Respiratory depression should be treated with artificial ventilation and oxygen administration. In case of cardiovascular depression, the patient's head should be lowered, and in severe cases, plasma expanders and pressor medicinal agents should be administered.

Adverse reactions

Systemic

Induction and maintenance of anesthesia or sedation usually proceed smoothly, with minimal signs of excitation. The most frequently reported adverse reactions are pharmacologically predictable side effects for an anesthetic agent / central nervous system depressant, such as hypotension. The nature, severity, and frequency of adverse reactions observed in patients receiving the drug may be related to the patient's condition and the surgical or therapeutic procedures performed.

The following definitions of adverse reaction frequencies are used: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (frequency cannot be estimated from available data).

Table 2

(1) Severe bradycardia is rare. Isolated reports of progression to asystole have been reported.

(2) Hypotension may sometimes require administration of intravenous fluids and reduction in the infusion rate of the medicinal product.

(3) Rhabdomyolysis has very rarely been reported when the drug was administered at doses exceeding 4 mg/kg/hour for sedation in intensive care units.

(4) This can be minimized by administering the medicinal product into larger veins of the forearm and antecubital fossa. In case of injection, local pain can also be minimized by simultaneous administration of lidocaine.

(5) Combinations of these events, reported as "propofol infusion syndrome," may occur in critically ill patients who often have various risk factors for developing such events; see section "Special precautions for use."

(6) Brugada syndrome on ECG: elevated ST segment and abnormal convex T-wave elevation on ECG.

(7) Rapidly progressive heart failure (in some cases fatal) in adults. Heart failure in these cases was typically unresponsive to inotropic supportive therapy.

(8) Abuse and drug dependence on propofol, primarily among healthcare professionals.

(9) Unknown, as it cannot be assessed from available clinical data.

(10) Necrosis has been reported at sites where tissue viability was compromised.

(11) After abrupt discontinuation of the medicinal product during intensive care treatment.

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

Pulmonary edema, arterial hypotension, asystole, bradycardia, seizures, and cases of dystonia/dyskinesia have been reported. Rhabdomyolysis, metabolic acidosis, hyperkalemia, or heart failure, sometimes fatal, have been rarely observed with the use of propofol at doses exceeding 4 mg/kg/hour for sedation in intensive care settings.

Reports on off-label use of the medicinal product for induction of anesthesia in neonates indicate that cardiovascular and respiratory depression may occur when pediatric dosing regimens are applied.

Local

Local pain, which may occur during the induction phase of anesthesia, can be minimized by concomitant administration of lidocaine (see section "Dosage and administration") and by administration into larger diameter veins such as those in the forearm and antecubital fossa. Cases of thrombosis and phlebitis are rare. Cases of inadvertent extravascular administration and animal studies indicate minimal tissue reaction. Intra-arterial administration in animals did not show local tissue effects.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions after medicinal product authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions in accordance with pharmacovigilance legislation requirements.

Shelf life.

3 years.

Do not use after the expiry date stated on the packaging.

After opening the ampoule, the product should be used immediately.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C. Do not freeze.

Keep out of reach and sight of children.

Incompatibilities.

Muscle relaxants, atracurium and mivacurium, should not be administered through the same intravenous line used for Propofol Farmunion without prior flushing of the line.

Propofol Farmunion must not be mixed prior to intravenous administration with solutions or infusion fluids other than those specified in the section "Dosage and administration."

Packaging.

20 ml in an ampoule; 5 ampoules in a cassette in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

Dong Kook Pharmaceutical Co., Ltd. / Dongkook Pharmaceutical Co., Ltd.

Manufacturer's address and place of business.

33-19, Yongso 2-gil, Gwanghyewon-myeon, Jincheon-gun, Chungcheongbuk-do, Korea /
33-19, Yongso 2-gil, Gwanghyewon-myeon, Jincheon-gun, Chungcheongbuk-do, Korea.