Prospecto: information for the user

SEVORANE

100% liquid for inhalation of vapor

Sevoflurane

Read this prospect thoroughly before starting to use this medication, because it contains important information for you.

• Keep this prospect as you may need to read it again.
  If you have any doubts, consult your doctor, pharmacist or nurse.
• This medication has been prescribed to you and should not be given to other people, even if they have the same symptoms, as it may harm them.
• If you experience adverse effects, consult your doctor, pharmacist or nurse, even if they do not appear in this prospect. See section 4.

1. What is SEVORANE and for what it is used

2. What you need to know before starting to use SEVORANE

3. How to use SEVORANE

4. Possible adverse effects

5. Storage of SEVORANE

6. Contents of the package and additional information

SEVORANE is an inhalational anesthetic that belongs to the group of halogenated hydrocarbons.

SEVORANE is used for the induction and maintenance of general anesthesia in adults and children, both inpatients and outpatients.

Do not use SEVORANE,

• If you are allergic to sevoflurane or any of the other components of this medication (listed in section 6) or to other halogenated anesthetics.
• If you are susceptible to malignant hyperthermia.
• If you have been told that you should not undergo general anesthesia.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use SEVORANE.

• It should be administered by or under the supervision of trained personnel for the administration of general anesthetics, with suitable facilities for maintaining the airway, artificial ventilation, and additional oxygen and circulatory resuscitation.
• The exact concentration of sevoflurane being released from the vaporizer must be known. Since volatile anesthetics differ in their physical properties, only vaporizers specifically calibrated for sevoflurane can be used. General anesthesia administration should be individualized based on the patient's response.
• As anesthesia becomes deeper, there is a greater decrease in blood pressure and respiratory depression.
• If you are sensitive to malignant hyperthermia, it may trigger an increase in skeletal muscle metabolism, resulting in a high need for oxygen, hypercapnia (increased carbon dioxide in the blood), and may include muscle rigidity, rapid pulse (tachycardia), respiratory alteration, blue discoloration of the skin, arrhythmias, and/or unstable blood pressure. During superficial anesthesia, other signs may appear: acute hypoxia (sudden decrease in oxygen in the body), hypercapnia (increased carbon dioxide in the blood), and hypovolemia (decrease in circulating blood volume).
• In clinical trials, a case of malignant hyperthermia was reported. Additionally, there have been reports of malignant hyperthermia during post-marketing. Some of these reports have been fatal.
• The treatment of malignant hyperthermia includes discontinuing SEVORANE and administering dantrolene sodium intravenously.
• In rare cases, cardiac arrhythmias and death have occurred in children during the postoperative period, mainly in patients with diseases affecting the nervous system and muscles (such as Duchenne muscular dystrophy) and in many cases with the concomitant administration of other drugs acting at this level (succinylcholine).
• If you have heart problems, a type of tachycardia may occur that your doctor should treat, as in exceptional cases it may be fatal.
• In pediatric patients with Pompe disease, isolated cases of ventricular arrhythmia have been reported.
• • Care should be taken in the administration of general anesthesia, including when using SEVORANE, in patients with mitochondrial disorders.
  • After marketing, there have been rare cases of moderate to severe liver disease or hepatitis (inflammation of the liver) with or without jaundice (yellow discoloration of the skin and eyes).
  • When SEVORANE is used in patients with pre-existing liver disease or those being treated with medications known to cause liver damage, the doctor should decide whether to use it or not.
  • If you are repeatedly exposed to halogenated hydrocarbons, including SEVORANE, in a relatively short period, your risk of liver damage may increase.
  • Blood pressure decrease is related to the concentration of SEVORANE and the depth of anesthesia. Special caution should be taken in patients with lower-than-usual blood pressure, in patients with lower blood volume, or those with similar problems caused by other medications.
  • As with all anesthetics, it is essential to maintain blood pressure and blood volume stability to avoid myocardial ischemia (obstruction of blood flow to the heart muscle) in patients with coronary artery disease.
  • The recovery of general anesthesia should be carefully evaluated before leaving the recovery room.
  • Although recovery of consciousness after SEVORANE administration usually occurs in minutes, its impact on intellectual function has not been studied for 2-3 days after anesthesia. As with other anesthetics, small mood changes may persist for several days after administration.
  • If you have kidney function problems.
  • If you are at risk of increased intracranial pressure.
  • The use of SEVORANE has been associated with seizures that have occurred in young and adult patients with or without predisposing risk factors. The anesthesiologist will decide whether to use this medication or not in cases where there may be a risk of seizures.
  • Seizures may occur in children from the age of 2. The anesthesiologist will decide whether to use this medication in cases where there may be a risk of seizures.
  • The anesthesiologist should replace the CO2 dry absorbents properly.
  • If you have taken narcotic medications or other medications that may cause respiratory depression, your doctor will monitor your breathing and provide assistance if necessary.

Use in patients over 80 years old

If you are an 80-year-old patient, the required dose is approximately half of that required for a 20-year-old patient.

Use of SEVORANE with other medications

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication, especially those used to treat high blood pressure, heart problems, anxiety, tuberculosis, muscle relaxants, herbal preparations, or alcohol.

Inform your doctor if you are being treated with opioids such as alfentanil and sufentanil, as their combination with SEVORANE may lead to a combined and more significant alteration of heart rhythm, blood pressure, and respiratory frequency.

It is essential to inform your doctor if you are taking or have taken recently any of the following medications:

Pregnancy, lactation, and fertility

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication.

Driving and operating machines

Do not drive or operate tools or machines after receiving SEVORANE, as this medication may affect your reaction time. Your doctor will indicate how long you should wait before driving or operating machines.

Follow exactly the medication administration instructions contained in this leaflet or those indicated by your doctor, pharmacist, or nurse. If in doubt, ask your doctor, pharmacist, or nurse.

SEVORANE is administered by a trained healthcare professional using a specially calibrated vaporizer for this product, allowing for exact control of the released concentration.

Your doctor will decide on the most suitable dose of SEVORANE for you.

If you use more SEVORANE than you should

If you receive more SEVORANE than you shouldyour doctor will stop administration and take necessary measures.

In case of overdose or accidental ingestion, consult the Toxicological Information Service, phone 91.562.04.20, indicating the medication and the amount ingested.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Most side effects are of a mild or moderate nature and are transient.

Sevoflurane may cause decreases in cardiac and respiratory function.

Nausea and vomiting have been observed in the postoperative period, common sequelae of surgery and general anesthesia, which may be due to inhalational anesthesia, other agents administered during or after the operation, and the patient's response to the surgical procedure.

The most commonly observed side effects are as follows:

In adult patients: decreased blood pressure, nausea, delirium, and vomiting;

In elderly patients: bradycardia, decreased blood pressure, and nausea; and

In children: agitation, cough, vomiting, and nausea.

The following table shows all side effects, at least possibly related to sevoflurane in clinical trials and post-marketing experience, ordered by frequency and classified by organ and system of MedDRA. The following frequency groups have been used:Very common(in more than 1 in 10 people);Common(between 1 and 10 in 100 people);Uncommon(between 1 and 10 in 1,000 people);Rare(between 1 and 10 in 10,000 people);Very rare(less than 1 in 10,000 people), even isolated events. Post-marketing adverse reactions are reported voluntarily in a population with an unknown exposure frequency. Therefore, it is not possible to estimate the frequency of adverse reactions and the frequency is "unknown". The type, severity, and frequency of side effects in patients who received SEVORANE in clinical trials are comparable to the side effects in patients receiving the reference treatment.

Side effects derived from Clinical Trials and Post-marketing Experience

Description of selected adverse reactions

Transient increases in inorganic fluoride levels in serum may occur during and after anesthesia with SEVORANE. Fluoride levels generally reach their maximum in the 2 hours following the end of anesthesia with SEVORANE and return to preoperative levels within 48 hours. In clinical trials, elevated fluoride levels were not associated with renal dysfunction.

There have been few reports of postoperative hepatitis. Additionally, there have been rare reports of liver insufficiency and liver necrosis associated with the use of potent inhalational anesthetics, including SEVORANE. However, the true incidence and relationship of SEVORANE to these events cannot be established with certainty.

There have been few reports of hypersensitivity (including contact dermatitis, skin eruption, dyspnea, sibilant breathing, chest discomfort, facial swelling, or anaphylactic reaction), particularly in association with long-term professional exposure to inhaled anesthetics, including SEVORANE.

In sensitive individuals, potent inhalational anesthetics may trigger a hypermetabolic state of skeletal muscle, producing a high demand for oxygen and the clinical syndrome known as malignant hyperthermia.

Pediatric population

The use of SEVORANE has been associated with convulsions. Many of these have occurred in children from 2 years of age and in young people, most of whom did not have risk factors that predisposed them to seizures. A clinical judgment should be made prior to the use of SEVORANE in patients who may be at risk of seizures.

Reporting of adverse reactions

If you experience any type of adverse reaction, consult your doctor, pharmacist, or nurse, even if it is a possible adverse reaction that does not appear in this leaflet. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es. By reporting adverse reactions, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

It should be stored at room temperature between 15 and 30°C.

Do not use this medication after the expiration date that appears on the packaging after CAD.:. The expiration date is the last day of the month indicated.

Composition of SEVORANE

The active ingredient is sevoflurane. This medication contains sevoflurane 100%.

It contains at least 300 ppm of water as protection against environmental Lewis acid. It does not contain other additives or preservatives.

Appearance of the product and contents of the package

SEVORANE is presented as a non-flammable volatile liquid in amber-colored polyethylene terephthalate containers of 250 ml. The vaporized liquid is administered by inhalation with a specific vaporizer.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization:

AbbVie Spain S.L.U. Avenida de Burgos, 91- 28050 Madrid.

Responsible for manufacturing:

AbbVie S.r.l., S.R. 148 Pontina km 52 SNC, 04011 Campoverde di Aprilia (LT) Italy.

Date of the last review of this leaflet: February 2016

The detailed information of this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/

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Additional information for healthcare professionals

POSOLGÍA

The premedication should be selected according to the needs of each patient and at the discretion of the anesthesist.

Surgical anesthesia

Sevoflurane should be administered through a calibrated vaporizer specifically designed for use with this medication, so that the released concentration can be adjusted.

The concentration of sevoflurane released by the vaporizer during anesthesia should be known. The dosage should be individualized and adjusted to achieve the desired effect, according to the age and clinical status of the patient.

Induction of anesthesia

The dose should be individualized and adjusted to achieve the desired effect, according to the age and clinical status of the patient. Sevoflurane can be administered by inhalation in oxygen (O2) or in combination with a mixture of oxygen-nitrous oxide (O2/N2O). For the induction of anesthesia, concentrations of up to 8% sevoflurane inhaled produce surgical anesthesia in less than 2 minutes, both in adults and children.

Maintenance of anesthesia

Surgical anesthesia levels can be maintained with concentrations of 0.5 - 3% sevoflurane in O2, with or without the concomitant use of nitrous oxide.

Table 1

Values of CAM (minimum alveolar concentration) for adults and pediatric patients according to age

Awakening

The times of awakening after anesthesia with sevoflurane are generally short. Therefore, patients may need early treatment for postoperative pain.

Geriatric patients

CAM decreases with age. The average concentration of sevoflurane required to achieve CAM in an 80-year-old patient is approximately 50% of that required in a 20-year-old patient.

Pediatric population

Consult Table 1 for CAM values according to age in pediatric patients.

INSTRUCTIONS FOR CORRECT ADMINISTRATION OF THE PREPARATION

Sevoflurane should be administered with a vaporizer specifically calibrated for this product, using a designated filling system for the vaporizers specific to sevoflurane or other appropriate filling systems for vaporizers.

Replacement of CO2 absorbents:

Rare cases of spontaneous heat, smoke, and/or fire in the anesthesia machine have been reported during the use of sevoflurane with the use of desiccated CO2 absorbents, specifically those containing potassium hydroxide. An unusually delayed or unexpected decrease in the inspired concentration of sevoflurane compared to the vaporizer setting may be associated with excessive heating of the CO2 absorbent container.

A exothermic reaction may occur, increasing the degradation of sevoflurane and the production of degradation products when the CO2 absorbent becomes desiccated, such as after the passage of dry gas through the CO2 absorbent containers during a prolonged period. In an experimental anesthesia machine circuit that used desiccated CO2 absorbents and maximum concentrations of sevoflurane (8%) for prolonged periods (> 2 hours), degradation products of sevoflurane (methanol, formaldehyde, carbon monoxide, and compounds A, B, C, and D) were observed. The concentrations of formaldehyde observed in the anesthesia machine circuit (using absorbents containing sodium hydroxide) were consistent with levels known to cause mild respiratory irritation. The clinical relevance of the observed degradation products is unknown.

When an anesthesist suspects that the CO2 absorbent may be desiccated, it should be replaced before sevoflurane administration. The color indicator of many CO2 absorbents does not change as a result of desiccation. Therefore, the lack of significant color change should not be taken as a guarantee of adequate hydration. CO2 absorbents should be replaced routinely, regardless of the color indicator of the CO2 absorbent.

INTERACTIONS

Sevoflurane should be used with caution during narcosis with sevoflurane, beta-sympathomimetic agents such as isoproterenol, and alpha and beta-sympathomimetic agents, such as adrenaline and noradrenaline, due to a potential risk of ventricular arrhythmias.

Non-selective MAO inhibitors:

The combination of non-selective MAO inhibitors and sevoflurane should be avoided due to the risk of preoperative collapse. Treatment should be interrupted 2 weeks before surgery.

Calcium channel blockers:

Sevoflurane may produce a marked hypotension, particularly in combination with dihydropyridine derivatives. Caution should be exercised in the use of calcium channel blockers concomitantly with inhaled anesthetics, due to the risk of additive negative inotropic effect.

Succinylcholine:

The simultaneous administration of succinylcholine and inhaled anesthetics has been associated with rare cases of increased serum potassium levels, which resulted in cardiac arrhythmias and death in pediatric patients.

Sevoflurane has been shown to be safe and effective when administered concomitantly with a wide variety of medications commonly used in surgical interventions, such as central and peripheral nervous system drugs, muscle relaxants, anti-infective agents, including aminoglycosides, hormones and synthetic substitutes, blood derivatives, and cardiovascular drugs, including epinephrine.

Epinephrine/Adrenaline

Sevoflurane is similar to isoflurane in sensitizing the myocardium to the arrhythmogenic effect produced by the exogenous administration of adrenaline.

Indirect-acting sympathomimetics

There is a risk of acute hypertensive episode with the concomitant use of sevoflurane and indirect-acting sympathomimetics (amphetamine, ephedrine).

Beta-blockers

Sevoflurane may increase the negative inotropic, chronotropic, and dromotropic effects of beta-blockers through the blockade of cardiovascular compensatory mechanisms.

Verapamil

When verapamil and sevoflurane were administered simultaneously, deterioration of atrioventricular conduction was observed.

St. John's Wort

Severe hypotension and delayed awakening of anesthesia have been reported in patients treated for a long time with St. John's Wort after the use of halogenated inhalation anesthetics.

Barbiturates

The administration of sevoflurane is compatible with the use of barbiturates commonly used in surgical interventions.

Benzodiazepines and opioids

It is expected that the administration of benzodiazepines and opioids will decrease the CAM of sevoflurane, as occurs with other inhalation anesthetics. The administration of sevoflurane is compatible with the use of benzodiazepines and opioids commonly used in surgical interventions.

When sevoflurane is combined with opioids such as alfentanil and sufentanil, it may lead to a synergistic failure of cardiac rhythm, blood pressure, and respiratory rate.

CYP2E1 inducers

Drugs and compounds that increase the activity of the CYP2E1 isoenzyme of cytochrome P450, such as isoniazid and alcohol, may increase the metabolism of sevoflurane and lead to significant increases in plasma fluorine concentrations. The concomitant use of sevoflurane and isoniazid may potentiate the hepatotoxic effects of isoniazid.

Nitrous oxide

As with other halogenated volatile anesthetics, the CAM of sevoflurane decreases when administered in combination with nitrous oxide. The equivalent CAM is reduced by 50% in adults and 25% in pediatric patients, approximately.

Neuromuscular blockers

As occurs with other inhalation anesthetics, sevoflurane affects the intensity and duration of the neuromuscular blockade produced by non-depolarizing muscle relaxants. When administered to supplement anesthesia with alfentanil-N2O, sevoflurane potentiates the neuromuscular blockade induced with pancuronium, vecuronium, or atracurium. The dosage adjustments for these muscle relaxants when administered with sevoflurane are similar to those required with isoflurane. The effect of sevoflurane on succinylcholine and the duration of depolarizing neuromuscular blockade has not been studied.

The reduction of the dosage of neuromuscular blockers during anesthesia induction may cause a delay in optimal conditions for endotracheal intubation or inadequate muscle relaxation, due to the potentiation of neuromuscular blockers observed a few minutes after starting sevoflurane administration.

Among non-depolarizing agents, interactions have been studied with vecuronium, pancuronium, and atracurium. In the absence of specific guidelines: (1) for endotracheal intubation, do not reduce the dosage of non-depolarizing muscle relaxants; and (2) during anesthesia maintenance, it is likely that the dosage of non-depolarizing muscle relaxants will need to be reduced compared to anesthesia with N2O/opioids. Administration of supplementary muscle relaxants should be made taking into account the response to nerve stimulation.

OVERDOSE

In case of apparent overdose, the following should be done: interrupt the administration of SEVORANE, establish an airway, initiate assisted or controlled ventilation with oxygen, and maintain adequate cardiovascular function.