Aerrane 100% lÍquido para inhalaciÓn del vapor

PROSPECTO: INFORMATION FOR THE USER

Aerrane 100% liquid for inhalation of vapor

isoflurane

Read this prospectus carefully before starting to use this medication, as it contains important information for you.

• Keep this prospectus, as you may need to read it again.
• If you have any doubts, consult your doctor or nurse.
• If you experience adverse effects, consult your doctor or nurse, even if they are not listed in this prospectus. See section 4.

In this prospectus:

1.What Aerrane 100% is and for what it is used

2.Before using Aerrane 100%

3.How to use Aerrane 100%

4.Possible adverse effects

5.Storage of Aerrane 100%

6.Contents of the package and additional information

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

Aerrane is used for the induction and maintenance of general anesthesia.

No use Aerrane

• If you are allergic to isoflurane or any of the other components of this medication (listed in section 6).
• If you are allergic to other halogenated agents, especially if you have experienced liver dysfunction (alteration of the liver with increased bilirubin and transaminases), jaundice (yellow discoloration of the skin and eyes), unexplained fever, leukocytosis (increase in white blood cells in the blood), or eosinophilia (increase in a type of white blood cell, eosinophils), after administration of halogenated anesthetics.
• If you have a known or suspected genetic susceptibility to malignant hyperthermia (malignant hyperthermia is a rapid elevation of the body's temperature and acute muscle contractions).
• If you are to undergo dental procedures outside the hospital or day care center.

Warnings and precautions

Consult your doctor or nurse before starting to use Aerrane.

Be especially careful with Aerrane

Inform your doctor:

• If you have a risk of increased intracranial pressure.
• If you are sensitive to malignant hyperthermia, as it may trigger an increase in muscle skeletal metabolism, producing a high need for oxygen, hypercapnia (CO2 in the blood), rapid pulse (tachycardia), respiratory alteration, blue discoloration of the skin, arrhythmias, and/or unstable blood pressure.
• If you have pre-existing liver disease and have been administered a halogenated anesthetic in the past 3 months, as the associated hypoxia (lower supply of oxygen to the body or tissue) and repeated exposure to isoflurane increase the risk of hepatotoxicity (liver toxicity).
• If you have severe coronary insufficiency.
• If you have myasthenia gravis (fluctuating weakness of the voluntary muscles of the body).

Be especially careful as:

• All patients anesthetized with isoflurane must be closely monitored, including electrocardiogram (ECG) and blood pressure.
• Aerrane may cause a slight decrease in intellectual function 2 to 4 days after anesthesia. As with other anesthetics, mood changes and symptoms may persist for up to 6 days after administration.
• If you are an elderly patient, the concentration of Aerrane required to maintain anesthesia will be lower.
• There have been reports of prolonged QT interval, associated with torsade de pointes (mortal, in exceptional cases). Caution should be exercised when administering isoflurane to patients at risk of QT interval prolongation.
• Caution should be exercised in the administration of general anesthesia, including isoflurane, to patients with mitochondrial disorders.
• Isoflurane relaxes the uterine muscle, so the use of the lowest possible concentration is recommended in gynecological operations.
• In rare cases, cardiac arrhythmias (irregular heartbeat) have been produced by increased serum potassium levels and death 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 concurrent administration of other drugs acting at this level (succinylcholine).
• Repeated exposure to this type of anesthetic, especially if the interval is less than 3 months, may increase the risk of liver damage.
• If you have pre-existing liver disease, your doctor may select another non-halogenated anesthetic.
• Cases of extreme heat, smoke, or spontaneous fire in the anesthesia machine with this type of drug, along with the use of CO2 desiccant absorbers, have been reported.
• If you have hypovolemia (low blood volume), hypotension (low blood pressure), or are debilitated, it is recommended to use a low concentration of isoflurane.
• If you have a neuromuscular disease, such as myasthenia gravis (a disease characterized by muscle weakness), it may produce an increase in neuromuscular fatigue.
• If you are prone to bronchoconstriction (narrowing of the airways), bronchospasms may occur.
• 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.
• If you have taken any of the commonly used muscle relaxants, as they significantly potentiate the effect of Aerrane.

Children under two years:

Isoflurane may be used in neonates and children under 2 years of age with an acceptable margin of efficacy and safety, and is compatible with all medications used in routine anesthetic practice.

Use of Aerrane with other medications

Inform your doctor or nurse if you are using, have used recently, or may need to use any other medication.

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

• Non-selective IMAO antidepressants. Treatment with these medications should be suspended 2 weeks before the operation.
• Beta-sympathomimetics (such as isoproterenol for asthma) and alpha and beta sympathomimetics (such as epinephrine and norepinephrine, medications that act on blood pressure and the heart): due to the potential risk of ventricular arrhythmias, isoflurane should be used with caution in conjunction with these medications.
• Beta-blockers (medications used in heart rhythm disorders, hypertension, and after a heart attack).
• Succinylcholine (used as a muscle relaxant during anesthesia): its use in combination with isoflurane may cause severe cardiac arrhythmias during the postoperative period.
• Isoniazid (for tuberculosis). Treatment with isoniazid should be suspended 1 week before the operation and not resumed until 15 days after the operation, as the concurrent use of isoflurane and isoniazid may increase the risk of liver toxicity.
• Amphetamines and their derivatives, psychoestimulants, appetite suppressants, ephedrine, and its derivatives (for hypertension, sinusitis, and rhinitis, and other disorders): it is recommended to interrupt treatment with these medications a few days before the operation, as there is a risk of hypertension.
• Inducers of CYP2E1 (isoniazid, alcohol) that may increase serum fluoride levels.
• All commonly used muscle relaxants, as they significantly potentiate the effect of Aerrane.
• Opioid analgesics (opium derivatives for pain relief), benzodiazepines, and other sedatives (used to treat anxiety): these medications potentiate the depressive effect of isoflurane on respiration, so they should be administered with caution when used concurrently.
• Calcium channel blockers, as there is a risk of hypotension, particularly dihydropyridine derivatives.
• Clonidine.

Pregnancy, lactation, and fertility

Use during pregnancy

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

Isoflurane should only be used during pregnancy when the benefit outweighs the potential risk.

Isoflurane relaxes the uterine muscle, so in gynecological operations, the lowest possible concentration should be used.

Use in cesarean sections

Isoflurane has been shown to be safe and effective in maintaining anesthesia in cesarean sections at concentrations up to 0.75%.

Lactation

The passage of isoflurane into breast milk is unknown, so caution should be exercised if isoflurane is administered to breastfeeding women. Consult your doctor or nurse if you are breastfeeding.

Driving and operating machines

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

The performance of activities requiring mental agility, such as driving or operating heavy machinery, may be impaired for 1 day after anesthesia with isoflurane.

Before resuming your normal daily activities, including driving or operating machinery, consider that mood changes and decreased mental alertness may last up to 6 days after anesthesia.

Aerrane will always be administered to you by an anesthesiologist using a specially calibrated vaporizer for this product, allowing for exact control of the concentration released. The anesthesiologist will decide the dose you receive, based on your age, weight, and the type of procedure you are undergoing.

Your child must be closely monitored during the administration of isoflurane.

Induction of sleep at the beginning of anesthesia

Isoflurane is not recommended for babies and children to induce sleep at the beginning of anesthesia.

Medication before anesthesia

The anesthesiologist may decide to give your child medication to counteract the possible decrease in breathing and heart rate, effects that may occur with the use of isoflurane.

Aerrane should only be administered under the supervision of specialized anesthesia personnel, with suitable facilities for airway maintenance, artificial ventilation, additional oxygen, and circulatory resuscitation.

An increase in concentration produces a decrease in blood pressure and respiratory depression that depends on the dose of Aerrane.

The recovery from general anesthesia should be carefully evaluated before leaving the recovery room.

If you receive more Aerrane than you should

The doctor will interrupt the administration and apply the necessary measures.

In case of overdose or accidental ingestion, consult the Toxicological Information Service, phone 915.620.420.

Like all medications,this medicationmay cause side effects, although not everyone will experience them.

The following side effects have been observed with an unknown frequency:

• Respiratory alterations such asbronchospasm (narrowing of the airways) and respiratory difficulty),insufficient ventilationor laryngospasm (laryngeal closure), respiratory depression.
• Increased levels of blood sugar or potassium. Rare cases of abnormal heart rhythms (arrhythmias) and death associated with the use of inhaled anesthetics in children shortly after surgery have been reported.
• Carboxyhemoglobinemia (excess of hemoglobin bound to carbon monoxide in the blood), with the use of fluorinated inhalation medications such as desflurane, enflurane, and isoflurane.
• Seizures, agitation, and delirium.
• Mild changes in mood. Symptoms may last up to 6 days after isoflurane administration.
• Decreased intellectual function. Symptoms may persist for 2-4 days after anesthesia.
• Cardiac disorders such as arrhythmias,bradycardia, and tachycardia (slow or fast heart rate), cardiac arrest, or electrocardiogram alteration.
• Decreased blood pressure.
• Bleeding in patients who have undergone uterine scraping (dilatation and curettage).
• Respiratory alterations such as bronchospasm (narrowing of the airways),insufficient ventilationor laryngospasm (laryngeal closure).
• Intestinal obstruction, vomiting, and nausea.
• Liver cell damage that may cause liver tissue death.

• Blood value alterations with increased white blood cell count, creatinine,liver enzymes, bilirubin,fluor; and decreased urea, cholesterol, and alkaline phosphatasein the blood.
• Malignant hyperthermia (a disease characterized by increased intramuscular calcium, leading to sustained muscle contraction, increased body temperature, tachycardia, skin changes, renal changes, metabolic acidosis, increased potassium in the blood, etc.).
• Cold.
• Abnormal electroencephalogram.
• Potential risk of uterine bleeding, due to the relaxing effects of isoflurane on the uterus, as well as other inhalation agents.
• Myoglobinuria (excretion of myoglobin through urine).
• Rhabdomyolysis (abnormal muscle breakdown).

In rare cases, hypersensitivity reactions have been detected, including facial swelling, contact dermatitis, skin rash, difficulty breathing (dyspnea), wheezing (sound of air passing through a congested airway), chest discomfort, or severe allergic reaction (anaphylaxis), especially when exposed to isoflurane for an extended period, for example, due to work-related reasons.

Pediatric population:

In rare cases, an increase in blood potassium levels has been observed, which may cause arrhythmias and death in pediatric patients during the postoperative period.

During anesthesia induction, more saliva may be produced, and tracheal and bronchial secretion may increase, which may cause laryngospasm.

Other special populations:

Neuromuscular diseases: in rare cases, an increase in blood potassium levels has been observed, which may cause arrhythmias and death in pediatric patients during the postoperative period. Patients with neuromuscular diseases, especially those with Duchenne muscular dystrophy, are the most vulnerable.

Geriatric patients:

In geriatric patients, the required doses of isoflurane to maintain anesthesia are lower.

Reporting of side effects

If you experience any type of side effect, consult your doctor or nurse, even if it is a possible side effect not listed in this prospectus. You can also report them directly through the Spanish System for the Pharmacovigilance of Medications for Human Use: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

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

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.

Store in an upright position.

The disposal of unused medication and all materials that have been in contact with it, will be carried out in accordance with local regulations.

Composition of Aerrane 100%

The active principle is isoflurane.Each ml contains 1 ml of isoflurane.

There are no other ingredients.

Appearance of the product and contents of the container

Aerrane is presented as an inhalation liquid vapor in 250 ml bottles. The non-inflammable vaporized liquid is administered by inhalation with a specific calibrated vaporizer.

The presentations are:

1 bottle of 250 ml

6 bottles of 250 ml per box.

Only some sizes of containers may be commercially marketed.

Marketing Authorization Holder

Baxter S.L.

Pouet de Camilo 2,

46394 Ribarroja del Turia (Valencia)

Responsible for manufacturing

Baxter SA,

Boulevard Rene Branquart 80,

B-7860 Lessines.

Belgium

Further information on this medicinal product can be obtained by contacting the marketing authorization holder:

Last review date of this leaflet: November 2018

Detailed and updated information on this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es.

This information is intended solely for healthcare professionals:

Isoflurane should be administered exclusively by persons trained in general anesthesia, and a specific vaporizer designed and conceived for use with isoflurane will be used.

Aerrane, like other halogenated anesthetics, may interact with dry carbon dioxide absorbents, forming carbon monoxide. To minimize this risk in closed anesthesia circuits and thus the possibility of elevated carboxyhemoglobin levels, the use of effective absorbents (wet) should be ensured.

The elimination of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.

Dosage and administration

Aerrane should be administered with vaporizers specifically calibrated to allow the anesthetic concentration released to be calculated with accuracy.

Anesthesia induction.

If isoflurane is used to induce anesthesia, an initial concentration of 0.5% is recommended. Concentrations of 1.3-3.0% generally achieve surgical anesthesia in 7 to 10 minutes.

The use of a hypnotic dose of a rapid-acting barbiturate or another product such as propofol, etomidate, or midazolam is recommended to avoid coughing or laryngospasm, which may occur if induction is performed with Aerrane alone or in combination with oxygen or a mixture of oxygen-nitrous oxide.

Maintenance of anesthesia.

Anesthesia can be maintained during surgery using a concentration of 1.0 to 2.5%, with simultaneous administration of nitrous oxide and oxygen.

A higher concentration, 1.5 to 3.5%, of Aerrane is required if oxygen is used alone.

The alveolar minimum concentration (C.A.M.) values for Aerrane (isoflurane) decrease with age, decreasing from 1.28% in oxygen at 20 years to 1.15% at 40 years, and 1.05% at 60 years.

Recovery.

The concentration of Aerrane should be reduced to 0.5% at the end of the operation, or to 0% during wound closure to allow for immediate recovery.

If all anesthetic agents have been discontinued, the patient's airways should be ventilated several times with 100% oxygen until they are fully awake.

If the carrier gas is a mixture of 50%/02and 50%/N20, the volume of the alveolar minimum concentration of isoflurane is approximately 0.65%.

Premedication.

Medicines used for premedication should be selected on an individual basis, taking into account the depressive effect of isoflurane on respiration. The use of anticholinergic drugs is a matter of choice, but may be advisable for inhalation induction in pediatrics.

Anesthesia induction in children.

Isoflurane is not recommended for use as an inhalation induction agent in infants and children due to the occurrence of coughing, apnea, desaturation, increased secretions, and laryngospasm (see section 4.4).