Sevorane^® (Liquid) Instructions for Use

ATC Code

N01AB08 (Sevoflurane)

Active Substance

Sevoflurane (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Inhalation anesthesia preparation

Pharmacotherapeutic Group

Inhalation anesthetic agent

Pharmacological Action

Inhalation anesthetic agent. Inhalation use of sevoflurane for induction of anesthesia causes rapid loss of consciousness, which is quickly restored after cessation of anesthesia.

Induction of anesthesia is accompanied by minimal excitation and signs of irritation of the upper respiratory tract and does not cause excessive secretion in the tracheobronchial tree or stimulation of the CNS. Sevoflurane (like other potent inhalation anesthetic agents) causes dose-dependent respiratory depression and decreased BP. In humans, the threshold level of sevoflurane causing arrhythmias under the influence of epinephrine (adrenaline) was comparable to that of isoflurane and exceeded the threshold level of halothane.

Sevoflurane has a minimal effect on intracranial pressure and does not reduce the response to CO₂. It does not have a clinically significant effect on liver or kidney function and does not cause progression of renal or hepatic insufficiency. It does not affect the concentrating function of the kidneys even during prolonged anesthesia (approximately up to 9 hours).

Minimum Alveolar Concentration (MAC) is the concentration at which 50% of patients do not show a motor response to a single stimulus (skin incision). The MAC of sevoflurane in oxygen is 2.05% in an adult aged 40 years. The MAC of sevoflurane, like other halogenated drugs, decreases with age and with the addition of nitrous oxide.

Pharmacokinetics

The low solubility of sevoflurane in blood ensures a rapid increase in alveolar concentration during induction of anesthesia and a rapid decrease after cessation of inhalation. The ratio of alveolar concentration to the concentration in the inhaled mixture in the accumulation phase 30 minutes after inhalation of sevoflurane is 0.85. In the elimination phase, the ratio of alveolar concentrations 5 minutes after inhalation of sevoflurane is 0.15.

The rapid elimination of sevoflurane from the lungs minimizes the metabolism of sevoflurane. In humans, less than 5% of the absorbed dose of sevoflurane is metabolized with the participation of the isoenzyme CYP2E1 to form hexafluoroisopropanol, with the release of inorganic fluoride and carbon dioxide (or one carbon dioxide). The resulting hexafluoroisopropanol is rapidly conjugated with glucuronic acid and excreted in the urine. Other pathways of sevoflurane metabolism have not been established. Sevoflurane is the only fluorinated volatile anesthetic agent that is not metabolized to trifluoroacetic acid.

The concentration of fluoride ions depends on the duration of anesthesia, the concentration of administered sevoflurane, and the composition of the anesthetic mixture.

Barbiturates do not cause defluorination of sevoflurane.

Indications

Induction and maintenance of general anesthesia in adults and children for surgical procedures in hospital and outpatient settings.

ICD codes

Dosage Regimen

Liquid

Premedication agents should be selected individually by the anesthesiologist.

During induction of anesthesia, the dose is selected individually and titrated to achieve the desired effect, taking into account the patient’s age and condition. For induction of general anesthesia, Sevoflurane can be used in oxygen or in a mixture of oxygen and nitrous oxide.

Before surgical interventions in adults and children, inhalation of sevoflurane at concentrations up to 8% usually provides induction of general anesthesia within less than 2 minutes.

The required level of general anesthesia can be maintained by inhalation of sevoflurane at a concentration of 0.5-3% in combination with nitrous oxide or without it.

MAC decreases with age. The average concentration of sevoflurane providing MAC for a patient aged 80 years is approximately 50% of that for a patient aged 20 years.

Adverse Reactions

From the CNS and peripheral nervous system: agitation, drowsiness after recovery from general anesthesia, dizziness; in isolated cases, short-term convulsions were noted after the use of sevoflurane. Although consciousness is usually restored within a few minutes after stopping sevoflurane administration, the state of intellectual capabilities within 2-3 days after anesthesia has not been studied. For several days after the use of sevoflurane (as with other anesthetic agents), minor mood changes may be noted.

From the respiratory system: dose-dependent respiratory depression, increased cough, respiratory disorders (post-intubation apnea, laryngospasm).

From the cardiovascular system: dose-dependent depression of cardiac activity, decrease or increase in BP, bradycardia, tachycardia.

From the digestive system: nausea, vomiting, increased salivation; in some cases – transient impairment of liver function parameters.

Allergic reactions: in some cases – rash, urticaria, itching, bronchospasm, anaphylactic or anaphylactoid reactions.

From laboratory parameters: transient increase in glucose level and leukocyte count is possible.

Other: chills, fever.

In predisposed patients, potent inhalation anesthetic agents, including Sevoflurane, can induce a state of skeletal muscle hypermetabolism, leading to an increase in their oxygen demand and the development of a clinical syndrome known as malignant hyperthermia. The first sign of this syndrome is hypercapnia, and clinical symptoms may include muscle rigidity, tachycardia, tachypnea, cyanosis, arrhythmias and/or BP instability. Some of these nonspecific symptoms may also appear during light anesthesia, acute hypoxia, hypercapnia, and hypovolemia. Renal failure may develop later (diuresis should be monitored and maintained if possible).

Most adverse reactions are mild or moderate and transient.

Contraindications

Confirmed or suspected genetic predisposition to the development of malignant hyperthermia; hypersensitivity to sevoflurane or other halogenated drugs.

Use in Pregnancy and Lactation

Adequate and strictly controlled studies on the safety of sevoflurane use during pregnancy have not been conducted. Use during pregnancy is only possible in cases of extreme necessity.

It is not known whether Sevoflurane is excreted in breast milk. Use with caution during lactation (breastfeeding).

Use in Renal Impairment

Use with caution in case of impaired renal function.

Geriatric Use

MAC decreases with age. The average concentration of sevoflurane providing MAC for a patient aged 80 years is approximately 50% of that for a patient aged 20 years.

Special Precautions

Use with caution in case of impaired renal function, during neurosurgical interventions, if the patient has a threat of increased intracranial pressure (in combination with measures aimed at reducing intracranial pressure, such as hyperventilation).

Sevoflurane should only be used by physicians experienced in administering general anesthesia. Equipment for airway management, artificial lung ventilation, oxygen therapy, and resuscitation must be readily available.

The level of general anesthesia can change easily and quickly, so only specially calibrated vaporizers should be used for sevoflurane delivery. Deepening of general anesthesia is accompanied by increasing arterial hypotension and respiratory depression.

During maintenance anesthesia, an increase in sevoflurane concentration causes a dose-dependent decrease in BP. Excessive decrease in BP may be associated with deep general anesthesia; in such cases, it can be increased by reducing the concentration of administered sevoflurane.

As with the use of any general anesthetic agents in patients with coronary artery disease, stable hemodynamics must be maintained to avoid myocardial ischemia.

Patients recovering from general anesthesia should be carefully observed before transportation to the ward.

For the treatment of malignant hyperthermia, discontinuation of the drugs that caused its development, intravenous administration of dantrolene sodium, and supportive symptomatic therapy are indicated.

Effect on the ability to drive vehicles and operate machinery

Patients should be informed that for some time after anesthesia, the ability to perform work requiring quick reactions, such as driving a car or using potentially dangerous machinery, may be impaired.

Drug Interactions

It is assumed that benzodiazepines and opioid analgesics reduce the MAC of sevoflurane.

The MAC of sevoflurane is reduced with the simultaneous use of nitrous oxide.

Sevoflurane affects the intensity and duration of neuromuscular blockade caused by non-depolarizing muscle relaxants. When sevoflurane is administered as an adjunct to alfentanil/N₂O anesthesia, the effects of pancuronium, vecuronium, and atracurium are enhanced. When prescribing these muscle relaxants in combination with sevoflurane, their doses should be adjusted in the same way as when used with isoflurane. The effect of sevoflurane on the effect of succinylcholine and the duration of action of depolarizing muscle relaxants has not been studied.

Since the enhancement of the effect of muscle relaxants is observed several minutes after the start of sevoflurane inhalation, reducing the dose of muscle relaxants during induction anesthesia may lead to delayed tracheal intubation or inadequate muscle relaxation.

Among non-depolarizing drugs, the interaction of sevoflurane with vecuronium, pancuronium, and atracurium has been studied. Although there are no specific recommendations for their use, nevertheless, during endotracheal intubation, the doses of non-depolarizing muscle relaxants should not be reduced; during maintenance anesthesia, the doses of non-depolarizing muscle relaxants should probably be lower than with N₂O/opioid analgesic anesthesia. Additional doses of muscle relaxants are administered taking into account the response to nerve stimulation.

Storage Conditions

Store at 15°C (59°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.