Leaflet: information for the user

Etoxisclerol 20 mg/ml injectable solution

Lauromacrogol 400

Read this leaflet carefully before you start taking this medicine, because

it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only and should not be given to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

Etoxisclerol is a sclerosant whose active principle is lauromacrogol 400.

Etoxisclerol 20 mg/ml is indicated for sclerosing or destruction of varicose veins and telangiectasias (vascular spiders).

No use Etoxisclerol in sclerosing treatment of varices

• If you are allergic to lauromacrogol 400 or any of the other components of this medication (listed in section 6),
• If you have a severe acute systemic disease (affecting the entire body) (especially in untreated patients),
• If you must stay in bed or cannot walk,
• If you have severe arterial circulation disorder (arterial occlusive disease, Fontaine stages III and IV),
• If you have a vascular occlusion due to a blood clot or thrombus (thromboembolic diseases),
• If you have a high risk of vascular occlusions (thrombosis), for example, patients with a hereditary predisposition to produce blood clots or with multiple risk factors such as:

use of hormonal contraceptives (e.g. the pill), hormone replacement therapy, obesity, smoking, prolonged periods of immobility, etc.

Do not use Etoxisclerol in sclerosing treatment of varices with microfoam

• If you have symptoms due to a known hole in the interatrial septum of the heart (symptomatic patent foramen ovale).

Warnings and precautions

Etoxisclerol should be administered by a healthcare professional with experience in sclerotherapy techniques.

Consult your doctor, pharmacist, or nurse before starting to use Etoxisclerol

• If you have a fever,
• If you have an acute respiratory distress crisis (asthma bronchial),
• If you have a strong predisposition to allergies,
• If your general state of health is poor,
• If you are to undergo sclerosing treatment of spider veins: in patients with arterial circulation disorders (arterial occlusive diseases, Fontaine stage II),
• If you have swollen legs due to fluid accumulation (edema) and cannot be relieved by compression,
• If you have skin inflammatory disease in the treatment area,
• If you have symptoms of occlusion of small blood vessels, for example due to diabetes (microangiopathy) and nerve damage (neuropathy),
• If you have reduced mobility,
• If you have frequent migraines.

Consult your doctor, pharmacist, or nurse before starting sclerosing treatment with microfoam:

• If you have a known hole in the interatrial septum of the heart, even if it does not cause symptoms (known as asymptomatic patent foramen ovale),
• If you have a history of visual defects (visual symptoms or neurological symptoms) after a previous sclerosing treatment with microfoam.

Other medications and Etoxisclerol

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

The use of Etoxisclerol with anesthetics may increase the anesthetic effect on the cardiovascular system.

Pregnancy, breastfeeding, and fertility

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

If you are pregnant, your doctor should not administer Etoxisclerol, unless it is strictly necessary, as there is insufficient information on the use of Etoxisclerol in pregnant women. Animal studies showed no evidence of malformations.

If treatment with Etoxisclerol 20 mg/ml is necessary during breastfeeding, it is recommended to suspend it for 2-3 days, as there is no data in humans on the passage of lauromacrogol 400 to breast milk.

Driving and operating machinery

No adverse effects on the ability to drive and operate machinery have been reported due to the use of Etoxisclerol.

Etoxisclerol contains ethanol, potassium, and sodium

• This medication contains 84.00 mg of alcohol (ethanol at 96%) in each 2 ml ampoule, equivalent to 5% (v/v). The amount in a 2 ml ampoule of this medication is equivalent to less than 3ml of beer or 1 ml of wine.

It is unlikely that the amount of alcohol contained in this medication will have any perceptible effect in adults or adolescents.

The amount of alcohol contained in this medication may alter the effect of other medications.

Consult your doctor or pharmacist if you are taking other medications. If you are pregnant or breastfeeding, consult your doctor or pharmacist before taking this medication.

If you have a history of alcohol addiction, consult your doctor or pharmacist before taking this medication.

• This medication contains less than 39 mg (1 mmol) of potassium per ampoule, making it essentially "potassium-free".
• This medication contains less than 23 mg (1 mmol) of sodium per ampoule, making it "sodium-free".

Etoxisclerol is a medication whose administration must be practiced by a doctor, so it is up to the doctor to know and choose the most suitable dosage and technique in each case.

Etoxisclerol can be used in both liquid and microfoam form (viscous microfoam, standardized, homogeneous, and fine bubble).

In accordance with the size of the varicose vein to be treated and the individual situation of each patient, the doctor will decide which treatment to apply. In case of doubt, the lowest possible dose should be chosen. Generally, the dose of 2 mg/kg/day of lauromacrogol 400 should not be exceeded.

In routine cases, it is recommended to use a maximum volume of 10 ml of microfoam per session, regardless of the patient's body weight and the concentration of lauromacrogol 400.

To avoid a possible allergic reaction, especially in a patient with a high predisposition to hypersensitivity reactions, it is recommended that for the first treatment, only a small test dose of Etoxisclerol be administered. Depending on the response, several injections can be administered in subsequent treatment sessions, as long as the maximum dose is not exceeded.

Since the volume to be injected per session is limited, multiple sessions (usually 2 to 4 on average) are often needed.

After being treated with Etoxisclerol, you should follow your doctor's advice. They may recommend wearing a bandage or compression stockings to help reduce inflammation and skin pigmentation.

Use in children and adolescents

There is no relevant use of Etoxisclerol in pediatric populations.

If you use more Etoxisclerol than you should

In case of overdose or accidental ingestion, consult your doctor, pharmacist, or call the Toxicological Information Service at 91 562 04 20, indicating the medication and the amount ingested.

Overdose can cause local tissue death (necrosis), especially after injection near the varicose vein.

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

In this section, we inform you about the adverse reactions that have been reported associated with the extended use of the active substance. In some cases, these reactions were annoying but, in most cases, they were only temporary. Since they were often spontaneous reports, without any reference to a defined group of patients and without any reference group, it is not possible to calculate exactly the frequencies or establish a clear causal relationship with the drug in each case. However, a reasonable estimate can be made from long-term experience.

Local adverse effects (e.g. necrosis) have been observed, especially on the skin and tissue near the varicose vein (and, in rare cases, on the nerves), when varicose veins of the legs are treated after accidental injections in the tissue near them.

The risk increases when the concentration and volume of Etoxisclerol increase.

The following adverse effects have been observed with the frequencies described below:

• Frequent(may affect up to 1 in 10 people):appearance of blood vessels in the treated area not visible before treatment (neovascularization), bruising (hematoma), skin discoloration (hyperpigmentation), skin bleeding (ecchymosis), pain at the injection site (short-term), thrombosis at the injection site (local intravaricosus blood clots).

• Infrequent(may affect up to 1 in 100 people):inflammation of the vein (superficial thrombophlebitis, phlebitis), allergic skin inflammation (dermatitis), contact urticaria, skin reaction, skin redness (erythema), local tissue death (necrosis), tissue hardening, swelling, nerve damage.

• Rare(may affect up to 1 in 1,000 people):deep vein thrombosis (possibly due to another underlying condition), limb pain.

• Very rare(may affect up to 1 in 10,000 people):anaphylactic shock (severe and sudden allergic reaction, symptoms include difficulty breathing, dizziness, fall in blood pressure), angioedema (symptoms include sudden swelling, especially on the face, for example, eyelids, lips or larynx), generalized urticaria, asthma (asthmatic crisis), stroke (cerebrovascular accident), weakness causing loss of mobility in a part of the body (hemiparesis), headache, migraine (rare when using sclerosing treatment with microfoam), local sensory disturbances (paresthesia), decreased sensitivity or sensations in the mouth (hypoaesthesia oral), loss of consciousness, confusion, central speech disorders (aphasia), difficulty controlling movements (ataxia), dizziness, visual disturbances (rare when using sclerosing treatment with microfoam), heart attack (cardiac arrest),heart failure syndrome (stress cardiomyopathy),rapid or irregular heartbeats (palpitations), abnormal heart rate, pulmonary embolism (obstruction of the pulmonary artery), fainting (vasovagal syncope), circulatory collapse, inflammation of the blood vessel wall (vasculitis), difficulty breathing (dyspnea), sensation of pressure in the chest, cough, taste disorders, nausea, vomiting, excessive hair growth (hypertrichosis) in the treated area, fever, hot flashes, unusual weakness (asthenia), general discomfort, abnormal blood pressure.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that does not appear in this prospectus. 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 effects, you can contribute to providing more information on the safety of this medicine.

This medication does not require any special temperature for conservation.

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.

Medicines should not be thrown down the drains or in the trash. Dispose of the packaging and medicines that you no longer need at the SIGRE point of the pharmacy.In case of doubt, ask your pharmacist how to dispose of the packaging and medicines that you no longer need. In this way, you will help protect the environment.

Composition of Etoxisclerol

• The active principle is lauromacrogol 400.
• Each milliliter of injectable solution contains 20 mg of lauromacrogol 400.

Each ampoule of 2 ml of injectable solution contains 40 mg of lauromacrogol 400.

• The other components (excipients) are: ethanol 96%, potassium dihydrogen phosphate, disodium dihydrogen phosphate dihydrate, water for injectable preparations.

Aspect of the product and content of the package

Etoxisclerol is a transparent solution, with a light yellowish green color. It is presented as an injectable solution in a package containing 5 ampoules of 2 ml each.

Other presentations

• Etoxisclerol 5 mg/ml injectable solution. Package containing 5 ampoules of 2 ml each.
• Etoxisclerol 10 mg/ml injectable solution. Package containing 5 ampoules of 2 ml each.
• Etoxisclerol 30 mg/ml injectable solution. Package containing 5 ampoules of 2 ml each.

Holder of the marketing authorization and responsible for manufacturing

Chemische Fabrik Kreussler & Co. GmbH

Rheingaustrasse 87-93

65203 Wiesbaden, Germany

tel.: +49 611 9271-0

fax: +49 611 9271-111

e-mail:[email protected]

You can request more information about this medication by contacting the local representative of the holder of the marketing authorization:

FERRER FARMA, S.A.

Av. Diagonal 549 5ª Planta,

08029 Barcelona (Spain)

Date of the last review of this leaflet: FJune 2023

The detailed and updated information about 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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This information is intended solely for healthcare professionals

For more information, see the Technical Dossier.

Important precautions for use

• Etoxisclerol should only be administered by an experienced healthcare professional in venous anatomy and in the diagnosis and treatment of diseases affecting the venous system and familiar with a correct injection technique.
• Before treatment, the healthcare professional must investigate the patient's risk factors and inform them about the risks of this technique. Sclerotherapy is particularly not recommended in patients with a history of thromboembolic events. However, if sclerotherapy is deemed necessary, preventive anticoagulation can be initiated.
• Due to the risk of product circulation, bubbles, or particles in the right heart, the presence of a right-left communication (e.g., a patent foramen ovale) may increase the occurrence of severe arterial adverse events. In patients with a history of migraine with aura, severe cerebrovascular events, or pulmonary hypertension, it is recommended to search for a right-left communication (e.g., a patent foramen ovale) before sclerotherapy.
• In asymptomatic patients, but with known right-left communication (e.g., a patent foramen ovale), it is recommended to use smaller volumes and avoid the Valsalva maneuver in the minutes following injection.
• Use smaller volumes in patients with a history of migraine.
• Severe local adverse effects, such as tissue necrosis, may occur after extravasation, so great care must be taken in the placement of the intravenous needle and it is essential to use the minimum effective volume at each injection site.
• Scalerosants should never be injected intraarterially, as this may cause severe necrosis that may require amputation. In the event of an accident, immediate surgical vascular treatment should be sought.
• The use of any type of sclerosant in the facial area should be strictly evaluated, as intravascular injections may cause irreversible loss of vision.
• In some parts of the body, such as the feet or the ankle region, the risk of inadvertently infiltrating the interior of the artery may be increased. Therefore, only small amounts and low concentrations should be used with special care during this type of treatment.
• When treating major saphenous veins, the injection of microfoam should be administered at a minimum distance of 8 to 10 cm from the sapheno-femoral junction. If ultrasound monitoring reveals a foam bolus in the deep venous system, the patient should perform muscle activation, such as dorsiflexion of the ankle.
• When using Etoxisclerol in the form of microfoam, it is recommended to use disposable syringes with low silicone content, as this ensures better foam quality.

Dosage and administration

Adults and elderly

Generally, the dose of 2 mg/kg/day of lauromacrogol 400 should not be exceeded.

In routine cases, a maximum volume of 10 ml of microfoam (the volume of microfoam corresponds to the sum of the liquid and the gas) per session, regardless of the patient's weight and the concentration of lauromacrogol 400, is recommended. Larger volumes of microfoam may be applied on an individual benefit-risk evaluation. The volumes of microfoam injected per session are generally kept below the maximum values, i.e., between 2 and 8 ml.

* The volume is the sum of the liquid and the gas.

** In routine cases.

When using Etoxisclerol 20 mg/ml in liquid form for sclerotherapy of medium-sized varicose veins, and depending on the length of the segment to be treated, several injections with a maximum of 2 ml of liquid per injection may be administered.

When using Etoxisclerol 20 mg/ml in microfoam, for example, for the treatment of perforating veins or tributary varicose veins, up to 2 ml of microfoam per puncture may be injected. For the treatment of the saphenous vein, up to 4 ml per puncture and up to 6 ml for the treatment of the saphenous vein may be injected.

To avoid a possible allergic reaction, especially in a patient with a high predisposition to hypersensitivity reactions, it is recommended that for the first treatment, only a small test dose of Etoxisclerol be administered. Depending on the response, several injections may be administered in subsequent treatment sessions, provided that the maximum dose is not exceeded.

Since the volume to be injected per session is limited, multiple sessions (usually 2 to 4) are generally required.

Pediatric population

There is no relevant use of Etoxisclerol in the pediatric population.

Administration

All injections must be administered by intravenous route; the position of the needle must be checked (e.g., by aspirating blood).

Regardless of the venous puncture method (in a patient standing with only one cannula or in a patient sitting with a syringe ready for injection), the injections will be performed normally in one leg in a horizontal position. Disposable syringes with smooth movement are recommended for sclerotherapy, as well as needles of different diameters, depending on the indication.

When using microfoam, the leg may be placed horizontally or elevated approximately 30-45° above the horizontal for injection. The ideal injection of microfoam should be administered under the guidance of ultrasound. Direct puncture and injection in non-visible veins should be guided by duplex ultrasound. The needle should not be smaller than 25G.

The sclerosant must be administered by intravenous route in small aliquots in multiple points of the vein to be treated, either in liquid or in microfoam. In the treatment of perforating veins, it is recommended not to inject directly into the target vein. The goal is to achieve optimal destruction of the vessel wall with the minimum concentration of sclerosant necessary for a clinical result. If the concentration is too high, necrosis or other adverse sequelae may occur.

The microfoam must be prepared just before use and administered by a doctor adequately trained in the correct generation and administration of microfoam. The preparation of microfoam is described in section 6.6 of the Technical Dossier. Most techniques involve mixing sclerosant and gas (e.g., sterile air) by repeatedly transferring it through 2 connected syringes.

Depending on the degree and extent of varicose veins, multiple treatment sessions may be required.

Strict aseptic technique should be maintained during the handling of Etoxisclerol.

Treatment with compression after Etoxisclerol injection

After sclerosant treatment with Etoxisclerol liquid, a compression bandage or elastic stocking should be applied.

After sclerosant treatment with microfoam, the patient's leg is initially immobilized for 2-5 minutes. The Valsalva maneuver and muscle activation should be avoided during this time, and compression should not be applied immediately, but 5-10 minutes after injection.

After this, the patient should walk for 30 minutes, preferably within the clinic or consultation where the injection was performed.

Compression should be applied from several days to several weeks, depending on the extent and severity of varicose veins.

Occasional thrombi may appear, which can be eliminated by incision and evacuation of the thrombus.