Sevorane

Leaflet accompanying the packaging: patient information

Sevorane, 100%, inhalation liquid

Sevofluranum

Please read this leaflet carefully before using the medicine, as it contains important information for the patient.

• Please keep this leaflet, you may need to read it again.
• If you have any doubts, consult your doctor, surgeon, or anesthesiologist.
• If the patient experiences any side effects, including any not listed in this leaflet, they should inform their doctor or pharmacist. See section 4.

Table of contents of the leaflet

• 1. What is Sevorane and what is it used for
• 2. Important information before using Sevorane
• 3. How to use Sevorane
• 4. Possible side effects
• 5. How to store Sevorane
• 6. Package contents and other information

1. What is Sevorane and what is it used for

Sevorane is an inhalation (inhaled by the patient) anesthetic, available in liquid form. The active substance is sevoflurane - the only component of the medicine. In a special device (vaporizer), the medicine is converted into a gas, which, after mixing with oxygen or a mixture of oxygen and nitrous oxide, is inhaled by the patient.
Sevorane can only be administered by an anesthesiologist or under their supervision.
Sevorane is used to induce deep sleep and pain relief (general anesthesia) in adults and children undergoing surgical procedures in hospital and outpatient settings.

2. Important information before using Sevorane

Sevorane should only be administered by an anesthesiologist or under their supervision by persons trained in the use of general anesthesia. Direct access to equipment for maintaining airway patency, artificial ventilation, oxygen supply, and cardiopulmonary resuscitation should be ensured.

When not to use Sevorane

• If the patient or any of their family members have experienced a condition called malignant hyperthermia (very high fever with hypertension, muscle stiffness, and tachycardia during or shortly after surgery) during an operation.
• If the patient has been diagnosed with or is suspected of being allergic (hypersensitive) to Sevorane or another halogenated general anesthetic.
• If general anesthesia is contraindicated.

If any of the above points apply to the patient, they should inform the anesthesiologist before the procedure.

Warnings and precautions

Particular caution should be exercised if:

• the patient has been administered general anesthetics in the past, especially if they were administered multiple times in a short period, as some anesthetics may occasionally cause liver damage, manifested by, among other things, jaundice (yellowing of the skin),
• the patient is taking medications that cause liver disorders,
• the patient has another disease unrelated to the operation: ○ kidney disease, ○ heart disease, including congenital long QT syndrome, ○ liver function disorders, ○ abnormal blood pressure, ○ increased intracranial pressure, ○ neuromuscular disorders (e.g., Duchenne muscular dystrophy), ○ Pompe disease (genetic glycogen metabolism disorder), especially in children, ○ mitochondrial disease (a genetic disease caused by disorders in the functioning and structure of mitochondria),
• the patient has hypovolemia (reduced blood volume), hypotension, or other hemodynamic disorders (related to blood circulation).
• the patient has a tendency to seizures (especially in children and young adults).

If any of the above warnings apply to the patient, they should inform their doctor. The doctor will decide whether Sevorane can be used.
Particular caution should be exercised because Sevorane:

• may inhibit respiratory function and thus enhance the effect of narcotic or other respiratory depressant medications used during preparation for surgery. The doctor should monitor the patient's respiratory function and, if necessary, support breathing.
• may cause postoperative liver function disorders (ranging from mild to severe) or hepatitis with or without jaundice. The risk of liver damage increases if the patient has previously been administered halogenated general anesthetics, especially if they were administered at intervals of less than three months.
• may cause life-threatening malignant hyperthermia. The patient should inform the doctor if they or any of their family members have experienced this condition in the past (see "When not to use Sevorane").
• may, in rare cases, like other inhalation anesthetics, cause an increase in serum potassium levels, which has been associated with postoperative cardiac arrhythmias and deaths in children.

Sevorane and other medications

The patient should inform their doctor about all medications they are currently taking or have recently taken, including those available without a prescription. This also applies to herbal medicines and dietary supplements.
Sevorane canbe used with the following medications commonly used during surgical procedures:

• medications acting on the central nervous system (barbiturates, benzodiazepines, opioids),
• medications acting on the autonomic nervous system (the system that controls metabolism and the proper functioning of internal organs),
• muscle relaxants (pancuronium, vecuronium, atracurium),
• antibacterial medications (including aminoglycoside antibiotics),
• hormonal medications,
• blood preparations,
• medications acting on the cardiovascular system (including adrenaline).

However, caution should be exercised if Sevorane is administered simultaneously with:

• adrenergic medications, such as isoproterenol, adrenaline, and noradrenaline, due to the possible risk of ventricular arrhythmias and sympathomimetics with indirect action (e.g., amphetamine and ephedrine), as there is a risk of an acute episode of hypertension,
• non-selective MAO inhibitors, as a hypertensive crisis may occur during surgery. Therefore, it is recommended to discontinue treatment with a non-selective MAO inhibitor two weeks before surgery,
• beta-adrenergic blockers, which are commonly used to treat cardiovascular diseases,
• calcium channel blockers, especially dihydropyridine derivatives, as sevoflurane may cause significant hypotension, and verapamil, as conduction disturbances have been observed during concurrent administration,
• substances inducing the CYP2E1 isoenzyme, such as isoniazid and alcohol, as they may increase the metabolism of sevoflurane and cause a significant increase in serum fluoride levels. Concurrent use of sevoflurane and isoniazid may enhance the hepatotoxic effect of isoniazid,
• St. John's Wort, as severe hypotension and prolonged recovery from inhalation anesthesia have been reported in patients taking St. John's Wort for a long time.

If the above applies to the patient, they should inform their doctor.

Pregnancy, breastfeeding, and fertility

If the patient is pregnant or suspects they may be pregnant, they should inform their doctor, surgeon, or anesthesiologist. In pregnant women, due to the lack of data, the medicine can only be used when it is absolutely necessary.
If the patient is breastfeeding, they should inform their doctor. The doctor will recommend stopping breastfeeding for 48 hours after Sevorane administration and discarding the milk produced during this period.

Driving and operating machinery

Sevorane may cause temporary impairment of psychophysical fitness, and therefore, the patient should not drive vehicles or operate any mechanical devices until these impairments have resolved.

3. How to use Sevorane

The dose of Sevorane administered to the patient is determined by the anesthesiologist. It depends on the patient's age, weight, and the type of surgical procedure.
Sevorane is an inhaled (inhalation) anesthetic gas. Sevorane is available in liquid form, which is then converted into a gas in a specially calibrated sevoflurane vaporizer. This allows for precise control of the administered dose.

4. Possible side effects

Like all medicines, Sevorane can cause side effects, although not everybody gets them.
Most side effects are mild or moderate and are temporary.
Very common (more than 1 in 10 patients) side effects include:

• adult patients: hypotension, nausea, and vomiting;
• elderly patients: bradycardia, hypotension, and nausea;
• children: agitation, cough, vomiting, and nausea.

Common (1 to 10 patients in 100) side effects include:

• confusion,
• drowsiness,
• dizziness,
• headache,
• tachycardia,
• hypertension,
• respiratory disorders,
• laryngospasm,
• excessive salivation,
• shivering,
• fever,
• abnormal blood glucose levels,
• abnormal liver function test results,
• abnormal white blood cell count,
• transient increase in serum fluoride levels (a breakdown product of the medicine). (During and after Sevorane anesthesia, a transient increase in inorganic fluoride levels in serum may occur. This has no effect on renal function.),
• hypothermia (significant drop in body temperature).

Uncommon (1 to 10 patients in 1,000) side effects include:

• complete atrioventricular block (a type of heart rhythm disorder).

Other side effects that have been reported after Sevorane was introduced to the market, with an unknown frequency:

• anaphylactic reaction (a severe allergic reaction that can lead to life-threatening shock),
• pseudo-anaphylactic reaction (similar to the above, but with a different mechanism of action),
• hypersensitivity,
• seizures,
• dystonia (muscle tone disorders),
• cardiac arrest (in individual cases),
• bronchospasm,
• dyspnea,
• wheezing,
• hepatitis,
• liver failure,
• liver necrosis,
• contact dermatitis,
• pruritus,
• rash,
• facial edema,
• urticaria,
• chest discomfort,
• malignant hyperthermia (manifested by, among other things, very high fever),
• QT interval prolongation (a heart electrical activity disorder resulting in changes in the ECG) associated with torsades de pointes (a life-threatening irregular heartbeat).

After using Sevorane

The patient wakes up within a few minutes.
If any unusual or unexpected side effects occur after anesthesia, the patient should immediately inform their doctor or anesthesiologist.
If the patient has any questions about Sevorane that are not answered in this leaflet, they should consult their doctor or anesthesiologist.

Reporting side effects

If any side effects occur, including any not listed in the leaflet, the patient should inform their doctor, anesthesiologist, pharmacist, or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products:
Al. Jerozolimskie 181C
02-222 Warsaw
tel.: 22 49-21-301
fax: 22 49-21-309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help gather more information on the safety of the medicine.

5. How to store Sevorane

The medicine should be stored out of sight and reach of children.
There are no special storage instructions for the medicine.
Do not use this medicine after the expiration date (EXP) stated on the packaging. The expiration date refers to the last day of the specified month.
Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of unused medicines. This will help protect the environment.

6. Package contents and other information

What Sevorane contains

Sevorane contains only sevoflurane. It does not contain any excipients or chemical stabilizers. The water present in the medicine in trace amounts protects it from the action of Lewis acids (substances present in the environment that can cause the breakdown of sevoflurane).

What Sevorane looks like and what the package contains

Sevorane is a clear, colorless liquid. The medicine is packaged in 250 ml polyethylene naphthalate (PEN) bottles with a Quik-Fil Mark II closure in a cardboard box.

Marketing authorization holder and manufacturer

Marketing authorization holder
AbbVie Sp. z o.o.
ul. Postępu 21B
02-676 Warsaw
Manufacturer
AbbVie S.r.l.
S.R. 148 Pontina km 52 SNC
04011 Campoverde di Aprilia (LT)
Italy
To obtain more detailed information, please contact the marketing authorization holder:
AbbVie Sp. z o.o.
ul. Postępu 21B
02-676 Warsaw
Tel.: + 48 22 372 78 00

Date of last update of the leaflet:

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Sevorane, 100%, inhalation liquid

Sevofluranum

Information intended for healthcare professionals only

Please refer to the detailed information about this medicine (Summary of Product Characteristics), which is available on the website of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products.

INSTRUCTIONS FOR THE ADMINISTRATOR OF THE MEDICINE

Warnings and precautions

See also section 2 of the patient leaflet.
QT interval prolongation
There have been single reports of QT interval prolongation, very rarely associated with torsades de pointes (in exceptional cases leading to death). Caution should be exercised when administering sevoflurane to patients who are prone to such disorders (e.g., patients with congenital long QT syndrome).
Malignant hyperthermia
In susceptible individuals, potent inhalation anesthetics, including sevoflurane, may trigger increased muscle metabolism, leading to increased oxygen demand and a syndrome of clinical symptoms known as malignant hyperthermia.
Hypercapnia is the first sign of this syndrome, which may be manifested by muscle stiffness, tachycardia, increased respiratory rate, cyanosis, cardiac arrhythmias, and (or) fluctuations in blood pressure. Some of these non-specific signs may also occur during light anesthesia, acute hypoxia, hypercapnia, and hypovolemia.
In clinical trials, one case of malignant hyperthermia was reported. Additionally, cases of malignant hyperthermia have been reported after the medicine was introduced to the market. In some of these cases, the patient died.
Treatment of malignant hyperthermia involves discontinuing the causative agent (e.g., sevoflurane), intravenous administration of sodium dantrolene (additional information on patient management can be found in the dantrolene sodium labeling), and supportive therapy. This therapy involves taking decisive action to restore normal body temperature, supporting respiration and circulation if necessary, and correcting water-electrolyte and acid-base balance disturbances.
Due to the risk of subsequent renal failure, it is essential to monitor and maintain diuresis.
Perioperative hyperkalemia
The use of inhalation anesthetics has been associated with rare cases of increased serum potassium levels, which have caused cardiac arrhythmias and deaths in children during the postoperative period. It appears that the greatest risk occurs in patients with latent or overt neuromuscular disease, especially Duchenne muscular dystrophy. The concurrent use of succinylcholine was associated with most, but not all, of these cases. In these patients, significant increases in serum creatine kinase activity and, in some cases, changes in urine suggesting myoglobinuria were also observed. Despite the similarity of symptoms to those observed in malignant hyperthermia, none of the patients exhibited objective or subjective signs of muscle stiffness or a hypermetabolic state. It is recommended to take early and vigorous action to treat hyperkalemia and persistent cardiac arrhythmias, followed by investigations for latent neuromuscular disease.

General warnings

Increasing the concentration of sevoflurane during maintenance of anesthesia causes a dose-dependent decrease in blood pressure. Excessive hypotension may be related to the depth of anesthesia and can be corrected by reducing the inhaled sevoflurane concentration. Particular caution should be exercised in patients with hypovolemia, hypotension, or other hemodynamic disorders, e.g., caused by concomitantly administered medications.
As with all general anesthetics, in patients with coronary artery disease, it is essential to maintain stable hemodynamic parameters to avoid myocardial ischemia.
Before transferring the patient from the post-anesthesia care unit, it is crucial to thoroughly assess the level of recovery from general anesthesia.
Recovery of consciousness after sevoflurane administration usually occurs within a few or several minutes. However, the effect of this agent on intellectual function within the first 2-3 days after anesthesia has not been investigated. As with other general anesthetics, minor mood changes may persist for several days after administration.

Renal impairment

Due to the limited number of patients studied, the safety of sevoflurane in patients with renal impairment (initial creatinine levels above 1.5 mg/100 ml) has not been fully established. Therefore, sevoflurane should be used with caution in patients with renal impairment.

Neurosurgical procedures

Sevoflurane should be used with caution in patients at risk of increased intracranial pressure. In these patients, measures should be taken to reduce intracranial pressure, e.g., by using hyperventilation.

Seizures

There have been rare reports of seizures associated with the use of sevoflurane. Sevoflurane has caused seizures in children and young adults, as well as older adults, with or without a history of seizure disorders. The decision to use sevoflurane in patients at risk of seizures should be based on clinical judgment. In children, the depth of anesthesia should be limited. EEG monitoring may help determine the optimal dose of sevoflurane and prevent the development of seizure activity in patients with a history of seizure disorders (see "Children and adolescents" below).

Children and adolescents

Sevoflurane has caused seizures in children and young adults. In many cases, these occurred in children (from 2 months of age) and young adults, most of whom had no history of seizure disorders. When using sevoflurane in patients who may be at risk of seizures, clinical judgment should be exercised (see "Seizures" above).

Drying of CO2 absorbers

There have been rare reports of extreme heating of the apparatus, escaping smoke, or self-ignition of the anesthesia apparatus during the passage of sevoflurane through a dried CO2 absorber, especially one containing potassium hydroxide. Excessive heating of the CO2 absorber container may lead to delayed increase or sudden decrease in the inhaled sevoflurane concentration compared to the vaporizer settings.
A thermic reaction, rapid breakdown of sevoflurane, and formation of breakdown products may occur when the CO2 absorber dries out, e.g., due to the passage of dry gas through the CO2 absorber containers for an extended period. The presence of sevoflurane breakdown products (methanol, formaldehyde, carbon monoxide, and compounds A, B, C, and D) has been detected in the respiratory circuit of an experimental anesthesia apparatus using dried CO2 absorbers and sevoflurane at maximum concentration (8%) for an extended period (≥ 2 hours).
The concentrations of formaldehyde detected in the experimental anesthesia apparatus (using soda lime absorbers) were similar to those causing mild respiratory irritation. The clinical significance of sevoflurane breakdown products formed in this extreme experimental model is unknown.
If the anesthesiologist suspects that the CO2 absorber is dried out, it should be replaced before administering sevoflurane. Not all drying of the CO2 absorber results in a color change of the indicator. The absence of a significant color change of the indicator does not necessarily mean that the CO2 absorber is properly hydrated. CO2 absorbers should be replaced routinely, regardless of the color of the indicator.

Interactions with other medications (see patient leaflet, section 2 "Sevorane and other medications")

Information on certain interactions
Barbiturates
Sevoflurane can be administered with barbiturates commonly used during surgical procedures.
Benzodiazepines and opioids
It can be expected that benzodiazepines and opioids will reduce the MAC value of sevoflurane to the same extent as other inhalation anesthetics. Sevoflurane can be administered with benzodiazepines and opioids commonly used during surgical procedures.
Mutual potentiation of pharmacological effects may occur when opioids such as alfentanil and sufentanil are administered in combination with sevoflurane, resulting in decreased heart rate, blood pressure, and respiratory rate.
Nitrous oxide
As with other halogenated inhalation anesthetics, the MAC value of sevoflurane is reduced when administered with nitrous oxide - by approximately 50% in adults and 25% in children.
Muscle relaxants
Like other inhalation anesthetics, sevoflurane potentiates and prolongs the effect of non-depolarizing muscle relaxants. Sevoflurane used as a supplementary anesthetic during anesthesia with alfentanil and nitrous oxide potentiates the muscle relaxant effect of pancuronium, vecuronium, or atracurium. When using these muscle relaxants with sevoflurane, their doses should be adjusted similarly to when used with isoflurane. The effect of sevoflurane on succinylcholine and the duration of non-depolarizing muscle relaxant action has not been investigated. Concurrent use of succinylcholine with inhalation anesthetics has been associated with rare cases of increased serum potassium levels, resulting in cardiac arrhythmias and deaths in children.

Dosage and administration

Sevoflurane should only be administered using a vaporizer specifically calibrated for this product.
The exact concentration of sevoflurane delivered from the vaporizer should be known. Since inhalation anesthetics have different physical properties, sevoflurane should only be administered using a vaporizer specifically calibrated for this medicine. The administration of the anesthetic should be individualized based on the patient's response. Hypotension and respiratory disorders worsen with the depth of anesthesia.
Inhalation administration.
Premedication
The dose of the premedication medication should be individualized based on the patient's needs and the anesthesiologist's judgment.

MAC values according to age

Recovery
The recovery time from sevoflurane anesthesia is usually short. Therefore, patients anesthetized with sevoflurane should be given analgesics before surgery.
Elderly patients
The MAC value decreases with age. The average sevoflurane concentration required to achieve MAC in an 80-year-old patient is approximately 50% of the concentration required in a 20-year-old patient.