ETOXISCLEROL 30 mg/ml INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Etoxisclerol 30 mg/ml injectable solution

Lauromacrogol 400

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, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the package leaflet

1. What is Etoxisclerol and what is it used for
2. What you need to know before you use Etoxisclerol
3. How to use Etoxisclerol
4. Possible side effects
5. Storage of Etoxisclerol
6. Contents of the pack and other information

1. What is Etoxisclerol and what is it used for

Etoxisclerol is a sclerosing agent whose active substance is lauromacrogol 400.

Etoxisclerol 30 mg/ml is indicated for sclerosing treatment or destruction of:

• Varicose veins,
• Spider veins (telangiectasias),
• Hemorrhoids.

2. What you need to know before you use Etoxisclerol

Do not use Etoxisclerol for sclerosing treatment of varices

• If you are allergic to lauromacrogol 400 or any of the other ingredients of this medicine (listed in section 6),
• If you have acute severe systemic disease (affecting the whole body), especially in untreated patients,
• If you are bedridden or unable to walk,
• If you have severe arterial circulatory disorders (arterial occlusive disease, Fontaine stages III and IV),
• If you have a vascular occlusion due to a blood clot (thromboembolic diseases),
• If you are at 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, overweight, smoking, prolonged periods of immobility, etc.

Do not use Etoxisclerol for sclerosing treatment of varices with microfoam

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

Do not use Etoxisclerol for sclerosing treatment of hemorrhoids

• If you are allergic to lauromacrogol 400 or any of the other ingredients of this medicine (listed in section 6),
• If you have acute severe systemic disease (affecting the whole body), especially in untreated patients,
• If you have acute inflammation in the anal region (acute proctitis).

Warnings and precautions for sclerosing treatment of varices

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

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

• If you have a fever,
• If you have bronchial asthma,
• If you have a strong predisposition to allergies,
• If your general state of health is poor,
• If you are to undergo sclerosing treatment for spider veins: in patients with arterial circulatory disorders (arterial occlusive disease, Fontaine stage II),
• If you have swollen legs due to fluid accumulation (edema) and it cannot be modified by compression,
• If you have inflammatory skin disease in the area to be treated,
• If you have symptoms of occlusion of the smallest blood vessels, for example, due to diabetes (microangiopathy) and deterioration of sensitivity (neuropathy),
• If you have reduced mobility,
• If you frequently have migraines.

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

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

Warnings and precautions for sclerosing treatment of hemorrhoids

Consult your doctor, pharmacist, or nurse before starting treatment with Etoxisclerol

• If you have a fever,
• If you have bronchial asthma,
• If you have a strong predisposition to allergies,
• If your general state of health is poor,
• If you have a chronic inflammatory bowel disease (e.g., Crohn's disease),
• If you have an excess of blood coagulation (hypercoagulability).

Other medicines and Etoxisclerol

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

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

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

If you are pregnant, your doctor should not administer Etoxisclerol 30 mg/ml to you unless it is strictly necessary, as there is not enough information available on the use of Etoxisclerol 30 mg/ml in pregnant women. Animal studies did not show any evidence of malformation.

If treatment with Etoxisclerol 30 mg/ml is necessary during breastfeeding, it is recommended to suspend it for 2-3 days, as there is no data available in humans on the passage of lauromacrogol 400 into breast milk.

Driving and using machines

No negative effects on the ability to drive and use machines have been reported due to the use of Etoxisclerol.

Etoxisclerol contains ethanol, potassium, and sodium

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

It is unlikely that the amount of alcohol in this medicine will have any noticeable effect on adults or adolescents.

The amount of alcohol in this medicine may alter the effect of other medicines.

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

If you are addicted to alcohol, consult your doctor or pharmacist before taking this medicine.

• This medicine contains less than 39 mg (1 mmol) of potassium per ampoule, so it is considered essentially "potassium-free".
• This medicine contains less than 23 mg (1 mmol) of sodium per ampoule, which is "sodium-free".

3. How to use Etoxisclerol

Etoxisclerol is a medicine whose administration must be performed by a doctor, and it is up to the doctor to know and choose the most convenient dosage and technique in each case.

-Sclerosing treatment of varices

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

Depending on the size of the varice to be treated and the individual situation of each patient, your 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, a maximum volume of 10 ml of microfoam (the volume of microfoam corresponds to the sum of the liquid and the gas) per session is recommended, 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 should 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, repeated sessions are usually necessary (on average 2 to 4).

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

-Sclerosing treatment of hemorrhoids

Dose

The dose of Etoxisclerol should not exceed 2 ml per session. Depending on the type of hemorrhoids, 1 to 4 sessions are usually necessary.

Method of administration

For sclerotherapy of hemorrhoids, Etoxisclerol should be used in liquid form.

The injection should be strictly submucosal (under the mucous membrane) and applied directly to the hemorrhoid or above it.

Use in children and adolescents

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

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, phone 91 562 04 20, indicating the medicine and the amount ingested.

-Sclerosing treatment of varices

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

-Sclerosing treatment of hemorrhoids

Overdose can cause local tissue death (necrosis), possibly extending to tissue near the hemorrhoid.

4. Possible side effects

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

In this section, we inform you about the adverse reactions that have been reported in association with the widespread use of the active substance. In some cases, these reactions were annoying but, in most cases, only temporary. As 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 the exact frequencies or establish a clear causal relationship with the drug in each case. However, a reasonable estimate can be made based on long-term experience.

-Sclerosing treatment of varices

Local side effects (e.g., necrosis) have been observed, especially in the skin and tissue near the varice (and, in rare cases, in the nerves), when treating varices of the legs after accidental injections into tissue near the varices. The risk increases when the concentration and volume of Etoxisclerol 30 mg/ml increase.

The following side 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 spots (hyperpigmentation), skin bleeding (ecchymosis), pain at the injection site (short-term), thrombosis at the injection site (local intravascular blood clots).

• Uncommon (may affect up to 1 in 100 people):venous inflammation (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 disease you have at the same time), pain in the limbs.

• Very rare (may affect up to 1 in 10,000 people):anaphylactic shock (severe and sudden allergic reaction, whose symptoms are difficulty breathing, dizziness, drop in blood pressure), angioedema (whose symptoms include sudden swelling, especially in the face, e.g., 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 (oral hypoesthesia), loss of consciousness, confusion, central speech disorder (aphasia), difficulty controlling movements (ataxia), dizziness, visual disturbances (rare when using sclerosing treatment with microfoam), heart attack (cardiac arrest), broken heart syndrome (stress cardiomyopathy), rapid or irregular heartbeats (palpitations), abnormal heart rate, pulmonary artery obstruction (pulmonary embolism), fainting (vasovagal syncope), circulatory collapse, inflammation of the blood vessel wall (vasculitis), difficulty breathing (dyspnea), feeling 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 malaise, abnormal blood pressure.

-Sclerosing treatment of hemorrhoids

Local adverse reactions such as burning, pain, discomfort, and feeling of pressure have been observed when treating hemorrhoids during and after injection, especially when they are located in the upper left region (prostatic region) of the anus. These reactions are temporary and can last from 2-3 days in rare cases.

Sclerosing treatment of hemorrhoids is painless if the correct technique is used, as there are no sensitive nerve fibers in the injection area.

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

• Frequent (may affect up to 1 in 10 people):burning sensation of the mucosa at the injection site, pain at the injection site, discomfort at the injection site, feeling of pressure.

• Uncommon (may affect up to 1 in 100 people):inflammation of the anus and/or rectum (proctitis), itching of the skin around the anus (anal pruritus), allergic skin inflammation (allergic dermatitis), contact urticaria, skin reactions, tissue hardening.

• Rare (may affect up to 1 in 1,000 people):local tissue death (necrosis), rarely with extension to tissue near the hemorrhoid, bleeding at the injection site, thrombosis at the injection site (intrahemorrhoidal).

• Very rare (may affect up to 1 in 10,000 people):anaphylactic shock (severe and sudden allergic reaction, whose symptoms are difficulty breathing, dizziness, drop in blood pressure), angioedema (whose symptoms include sudden swelling, especially in the face, e.g., eyelids, lips, or larynx), generalized urticaria, asthma (asthmatic crisis), loss of consciousness, confusion, dizziness, rapid or irregular heartbeats (palpitations), fainting (vasovagal syncope), circulatory collapse, nausea, erectile dysfunction, fever, abnormal blood pressure.

Reporting of side effects

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

5. Storage of Etoxisclerol

This medicine does not require any special storage temperature.

Keep this medicineout of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton, after EXP. The expiry date is the last day of the month shown.

Medicines should not be disposed of via wastewater or household waste. Dispose of the packaging and any unused medicine in the pharmacy's SIGRE point. If you are unsure, ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Contents of the pack and other information

Composition of Etoxisclerol 30 mg/ml

• The active substance is lauromacrogol 400.

Each ml of injectable solution contains 30 mg of lauromacrogol 400.

Each 2 ml ampoule of injectable solution contains 60 mg of lauromacrogol 400.

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

Appearance of the product and contents of the pack

Etoxisclerol is a clear solution with a slight yellowish-green color. It is presented as an injectable solution in a pack containing 5 ampoules of 2 ml each.

Other presentations

• Etoxisclerol 5 mg/ml injectable solution. Pack containing 5 ampoules of 2 ml each.
• Etoxisclerol 10 mg/ml injectable solution. Pack containing 5 ampoules of 2 ml each.
• Etoxisclerol 20 mg/ml injectable solution. Pack containing 5 ampoules of 2 ml each.

Marketing authorization holder and manufacturer

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 marketing authorization holder:

FERRER FARMA, S.A.

Av. Diagonal 549 5th Floor,

08029 Barcelona (Spain)

Date of the last revision of this prospectus:June 2023

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

This information is intended solely for healthcare professionals

For more information, see the Technical Sheet.

Important precautions for use

-Sclerosing treatment of varices

• Etoxisclerol should only be administered by a healthcare professional experienced in venous anatomy and in the diagnosis and treatment of diseases affecting the venous system and who is 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 may be initiated.
• Due to the risk of product, bubbles, or particles circulating in the right heart, the presence of a right-to-left communication (e.g., 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 look for a right-to-left communication (e.g., patent foramen ovale) before sclerotherapy.
• In asymptomatic patients but with a known right-to-left communication (e.g., patent foramen ovale), it is recommended to use smaller volumes and avoid the Valsalva maneuver in the minutes following the injection.
• Use smaller volumes in patients with a history of migraine.
• Severe local adverse effects, such as tissue necrosis, can occur after extravasation; therefore, great care should be taken in the placement of the intravenous needle, and it is essential to use the minimum effective volume at each injection site.
• Sclerosing agents should never be injected intra-arterially, as severe necrosis may occur, which may require amputation. In the event of an accident, immediate surgical vascular treatment should be sought.
• The use of any type of sclerosing agent in the facial area should be strictly evaluated, as intravascular injections can lead to negative pressure in the arteries and cause irreversible vision loss.
• In some parts of the body, such as the feet or the maleolar region, the risk of inadvertently infiltrating the interior of the artery may be increased. Therefore, only small amounts should be used, and at low concentrations, with special care during this type of treatment.
• When treating larger saphenous veins, the microfoam injection is 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 dorsal flexion of the ankle joint.
• When using Etoxisclerol in microfoam form, it is recommended to use disposable syringes with low silicon content, as this guarantees better foam quality.

-Sclerosing treatment of hemorrhoids

• When treating hemorrhoids, care should be taken not to damage the internal anal sphincter muscle to prevent incontinence problems.
• For the treatment of hemorrhoids in the 11 o'clock position in men, due to the proximity to other structures (urethra and prostate), the amount injected should not exceed 0.5 ml of Etoxisclerol 30 mg/ml.

Posology

-Sclerosing treatment of varices

Single and daily dose posology

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 is recommended, regardless of the patient's body weight and the concentration of lauromacrogol 400. Larger volumes of microfoam are applicable subject to an individual benefit-risk assessment. 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 30 mg/ml in liquid form for the sclerotherapy of medium and large varicose veins, and depending on the length of the segment to be treated, several injections can be administered with a maximum of 2 ml of liquid per injection.

When using Etoxisclerol 30 mg/ml in microfoam, up to 4 ml can be injected per puncture for the treatment of the smaller saphenous vein, and up to 6 ml for the treatment of the larger saphenous vein.

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, repeated sessions (on average 2 to 4) are usually necessary.

Pediatric population

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

Method of administration

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

Regardless of the mode of venous puncture (in a standing patient with only a cannula or in a seated patient with a syringe ready for injection), the injections are normally performed in a 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 can be placed horizontally or elevated approximately 30-45° above the horizontal for injection. The injection of the microfoam should ideally be administered under ultrasound guidance. Direct puncture and injection into non-visible veins should be guided by duplex ultrasound. The needle should not be smaller than 25G.

The sclerosing agent must be administered intravenously in small aliquots at multiple points of the vein to be treated, either in liquid or microfoam form. 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 sclerosing agent 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 physician adequately trained in the correct generation and administration of microfoam. The preparation of the microfoam is described in section 6.6 of the Technical Sheet. Most techniques consist of mixing the sclerosing agent and gas (e.g., sterile air) by performing repeated transfers through 2 connected syringes.

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

A strictly aseptic technique should be maintained during the handling of Etoxisclerol.

Compression treatment after Etoxisclerol injection

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

After sclerosing 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 the injection.

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

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

Thrombi may occasionally appear, which are eliminated by incision and evacuation of the thrombus.

-Sclerosing treatment of hemorrhoids

• For the sclerotherapy of hemorrhoids, Etoxisclerol 30 mg/ml in liquid form should be used.
• During a treatment session, no more than a total of 2 ml of Etoxisclerol 30 mg/ml should be administered. Depending on the results, a maximum of 1 ml per hemorrhoid can be administered. For the treatment of hemorrhoids in the 11 o'clock position in men, the amount injected should not exceed 0.5 ml. Depending on the type of hemorrhoids, 1 to 4 sessions may be necessary. The injection should be strictly submucosal and applied directly to the hemorrhoid or above (cranial to) it in the tissue surrounding the hemorrhoid's nutrient vessels.