Propofol of a kaba

General characteristics. Structure:

Active ingredient: 10 mg of a provofol in 1 ml of solution or 200 mg in 1 ampoule.

Excipients: soybeans oil, triglycerides srednetsepochny, phospholipids of an egg yolk, глицерол, oleic acid, sodium hydroxide - q.s., water for injections.

Pharmacological properties:

Pharmacodynamics. Propofol Kabi of 20 mg/ml represents high-speed intravenous anesthetic for introduction to the general anesthesia, for its maintenance, and also for sedation of patients during an intensive care.

After intravenous administration of a propofol hypnotic action begins quickly. Depending on rate of administering time before introduction to anesthesia makes 30-40 seconds.

After single introduction of a bolus action duration short (4-6 minutes) due to bystry metabolism and removal.

Duration of the general anesthesia, depending on a dose and the accompanying drugs, makes of 10 minutes till 1 o'clock.

From anesthesia the patient wakens quickly and with clear consciousness. An opportunity to open eyes appears in 10 minutes, recovery to the speech answer occurs within 3 minutes after disclosure of eyes.

Special places of cumulation are not revealed.

At Propofol Kabi's use 20 mg/ml for introduction to anesthesia and for its maintenance are observed decrease in average values of arterial pressure and little changes of heart rate. Nevertheless, hemodynamic parameters usually remain rather steady during maintenance of the general anesthesia and the frequency of adverse hemodynamic changes low.

After Propofol Kabi's introduction 20 mg/ml can arise respiratory depression, but these effects qualitatively similar to those that arise at use of other intravenous means for the general anesthesia, and easily give in to control in clinical conditions.

Propofol Kabi of 20 mg/ml reduces a cerebral blood stream, intracranial pressure and reduces cerebral metabolism. Patients had a considerable reduction of intracranial pressure with the raised reference value of intracranial pressure.

Propofol Kabi of 20 mg/ml represents the emulsion containing active active ingredient пропофол and mix of long-chain (LCT) and srednetsepochechny (MST) triglycerides.

The srednetsepochny triglycerides (MST) which are a part of a fatty emulsion reduce quantity of a free propofol in a water phase of an emulsion that leads to decrease in morbidity at administration of drug.

Besides, srednetsepochny triglycerides strengthen metabolism that leads to decrease in concentration of triglycerides in plasma.

Pharmacokinetics. Propofol for 98% contacts proteins of plasma. The kinetics of a propofol after an intravenous bolyusny injection can be presented in the model form from three parts: bystry phase of distribution (elimination half-life 2-4 minutes), elimination β-phase (elimination half-life of 30-60 minutes) and elimination γ-phase (elimination half-life of 200-300 minutes).

During a γ-phase decrease in concentration of a propofol in blood comes slowly owing to long redistribution from fatty tissue. In clinical conditions this phase does not influence awakening time. The central volume of distribution makes 0,2-0,79 l/kg, the equilibrium volume of distribution - 1,8-5,3 l/kg.

Propofol is metabolized preferential by conjugation in a liver at clearance about 2 l/min, but metabolism happens also out of a liver.

The clearance at children is higher, than at adults.

The elimination half-life after intravenous infusion made from 277 to 403 minutes. Inactive metabolites are removed by the most part kidneys (about 88%). Only 0,3% of a dose are removed in not changed view with urine.

At maintenance of the general anesthesia in the usual mode considerable cumulation of a propofol after the surgical procedures lasting not less than 5 watch was not observed.

Within the recommended injection speeds the pharmacokinetics of a propofol has linear character.

Indications to use:

- Induction and maintenance of the general anesthesia at adults and children are more senior than 3 years;

- sedation, the patients who are on the artificial ventilation of the lungs (AVL) at adults and children is more senior than 16 years.

Route of administration and doses:

Only intravenously. Propofol Kabi of 20 mg/ml can be applied only by anesthesiologists in hospitals or adequately equipped out-patient departments, and also in intensive care units.

At Propofol Kabi's introduction 20 mg/ml at the disposal of the doctor there has to be an equipment which is usually used when carrying out the general anesthesia, including a control facility of function of cardiovascular system (an ECG, pulse-oksimetriya) and means of resuscitation. Propofol Kabi's dose of 20 mg/ml needs to be selected individually taking into account the answer of the patient and premedication.

As a rule, at use of drug additional administration of analgeziruyushchy drugs is required.

The general anesthesia at adults. Introduction to the general anesthesia. At introduction to the general anesthesia of Propofol Kabi of 20 mg/ml it is necessary to enter fractionally (about 20-40 mg of a propofol each 10 seconds), before emergence of clinical signs of anesthesia.

The usual dose for adults aged up to 55 years makes 1,5-2,5 mg/kg of body weight.

Patients of advanced age and at patients with III and IV severity have states on classification of the American society of anesthesiologists (ASA), especially with the broken function of heart, the required dose is usually lower.

The general dose of Propofol Kabi of 20 mg/ml it is possible to lower a minimum to 1 mg/kg.

Slower introduction of Propofol Kabi of 20 mg/ml is required: approximately on 1 ml (20 mg of a propofol) each 10 seconds.

Anesthesia maintenance. For maintenance of the general anesthesia of Propofol Kabi of 20 mg/ml enter continuously kapelno or repeatedly in the form of a bolus.

пропофол apply to the supporting anesthesia in a dose 4-12 mg/kg of weight.

At less heavy surgical interventions, for example, of low-invasive, decrease in a maintenance dose approximately to 4 mg/kg of body weight/hour is possible.

At the elderly people sick with an unstable general state, patients with the broken function of heart or a hypovolemia and patients with the III-IV severity of a state on ASA classification the dose can be lowered still more taking into account weight of a state and the equipment of anesthesia.

The general anesthesia at children is more senior than 3 years. Propofol Kabi is not recommended to apply 20 mg/ml to the general anesthesia at children under 3 years as concentration of 20 mg/ml of an emulsion is difficult titrated, and very small volume of drug is necessary for small children. For children aged from 1 month up to 3 years, Propofol Kabi is recommended to apply 10 mg/ml, at the same time the dose has to make less than 100 mg/h.

Introduction to the general anesthesia. At introduction to the general anesthesia slow titration of a dose of Propofol Kabi of 20 mg/ml before emergence of clinical signs of the general anesthesia is recommended.

The dose is chosen taking into account age and/or body weight.

At children 8 years the dose necessary for introduction to the general anesthesia are aged more senior makes about 2,5 mg/kg of body weight.

At children of younger age the dose can be higher. Use of drug begin 3 mg/kg with a dose. If necessary it is possible to enter additional doses on 1 mg/kg.

Lower doses are recommended to children from groups of high risk (the III-IV severity of a state on ASA classification).

Anesthesia maintenance. For maintenance of the general anesthesia carry out continuous infusion in a dose of 9-15 mg/kg/h. For maintenance of the general anesthesia children have no data on repeated injections of a propofol.

Dose, select individually. It is necessary to pay special attention to adequacy of anesthesia.

Sedation at adults in intensive care units. For sedation during artificial ventilation of the lungs in intensive care units Propofol Kabi 20 mg/ml are recommended to be entered by continuous infusion. The dose is selected taking into account the necessary depth of sedation. Usually adequate sedation manages to be reached at rate of administering of a propofol 0,3-4,0 mg/kg/h. It is not recommended to increase rate of administering more than 4,0 mg/kg/h.

Propofol Kabi 20 mg/ml should not be applied to sedation in intensive care units at patients at the age of 16 years and is younger.

Ways of introduction. For intravenous administration. Propofol Kabi of 20 mg/ml is entered intravenously not divorced, in the form of continuous infusion.

Propofol Kabi 20 mg/ml cannot be applied to a repeated bolyusny injection for the purpose of anesthesia maintenance.

At introduction Propofol Kabi of 20 mg/ml, infusion speed by means of the burette is recommended to control, droppers of the spray or infusional pump.

The bottle should be stirred up before introduction.

To use only homogeneous drug from the unimpaired bottle.

Before use the rubber membrane should be processed alcohol.

As Propofol Kabi of 20 mg/ml represents the fatty emulsion which is not containing preservatives and not having antimicrobic activity, drug can serve as the favorable environment for rapid growth of microorganisms.

The emulsion should be gathered in the sterile syringe or a dropper right after opening of a bottle. Introduction needs to be begun without delay.

During the entire period of introduction of Propofol Kabi of 20 mg/ml rules of aseptic work with drug and system for parenteral injection have to be followed.

Other medicines or solutions which it is necessary to enter 20 mg/ml along with Propofol Kabi's introduction should be entered into a dropper via the Y-shaped connector or the valve.

Propofol Kabi 20 mg/ml cannot be mixed with other solutions for intravenous administration. However through a cannula of a dropper it is possible to enter at the same time 5% solution of glucose, 0,9% or 0,18% solution of sodium of chloride and 4% glucose solution.

Propofol Kabi 20 mg/ml cannot be entered via the antibacterial filter.

Propofol Kabi 20 mg/ml and other infusional systems containing пропофол are intended only for single use and only to one patient individually.

Any remains of an emulsion of Propofol Kabi of 20 mg/ml after use should be destroyed.

As well as at use of other fatty emulsions, introduction duration Propofola Kabi 20 mg/ml by means of one system for infusion should not exceed 12 h. In 12 h the system for infusion and a tank with Propofol Kabi of 20 mg/ml should be replaced.

To reduce pain at an injection, infusion should be entered into larger vein or just before the beginning of infusion of Propofol Kabi of 20 mg/ml it is possible to enter lidocaine solution.

Muscle relaxants, such as atrakuriya and mivakuriya, it is possible to enter through the same catheter only after jet washing.

Duration of use should not exceed 7 days.

Features of use:

Pregnancy and lactation. Propofol Kabi of 10 mg/ml gets through a placental barrier and can have the oppressing effect on a fruit. It is contraindicated during pregnancy, and also in high doses over 2,5 mg/kg for the general anesthesia or (6 mg/kg/h) for maintenance of anesthesia at delivery.

The exception is made by operations on abortion. A small amount of Propofol Kabi gets to breast milk. In this regard feeding by a breast during 24 h after introduction of a propofol is not recommended.

Propofol Kabi of 20 mg/ml does not reduce a tone of a vagus nerve, and its use in some cases is followed by bradycardia (sometimes expressed), and also an asystolia.

Before induction or in the course of maintenance of the general anesthesia by Propofol Kabi of 20 mg/ml it is necessary to consider the possibility of intravenous administration of m-holinoblokatorov, especially in cases of presumably strengthened tone of a vagus nerve or at Propofol Kabi's use 20 mg/ml together with other drugs capable to cause bradycardia.

For easing of pain in the place of an injection at induction of the general anesthesia by Propofol Kabi of 20 mg/ml before introduction of an emulsion of drug it is possible to enter lidocaine. At use of lidocaine it is necessary to consider that it cannot be applied at patients with a hereditary porphyria.

Propofol Kabi only the doctors who had training on anesthesiology or an intensive care can apply 20 mg/ml.

Propofol Kabi of 20 mg/ml should not be entered by the personnel which are carrying out surgical manipulations.

Efficiency and Propofol Kabi's safety of 20 mg/ml for (background) sedation of children are younger than 16 years is not studied. At unauthorized uses of drug for (background) sedation of children more young 16 years are registered cases of serious side effects, including death though relationship of cause and effect in these cases is not established. In particular, cases of a metabolic acidosis, a lipidemia, a rabdomioliz and/or heart failure are noted. These effects were most often observed at the children with respiratory infections receiving in the conditions of intensive care units of a dose of drug, the exceeding doses for adults. Similarly, at the adults receiving drug longer than 58 hours with a speed more than 5 mg/kg/h exceptional cases of a metabolic acidosis, rabdomioliz, hyperpotassemia and/or quickly progressing heart failure are celebrated (in certain cases from the death). This speed exceeds the maximum speed of 4 mg/kg/h recommended for use of drug for the purpose of sedation of patients in the conditions of intensive care units.

Heart failure in such cases is usually not sensitive to a maintenance therapy inotropic drugs.

Whenever possible it is not necessary to exceed the dose of 4 mg/kg/h usually sufficient for sedation of the patients who are on artificial ventilation of the lungs in the conditions of intensive care units (lasting treatment more than 1 day).

Doctors have to show vigilance concerning the specified side effects, and at the first signs of their emergence to lower a dose or to pass to other sedative drugs.

Rate of administering of Propofol Kabi of 20 mg/ml has to be lowered at patients with inborn weak-mindedness, patients with epilepsy, at dysfunctions of heart, lungs, a liver and kidneys, at hypovolemic states.

In some cases after Propofol Kabi's use 20 mg/ml the period of postoperative unconsciousness of the patient which is followed by the raised muscle tone was noted. Though consciousness independently was returned, for the patients who are in unconsciousness careful observation is required.

Before the patient's extract from clinic it is necessary to be convinced of his complete recovery after the general anesthesia.

Propofol Kabi of 20 mg/ml contains soy oil which in rare instances can cause heavy allergic reactions.

This medicine contains less than 1 mmol of sodium (23 mg of sodium) in 100 ml that practically allows to consider it the drug which is not containing sodium.

During the entire period of infusion it is necessary to observe the principles of an asepsis both concerning drug Propofol Kabi of 20 mg/ml, and concerning the infusional equipment. Parallel administration of other drugs through infusional system for Propofol Kabi of 20 mg/ml should be carried out as it is possible closer to a cannula.

Propofol Kabi of 20 mg/ml and all infusional equipment for its introduction can be used only once and only for one patient.

Influence on ability to manage vehicles and mechanisms. After Propofol Kabi's introduction 20 mg/ml the patient has to be during the appropriate time under observation of the doctor.

The patient should be informed that he should not manage vehicles and mechanisms, has to avoid alcohol intake and works in potentially dangerous conditions in day of administration of drug.

The patient can be allowed to go home only with the accompanying person.

Side effects:

Widespread side effects of Propofol Kabi of 20 mg/ml are the lowering of arterial pressure and suppression of function of breath. These effects depend on a dose of a propofol, and also like premedication and the accompanying therapy.

The following classification of side effects is included below:

Very frequent (> 1:10), frequent (from> 1:100 to <1:10), infrequent (from> 1:1000 to <1:100), rare (from> 1:10 000 to <1:1000), very rare (<1:10 000); unknown (side effects which frequency it is difficult to estimate, proceeding from available data).

Within each group undesirable effects are presented in decreasing order of their clinical importance:

Immune disturbances. Rare: anaphylactic reactions, including Quincke's edema, bronchospasm, erythema and lowering of arterial pressure.

Metabolic disturbances. Frequent: gipertriglitseridemiya

Mental disorders. Rare: euphoria and increase in sexual function during the recovery period.

Neurologic frustration. Frequent: the spontaneous movements and a myoclonus during introduction to anesthesia, the minimum excitement. Rare: a headache, dizziness, a fever and cryesthesias during the recovery period. Epileptiform attacks, including spasms and an opisthotonos. Very rare: the late epileptiform attacks developing in several hours or days. Risk of development of spasms in patients with epilepsy after introduction of a propofol. Cases of lack of consciousness after operation.

Changes from heart / vascular disorders. Frequent: during introduction to anesthesia a lowering of arterial pressure, bradycardia, tachycardia, "inflows". Infrequent: the expressed lowering of arterial pressure. Reduction in the rate of introduction of Propofol Kabi of 20 mg/ml and/or replaceable administration of liquid, if necessary - vasoconstrictors can be required. It is necessary to consider a possibility of sharp decrease in the ABP at patients with the broken coronary or cerebral blood-groove or patients with a hypovolemia. The accruing bradycardia, up to an asystolia, during the general anesthesia. Perhaps intravenous administration of m-holinoblokatorov during introduction to the general anesthesia or during the supporting anesthesia. Rare: arrhythmia during the recovery period. Thrombosis and phlebitis.

Changes from system of breath, a thorax and a mediastinum. Frequent: at introduction to anesthesia a hyperventilation, passing an apnoea, cough, a hiccups. Infrequent: cough during the supporting anesthesia. Rare: cough during the recovery period. Very rare: fluid lungs.

Gastrointestinal disturbances. Rare: nausea and vomiting during recovery. Very rare: after introduction of a propofol pancreatitis cases are described though relationship of cause and effect is not established.

Changes from skin and hypodermic fabrics. Very rare: heavy changes of fabrics after accidental paravenous introduction.

Changes from kidneys and uric ways. Rare: urine discoloration after prolonged use of a propofol.

General and local reactions. Very frequent: pain in the place of an injection. Pain in the place of an injection of a propofol can be minimized by simultaneous administration of lidocaine or infusion of drug in larger vein of a forearm or an elbow pole. At administration of lidocaine seldom (from> 1:10 000 to <1:1000) the following undesirable effects were observed: dizziness, vomiting, drowsiness, spasms, bradycardia, arrhythmias of heart and shock. Rare: postoperative fever. Very rare: separate cases of heavy undesirable effects in the form of a complex of symptoms are described: рабдомиолиз, a metabolic acidosis, a hyperpotassemia and heart failure, sometimes with a lethal outcome. In most cases these symptoms were observed in intensive care units at the patients receiving the dose exceeding 4 mg/kg/h.

Interaction with other medicines:

Propofol Kabi of 20 mg/ml can be used together with other medicines which are usually applied to premedication, an inhalation anesthesia, by analgetics, muscle relaxants or local anesthetics.

Some drugs of the central action can have overwhelming effect on cardiovascular system and system of breath and can strengthen effect of a propofol. If the general anesthesia is combined with local, lower doses can be applied.

Combined use of benzodiazepines, m-holinoblokatorov. or inhalation anesthetics sometimes causes lengthening of anesthesia and decrease in a respiration rate.

After premedication narcotic analgetics strengthening and extension of sedative action of a propofol, and also increase in frequency and duration of an apnoea is possible.

It is necessary to take into account that, Propofol Kabi's use 10 mg/ml against the background of premedication along with inhalation anesthetics or analgetics, can exponentiate anesthesia and side effects from cardiovascular system.

The combined use with it of the drugs suppressing the central nervous system, for example, of alcohol, the general anesthetics of narcotic analgetics leads to the expressed manifestation of their sedative action.

If Propofol Kabi's 20 introduction, mg/ml is combined with the medicines entered parenterally oppressing the central nervous system, perhaps heavy respiratory depression and cordial activity.

After administration of fentanyl perhaps passing increase in concentration of a propofol in blood which is followed by increase in frequency of an apnoea.

After administration of succinylcholine, or a neostigmin methyl of sulfate bradycardia and a cardiac standstill can be observed.

At the patients receiving cyclosporine leukoencephalopathy cases at introduction of fatty emulsions are described, such as пропофол.

Contraindications:

- Hypersensitivity to a propofol or any of drug components;

- pregnancy and in the period of a lactation (till 24 o'clock after use of a propofol);

- children's age up to 3 years. Propofol Kabi is not recommended to apply 20 mg/ml to the general anesthesia at children in (age 3 years are younger, to an oskolk concentration of 20 mg/ml is difficult titrated, and small children require very small volume of drug. For children from 1 month to 3 years Propofol Kabi's use 10 mg/ml is recommended provided that the planned dose will not exceed 100mg/h;

- for sedation of patients 16 years inclusive are aged younger;

- Propofol Kabi is not recommended to apply 20 mg/ml at the patients undergoing electroconvulsive therapy.

With care. As well as at use of other means for not inhalation general anesthesia, it is necessary to show care concerning patients with cardiovascular, respiratory, renal or hepatic disturbances, and also concerning patients with epilepsy, a hypovolemia, disturbances of lipidic exchange or at the weakened patients.

At patients with dysfunction of heart, lungs, kidneys or a liver, the elderly and weakened people, patients with a hypovolemia or epilepsy, patients with consciousness disturbances Propofol Kabi 20 mg/ml it is necessary to enter with a reduced speed.

Before Propofol Kabi's use of 20 mg/ml it is necessary to achieve compensation of cardiovascular or respiratory insufficiency and a hypovolemia.

Before anesthesia at the patient with epilepsy it is necessary to be convinced that he receives antiepileptic therapy. Though in several researches efficiency of a propofol in treatment of the epileptic status was shown, it can increase risk of development of spasms also.

At patients with heavy heart failure and other serious illness of heart Propofol Kabi 20 mg/ml can be entered only with exclusive care and under constant observation.

Extra care should be observed at patients with disturbance of lipid metabolism and other states at which it is necessary to enter fatty emulsions carefully. If the patient receives parenteral food, it is necessary to consider amount of the fat arriving at infusion of an emulsion of Propofol Kabi of 20 mg/ml. In 1,0 ml of an emulsion 0,1 g of fat contain. At treatment in intensive care unit in 3 days it is necessary to define concentration of lipids. Considering higher dose at patients with obesity, it is necessary to consider risk of development of disturbances of a hemodynamics.

Extra care should be observed at patients with the high intracranial pressure and low average arterial pressure, considering the increased risk of considerable falling of intracranial perfused pressure.

During therapy modification patients with the increased intracranial pressure should appoint adequate treatment to improve the perfused pressure of a brain.

Overdose:

The overdose can lead to oppression of functions of cardiovascular system and breath. At suppression of system of breath carry out artificial ventilation of the lungs. At dysfunction of cardiovascular system it is necessary to lower the head end of a bed and to begin administration of plasma substitutes and/or angiotonic means.

Storage conditions:

To store at a temperature not above 25 °C. Not to freeze! To store in the place, unavailable to children. A period of validity - 3 years. Not to use after expiry date.

Issue conditions:

According to the recipe

Packaging:

On 15 ml or 20 ml in ampoules of colourless flowed the I type (Evr. Pharm.), marked by a point. On 5 or 10 ampoules in cardboard or plastic strip packagings together with the application instruction in a cardboard pack. On 50 ml in bottles from colourless glass II of type (Evr. Pharm.), corked by traffic jams from galogenbutilovy rubber and rolled by aluminum caps with plastic covers for control of the first opening (Evr. Pharm.). On 1, 5 or 10 bottles together with the application instruction in a cardboard pack.