AERRANE 100% LIQUID FOR INHALATION

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE USER

Aerrane 100% liquid for vapor inhalation

isoflurane

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

In this leaflet:

1. What Aerrane 100% is and what it is used for
2. Before you use Aerrane 100%
3. How to use Aerrane 100%
4. Possible side effects
5. Storage of Aerrane 100%
6. Contents of the pack and other information

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

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

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

2. Before you use Aerrane 100%

Do not use Aerrane

• If you are allergic to isoflurane or any of the other components of this medicine (listed in section 6).
• If you are allergic to other halogenated agents, especially if you have suffered from hepatic dysfunction (liver alteration with increased bilirubin and transaminases), jaundice (yellowing 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 the administration of halogenated anesthetics.
• If you have a known or suspected genetic susceptibility to malignant hyperthermia (a rapid elevation of body temperature and acute muscle contractions).
• If you are going 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 careful with Aerrane

Tell your doctor

• If you have a risk of increased intracranial pressure.
• If you are sensitive to malignant hyperthermia, as it could trigger an increase in skeletal muscle metabolism, producing a high need for oxygen, hypercapnia (CO2 in the blood), rapid pulse (tachycardia), alteration of breathing, bluish discoloration of the skin, alteration of heart rhythm (arrhythmias), and/or unstable blood pressure.
• If you have pre-existing liver disease and have been administered a halogenated anesthetic in the last 3 months, as the associated hypoxia (lower oxygen supply 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 (a disease characterized by fluctuating muscle weakness).

Be careful because:

• All patients anesthetized with isoflurane must be closely monitored, including electrocardiogram (ECG) and blood pressure.
• Aerrane may produce a slight decrease in intellectual function between 2 to 4 days after anesthesia. As with other anesthetics, mood changes and symptoms can persist for up to 6 days after administration.
• If you are an elderly patient, the concentration of Aerrane needed to maintain anesthesia will be lower.
• There have been reports of prolonged QT interval, associated with torsade de pointes(potentially fatal, in exceptional cases). Caution should be exercised when administering isoflurane if you are a patient at risk of QT interval prolongation.
• Caution should be exercised when administering general anesthesia, including isoflurane, to patients with mitochondrial disorders.
• Isoflurane relaxes the uterine muscle, so the minimum possible concentration should be used in case of gynecological operations.
• Rarely, cardiac arrhythmias (irregular heartbeat) have occurred due to 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 concomitant administration of other drugs that act 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.
• In the case of pre-existing liver disease, your doctor may select a non-halogenated anesthetic.
• There have been reports of extreme heat, smoke, or spontaneous fire in the anesthesia machine with drugs of this class, along with the use of dried CO2 absorbents.
• 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 can suffer from 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 muscle relaxants commonly used, as they significantly enhance the effect of Aerrane.

Children under 2 years:

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

Use of Aerrane with other medications

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

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

• Non-selective IMAO antidepressants. Treatment with these medications should be suspended 2 weeks before surgery.
• Beta-sympathomimetics (such as isoprenaline 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 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). Isoniazid treatment should be suspended one week before surgery and should not be restarted until 15 days after surgery, as concomitant use of isoflurane and isoniazid may increase the risk of liver toxicity.
• Amphetamines and their derivatives, psychostimulants, appetite suppressants, ephedrine, and its derivatives (for treating hypotension, sinusitis, and rhinitis, and other disorders), it is preferable to interrupt treatment with these medications a few days before surgery because there is a risk of hypertension.
• CYP2E1 inducers (isoniazid, alcohol) that may increase blood fluoride levels.
• All muscle relaxants commonly used, as they significantly enhance the effect of Aerrane.
• Opioid analgesics (opium derivatives for pain relief), benzodiazepines, and other sedative agents (used to treat anxiety): these medications enhance the depressant effect of isoflurane on respiration, so they should be administered with caution when given concomitantly.
• Calcium channel blocker antihypertensives, as there is a risk of hypotension, particularly dihydropyridine derivatives.
• Clonidine.

Pregnancy, breastfeeding, and fertility

Use during pregnancy

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or nurse before using this medicine.

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 during cesarean section

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

Breastfeeding

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

Driving and using machines

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

Performing activities that require 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 using machinery, you should consider that mood changes and decreased mental alertness can last up to 6 days after anesthesia.

3. How to use Aerrane 100%

Aerrane will always be administered to you by an anesthesiologist using a vaporizer specifically calibrated for this product, so that the released concentration can be controlled exactly. The anesthesiologist will decide the dose you will receive, depending on your age, weight, and the type of intervention you will undergo.

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

Induction of sleep at the beginning of anesthesia

Isoflurane is not recommended for inducing sleep in infants and children at the beginning of anesthesia.

Medication before anesthesia

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

It should only be administered under the supervision of personnel specialized in anesthesia, with adequate facilities for maintaining the airway, artificial ventilation, additional oxygen, and circulatory resuscitation.

Increasing the 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 Toxicology Information Service, phone 915.620.420.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

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

• Respiratory disorders such as bronchospasm (narrowing of the airways), insufficient ventilation, or laryngospasm (closure of the larynx), respiratory depression.
• Increased blood sugar or potassium levels. 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 inhalational medications such as desflurane, enflurane, and isoflurane.
• Seizures, agitation, and delirium.
• Mild mood changes. Symptoms can last up to 6 days after isoflurane administration.
• Decreased intellectual function. Symptoms can persist for 2-4 days after anesthesia.
• Cardiac disorders such as arrhythmias, bradycardia, and tachycardia (slow or fast heart rate), cardiac arrest, or alteration of the electrocardiogram.
• Decreased blood pressure.
• Bleeding in patients who have undergone a uterine mucosa scraping (dilation and curettage).
• Respiratory disorders such as bronchospasm (narrowing of the airways), insufficient ventilation, or laryngospasm (closure of the larynx).
• Intestinal obstruction, vomiting, and nausea.
• Liver cell damage that can produce liver tissue death.

• Alteration of blood values with increased white blood cell count, creatinine, liver enzymes, bilirubin, fluor; and decreased urea, cholesterol, and alkaline phosphatase in the blood.
• Malignant hyperthermia (a disease characterized by increased intramuscular calcium, producing 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 inhalational agents.
• Myoglobinuria (excretion of myoglobin through urine).
• Rhabdomyolysis (abnormal breakdown of muscles).

Rarely, hypersensitivity reactions have been reported, including facial swelling, contact dermatitis, skin rash, difficulty breathing (dyspnea), wheezing (sound of air passing through a congested respiratory tract), chest discomfort, or severe allergic reaction (anaphylactic reaction), especially when exposed to isoflurane for a long time, for example, due to work-related reasons.

Pediatric population:

Rarely, an increase in blood potassium has been observed, which can produce cardiac arrhythmias and death in pediatric patients during the postoperative period.

During the induction of anesthesia, more saliva and increased tracheal and bronchial secretion may occur, which can cause laryngospasm.

Other special populations:

Neuromuscular diseases: rarely, an increase in blood potassium has been observed, which can produce cardiac arrhythmias and death in pediatric patients during the postoperative period. Patients with neuromuscular diseases, especially those with Duchenne muscular dystrophy, are the most vulnerable.

Elderly patients:

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

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse, even if it is possible side effects not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Aerrane 100%

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

Do not use this medicine after the expiry date stated on the packaging after EXP. The expiry date is the last day of the month indicated.

Store in an upright position.

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

6. Further information

Composition of Aerrane 100%

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

There are no other ingredients.

Appearance of the product and packaging contents

Aerrane is presented as a liquid for vapor inhalation in 250 ml bottles. The non-flammable vaporized liquid is administered by inhalation with a specifically calibrated vaporizer.

The presentations are:

1 bottle of 250 ml

6 bottles of 250 ml per box.

Not all pack sizes may be marketed.

Marketing authorization holder

Baxter S.L.

Pouet de Camilo 2,

46394 Ribarroja del Turia (Valencia)

Manufacturer

Baxter SA,

Boulevard Rene Branquart 80,

B-7860 Lessines.

Belgium

You can request more information about this medicine from the marketing authorization holder:

Date of last revision of this leaflet: November 2018

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es.

This information is intended only for healthcare professionals:

Isoflurane should be administered exclusively by persons trained in general anesthesia, and for this purpose, a vaporizer specifically designed and intended for use with isoflurane should be used.

Aerrane, like other halogenated anesthetics, may interact with dry CO2 absorbents, forming carbon monoxide. To minimize this risk in closed anesthesia circuits and thus the possibility of high carboxyhemoglobin levels, effective (humid) absorbents should be used.

The disposal of unused medicine 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 specially calibrated vaporizers so that the concentration of anesthetic released can be calculated with precision.

Induction of anesthesia.

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 arise if induction is performed with Aerrane alone or in combination with oxygen or an oxygen-nitrous oxide mixture.

Maintenance of anesthesia.

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

A higher concentration, 1.5 to 3.5%, of Aerrane is required if it is administered with pure oxygen.

The values of minimum alveolar concentration (MAC) for Aerrane (isoflurane) decrease with age, decreasing from 1.28% in oxygen at twenty years, to 1.15% at forty, to 1.05% at sixty 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 administration of all anesthetic agents has 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% O2 and 50% N2O, the volume of the minimum alveolar concentration of isoflurane is approximately 0.65%.

Pre-medication.

Medications used for pre-medication should be selected on an individual basis, taking into account the respiratory depressant effect of isoflurane. The use of anticholinergic drugs is a matter of choice, but may be advisable for inhalation induction in pediatrics.

Induction of anesthesia in children.

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