Composition, form of production and packaging
Emulsion for intravenous administration of white or almost white color, homogeneous; with prolonged standing, a slight stratification is observed.
1 ml
propofol 10 mg
Auxiliary substances: soybean oil - 100 mg, egg yolk phospholipids - 12 mg, glycerol - 22.5 mg, disodium salt of ethylenediaminetetraacetic acid - 55 Ојg, sodium hydroxide (to maintain the pH level 7.5-8.5), water d / u - up to 1 ml .
20 ml - glass ampoules (5) - plastic pallets (1) - cardboard packs.
Emulsion for intravenous administration of white or almost white color, homogeneous; with prolonged standing, a slight stratification is observed.
1 ml
propofol 10 mg
Auxiliary substances: soybean oil - 100 mg, egg yolk phospholipids - 12 mg, glycerol - 22.5 mg, disodium salt of ethylenediaminetetraacetic acid - 55 Ојg, sodium hydroxide (to maintain the pH level 7.5-8.5), water d / u - up to 1 ml .
50 ml - glass syringes (1) complete with a polypropylene plunger and a Luer connector - contour mesh packaging (1) - cardboard packs.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2008.
PHARMACHOLOGIC EFFECT
Propofol (2,6-diisopropylphenol) is a short-acting agent for general anesthesia with a rapid onset of action for about 30 seconds. Usually the output from general anesthesia occurs quickly. The mechanism of action of Diprivan, as well as of all agents for general anesthesia, is not clear enough.
Typically, when Diprivan is used to induce anesthesia and maintain it, there is a decrease in mean BP and a slight change in heart rate. Nevertheless, hemodynamic parameters usually remain relatively stable during maintenance of anesthesia, and the frequency of adverse hemodynamic changes is low.
Although Diprivan may cause respiratory depression, any of these effects are qualitatively similar to those that occur with the use of other intravenous anesthetics, and are easily amenable to clinical control.
Diprivan reduces cerebral blood flow, intracranial pressure and reduces cerebral metabolism. The decrease in intracranial pressure is more pronounced in patients with initially increased intracranial pressure.
The withdrawal from anesthesia usually occurs quickly, with clear consciousness and is accompanied by a low percentage of headache cases, postoperative nausea and vomiting.
As a rule, after anesthesia with Diprivan, cases of postoperative nausea and vomiting are less common than after inhalation anesthesia. Perhaps this is due to the antiemetic effect of propofol.
Diprivan at concentrations usually reached in clinical conditions does not suppress the synthesis of hormones of the adrenal cortex.
PHARMACOKINETICS
Reducing the concentration of propofol after the bolus dose or after stopping the infusion can be described using an open three-phase model. The first phase is characterized by a very rapid distribution (the half-period of the rapid distribution phase is 2-4 minutes), the second - rapid elimination (half-life is 30-60 minutes).Then follows a slower final phase, which is characterized by the redistribution of propofol from mildly perfused tissue into the blood.
Propofol is quickly distributed and rapidly excreted from the body (total clearance is 1.5-2 l / min). The excretion of propofol is carried out by metabolism, mainly in the liver, resulting in the formation of propofol conjugates and the corresponding quinol, the release of which occurs in the urine.
In cases where Diprivan is used to maintain anesthesia, its concentration in the blood asymptotically reaches an equilibrium value corresponding to the rate of administration. Within the recommended infusion rates, the pharmacokinetics of Diprivan are linear in nature.
INDICATIONS
- for induction and maintenance of general anesthesia;
- to provide sedative effect in adult patients who receive intensive therapy and who undergo artificial ventilation (IVL);
- in order to provide a sedative effect in patients who are conscious, for performing surgical and diagnostic procedures.
DOSING MODE
As a rule, Diprivan requires additional use of analgesic agents.
Diprivan is combined with spinal and enidural anesthesia; with drugs commonly used for premedication: with muscle relaxants, inhalation anesthetics and analgesics, while there was no pharmacological incompatibility. Lower doses of Diprivan may be required in cases where general anesthesia is used as a supplement to the methods of regional anesthesia used.
Guidelines for the introduction of Diprivan by target concentration (CI) using an infusion system that includes the appropriate Diprifuge software, see the appropriate section. This use is limited to induction and maintenance of general anesthesia in adults. It is not recommended to use the ICP Diprifuge system for sedation in patients in intensive care units, for a sedative effect with conserved consciousness, or in children.
Adults
Induction of general anesthesia
Diprivan can be used to induce anesthesia through slow bolus injections or infusion. Regardless of whether premedication was or was not performed, Diprivan administration is recommended to titrate (bolus injections or infusion of approximately 40 mg every 10 seconds - for the average adult patient in satisfactory condition), depending on the patient's response to the appearance of clinical signs of anesthesia. For most adult patients under 55 years of age, the average dose of Diprivan is 1.5-2.5 mg / kg. The required total dose can be reduced using lower administration rates (20-50 mg / min). For patients older than this age, usually a lower dose is required. Patients 3 and 4 classes of ASA should be administered at a lower rate (approximately 20 mg every 10 seconds).
Maintaining general anesthesia
Anesthesia can be maintained either by a constant infusion of Diprivan or by repeated bolus injections necessary to maintain the required depth of anesthesia.
Permanent infusion. The required rate of administration varies considerably depending on the individual characteristics of the patients. Typically, a rate of between 4-12 mg / kg / h ensures adequate anesthesia.
Repeated bolus injections. If a technique involving repeated bolus injections is used, then the administration of increasing doses from 25 mg to 50 mg, depending on the clinical need, is used.
Ensuring a sedative effect during intensive care
Introduction Diprivan with the help of the ITS system Diprifuge to provide sedative effect in patients during intensive care is not recommended.
When using Diprivan in order to provide a sedative effect in adult patients on ventilator and receiving intensive therapy, it is recommended to use it through continuous infusion. The rate of infusion should be adjusted to take into account the necessary depth of sedation, but a rate ranging from 0.3 to 4.0 mg / kg / h should ensure a satisfactory sedation.
Providing sedative effect with preservation of consciousness in patients during surgical and diagnostic procedures
Introduction Diprivan with the help of the ITS Diprifuge system to provide a sedative effect with preservation of consciousness is not recommended. To ensure a sedative effect during surgical and diagnostic procedures, the rate of administration and dose should be selected individually depending on the clinical response of the patient. Most patients require 0.5-1.0 mg / kg for 1-5 minutes - for the onset of sedation.
To maintain a sedative effect, the infusion rate should be adjusted according to the required depth of sedation; for most patients, a speed of 1.5-4.5 mg / kg / h is required. If a rapid increase in the depth of sedation is required, bolus administration of 10-20 mg Diprivan may be used as an adjunct to the infusion. For patients in grade 3 and 4, ASA may require a reduction in dose and rate of administration.
Elderly patients
In elderly patients on the day of anesthesia, lower doses of Diprivan are required. When reducing the dose should be guided by the physical status and age of the patient. A reduced dose should be administered at a lower rate than usual and titrated according to the patient's response. When Diprivan is used to maintain anesthesia or to provide a sedative effect, the infusion rate or "target concentration" of the drug should be reduced. For patients in grade 3 and 4, ASA may require a further reduction in dose and rate of administration. To avoid oppression of the heart and respiratory system, elderly patients are not recommended for rapid bolus administration (single or repeated).
Children
In children it is not recommended to administer Diprivan with the help of the Diprifuge system, under no circumstances.
Induction of general anesthesia
Diprivan is not recommended for use in children under 3 years of age .
When Diprivan is used to ensure the induction of anesthesia in children, it is recommended to inject it slowly until the appearance of clinical signs of anesthesia. The dose should be adjusted according to the age and / or weight of the child. For most children over the age of 8 , approximately 2.5 mg / kg Diprivan will probably be needed to induce anesthesia. For children under 8 years, the required dose may be higher. A lower dose is recommended for children of grade 3 and 4 ASA.
Maintaining general anesthesia
Diprivan is not recommended for use in children under 3 years of age. Maintenance of anesthesia is achieved by administering Diprivan through continuous infusion, or by repeated bolus injections required to maintain the required depth of anesthesia. The required rate of administration differs significantly in different patients;satisfactory anesthesia is usually provided at infusion rate of 9-15 mg / kg / h.
Ensuring a sedative effect with preservation of consciousness during surgical and diagnostic procedures
Diprivan is not recommended for sedation with conscious consciousness in children, since its safety and efficacy in this application have not yet been confirmed.
Ensuring a sedative effect during intensive care
Diprivan is not recommended for sedation in children, since its safety and effectiveness in this application have not yet been confirmed. With unlicensed use, serious adverse events (including deaths) were noted, although there was no causal relationship with the use of Diprivan. These adverse events were most often observed in children with respiratory tract infections that received doses exceeding the recommended doses for adults.
Introduction
Diprivan can be administered undiluted using plastic syringes or glass infusion bottles, or Diprivan-filled glass syringes. In cases where Diprivan is used undiluted to maintain general anesthesia, it is recommended to always use perfusors or infusomats in order to monitor the rate of administration.
Diprivan can also be used diluted with only 5% dextrose solution for intravenous administration, in bags of PBX or in glass bottles. The solution, the dilution of which should not exceed a ratio of 1: 5 (2 mg propofol / ml), should be prepared in accordance with the rules of aseptic immediately before use. The mixture is stable for 6 hours.
Diprivan diluted solution can be administered using a variety of adjustable infusion systems, but the use of only such devices does not completely avoid the risk of accidental, uncontrolled introduction of large volumes of diluted Diprivan. Burettes, drip counters or dosing pumps should always be part of the infusion line. When choosing the maximum volume of divorced Diprivan in a burette, one should keep in mind the risk of uncontrolled administration.
Diprivan can be administered via a tee with a valve near the injection site, concomitantly with the administration of 5% dextrose solution for IV infusion, 0.9% sodium chloride solution for IV infusion or 4% dextrose solution with 0.18% sodium chloride solution for IV infusion.
A ready-to-use glass syringe has less piston resistance than a plastic disposable syringe, and is easier to drive. When Diprivan is administered manually using a ready-to-use glass syringe, the infusion system between the syringe and the patient should not be left open if there is no observation from the medical staff.
Appropriate compatibility should be ensured if a ready-to-use glass syringe is used in a syringe pump. In particular, the design of the pump must prevent siphoning and should provide an alarm for clogging at a pressure of not more than 1000 mm Hg. If a programmable pump or equivalent pump is used, assuming the possibility of using different syringes, then in the case of using a ready-to-use glass syringe, only the "BD" mode of 50/60 ml of PLASTIPAK is selected.
Diprivan can be premixed with alfentanil for injection containing 500 Ојg / ml alfentanil in a volume ratio of 20: 1-50: 1. Mixtures should be prepared using sterile equipment, and applied within 6 hours after preparation.
To reduce pain at the start of the injection, the induction dose of Diprivan can be mixed immediately with lignocaine for injection in a plastic syringe in the following proportion: 20 parts of Diprivan and up to one part of either 0.5% or 1% of the lignocaine solution for injection.
Diprivan dilution and co-administration in combination with other drugs or infusion solutions
Method of simultaneous use Additive or diluent Preparation Cautions
Pre-mixing 5% dextrose solution for intravenous administration Mix 1 part of Diprivan and up to 4 parts of 5% dextrose solution for intravenous administration either in PVC bags or in glass bottles. When diluted in PVC bags it is recommended that the bag be full, the solution is prepared by removing a part of the volume of the dextrose solution, replacing it with an equivalent volume of Diprivan. Cook in aseptic conditions immediately before use. The mixture is stable for 6 hours.
Lignocaine hydrochloride d / and (0.5% or 1% without preservatives) Mix 20 parts of Diprivan and up to 1 part of 0.5% or 1% solution of lignocaine hydrochloride d / and prepare by observing the conditions of aseptic immediately before use. Use only for induction.
Alfentanil for Injection (500 Ојg / ml) Mix Diprivan with alfentanil d / and in a volume ratio of 20: 1-50: 1 Cook, following the conditions of aseptic, immediately before use. Apply within 6 hours after preparation.
Simultaneous introduction of the Y-shaped tee 5% dextrose solution for iv administration Simultaneous administration is carried out using a tee with a valve. The tee with the valve should be placed next to the injection site.
0.9% solution of sodium chloride for IV administration See above. See above.
4% dextrose solution with 0.18% sodium chloride solution for iv administration See above. See above.
Infusion on the target concentration - Diprivan administration with the help of the system for ICP Diprifuge in adults
The introduction of Diprivan with the help of the ITS Diprifuge system is limited to periods of induction and maintenance of general anesthesia in adults. It is not recommended to use sedation in intensive care, to provide a sedative effect with the preservation of consciousness, or in children. Diprivan can be introduced by the ICC method only with the help of the ITS Diprifusor system, which includes the Diprifuser software. These systems will function only after recognizing the electronic label on a ready-to-use glass syringe filled with Diprivan.
The ITS Diprifuser system will automatically adjust the rate of Diprivan administration to the concentration that was recognized by the system. Users should be familiarized with the manual for working with the infusion pump, with the introduction of Diprivan by the ICC method, with the correct use of the syringe recognition system, as described in the training manual provided by AstraZeneca.
This system gives the anesthesiologist the opportunity to achieve the desired rate of induction and depth of anesthesia and manage them by setting and regulating the target (predicted) concentration of propofol in the patient's blood.
The Diprifyuzor system assumes that the initial concentration of propofol in the patient's blood is 0. Therefore, for patients who received propofol earlier, it is possible to select lower initial target concentrations at the start of Diprivan administration with the help of the Diprifuser IC. Also not recommended to resume work ITSK "Diprifyuzor" in the same mode after you disconnect.
Guidance on the selection of target concentrations of propofol is attached below. Due to individual differences in pharmacokinetics and pharmacodynamics of propofol in patients as premedication received and not received such, propofol target concentration should be titrated according to the clinical response of the patient to achieve the desired depth of anesthesia.
In adult patients under 55 years of age anesthesia can usually be induced by propofol target concentration of 4 to 8 mcg / mL. The initial target concentration of propofol 4 mg / ml is recommended for patients who have received premedication, patients without premedication recommended concentration of 6 ug / ml. Induction time at target concentrations of the data is usually 60-120 seconds. Higher values ​​result in a more rapid induction of anesthesia, but may be associated with a more pronounced inhibition of hemodynamic and respiratory function.
Lower initial target concentration should be used in patients older than 55 years and in patients ASA 3 and 4 classes. The target concentration can be further increased gradually to a value of 0.5 to 1.0 g / ml, at intervals of 1 minute to achieve a gradual induction of anesthesia. Typically, additional analgesia, and the amount of reduction of target concentrations for maintenance of anesthesia will depend on the amount of additionally introduced analgesic agents. The target concentration of propofol in the range of from 3 to 6 mg / ml is generally maintained sufficient level of general anesthesia.
The predicted propofol concentration on waking is generally in the range 1.0 - 2.0 g / ml, and will depend on the level of analgesia during narcosis maintenance.
Providing sedation during intensive care
Usually target concentration of propofol in the blood is required in the range of 0.2 -2.0 mg / ml. Introduction Diprivan should be started at low target concentration and titrated dose depending on the patient's response to achieve the desired depth of sedation.
SIDE EFFECT
General information
As a rule, the induction of anesthesia proceeds smoothly, with minimal signs of arousal. The most common side effects are predictable, from the viewpoint of pharmacology, side effects of any means to sheathe anesthesia, eg hypotension. Cases of which was reported in connection with anesthesia and intensive therapy may also be associated with procedures or obtained from the patient.
Very common (> 1/10) Common reactions and injection site reactions Pain at the injection site during induction (1)
Often (> 1/100, <1/10) Common withdrawal symptoms in children (4)
On the part of the cardiovascular system : Hypertension (2) , bradycardia (3), Blood flow in children (4)
part of the intestine: nausea and vomiting during waking
CNS: Headache at awakening
part of the respiratory system: Temporary apnea during induction
Uncommon (> 1/1000, <1/100) Co side of the cardiovascular system: Thrombosis and phlebitis
rare (> 1/10000, <1/1000) CNS: Epileptiform movements, including convulsions and opisthotonos during induction and maintenance of anesthesia awakening
is very rare (<1/10 000) Skeletal -Muscular effects, connective tissue: Rhabdomyolysis (5)
procedural complications: postoperative th fever
From the gastrointestinal tract: Pancreatitis
From the kidneys and urinary system: Discoloration urine after prolonged use
on the part of the immune system: Anaphylaxis can manifest itself in the form angioneurotic edema, bronchospasm, hypotension and erythema
Reproductive system: sexual disinhibition
From the cardiovascular system: pulmonary edema
CNS: Postoperative unconsciousness
(1) Pain at the injection site can be reduced by administering the drug in large size forearm vein and elbow. Pain can also be reduced when co-administered with Diprivan 1% lignocaine.
(2)Hypotension may require on / in the liquid and reducing the rate of administration Diprivan.
(3) Severe cases of bradycardia are rare. There are isolated reports of progression to asystole, bradycardia up.
(4) arises during abrupt discontinuation of Diprivan during intensive care.
(5) report on very rare occasions when applying rhabdomyolysis Diprivan at doses greater than 4 mg / kg / h for sedation in intensive care.
CONTRAINDICATIONS
- an allergic reaction to a history of Diprivan;
- Children's age up to 3 years.
To provide sedation during intensive therapy is contraindicated in the following diseases for children of all age groups:
- cereals;
- epiglottitis.
With caution: as when using other I / anesthetics, caution should be exercised with regard to patients with cardiac, respiratory, renal or hepatic impairment, as well as for patients with hypovolemia or debilitated patients.
PREGNANCY AND LACTATION
Pregnancy
Diprivan should not be used during pregnancy. However, Diprivan is used during the abortion in the first trimester.
Obstetrics
Diprivan crosses the placental barrier and its application may be associated with neonatal depression. It should not be used in obstetrics as an anesthetic.
Lactation
for infants are breastfed, it has not been established safety of Diprivan in nursing mothers.
APPLICATION FOR FUNCTIONS OF THE LIVER
With caution: as when using other I / anesthetics in kidney disorders.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With caution: as when using other I / anesthetics in liver disorders.
APPLICATION FOR CHILDREN
Contraindicated: children up to 3 years.
APPLICATION IN ELDERLY PATIENTS
In elderly patients the day induction of anesthesia required lower doses of Diprivan.
SPECIAL INSTRUCTIONS
Diprivan should be used by personnel who have trained in anesthesia (or, where appropriate, doctors trained to assist patients during intensive care). Of patients necessary to carry out continuous monitoring. Equipment to maintain airway patency free, for artificial ventilation, oxygen enrichment and other resuscitative facilities should be constantly ready for use. Diprivan should not be given specialist performing the diagnostic or surgical procedure.
When using Diprivan during surgical or diagnostic procedures for sedation with preservation of consciousness, need constant monitoring of the patient to detect early signs of hypotension, airway obstruction and insufficient blood oxygen saturation.
As with other sedative agents, when administered Diprivan for sedation during surgical intervention possible involuntary patient motion. In procedures requiring compliance immobility, these movements may be hazardous to the site of surgical intervention.
We need an adequate period of time to monitor the patient to ensure full recovery after general anesthesia. In very rare cases, after using Diprivan possible lack of consciousness in the postoperative period, which may be accompanied by increased muscle tone. Sometimes loss of consciousness occurs after a period of wakefulness. Despite the spontaneous awakening of the patients who are unconscious, proper monitoring should be established.
Diprivan has a weak vagolytic activity, and its use is associated with cases of bradycardia (which is sometimes a serious nature), as well as asystole. It is expedient in / with the introduction of an anticholinergic agent before induction of anesthesia, or during its maintenance, especially in cases where there is a likelihood of dominance of vagal tone, or when Diprivan is used in combination with other drugs that may cause bradycardia.
If Diprivan is administered to a patient suffering from epilepsy, there is a risk of seizures. Proper attention should be given to patients with impaired lipid metabolism, as well as other conditions that require careful application of lipid emulsions.
It is recommended to monitor the level of lipids in the blood when administered Diprivan patients who are at particular risk of lipid accumulation. In that case, if monitoring indicates a lack of excretion of fat from the body, the introduction of Diprivan should be appropriately adjusted manner. With simultaneous on / in a patient other lipid agent its dose should be reduced by taking into account the amount of lipid administered as part of Diprivan; 1.0 ml of Diprivan contains about 0.1 g of fat.
The use of Diprivan for induction of anesthesia in infants (unregistered indication) can lead to inhibition of the respiratory and cardiovascular systems, if you use the standard dosing regimen recommended for children.
Information on the use of Diprivan for the sedation during intensive care for preterm newborns there.
Clinical studies of the use of Diprivan for the sedation during intensive care of children with croup or epiglottitis have been conducted.
Note to the list: Provision of sedation during intensive care.
It was reported about rare cases of metabolic acidosis, rhabdomyolysis, hyperkalemia and / or heart failure, in some cases with fatal outcome in critically ill patients receiving Diprivan for the sedation during intensive care. These reports show that most likely occurred insufficient supply of oxygen to tissues. Causal connection between these cases and using Diprivan not established. All therapeutic and sedative medications used during the intensive care (including Diprivan) should be titrated for optimal supply of oxygen to tissues and optimal hemodynamic parameters. Part of the preparation forms EDTA chelate complexes with metal ions including zinc ions.It should be considered supplemental assignment zinc Diprivan with prolonged use, especially in patients who have a predisposition to zinc deficiency, such as burns, diarrhea and / or sepsis.
Diprivan contains no antimicrobial preservatives, and can serve as a good medium for microbial growth.
Diprivan when filling a sterile syringe or infusion line should observe the rules of asepsis; the drug should be dialed immediately after opening the ampoule. Administration should begin immediately. Aseptic conditions must be ensured throughout the infusion period in relation Diprivan and equipment for administration.
Any infuzioinye solutions were added to the infusion line in combination with Diprivan should be administered as close as possible to the place of location of the cannula.
Diprivan must not be administered through a microbiological filter.
Syringe with Diprivan is disposable and designed for use in one patient. In accordance with established lipid emulsions for other rules Diprivan continuous infusion duration should not exceed 12 hours. At the end of infusion, or after a 12-hour period must be replaced as a container with Diprivan and infusion line.
Containers with Diprivan should be shaken before use. The contents of the container remaining in any number of after use, should be destroyed.
Aseptic conditions must be provided in respect of Diprivan and equipment for administration.
Impact on the ability to drive vehicles and manage mechanisms
Patients should be informed that a general anesthetic for some time after its implementation can degrade performance of work requiring skills such as driving a car or operating machinery.
OVERDOSE
Accidental overdose may possibly cause depression of the cardiovascular system and respiration. In the case of respiratory depression should be carried out artificial ventilation with oxygen. The oppression of cardiovascular activity of the patient's head should be deleted, in severe cases may require administration of plasma substitutes and pressor agents.
DRUG INTERACTION
Diprivan was used in combination with a spinal or epidural anesthesia, with means for sedation, muscle relaxants, inhalational anesthetics and analgesics;pharmacological incompatibility were noted. Lower doses of Diprivan may be required in cases where general anesthesia is used as an adjunct to the methods used regional anesthesia.
Diprivan should not be mixed before use with any other injection or infusion solutions, except for the 5% dextrose solution in PVC bags or glass bottles for infusion, lignocaine injection or alfentanil injection in plastic syringes.
When administered muscle relaxants atracurium and mivacurium should not use the same infusion line, and that for Diprivan, without its washing.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
At a temperature of 2 to 25 В° C. Do not freeze.
Shelf life: ampoule - 3 years, for syringes - 2 years.
