Expiration date: 03/2025
The composition and form of issue:
The liquid for inhalation is. 1 flask contains:
sevoflurane 100%
bottles PE naphthalate dark colors on a 100 or 250 ml cartons 1 a bottle.
Description pharmaceutical form:
Liquid for inhalations transparent, colorless, volatile.
Feature:
Sevoflurane is a non-flammable liquid for General anesthesia, which is used with the evaporator. It is a fluorinated derivative metilenovogo ether. Chemical name: 1, 1, 1, 3, 3, 3-hexaplar-2- (formatosi)-propyl. Molecular weight: — 200, 05.
Sevoflurane has the following physical and chemical properties:
the calculated vapor pressure in mm Hg. article** 157 mm Hg. St. at 20°C 197 mm Hg. article at 25°C 317 mm Hg. article at 36°C
**The equation for calculating the vapor pressure, mm Hg. article log10P=A+B/T where:
A = 8, 086, = -1726, 68, T = °C + 273, 16 °K (Kelvin)
The distribution coefficients at 37 °C
The blood/gas — 0, 63-0, 69
Water/gas — 0, 36
Olive oil/gas 47, 2-53, 9
Brain/gas — 1, 15
The average distribution coefficients of the component/gas at 25 °C for polymers that are usually used for medical reasons:
Conductive rubber 14, 0
Butyl rubber — 7, 7
PVC — 17, 4
PE — 1, 3
Sevoflurane is not flammable and not explosive, which meets the requirements of the International electrotechnical Commission 601-2-13.
Sevoflurane contains no additives or chemical stabilizers. Sevoflurane is not corrosive. It is miscible with ethanol, ether, chloroform, and benzene and slightly soluble in water.
The decay products of sevoflurane
Sevoflurane is stable if stored under normal room lighting. In the presence of strong acids or under the action of heat significant decay sevoflurane does not occur. Sevoflurane is not corrosive to stainless steel, copper, aluminum, copper coated with Nickel, copper coated with chromium and copper-beryllium alloy.
Anesthetic may collapse upon contact with the CO2 absorbent in the anesthesia machine. When using fresh absorbers, according to the recommendations, the destruction of sevoflurane is minimal, decomposition products not determined not toxic. The destruction of sevoflurane and the formation of breakdown products increases with increasing temperature of the absorber, using dry absorbent (especially potassium hydroxide-containing, e.g. Baralyme), the concentration of sevoflurane and the reduction in flow of fresh gas. The destruction of sevoflurane under the action of alkalis occurs in two ways. In the first — from molecules disrupted hydrogen fluoride and formed penopolietilenovy ether (compound a). The destruction of the sevoflurane in the second path occurs only in the presence of dry CO2 absorber, while the sevoflurane becomes hexafluoroisopropanol and formaldehyde. Hexafluoroisopropanol not active, not genotoxic, rapidly connects with glucuronic acid and excreted, toxicity toxicity comparable to sevoflurane. Formaldehyde is present in the reactions of normal metabolism and contact with dry sorbent in turn, breaks down to methanol and formate. From formate under the influence of high temperature forms carbon monoxide. Methanol can react with compound A, as a result of methoxylamine additionally produces compound V. in further removal of hydrogen fluoride from the compound To form compounds C, D and E. Formaldehyde, methanol, carbon monoxide, compound a and perhaps some of these fission products, compounds b, C and D may be formed in contact with a very dry absorber, especially if it contains potassium hydroxide (e.g. Baralyme).
*Full-term newborns. MAC in premature infants was not determined.
** In children from 1 year to 3 years used 60%N2O/40% O2.
With the age of the MAC is reduced. The average concentration of sevoflurane, which provides the MAC of the patient at the age of 80 years, approximately 50% of that of 20-year-old patient.
Exit from General anesthesia. Patients usually go quickly from General anesthesia with sevoflurane. In this regard, can early be required of postoperative analgesia.
Overdose:
In case of overdose you must stop the introduction of sevoflurane, maintain airway, begin assisted or controlled ventilation with oxygen injection to maintain adequate function of SSS.
Special instructions:
General guidelines
The drug Sevoran may only be applied by professionals with experience in General anesthesia, in the offices, equipped with everything necessary to restore the airway, artificial ventilation, oxygen therapy and resuscitation.
Depth of General anesthesia can easily and quickly change, so to supply Sevorane you should only use the specially calibrated vaporizers. When the concentration of the drug may experience a buildup of arterial hypotension and depression of respiratory function.
Was received separate reports of QT prolongation, very rarely associated with tachycardia type "pirouette" (in some cases with fatal outcome). The drug Sevoran should be used with caution in patients susceptible to these complications.
Increasing the concentration of sevoflurane to maintain General anaesthesia causes a dose-dependent decrease in blood pressure. Excessive BP reduction may be associated with deep General anesthesia in such cases can be improved by reducing the concentration of sevoflurane supplied.
In applying the drug, Sewaren, as well as other funds for General anesthesia, in patients with coronary artery disease is necessary to maintain stable hemodynamics, to avoid myocardial ischemia.
After anesthesia, the patients required additional observation prior to transfer to the relevant Department.
Replacement dry sorbents for CO2
When applying Sevorane in anaesthetic equipment containing dry CO2 absorbents (especially with potassium hydroxide, Baralyme), described rare cases of excessive overheating and/or spontaneous ignition of anaesthetic equipment. When overheating of the tanks with the CO2 sorbent may be an unusual delay increase or a sudden reduction in inhaled concentration of the drug, Sewaren. Exothermic reaction is the collapse of sevoflurane with the formation of degradation products that occurs in the interaction of sevoflurane with the CO2 sorbent is enhanced if the sorbent dries, for example with prolonged exposure to dry gas. The formation of degradation products sevoflurane (methanol, formaldehyde, carbon monoxide and components A, b, C and D) were observed in the respiratory circuit of an experimental anesthesia machine with dry sorbents, the concentration of sevoflurane reached a maximum (8%) for 2 hours or more. The concentration of formaldehyde created in such conditions, reached values capable of causing a mild irritation of the respiratory tract. Clinical assessment of effects of the products of degradation of sevoflurane on the body in extreme conditions was conducted. If the anesthesiologist suspects that CO2 absorbent is too dry, then it should be replaced before application of sevoflurane. When drying of the sorbent, the CO2 indicator color changes is not always. Consequently, the absence of colour change of the indicator cannot be considered proof of adequate hydration. The sorbent CO2 need to be changed regularly, regardless of the color of the indicator.
Neuromuscular disease
The use of means for inhalation anesthesia in children caused, in rare cases, increase the concentration of potassium in serum, which led to the development of cardiac arrhythmias and death in the postoperative period. The risk is higher in patients with latent and clinically manifest neuromuscular diseases, especially in patients with Duchenne's myodystrophy. In some cases there was a communication for the development of these complications with concurrent use of suxamethonium. In these patients there was also a significant increase in the activity of creatine kinase in the serum and myoglobinuria, but despite some similarities with the manifestations of malignant hyperthermia, they have never mentioned muscular rigidity or symptoms associated with increased metabolism in the muscles. You should immediately start measures for the relief of hyperkalemia and resistant arrhythmias, and to conduct a survey to identify latent flowing neuromuscular disease.
Violation of kidney function
The safety of the drug, Sevoran in this group of patients is not fully established, it should be used with caution in patients with renal insufficiency.
Halogenated means for inhalation anesthesia
There is evidence that the use of halogenated anesthetics in history, especially during the previous 3 months, may increase the risk of liver failure.
Neurosurgical intervention
If the patient has a risk of increasing intracranial pressure, Sewaren should be used with caution in combination with measures to reduce ICP, such as hyperventilation.
Influence on ability to driving or operating machinery that require special attention. Although after you stop the flow sevoflurane consciousness is usually restored after a few minutes, its effect on cognitive function for 2-3 days after General anesthesia has not been studied. For several days after application of sevoflurane, as other means for General anesthesia, may experience slight mood changes. Patients should be informed that after General anesthesia may worsen the ability to perform a variety of tasks that require speed of psychomotor reactions, such as driving a car or operating machinery that require special attention.
Solubility
The low solubility of sevoflurane in blood provides a rapid increase in alveolar concentration with the introduction of General anesthesia and a rapid decrease after cessation of inhalation. The ratio of the alveolar concentration at the end of inhalation and the concentration in the inhaled mixture in 30 min after inhalation of sevoflurane was 0, 85. In the phase of excretion, the ratio of the alveolar concentration after 5 minutes was equal to 0, 15.
Distribution and metabolism
The rapid elimination of sevoflurane from the lungs minimizes the metabolism of the drug. In humans, less than 5% of the intake dose of sevoflurane is metabolized by cytochrome P450 (CYP2E1 isoenzyme) in hexafluoroisopropanol with release of inorganic fluoride and carbon dioxide (or carbon dioxide). Formed hexafluoroisopropanol not active, not genotoxic, rapidly connects with glucuronic acid and excreted by the kidneys, toxicity toxicity comparable to sevoflurane. Other ways of metabolism of sevoflurane is not installed. He is the only fluorinated volatile means for anesthesia, is not metabolized to trifluoroacetic acid.
The concentration of fluorine ions depends on the duration of General anesthesia, sevoflurane concentrations are introduced and the composition of the mixture for anesthesia. Barbiturates do not raise detalirovka sevoflurane.
Approximately 7% of adults who have in clinical studies have measured concentrations of inorganic fluoride, they exceeded 50 µmol/l, clinically significant changes in renal function in any of these patients is not revealed.
Description pharmacological action:
Sevoflurane provides a quick introduction to the anesthesia and a quick exit. Depth of anaesthesia can change rapidly depending on changes in the concentration of sevoflurane in the inhaled mixture.
Induction of anesthesia with sevoflurane is accompanied by a slightly pronounced excitation or minimal signs of irritation of the upper respiratory tract, does not cause excess secretion in the tracheobronchial tree and CNS stimulation. Like other powerful tools for inhalation anesthetic, sevoflurane causes dose-dependent inhibition of respiratory function and decrease in blood pressure. Studies in children have shown that the incidence of cough was statistically less in the application of mask induction of anesthesia with sevoflurane than with halothane. The threshold to arrhythmogenic action epinephrine when applying sevoflurane is the same as in the application of isoflurane and higher than when using halothane. The incidence of myocardial ischemia and myocardial infarction in patients with risk factors for these diseases comparable in the application of sevoflurane and isoflurane.
Effect on blood circulation in the brain (intracranial pressure, cerebral blood flow, cerebral metabolic rate of oxygen cerebral perfusion pressure) are also comparable from sevoflurane and isoflurane. Sevoflurane has minimal effect on intracranial pressure and does not reduce response to CO2. Sevoflurane concentration does not affect kidney function, even with prolonged anesthesia (approximately 9 h).
The minimum alveolar concentration (MAC) is the concentration at which 50% of patients do not have motor response to a single irritation (skin incision). MAC sevoflurane in different age groups is given in the section "Method of application and dosage", MAC sevoflurane in oxygen is 2, 05% of 40-year-old adult. MAC sevoflurane, like other halogenated drugs, decreases with age and when you add dinitrogen oxide.
Indications:
Introductory and supportive General anesthesia in adults and children in surgical operations in hospital and outpatient settings.
Contraindications:
- hypersensitivity to sevoflurane galogenirovannami or other drugs
- confirmed or suspected genetic susceptibility to malignant hyperthermia
- the lactation period.
Caution: renal failure intracranial hypertension neuromuscular disease and coronary artery disease (see section "Special instructions").
Application of pregnancy and breast-feeding:
In reproductive studies in animals, sevoflurane at doses up to 1 MAC have no effect on reproductive function and damaging effect on the fetus. Studies in pregnant women have not been conducted.
Sevoflurane can be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.
Since information on the excretion of sevoflurane in breast milk no breast-feeding women should refrain from breastfeeding during the period of use of the drug.
Birth
In a clinical study demonstrated the safety of sevoflurane for mother and newborn when used for General anaesthesia for caesarean section. The safety of sevoflurane during labor and normal childbirth is not installed.
Side effects:
Like all powerful means of inhalation anesthesia, sevoflurane may cause dose-dependent suppression of cardiac function and respiration. Most adverse reactions are mild or moderate and transient. Often after surgery and General anesthesia have nausea and vomiting that may be associated with inhalation anesthetics, other drugs prescribed intraoperatively or in the postoperative period, and patient's response to surgical intervention.
The most common side effects registered in clinical trials presented by organ system with indication of frequency.
From the nervous system: agitation (in adults — 7-9%, children 15%), drowsiness (9%), dizziness (4%).
From the CCC: bradycardia (5%), tachycardia (2-6%), decrease in blood pressure (4-11%), increased blood pressure (2%).
On the part of the respiratory system: cough (5-11%), respiratory disorders (2-8%), laryngospasm (2-8%).
From the side of digestion system: nausea (25%), vomiting (18%), increased salivation (4%).
Other: fever (6%), fever (1%), transient disorders of the liver, increased glucose concentration and leukocyte count, increasing the concentration of fluoride*.
The following side effects registered during post-marketing observations and whose relationship to drug intake is not installed.
The immune system: anaphylactic reaction**, pseudoreflections reaction, hypersensitivity.
From the nervous system: convulsion, dystonia.
From the CCC: heart failure (<0, 01%).
From the side of respiratory system: bronchospasm, shortness of breath**, wheezing**.
From hepatobiliary system: hepatitis, hepatic failure, hepatic necrosis.
The skin: rash**, hives, itching, contact dermatitis** swelling face**.
Other: malignant hyperthermia***, discomfort in the chest**.
*During and after General anesthesia with sevoflurane may be a transient increase in serum concentrations of inorganic fluoride. Usually their concentration reaches a maximum within 2 h after cessation of sevoflurane and returned to the preoperative value within 48 h. In clinical studies, increasing the concentration of fluoride does not lead to impaired renal function.
** Effect, possibly associated with hypersensitivity reactions, especially associated with prolonged use of inhaled anesthetics.
*** Malignant hyperthermia.
In susceptible people a powerful means for inhalation anesthesia, including sevoflurane, can cause a state of hypermetabolism of skeletal muscles that increases their oxygen demand and development of the clinical syndrome known as malignant hyperthermia. The first sign of this syndrome is hypercapnia, and there may be muscle rigidity, tachycardia, dyspnea, cyanosis, arrhythmias, and/or instability HELL. Some of these nonspecific symptoms may also appear during light anesthesia, acute hypoxia, hypercapnia, and hypovolemia. Treatment of malignant hyperthermia involves withdrawal of drugs that caused its development, intravenous dantrolene and supportive symptomatic therapy. Later may develop renal failure, therefore, should be monitored and, if possible, to maintain diuresis.
Drug interactions:
The safety and efficacy of sevoflurane is confirmed with the simultaneous use of various drugs that are commonly used in surgical practice, including influencing the function of the Central and autonomic nervous system, muscle relaxants, antimicrobials, including aminoglycosides, hormones and synthetic substitutes, blood products and cardiovascular means, including epinephrine.
It has been shown that other fluorinated volatile compounds for inhalation anesthesia displace drugs from the blood in the blood and tissues in vitro. The ability of sevoflurane to displace the PM from its Association with serum and tissue proteins have not been studied. However, in clinical studies unwanted effects in the appointment of sevoflurane patients receiving drugs with a high ability to contact proteins of plasma and low Vd (eg phenytoin), was not observed.
Barbiturates, benzodiazepine, narcotic analgesics
Sevoflurane can be used with barbiturates, and also benzodiazepines and narcotic analgesics.
Benzodiazepines and narcotic analgesics presumably reduce the sevoflurane MAC.
Dinitrogen oxide
MAC sevoflurane reduced with simultaneous use of dinitrogen oxide. The MAC equivalent is reduced approximately 50% in adult and approximately 25% in children.
Muscle relaxants
Sevoflurane has an effect on the intensity and duration of neuromuscular blockade caused by non-depolarizing muscle relaxants. With the introduction of sevoflurane as a Supplement to General anesthesia with Alfentanil-dinitrogen oxide it enhances the effect pankuronia bromide, vecuronium bromide and atracurium of besilate. When prescribing these muscle relaxants in combination with sevoflurane dose should be adjusted in the same way as in the case of use with isoflurane. The effect of sevoflurane on the effect of suxamethonium and the duration of action of depolarizing muscle relaxants has not been studied.
As potentiation of muscle relaxants is observed a few minutes after the start of sevoflurane inhalation, lower doses of muscle relaxants during induction of General anesthesia may lead to delayed intubation or inadequate muscle relaxation.
Among non-depolarizing muscle relaxants studied the interaction with vecuronium bromide, pankuronia the bromide and atracurium by bezilata. Although specific recommendations for their use do not exist, however, (1) when endotracheal intubation should not reduce the dose of non-depolarizing muscle relaxants (2) the maintenance of General anesthesia doses of non-depolarizing muscle relaxants should probably be lower than under anesthesia dinitrogen oxide/narcotic analgesics. Additional doses of muscle relaxants administered to the subject to the response to nerve stimulation.
Incompatibility
Data not available.
Method of application and dose:
Inhalation.
Premedication
Means for premedication should be selected by the anesthesiologist individually.
General anesthesia during surgery. When General anaesthesia is necessary to know the concentration of sevoflurane coming from the evaporator. For precise control of the concentration of sevoflurane should be used specifically calibrated for it vaporizers.
Introduction to General anesthesia. Dose picked individually and titrated to achieve the desired effect, taking into account the age and condition of the patient. Before inhalation of sevoflurane can be administered a fast-acting barbiturate or other drugs for at/in the induction of General anesthesia. For the introduction of General anesthesia sevoflurane can be used in mixtures with oxygen or with oxygen and dinitrogen oxide. Before surgery inhalation of sevoflurane in concentrations up to 8% usually provides an introduction to General anesthesia in less than 2 min in both adults and children.
The maintenance of General anesthesia. The required level of General anesthesia can be maintained by inhalation of sevoflurane in a concentration of 0, 5-3% in combination with dinitrogen oxide.
MAC values for adults and children, considering the age
| The patient's age | Sevoflurane with oxygen, % | Sevoflurane with a mixture of 65% N2O and 35% O2, % |
| up to 1 month* | 3, 3 | - |
| 1–6 months | 3 | - |
| 6 months–3 years | 2, 8 | 2** |
| 3–12 years | 2, 5 | - |
| 25 years | 2, 6 | 1, 4 |
| 40 years | 2, 1 | 1, 1 |
| 60 years | 1, 7 | 0, 9 |
| 80 years | 1, 4 | 0, 7 |
*Full-term newborns. MAC in premature infants was not determined.
** In children from 1 year to 3 years used 60%N2O/40% O2.
With the age of the MAC is reduced. The average concentration of sevoflurane, which provides the MAC of the patient at the age of 80 years, approximately 50% of that of 20-year-old patient.
Exit from General anesthesia. Patients usually go quickly from General anesthesia with sevoflurane. In this regard, can early be required of postoperative analgesia.
Overdose:
In case of overdose you must stop the introduction of sevoflurane, maintain airway, begin assisted or controlled ventilation with oxygen injection to maintain adequate function of SSS.
Special instructions:
General guidelines
The drug Sevoran may only be applied by professionals with experience in General anesthesia, in the offices, equipped with everything necessary to restore the airway, artificial ventilation, oxygen therapy and resuscitation.
Depth of General anesthesia can easily and quickly change, so to supply Sevorane you should only use the specially calibrated vaporizers. When the concentration of the drug may experience a buildup of arterial hypotension and depression of respiratory function.
Was received separate reports of QT prolongation, very rarely associated with tachycardia type "pirouette" (in some cases with fatal outcome). The drug Sevoran should be used with caution in patients susceptible to these complications.
Increasing the concentration of sevoflurane to maintain General anaesthesia causes a dose-dependent decrease in blood pressure. Excessive BP reduction may be associated with deep General anesthesia in such cases can be improved by reducing the concentration of sevoflurane supplied.
In applying the drug, Sewaren, as well as other funds for General anesthesia, in patients with coronary artery disease is necessary to maintain stable hemodynamics, to avoid myocardial ischemia.
After anesthesia, the patients required additional observation prior to transfer to the relevant Department.
Replacement dry sorbents for CO2
When applying Sevorane in anaesthetic equipment containing dry CO2 absorbents (especially with potassium hydroxide, Baralyme), described rare cases of excessive overheating and/or spontaneous ignition of anaesthetic equipment. When overheating of the tanks with the CO2 sorbent may be an unusual delay increase or a sudden reduction in inhaled concentration of the drug, Sewaren. Exothermic reaction is the collapse of sevoflurane with the formation of degradation products that occurs in the interaction of sevoflurane with the CO2 sorbent is enhanced if the sorbent dries, for example with prolonged exposure to dry gas. The formation of degradation products sevoflurane (methanol, formaldehyde, carbon monoxide and components A, b, C and D) were observed in the respiratory circuit of an experimental anesthesia machine with dry sorbents, the concentration of sevoflurane reached a maximum (8%) for 2 hours or more. The concentration of formaldehyde created in such conditions, reached values capable of causing a mild irritation of the respiratory tract. Clinical assessment of effects of the products of degradation of sevoflurane on the body in extreme conditions was conducted. If the anesthesiologist suspects that CO2 absorbent is too dry, then it should be replaced before application of sevoflurane. When drying of the sorbent, the CO2 indicator color changes is not always. Consequently, the absence of colour change of the indicator cannot be considered proof of adequate hydration. The sorbent CO2 need to be changed regularly, regardless of the color of the indicator.
Neuromuscular disease
The use of means for inhalation anesthesia in children caused, in rare cases, increase the concentration of potassium in serum, which led to the development of cardiac arrhythmias and death in the postoperative period. The risk is higher in patients with latent and clinically manifest neuromuscular diseases, especially in patients with Duchenne's myodystrophy. In some cases there was a communication for the development of these complications with concurrent use of suxamethonium. In these patients there was also a significant increase in the activity of creatine kinase in the serum and myoglobinuria, but despite some similarities with the manifestations of malignant hyperthermia, they have never mentioned muscular rigidity or symptoms associated with increased metabolism in the muscles. You should immediately start measures for the relief of hyperkalemia and resistant arrhythmias, and to conduct a survey to identify latent flowing neuromuscular disease.
Violation of kidney function
The safety of the drug, Sevoran in this group of patients is not fully established, it should be used with caution in patients with renal insufficiency.
Halogenated means for inhalation anesthesia
There is evidence that the use of halogenated anesthetics in history, especially during the previous 3 months, may increase the risk of liver failure.
Neurosurgical intervention
If the patient has a risk of increasing intracranial pressure, Sewaren should be used with caution in combination with measures to reduce ICP, such as hyperventilation.
Influence on ability to driving or operating machinery that require special attention. Although after you stop the flow sevoflurane consciousness is usually restored after a few minutes, its effect on cognitive function for 2-3 days after General anesthesia has not been studied. For several days after application of sevoflurane, as other means for General anesthesia, may experience slight mood changes. Patients should be informed that after General anesthesia may worsen the ability to perform a variety of tasks that require speed of psychomotor reactions, such as driving a car or operating machinery that require special attention.
