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

Active substances:
propofol	10 mg
Excipients:
soy bean oil	100 mg
glycerol	22.5 mg
egg yolk phospholipids	12.0 mg
oleic acid (for pH correction)	0.4-0.8 mg
sodium hydroxide (for pH correction)	0.05-0.11 mg
water for injections	up to 1 ml

Description:

White or almost white color is a homogeneous emulsion.

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:

Propofol Fresenius is a rapid-acting intravenous anesthetic for administration to and maintenance of general anesthesia, as well as for sedation of patients during intensive care.

After intravenous administration of propofol hypnotic action begins quickly.

Depending on the speed of administration, the time to anesthesia is 30-40 seconds. After a single bolus administration, the duration of action is short (4-6 minutes) due to rapid metabolism and excretion. The duration of general anesthesia, depending on the dose and concomitant drugs, ranges from 10 minutes to 1 hour.

From anesthesia, the patient wakes up quickly and with clear consciousness. Opportunity to open eyes appears after 10 minutes. There is no specific adsorption site.

With the use of Propofol Fresenius for introductory anesthesia and for maintaining it, there is a decrease in the average indices of arterial pressure and a slight change in the heart rate.However, hemodynamic parameters usually remain relatively stable during maintenance of general anesthesia and the frequency of adverse hemodynamic changes is low.

After administration of Propofol Fresenius, respiratory depression may occur, but these effects are qualitatively similar to those that occur with the use of other intravenous agents for general anesthesia and are easily amenable to clinical control.

Propofol Fresenius reduces cerebral blood flow, intracranial pressure and reduces cerebral metabolism. The decrease in intracranial pressure was significant in patients with an elevated baseline value of intracranial pressure.

Pharmacokinetics:

Propofol Fresenius with 98% bondieswith plasma proteins. The propofol kinetics after intravenous bolus injection can be presented in the form of a three-part model: a rapid distribution phase (half-life of 2-4 minutes), β-phase (half-life 30-60 minutes) and γ-phase (half-life period 200-300 minutes). In the course of the γ-phase, a decrease in the concentration of the drug in the blood occurs slowly as a result of a prolonged redistribution from adipose tissue.In clinical settings, this phase does not affect the time of awakening. The central volume of distribution is 0.2-0.79 l / kg, the equilibrium volume of distribution is 1.8-5.3 l / kg.

Propofol Fresenius is metabolized predominantly by conjugation in the liver at a clearance of about 1.5-2 L / min, but the metabolism also occurs outside the liver. Clearance in children is higher than in adults.

The half-life after intravenous infusion was between 277 and 403 minutes. Inactive metabolites are mostly excreted by the kidneys (about 88%). Only 0.3% of the injected drug is excreted unchanged in the urine.

After a one-time intravenous dose of 3 mg / kg, the clearance of propofol per kg of body weight increased with age as indicated below: the median clearance was significantly lower in newborns younger than one month (n= 25) (20 ml / kg / min) compared with older children (n= 36, the age range from 4 months to 7 years). In addition, neonates showed significant interindividual variability (range 3.7-78 ml / kg / min). Due to the limited data of these studies, which indicate a high variability, it is not possible to give recommendations on dosing in this age group.

The median clearance of propofol in older children following a one-time bolus dose of 3 mg / kg was 37.5 ml / min / kg (4 to 24 months) (n= 8), 38.7 ml / min / kg (11 to 43 months) (n= 6), 48 ml / min / kg (1 to 3 years) (n= 12), 28.2 ml / min / kg (4 to 7 years) (n= 10) compared with 23.6 ml / min / kg in adults (n=6).

With maintenance of general anesthesia in the usual regime, there was no significant cumulation of propofol after surgical procedures lasting not less than 5 hours.

Within the recommended infusion rates, pharmacokinetics is linear.

Indications:

- For introductory anesthesia and maintenance in adults and children older than 1 month;

- to provide sedative effect in adults and children over 16 years of age who are receiving intensive therapy and are on mechanical ventilation (artificial ventilation);

- in order to provide a sedative effect in adults who are conscious, during surgical and diagnostic procedures.

Contraindications:

- Hypersensitivity to any of the components of the drug;

- pregnancy and lactation (up to 24 hours after propofol administration);

- children under 1 month;

- Propofol Fresenius is not recommended for sedation in patients under 16 years of age, inclusive;

- Propofol Fresenius is not recommended for patients undergoing electroconvulsive therapy.

Carefully:

As with other agents for non-general anesthesia, caution should be exercised in patients with cardiovascular, respiratory, renal or hepatic impairment, as well as patients with epilepsy, hypovolemia, lipid metabolism disorders or in weakened patients.

Elderly patients, patients with heart, respiratory, kidney or liver diseases, as well as patients with hypovolemia and epilepsy. Propofol Fresenius should be administered at a reduced rate.

In the presence of cardiac, circulatory or respiratory failure, it should be compensated before administration of Propofol Fresenius.

In patients with severe heart failure and other serious heart conditions, propofol Fresenius should be administered with extreme caution and under constant supervision.

Particular care should be taken in patients with high intracranial pressure and low mean arterial pressure who have an increased risk of a significant drop in intracranial perfusion pressure.

Pregnancy and lactation:

Propofol Fresenius penetrates the placental barrier and can exert a depressing effect on the fetus. For this reason, the drug is contraindicated during pregnancy, as well as in high doses above 2.5 mg / kg for general anesthesiaand or (6 mg / kg / h) to maintain anesthesia during delivery, except for termination of pregnancy. A small amount of Propofol Fresenius enters the breast milk. It is believed that this does not pose a danger to the infant if the mother starts breastfeeding 24 hours after the administration of Propofol Fresenius.

Dosing and Administration:

Only intravenously.

Propofol Fresenius can be used only by anesthetists in hospitals or specialized outpatient departments, as well as in intensive care units. With the introduction of Propofol Fresenius, the doctor should have at his disposal a device commonly used for general anesthesia, including cardiovascular monitoring (ECG, pulse, oximetry) and resuscitation facilities.

During sedation during surgical and diagnostic interventions, Propofol Fresenius should not be administered by the same doctor who carries out these manipulations.The dose of Propofol Fresenius is selected individually, depending on the response of the patient to premedication. As a rule, when using the drug, additional administration of analgesic drugs is required.

General anesthesia in adults

Introductory anesthesia

For the induction of general anesthesia, propofol Fresenius is administered fractional (approximately 20-40 mg every 10 seconds) until clinical signs of anesthesia appear.

The usual dose for adults under the age of 55 years is 1.5-2.5 mg / kg body weight. With continuous infusion, 0.3-4.0 mg / kg body weight / hour is administered. Do not exceed the infusion rate of 4.0 mg / kg body weight / hour.

In the older age, the required dose is generally reduced. In patients corresponding to III and IV classes according to the classification of the American Society of Anesthesiologists (ASA), induction of anesthesia develops more slowly, which requires a slower administration of Propofol Fresenius - approximately 2 ml (20 mg) every 10 seconds.

Maintaining anesthesia

When using Propofol Fresenius maintenance of anesthesia is achieved either through continuous infusion, or through repeated bolus injections.

To maintain anesthesia by continuous infusion, the dose and rate of administration are individually selected, usually 4-12 mg / kg body weight / hour propofol is administered.In small operations, for example, with minimally invasive procedures, a smaller maintenance dose may be sufficient, approximately 4 mg / kg body weight / hour.

Reduction of the dose of Propofol Fresenius to 4 mg / kg body weight / hour is also recommended for elderly patients with hypovolemia and patients with III-IV degree of severity of the condition by classification ASA.

To maintain anesthesia through repeated bolus injections, propofol Fresenius should be administered at a dose of 25 to 50 mg, which corresponds to 2.5-5 ml of the drug.

In elderly patients, rapid bolus administration is not indicated in connection with the possibility of cardiopulmonary depression.

General anesthesia in children older than 1 month

Because of the lack of experience with propofol, Fresenius should not be used in children younger than 1 month of age.

Introductory anesthesia

During induction, it is recommended that the dose be titrated before the appearance of clinical signs of the onset of general anesthesia.

The dose should be adjusted to the age and / or weight of the patient

Induction of general anesthesia in children older than 8 years usually requires Propofol Fresenius approximately 2.5 mg / kg body weight. It is necessary to administer the drug slowly in repeated fractional doses until clinical signs of general anesthesia appear.Children of a smaller age may require a higher dose. The initial dose of Propofol Fresenius should be 3 mg / kg body weight, and if necessary, you can additionally administer 1 mg / kg body weight.

Due to the lack of experience in clinical use for young children from high-risk groups (III-IV severity of the condition by classification ASA) lower doses are recommended.

Maintaining anesthesia

To maintain anesthesia in children through constant infusion, the recommended dose of Propofol Fresenius is 9-15 mg / kg body weight per hour.

Children under 3 years may require a higher maiden in the limit of recommended doses per kilogram of body weight, compared with older children.

The dose should be selected individually and especially should pay attention to the adequacy of anesthesia.

The maximum duration of use should not exceed about 60 minutes, except for specific situations requiring longer-term use, for example, malignant hyperthermia, when inhalation anesthetics can not be used.

Application of Propofol Fresenius as a sedative in the period of intensive therapy in adults

The dose is selected depending on the required depth of sedation. With the maintenance of general anesthesia, a dose of Propofol Fresenius 0.3 to 4.0 mg / kg / h is administered by continuous infusion. It is not recommended to increase the rate of administration more than 4.0 mg / kg / h.

When introducing fat emulsion to the patient, it is necessary to take into account that 1 ml of Propofol Fresenius contains 0.1 g of fat.

Propofol Fresenius should not be used as a sedative in children under 16 years of age.

Elderly patients, patients with heart, respiratory, kidney or liver diseases, as well as patients with hypovolemia and epilepsy. Propofol Fresenius should be administered at a reduced rate.

Methods of administration

For intravenous administration.

It is permissible to administer Propofol Fresenius in undiluted form. Propofol Fresenius is recommended only 5% glucose solution for intravenous administration or 0.9% sodium chloride solution for intravenous administration in glass bottles.

Shake before use!

Use only if the emulsion is homogeneous and the packaging is intact.Before use, the rubber membrane of the container or the neck of the ampoule is sprayed with an alcohol spray or wiped with a swab dipped in alcohol.

Since propofol Fresenius is a fat emulsion that does not contain preservatives and does not have antimicrobial activity, the preparation can serve as a favorable medium for rapid growth of microorganisms. When opening a vial or ampoule containing Propofol Fresenius, you must strictly follow the rules of asepsis. The preparation should be started without delay.

During the entire period of administration of Propofol Fresenius, the rules of aseptic work with the drug and the system for parenteral infusion should be observed.

When co-injecting Propofol Fresenius with other drugs and solutions in the same system, the administration of the latter is recommended through Y-shaped connector or valve. Propofol Fresenius can not be administered via a microbiological filter.

Propofol Fresenius and other infusion systems containing propofol, are intended for a single injection or infusion only one patient individually.

Infusion of undiluted Propofol Fresenius

When infusion of undiluted propofol Fresenius is recommended to always use devices to control the volume of the drug administered, such as a drop counter, syringe pumps or volumetric infusion pumps.

When introducing fat emulsions, including Propofol Fresenius, it is recommended to use the same infusion system for no more than 12 hours. After 12 hours of use, the system containing Propofol Fresenius or the container with the drug should be replaced.

Infusion of diluted Propofol Fresenius

For the introduction of diluted Propofol Fresenius it is possible to use different versions of the systems for intravenous infusions. However, the use of standard systems does not guarantee against the random uncontrolled introduction of large volumes of diluted Propofol Fresenius.

Into the system for intravenous infusionenA device for controlling the volume of the drug to be administered, such as a drip counter, a burette or a volumetric pump for infusion, should be included. When determining the maximum dilution of the burette, the risk of administering large doses of propofol should be taken into account.

Recommended Propofol Fresenius dilution is 1 part propofol and 4 parts 5% glucose solution for intravenous administration or 0.9% sodium chloride solution for intravenous administration (the active substance content in the diluted solution should not be less than 2 mg / ml). Breeding is prepared in aseptic conditions immediately before the administration of the drug, the infusion should be completed no later than 6 hours after the preparation of the dilution.

Propofol Fresenius should not be diluted with other solutions for infusions or injections. Joint introduction 5% glucose solution, 0.9% sodium chloride solution with Propofol

Fresenius is allowed through a tee with a valve in the immediate vicinity of the injection site.

To reduce pain at the site of administration of Propofol Fresenius, it is permissible to mix it immediately before administration with a 1% solution of lidocaine hydrochloride for injection (20 parts of Propofol Fresenius + 1 part of 1% solution of lidocaine hydrochloride for injection) free from preservative.

Preparations of muscle relaxants of the type atracurium bezylate and miwakuria chloride can be administered at the site of administration of Propofol Fresenius only after jetting.

Propofol Fresenius should not be used after the expiration date.

The introduction of the emulsion of Propofol Fresenius should be started immediately after opening the ampoule or vial.

The system for the introduction of undiluted propofol Fresenius should be replaced at the end of the 12-hour period after the opening of the ampoule or vial. Dilutions of Propofol Fresenius 5% glucose solution for intravenous administration or 0.9% solution of sodium chloride for intravenous administration should be prepared under aseptic conditions immediately before infusion, their administration should be completed within 6 hours after the preparation of the dilution.

Any residues of the contents of ampoules or vials after use should be destroyed.

Duration of application should not exceed 7 days.

Side effects:

The following classification of side effects is given 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, the frequency of which is difficult to estimate based on the available data).

Within each group, adverse effects are presented in order of decreasing clinical importance:

Immune disorders:

Rare:

Anaphylactic reactions, including Quincke's edema, bronchospasm, erythema and lowering of blood pressure.

Very rare:

Allergic reaction to soybean oil.

Metabolic disorders:

Frequent:

Hypertriglyceridemia

Mental disorders:

Rare:

Euphoria and increased sexual function during the recovery period.

Neurological disorders:

Frequent:

Spontaneous movements and myoclonus during administration to anesthesia, minimal excitation.

Rare:

Headache, dizziness, chills and cold sensations during the recovery period. Epileptiform seizures, including convulsions and opisthotonus.

Very rare:

Late epileptiform seizures that develop after a few hours or days.

The risk of seizures in patients with epilepsy after the administration of propofol.

Cases of unconsciousness after surgery.

Changes in the heart / vascular disorders:

Frequent:

During the introduction to anesthesia, lowering blood pressure, bradycardia, tachycardia, "hot flashes".

Infrequent:

A marked decrease in blood pressure. It may be necessary to reduce the rate of administration of Propofol Fresenius and / or the substitution of fluid, if necessary, vasoconstrictor.It should be considered the possibility of a sharp decrease in blood pressure in patients with impaired coronary or cerebral blood flow or patients with hypovolemia.

Increasing bradycardia, up to asystole, during general anesthesia.

Possible intravenous injection of m-holinoblokatorov during the introduction of a general anesthesia or during anesthesia supporting anesthesia.

Rare:

Arrhythmia in the recovery period. Thrombosis and phlebitis.

Changes in the respiratory, thoracic and mediastinal systems:

Frequent:

With the introduction of anesthesia, hyperventilation, transient apnea, cough, hiccough.

Infrequent:

Cough during anesthesia.

Rare:

Cough during the recovery period.

Very rare:

Pulmonary edema.

Gastrointestinal disorders:

Rare:

Nausea and vomiting during recovery.

Very rare:

After the administration of propofol, cases of pancreatitis have been described, although a causal relationship has not been established.

Changes in the skin and subcutaneous tissues:

Very rare:

Severe tissue changes after accidental paravenosis.

Changes in the kidney and urinary tract:

Rare:

Change in the color of urine after prolonged use of propofol.

General and local reactions:

Very Frequent:

Pain at the injection site. Pain at the injection site of propofol can be minimized by the simultaneous administration of lidocaine or infusion of the drug into the larger vein of the forearm or the ulnar fossa.

When combined with lidocaine rarely (> 1:10 000 to <1: 1000), the following adverse effects were observed: dizziness, vomiting, drowsiness, convulsions, bradycardia, cardiac arrhythmias and shock.

Rare:

Postoperative fever.

Very rare:

Separate cases of severe adverse effects in the form of a complex of symptoms are described: rhabdomyolysis, metabolic acidosis, hyperkalemia and heart failure, sometimes with a fatal outcome. In most cases, these symptoms were observed in intensive care units in patients receiving a dose exceeding 4 mg / kg / h.

Overdose:

Symptoms: oppression of the cardiovascular and respiratory systems.

Treatment: with respiratory depression, artificial ventilation with oxygen is recommended, and in case of cardiovascular depression, the position of the patient should be changed so that his head is in a raised position.If necessary, you can use vasopressor agents, plasma-substituting agents or solutions of electrolytes such as Ringer's solutions, symptomatic therapy.

Common side effects of Propofol Kabi 10 mg / mL are lowering blood pressure and suppressing respiratory function. These effects depend on the dose of propofol, as well as the type of premedication and concomitant therapy.

Interaction:

Propofol Fresenius can be used in conjunction with other medicinal drugs commonly used for premedication, inhalation anesthesia, muscle relaxants or local anesthetics.

Cases of pharmacological incompatibility have not been reported to date.

A reduction in the dose of the drug is required if the general anesthesia is accompanied by local anesthesia.

The use of benzodiazepines, parasympatholytics or inhalational anesthetics in conjunction with Propofol Fresenius prolongs the anesthetic effect and reduces the respiratory rate.

After joint premedication with narcotic analgesics, the frequency and duration of apnea may increase.

On the background of administration of suxamethonium or neostigmine methyl sulfate, bradycardia and cardiac arrest may occur.

Propofol Fresenius in combination with these drugs, which have an antihypertensive effect and affect breathing, can enhance these phenomena.

It should be taken into account that the use of Propofol Fresenius against a background of premedication concomitantly with inhalation or other analgesics may potentiate anesthesia and side effects from the cardiovascular system.

The combined use of drugs that oppress the central nervous system, such as alcohol, general anesthetics or narcotic analgesics with Propofol Fresenius, leads to a marked manifestation of their sedative effect. If the administration of Propofol Fresenius is combined with parenterally administered drugs that depress the central nervous system, severe respiratory and cardiac oppression is possible.

After the administration of fentanyl, the level of propofol in the blood temporarily increases.

There is evidence that the administration of fat emulsions, such as Propofol Fresenius, to patients receiving ciclosporin, causes leukoencephalopathy.

Special instructions:

Propofol Fresenius does not reduce the tone of the vagus nerve, and its use in a number of cases is accompanied by bradycardia (sometimes pronounced), as well as asystole. Before induction or during maintenance of general anesthesia with Propofol Fresenius, the possibility of intravenous administration of m-cholinergic blockers should be considered, especially in cases of supposedly strengthened vagal tone or with the use of Propofol Fresenius in conjunction with other drugs capable of causing bradycardia.

To relieve pain at the injection site with the induction of general anesthesia, Propofol Fresenius may be administered before the administration of the emulsion of the drug lidocaine. When using lidocaine should be considered that it can not be used in patients with hereditary porphyria.

Propofol Fresenius can be used only by doctors who have been trained in anesthesia or intensive care.

Propofol Fresenius should not be administered by personnel performing diagnostic or surgical procedures.

Efficacy and safety of Propofol Fresenius for (background) sedation of children under 16 years of age has not been studied.In cases of unsuitable indications for the preparation of (background) sedation of children under 16 years of age, serious side effects have been reported, including death, although no causal relationship has been established in these cases. In particular, cases of metabolic acidosis, hyperlipidemia, rhabdomyolysis and / or heart failure . These effects were most often observed in children with respiratory infections receiving doses of the drug in intensive care units that exceed the doses for adults.

Similarly, in adults who received the drug for more than 48 hours at a rate greater than 5 mg / kg / h, rare cases of metabolic acidosis, rhabdomyolysis, hyperkalemia and / or rapidly progressive heart failure (in some cases fatal) were noted. This speed exceeds the maximum speed of 4 mg / kg / h, recommended for the use of the drug for the purpose of relaxation of patients in intensive care units. Heart failure in such cases is usually not sensitive to maintenance therapy with inotropic drugs.

Once again, doctors are reminded, if possible, not to exceed the dose of 4 mg / kg / h,which is usually sufficient for relaxation of patients undergoing mechanical ventilation in intensive care units (with a treatment duration of more than 1 day). Doctors should be cautious about these side effects, and at the first signs of their occurrence, reduce the dose or switch to other sedatives.

In some cases, after the application of Propofol Fresenius, a period of postoperative unconsciousness of the patient was noted, accompanied by an increased muscle tone. Although consciousness returns on its own, patients who are in an unconscious state require careful observation.

Before discharging the patient from the clinic, you should make sure of his complete recovery after general anesthesia.

Before anesthesia, a patient with epilepsy must be convinced that he is receiving antiepileptic therapy. Although several studies have shown the effectiveness of propofol in the treatment of epileptic status, it can also increase the risk of seizures.

The use of Propofol Fresenius for sedation during surgery, as well as the use of other sedatives,can cause involuntary movements of the patient. Care should be taken if the procedure requires patient immobility. Propofol Fresenius is not recommended for patients undergoing electroconvulsive therapy.

Propofol Fresenius contains soybean oil, which in rare cases can cause severe allergic reactions.

Caution should be exercised when using propofol for anesthesia in newborns and children under 3 years of age, although currently available data do not indicate significant differences in terms of safety compared to children older than 3 years.

During the entire infusion period, the principles of asepsis should be observed both with respect to the preparation of Propofol Fresenius and with regard to infusion equipment. Parallel administration of other substances through the infusion system for Propofol Fresenius should be carried out as close as possible to the cannula. The drug should not be administered through an antibacterial filter.

Propofol Fresenius and all infusion equipment for its administration can only be used once and only for one patient.

The rate of administration of propofol Fresenius should be reduced in patients with congenital dementia,patients with epilepsy, with violations of the heart, lungs, liver and kidneys, with hypovolemic conditions.

Special precautions should be taken in patients with impaired fat metabolism, as well as in other conditions requiring caution when injecting fat emulsion, since 1 ml of Propofol Fresenius contains 0.1 g of fat.

If it is necessary to introduce an increased dose of the drug to patients with excessive body weight, the increased risk of hemodynamic disorders and adverse effects on the cardiovascular system should be taken into account.

In intensive care, the concentration of lipids should be monitored every 2 days.

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

After the administration of Propofol Fresenius, the patient should be under appropriate medical supervision. The patient should be informed that he should not drive vehicles and mechanisms, should avoid drinking alcohol and work in potentially dangerous conditions. The patient can only be released home with an accompanying person.

Form release / dosage:

Emulsion for intravenous administration, 10 mg / ml.

Packaging:

To 20 ml in ampoules of colorless glass (Hebr. F.), marked with a dot, 5 ampoules per pack of cardboard with instructions for use.

To 50 or 100 ml in a bottle of colorless glass, ukuporenny rubber (brombutilubuchuk) stopper and obkatanny aluminum cap with a plastic cap-control the first opening (He.F.). 1 or 10 bottles per carton box with instructions for use.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Do not freeze!

Keep out of the reach of children.

Shelf life:

3 years.

Terms of leave from pharmacies:For hospitals

Registration number:П N012345 / 01

Date of registration:27.12.2011

The owner of the registration certificate:Fresenius Kabi Deutschland GmbHFresenius Kabi Deutschland GmbH Germany

Manufacturer: & nbsp

FRESENIUS KABI AUSTRIA, GmbH Austria

Representation: & nbspFRESENIUS KABI DEYCHLAND GmbH FRESENIUS KABI DEYCHLAND GmbH Germany

Information update date: & nbsp06.09.2015

Illustrated instructions

Instructions

Propofol Fresenius (Propofol Fresenius)