Propofol-Lipuro - instructions for use, dose, side effects, contraindications

1000 ml of emulsion contains:
Active substance:
Propofol	20.00 g
Excipients:
Soybean oil beans	50.00 grams
Medium chain triglycerides	50.00 grams
Egg lecithin	12.00 g
Glycerol	25.00 grams
Sodium oleate	0.30 g
Water for injections	up to 1000 ml

Description:

emulsion of milk-white color of the oil-in-water type, with a weak phenolic odor.

Pharmacotherapeutic group:means for non-induction general anesthesia

ATX: & nbsp

N.01.A.X Other drugs for general anesthesia

N.01.A.X.10 Propofol

Pharmacodynamics:

After intravenous administration of the drug, a hypnotic effect quickly sets in. Depending on the injection rate, the period of administration to anesthesia is 30 to 40 seconds. The duration of action after a single bolus is short (4-6 minutes) because of the high rate of metabolism and excretion.

When observing the recommendations for the use of propofol, clinically significant accumulation with repeated bolus injections or with infusion does not occur. Consciousness in patients is quickly restored.

During the introduction to anesthesia, probably due to the lack of vagolytic activity, sometimes bradycardia and a decrease in blood pressure develops. The function of the cardiovascular system while maintaining anesthesia is usually normalized.

As a propofol delivery system, a fat emulsion based on medium- and long-chain triglycerides was used,so that the aqueous phase of the emulsion contains a significantly lower concentration of the active substance than when using emulsions containing only long chain triglycerides. This provides a reduction in the incidence of pain and its intensity, demonstrated in comparative clinical trials with the use of the drug Propofol-Lipuro 20 mg / ml and due to a very low concentration of free propofol.

Patients of childhood

Some studies show that the safety and efficacy of propofol in children do not change with anesthesia lasting up to 4 hours. There are published data on the use of the drug Propofol-Lipuro 20 mg / ml in children with prolonged operations without changing the safety profile and effectiveness.

Pharmacokinetics:

Distribution

After intravenous administration, about 98% of propofol binds to plasma proteins. After bolus intravenous administration, the initial concentration of propofol in the blood rapidly decreases due to rapid distribution in various tissues (α-phase). The half-distribution period is 2-4 minutes.

During elimination, the rate of decrease in concentration in the blood slows down. Half-life during β-phase is from 30 to 60 minutes. Then follows a slower final phase, which is characterized by the redistribution of propofol from weakly perfused tissues into the blood.

The central volume of distribution lies in the range 0.2-0.79 l / kg of body weight, stable volume of distribution is 1.8-5.3 l / kg of body weight.

Metabolism

Metabolism occurs mainly in the liver with the formation of propofol glucuronides and glucuronides and sulfates of its corresponding quinol. All metabolites are inactive.

Excretion

Propofol is rapidly excreted from the body (the total clearance is approximately 2 l / min). Clearance is provided mainly by the metabolism in the liver, which depends on the intensity of the blood flow. Clearance in children is higher than in adults. About 88% of the administered dose is excreted in the form of metabolites with urine, about 0.3% - in the unchanged form with urine.

Patients of childhood

After intravenous administration of a single dose of 3 mg / kg body weight, propofol clearance increased with age as follows: the clearance median was significantly lower in children younger than 1 month (n= 25) (20 ml / min / kg body weight) compared with older children (n= 36, age from 4 months to 7 years). In addition, neonates showed significant individual variability (range 3.7-78 ml / min / kg body weight). Recommendations for the selection of a dose for this age group can not be given, as the clinical trial data showed high variability. The median clearance of propofol in older children after a single bolus injection at a dose of 3 mg / kg body weight was 37.5 ml / min / kg body weight (4-24 months (n= 8), 38.7 ml / min / kg body weight (11-43 months) (n= 6), 48 ml / min / kg body weight (1-3 of the year) (n= 12), 28.2 ml / min / kg body weight (4-7 years) (n= 10) compared with 23.6 ml / min / kg body weight in adults (n=6).

Indications:

Propofol is a general short-acting anesthetic for intravenous anesthesia, used in the following cases:

- Introduction to general anesthesia and maintenance in adults and children older than 3 years;

- sedation in patients with intensive care units older than 16 years who are on artificial ventilation (IVL);

- sedation in adults and children over 3 years of age when performing diagnostic or surgical procedures as a single agent or in combination with local or regional anesthesia.

Contraindications:

Propofol-Lipuro 20 mg / ml is contraindicated in patients with known hypersensitivity to propofol or any of the excipients. Propofol-Lipuro 20 mg / ml contains soybean oil and should not be used in patients with hypersensitivity to soy or peanuts.

Propofol-Lipuro 20 mg / ml should not be used in patients under 16 years of age for sedation with intensive therapy.

Carefully:

Like other intravenous anesthetics, propofol should be used with caution in patients with cardiac, respiratory, renal or hepatic insufficiency, as well as in patients with hypovolemia or weakened patients.

The introduction of propofol to patients with epilepsy can cause the risk of developing a convulsive attack.

Pregnancy and lactation:

Pregnancy

The safety of propofol during pregnancy is not established. therefore propofol Do not use in pregnant women without clear indications. The drug penetrates the placental barrier and its use can cause fetal oppression. but propofol can be used in the conduct of induced abortion.

Breastfeeding period

Studies with lactating women showed that small amounts of propofol are excreted into breast milk. It is necessary to suspend breastfeeding during the period of drug use and within 24 hours after administration of propofol. Milk, secreted during this period, should not be used for feeding.

Dosing and Administration:

General instructions

Propofol-Lipuro 20 mg / ml should be used only in hospitals or appropriately equipped day hospitals with staff trained in anesthesia or intensive care. Under constant monitoring should be the functions of blood circulation and respiration (eg, ECG, pulse oximetry). Conditions must be provided for the restoration and maintenance of airway patency, ventilation, and conditions for resuscitation. For sedation during surgical procedures or diagnostic procedures, Propofol-Lipuro 20 mg / mL should not be used by personnel who perform a surgical procedure or a diagnostic procedure.

When administering the drug Propofol-Lipuro 20 mg / ml usually requires additional administration of an anesthetic.

Mode of application

Intravenously.

Propofol-Lipuro 20 mg / ml is administered intravenously by prolonged infusion in undiluted form.

Before use, the preparation must be shaken, the surface of the rubber bottle stopper must be disinfected with medical alcohol (by rubbing or by spraying). Used vials should be discarded.

For prolonged infusion of the drug, Propofol-Lipuro 20 mg / ml, it is recommended to always use infusion systems, syringe and volumetric infusion pumps to control the infusion rate.

To reduce pain, lidocaine injection can be used immediately before the infusion of the drug Propofol-Lipuro 20 mg / ml. The infusion system used for the drug Propofol-Lipuro 20 mg / ml should be washed before the introduction of muscle relaxants atracurium and myvacurium. Propofol can also be administered by infusion at the target concentration. Since there are various devices on the market that allow infusion to be carried out at the target concentration, please use the recommended dosage in accordance with the operating instructions for the device.

Doses

Propofol-Lipuro 20 mg / ml is administered intravenously. The dose is selected individually, according to the patient's response.

General anesthesia for adults

Introductory anesthesia

For introductory anesthesia, the drug is administered by titration (20-40 mg propofol every 10 seconds) until clinical signs of anesthesia appear.

Adult patients under 55 years of age usually require 1.5 to 2.5 mg propofol / kg body weight.

Patients over 55 years of age and patients of grades III and IV ASA (American Society of Anesthesiologists), especially with heart failure, the dose of propofol should be reduced. The total dose can be reduced to 1 mg / kg body weight or less, the rate of administration of the drug in such patients also decreases and should be about 1 ml, corresponding to 20 mg every 10 seconds.

Supportive anesthesia

Anesthesia is maintained by prolonged infusion of the drug. To maintain anesthesia by prolonged infusion, the required dose is usually in the range 4-12 mg / kg body weight / hour.

Elderly patients and patients with severe general condition, patients of grades III and IV ASA, as well as in patients with hypovolemia, the dose may be reduced if necessary, depending on the severity of the patient's condition and the procedure of anesthesia.

General anesthesia in children older than 3 years

Introductory anesthesia

For introductory anesthesia propofol is introduced by the method of slow titration in accordance with the patient's reaction before the appearance of clinical signs of anesthesia. The dose is selected depending on the age and / or body weight.

Most children over the age of 8 years for introductory anesthesia require about 2.5 mg propofol / kg body weight. For children younger than 8 years, the required dose may be higher (2.5-4 mg propofol / kg body weight).

Supportive anesthesia

Maintenance of general anesthesia is carried out by prolonged infusion of the drug Propofol-Lipuro 20 mg / ml to maintain the necessary depth of anesthesia. The required rate of administration varies significantly in different patients, but the rate of administration in the range 9-15 mg / kg body weight / h usually provides satisfactory anesthesia. In young children, the required dose may be higher.

In children of grades III and IV ASA a dose reduction is recommended.

Provision of sedation in patients who are on artificial ventilation in the intensive care unit

In the case of application of the drug in patients who are on ventilator, the method of prolonged infusion is recommended.In this case, the rate of administration will depend on the desired degree of sedation and is usually 0.3-4.0 mg / kg body weight / h.

Children under 16 years to ensure sedation in intensive care propofol not assigned.

The introduction of propofol at the target concentration for sedation in the intensive care unit is not recommended.

Provision of sedation in diagnostic and surgical procedures in adults

The dose and rate of administration of the drug are chosen depending on the response of the patient. Most patients require a dose of 0.5-1.0 mg / kg body weight for 1-5 minutes to achieve sedation. Maintenance of sedative effect is achieved by titration of propofol until the required level of sedation. Most patients require 1.5-4.5 mg / kg body weight / h.

For patients older than 55 years and patients in grades III and IV ASA dose and rate of administration should be reduced. In this case, with a significant reduction in the required dose, Propofol-Lipuro 10 mg / ml can be used.

Provision of sedation in diagnostic and surgical manipulations in children over 3 years of age

The dose and rate of administration should be adjusted in accordance with the necessary depth of sedation and the response of the patient. Most pediatric patients require a dose of 1-2 mg propofol / kg body weight to achieve a sedative effect. Maintenance of sedation can be provided by titrating the drug Propofol-Lipuro 20 mg / ml to the required level of sedation. Most patients need a dose of propofol 1,5-9 mg / kg / h.

In children of grades III and IV ASA a dose reduction is recommended.

Duration of application

The maximum period of administration of propofol is 7 days.

Side effects:

Introduction to anesthesia, maintenance of anesthesia, sedation with propofol usually pass with minimal signs of excitation. The most frequent adverse adverse reactions are pharmacologically caused side effects that occur when prescribing drugs for anesthesia or sedation, such as lowering blood pressure. The nature, severity and frequency of adverse adverse reactions in patients who are prescribed propofol, may be due to the patient's condition,as well as ongoing surgical procedures and therapeutic procedures.

Table of Adverse Reactions

Class of organ system	Frequency of development	Adverse Reactions
Immune system disorders	Very rare (<1/10 000)	Anaphylaxis may include angioedema, bronchospasm, erythema, and lowering of blood pressure
Disorders from the metabolism and nutrition	Developmental frequency is unknown (9)	Metabolic acidosis (5), hyperkalemia (5), hyperlipidemia (5)
Disorders of the psyche	Developmental frequency is unknown (9)	Euphoria, drug dependence (8)
Disturbances from the nervous system	Frequent (>1/100, <1/10)	Headache in the stage of awakening
	Rare (>1/10 000, <1/1000)	Epileptiform twitching, including convulsions and opisthotonus during insertion into anesthesia, maintenance and in the awakening stage
	Very rare (<1/10 000)	Unconscious state after surgery
	Developmental frequency is unknown (9)	Involuntary movements
Heart Disease	Frequent (>1/100, <1/10)	Bradycardia (1)
	Very rare (<1/10 000)	Pulmonary edema
	Developmental frequency is unknown (9)	Cardiac arrhythmia (5), heart failure (5), (7)
Vascular disorders	Frequent (>1/100, <1/10)	Reduction of blood pressure (2)
Vascular disorders	Infrequent (> 1/1000, <1/100)	Thrombosis and phlebitis
Disturbances from the respiratory system, chest and mediastinal organs	Frequent (>1/100, <1/10)	Transient apnea when injected into anesthesia
Disorders from the gastrointestinal tract	Frequent (>1/100, <1/10)	Nausea and vomiting in the awakening stage
Disorders from the gastrointestinal tract	Very rare (<1/10 000)	Pancreatitis
Disturbances from the liver and bile ducts	Developmental frequency is unknown (9)	Hepatomegaly (5)
Disturbances from musculoskeletal and connective tissue	Developmental frequency is unknown (9)	Rhabdomyolysis (3), (5)
Disorders from the kidneys and urinary tract	Very rare (<1/10 000)	Discoloration of urine with prolonged infusion
Disorders from the kidneys and urinary tract	Developmental frequency is unknown (9)	Renal insufficiency (5)
Violations of the genitals and mammary gland	Very rare (<1/10 000)	Sexual disinhibition
General disorders and disorders at the site of administration	Very frequent (> 1/10)	Pain at the injection site (4)
Laboratory and instrumental data	Developmental frequency is unknown (9)	ECG type Brugada (5), (6)
Trauma, intoxication and complications of manipulation	Very rare (<1/10 000)	Postoperative fever

⁽¹⁾Severe bradycardia develops rarely. In individual reports, the development of asystole is reported.

⁽²⁾Occasionally, with lowering blood pressure, it may be necessary to perform infusion therapy and reduce the rate of propofol administration.

⁽³⁾Very rarely reported rhabdomyolysis with propofol administration at a dose of more than 4 mg / kg body weight / h for sedation during intensive therapy.

⁽⁴⁾Can be minimized by injecting the drug into the large veins of the forearm and the elbow fold. In addition, pain at the site of administration can be minimized by co-administration with lidocaine.

⁽⁵⁾A combination of symptoms, called "Propofol Infusion Syndrome," can be observed in severely ill patients with a predisposition to their development.

⁽⁶⁾ECG type Brugada - rise STsegment and a decrease in the T-segment on the ECG.

⁽⁷⁾ Rapidly increasing heart failure (in some cases, fatal) in adults. Heart failure in such cases usually did not yield to inotropic replacement therapy.

⁽⁸⁾Drug addiction (mainly from medical personnel).

⁽⁹⁾The frequency of development is unknown, since it is not possible to estimate the frequency of development according to available data.

Overdose:

In case of an overdose, the respiratory and cardiovascular system may be depressed.

Treatment: Ventilation with oxygen. When oppressing the cardiovascular activity, the patient should be given a position with an elevated leg end, if necessary, plasma-substituting and vasopressor preparations should be administered.

Interaction:

With the use of propofol together with spinal and epidural anesthesia, as well as widely used preparations for premedication, muscle relaxants, preparations for inhalation anesthesia, anaesthetizing drugs of pharmacological incompatibility were not revealed.

The use of general anesthesia or sedation in addition to regional anesthesia may require a reduction in the dose of propofol.

Propofol-Lipuro 20 mg / ml should not be mixed with other drugs for injection or infusion. However, it is possible to administer the preparation Propofol-Lipuro 20 mg / ml with 5% dextrose solution, 0.9% sodium chloride solution, 0.18% sodium chloride solution, 4% dextrose solution is recommended through Y-shaped connector, placed as close as possible to the place of injection.

Special instructions:

Propofol should be administered only by personnel with appropriate training in anesthesia or intensive care.

Patients who are being injected propofol, should be under constant supervision. Means to maintain airway patency, for ventilation, oxygen therapy, and resuscitation should be in constant readiness for use.

Propofol should not be used by personnel who perform a surgical procedure or a diagnostic procedure.

There is information about the drug dependence of propofol, identified mainly by medical personnel. The use of propofol, as well as other drugs for general anesthesia, without monitoring the functions of external respiration can lead to life-threatening abnormalities on the part of the respiratory system.

When propofol is introduced for sedation with preservation of consciousness during surgical and diagnostic procedures, patients should be under constant supervision to identify early symptoms of lowering blood pressure, obstructing the airways and reducing blood saturation with oxygen.

When propofol, as well as other sedatives, is used for sedation during surgical manipulation, involuntary movements in the patient may occur. When carrying out procedures that require immobility, such movements may be dangerous for the operated area.

To ensure complete recovery after using propofol, patients need a sufficient period of time. Very rarely, the use of propofol may be associated with the development of an unconscious state after surgery, which may be accompanied by an increase in muscle tone. This may be preceded by a period of wakefulness. Although the restoration of consciousness occurs spontaneously, the patient in an unconscious state must be under observation.

The action of propofol usually stops 12 hours after the end of the injection. The effect of propofol, treatment methods, concomitant drugs, the age and condition of the patient should be considered for deciding on:

- the need for escort at discharge from a medical institution;

- the timing of the resumption of the ability to perform dangerous or skill-specific activities, such as driving a car;

- use of other agents that may have a sedative effect (eg, benzodiazepines, opiates, alcohol).

The clearance of propofol depends on the state of the blood circulation, therefore, concomitant therapy, which reduces cardiac output, also reduces the clearance of propofol.

There are reports of the development of bradycardia (sometimes pronounced), as well as asystole, associated with insufficient vagolytic activity of propofol. Intravenous administration of anticholinergic drugs should be considered prior to administration or during maintenance of anesthesia, especially in situations where the tone of the vagus nerve is likely to predominate or when propofol It is used in combination with other drugs that can cause bradycardia.

Particular attention is required by patients with impaired fat metabolism and other disorders that require caution in the appointment of fat emulsions. It is recommended to monitor the concentration of lipids in the blood plasma when prescribing propofol to patients at risk of developing fat overload. The dose of propofol should be adjusted appropriately, if monitoring shows a slowdown in the removal of lipids from the body.If other lipids are administered intravenously simultaneously, the dose should be reduced taking into account the amount of lipids administered in the propofol formulation; 1.0 ml of the drug Propofol-Lipuro 20 mg / ml contains 0.1 g of fat.

The use of propofol in newborns is not recommended, as there is insufficient data on the use of the drug in this population of patients. These pharmacokinetics show that the clearance in newborns is significantly reduced and has a very high interindividual variability. A relative overdose can occur when a dose recommended for older children is given and severe cardiovascular function depression is caused.

Recommendations for treatment in intensive care units

Safety and efficacy of propofol in prescribing to children under 16 years of age for (background) sedation are not established. Despite the fact that the causal relationship was not established, serious undesirable effects (background) sedation in patients younger than 16 years (including fatal cases) were recorded during unauthorized use.In particular, these effects concern the occurrence of metabolic acidosis, hyperlipidemia, rhabdomyolysis and / or heart failure. These effects were most often observed in children with respiratory infections receiving doses exceeding those recommended in adults for sedation in intensive care units.

A combination of the following disorders has been reported: metabolic acidosis, rhabdomyolysis, hyperkalemia, hepatomegaly, renal failure, hyperlipidemia, cardiac arrhythmia, Brugada ECG (ST-segment elevation and T-segment reduction) and rapidly progressive heart failure, usually not responding to inotropic therapy (in some cases fatal) in adults. The combination of these symptoms is known as Infusion syndrome propofol. The main risk factors for the development of these symptoms can be: reduced delivery of oxygen to tissues; severe neurotrauma and / or sepsis, high doses of one or more of the following pharmacological agents - vasoconstrictors, steroids, inotropes and / or propofol (usually in high doses and at a rate of administration of more than 4 mg / kg body weight / h).

If the first signs of the above symptoms occur, it is necessary to be ready to reduce the dose of propofol and transfer the patient to the introduction of alternative sedatives. The dose and speed of administration of all sedative and other medications used in the intensive care unit, including propofol, should be individually selected to maintain optimal delivery of oxygen and hemodynamics, and appropriate measures should be taken to maintain cerebral perfusion pressure at the proper level in patients with increased intracranial pressure. If possible, do not exceed the dose of propofol at 4 mg / kg body weight / h.

Additional precautions

Propofol-Lipuro 20 mg / ml does not contain preservatives, so the growth of microorganisms is possible.

The extraction of propofol should be performed aseptically with a sterile syringe or a sterile infusion system immediately after opening the ampoule or vial. The introduction should begin immediately. It is necessary to maintain aseptic conditions for the drug Propofol-Lipuro 20 mg / ml and infusion equipment during the entire infusion.When several drugs are administered together with propofol when using one infusion system, these drugs should be administered as close to the intravenous cannula as possible. Propofol-Lipuro 20 mg / ml should not be administered through an infusion system with a microbiological filter.

The contents of the ampoule or vial with propofol or a syringe containing propofol, are used once for only one patient. In accordance with the established application rules for all fat emulsions, the duration of one continuous infusion of propofol should not exceed 12 hours. At the end of the procedure or after 12 hours, depending on what comes first, the propofol container and the infusion line should be replaced.

Propofol-Lipuro 20 mg / ml contains less than 1 mmol (23 mg) of sodium in 100 ml, i.e. practically does not contain sodium.

Shake before use.

The drug should not be used if its color is different from milky white or the separation of the phases of the emulsion remains after stirring.

Only for single use.

Remaining unused quantities of the drug are subject to destruction.

Effect on the ability to drive transp. cf. and fur:

When using the drug, it is necessary to refrain from controlling vehicles, mechanisms and from practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions. The action of propofol usually stops 12 hours after the end of the injection.

Form release / dosage:

Emulsion for intravenous administration, 20 mg / ml.

Packaging:

50 ml each in glass bottles (type I, Eurasian Pharmacopoeia), sealed with a rubber stopper of gray color and an aluminum cap of golden color with a plastic plug of red-brown color.

Ten bottles with instructions for use in a cardboard box (for hospitals).

Storage conditions:

Store at a temperature of no higher than 25 ° C in a dark place. Do not freeze.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-002090/08

Date of registration:25.03.2008

The owner of the registration certificate:B. Brown Mehlungen AGB. Brown Mehlungen AG Germany

Manufacturer: & nbsp

B. BRAUN MELSUNGEN, AG Germany

Representation: & nbspB. Brown Medikal, Open CompanyB. Brown Medikal, Open Company

Information update date: & nbsp07.09.2015

Illustrated instructions

Instructions

Propofol-Lipuro (Propofol Lipuro)