Etoxisclerol 30 mg/ml solution for injection

Patient Information Leaflet

Introduction

Patient Information Leaflet

Etoxisclerol 30 mg/ml injectable solution

Lauromacrogol 400

Read the entire leaflet carefully before you start using this medicine, as it contains important information for you.

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

Package leaflet contents

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

1. What Etoxisclerol is and what it is used for

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

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

• Varicose veins,
• Telangiectasias (spider veins),
• Hemorrhoids.

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

Do not use Etoxisclerol for sclerotherapy of varicose veins

• If you are allergic to lauromacrogol 400 or any of the other components of this medicine (listed in section 6),
• If you have a severe acute systemic illness (affecting the whole body) (especially in untreated patients),
• If you must remain in bed or are unable to walk,
• If you have severe arterial circulation disorders (arterial occlusive disease, Fontaine stages III and IV),
• If you have a vascular occlusion due to a thrombus or blood clot (thromboembolic diseases),
• If you are at high risk of vascular occlusions (thrombosis), for example, patients with hereditary predisposition to form 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 sclerotherapy of varicose veins with microfoam

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

Do not use Etoxisclerol in the sclerosing treatment of haemorrhoids

• If you are allergic to lauromacrogol 400 or to any of the other components of this medicine (listed in section 6),
• If you have a severe acute 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 sclerotherapy treatment of varicose veins

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

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

• If you have a fever,
• If you suffer from respiratory distress attacks (bronchial asthma),
• If you have a strong tendency towards allergies,
• If your general health condition is poor,
• If you are to undergo sclerotherapy treatment for spider veins: in patients with arterial circulation disorders (arterial occlusive diseases, Fontaine stage II),
• If you have swollen legs due to fluid accumulation (edema) that cannot be managed with compression,
• If you have inflammatory skin disease in the area to be treated,
• If you have symptoms of occlusion in the smaller blood vessels, for example due to diabetes (microangiopathy) and impaired sensitivity (neuropathy),
• If you have reduced mobility,
• If you frequently suffer from migraines.

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

• If you have a known opening in the atrial septum of the heart, even if it causes no signs of disease or is not accompanied by any symptoms (known as asymptomatic patent foramen ovale),
• If you have a history of visual disturbances (visual or neurological symptoms) following a previous sclerotherapy treatment with microfoam.

Warnings and precautions for sclerotherapy treatment of hemorrhoids

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

• If you have fever,
• If you suffer from respiratory distress attacks (bronchial asthma),
• If you have a strong tendency towards allergies,
• If your general health condition is poor,
• If you have a chronic inflammatory bowel disease (e.g. Crohn's disease),
• If you have excessive blood coagulation (hypercoagulability).

Other medicines and Etoxisclerol

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

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

Pregnancy, lactation and fertility

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

If you are pregnant, your doctor should not administer Etoxisclerol 30 mg/ml to you unless strictly necessary, as there is insufficient information regarding the use of Etoxisclerol 30 mg/ml in pregnant women. Animal studies showed no evidence of malformations.

If treatment with Etoxisclerol 30 mg/ml is required during breastfeeding, it is recommended to discontinue breastfeeding for 2–3 days, as there are no human data available on the passage of lauromacrogol 400 into breast milk.

Driving and operating machinery

No adverse effects on the ability to drive and operate machinery are known 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, 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 contained in this medicine will have any noticeable effect in adults or adolescents.

The amount of alcohol contained 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 and is therefore considered essentially “potassium-free”.
• This medicine contains less than 23 mg (1 mmol) of sodium per ampoule, which means it is “sodium-free”.

3. How to use Etoxisclerol l

Etoxisclerol is a medication whose administration must be performed by a physician; therefore, it is the physician's responsibility to determine and select the most appropriate dosage and technique in each individual case.

-Sclerotherapy of varicose veins

Etoxisclerol can be used either in liquid form or as microfoam (standardized, homogeneous, viscous microfoam with fine bubbles).

Depending on the size of the varicose vein to be treated and the individual condition of each patient, your doctor will decide which treatment to administer. 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 is recommended per session (the volume of microfoam corresponds to the sum of the liquid plus the gas), regardless of the patient's body weight and the concentration of lauromacrogol 400.

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

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

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

-Sclerotherapy Treatment for Hemorrhoids

Dosing

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

Administration Method

For hemorrhoid sclerotherapy, Etoxisclerol should be used in liquid form.

The injection must be strictly submucosal (under the mucous membrane) and administered directly into or just above the hemorrhoid.

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 or pharmacist immediately or call the Toxicology Information Service at telephone number 91 562 04 20, indicating the medication and the amount ingested.

-Sclerotherapy of varicose veins

Overdose may cause local tissue death (necrosis), especially after injection into tissue adjacent to the varicosity.

-Sclerotherapy treatment of hemorrhoids

Overdose may cause local tissue death (necrosis), possibly extending to the tissue adjacent to the hemorrhoid.

4. Possible adverse effects

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

This section provides information on adverse reactions that have been reported in association with the widespread use of the active substance. In some cases, these reactions were bothersome, but in most cases, they were only temporary. Since many of these reports were spontaneous, lacking reference to a specific patient population or a control group, it is not possible to precisely calculate frequencies or establish a definite causal relationship to drug exposure in each individual case. However, a reasonable estimation can be made based on long-term experience.

-Sclerotherapy of varicose veins

Local adverse effects (e.g., necrosis) have been observed, particularly in the skin and tissue adjacent to the varicose vein (and, rarely, in nerves), following accidental injection into the surrounding tissue during treatment of leg varicose veins. The risk increases with higher concentrations and larger volumes of Etoxisclerol 30.

The following adverse reactions have been observed at the frequencies described below:

• Common (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 intravaricose blood clots).

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

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

• Very rare (may affect up to 1 in 10,000 people): anaphylactic shock (severe and sudden allergic reaction, with symptoms such as difficulty breathing, dizziness, drop in blood pressure), angioedema (symptoms include sudden swelling, especially of the face, e.g., eyelids, lips, or larynx), generalized urticaria, asthma (asthmatic attack), stroke (cerebrovascular accident), weakness causing loss of mobility in part of the body (hemiparesis), headache, migraine (rare when using sclerotherapy with microfoam), local sensory disturbances (local paresthesia), reduced sensitivity or sensations in the mouth (oral hypoesthesia), loss of consciousness, confusion, centrally-originated speech disorder (aphasia), difficulty controlling movements (ataxia), dizziness, visual disturbances (rare when using sclerotherapy with microfoam), heart attack (cardiac arrest), broken heart syndrome (stress cardiomyopathy), rapid or irregular heartbeat (palpitations), abnormal heart rate, blockage of the pulmonary artery (pulmonary embolism), fainting (vasovagal syncope), circulatory collapse, inflammation of blood vessel walls (vasculitis), difficulty breathing (dyspnea), sensation of chest pressure, cough, taste disturbances, nausea, vomiting, excessive hair growth (hypertrichosis) in the treated area, fever, hot flushes, unusual weakness (asthenia), general malaise, abnormal blood pressure.

-Sclerotherapy treatment of haemorrhoids

Local adverse reactions such as burning, pain, discomfort, and sensation of pressure have been observed during and after injection treatment of haemorrhoids, particularly when located in the upper left (prostatic region) of the anus. These reactions are temporary in nature and may last for 2–3 days, in rare cases.

Sclerotherapy treatment of haemorrhoids is painless when the appropriate technique is used, as there are no sensitive nerve fibres in the injection area.

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

• Frequent (may affect up to 1 in 10 people): mucosal burning sensation at the injection site, pain at the injection site, discomfort at the injection site, sensation 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 extending to tissue adjacent to the haemorrhoid, bleeding at the injection site, thrombosis at the injection site (intrahaemorrhoidal).

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

Reporting of adverse effects

If you experience any adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Etoxiscleroll

This medicine does not require any special storage temperature.

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

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

Medicines must not be disposed of via wastewater drains or household waste. Dispose of unused containers and medicines at the SIGRE collection point at your pharmacy. If you are unsure, ask your pharmacist how to properly dispose of unused containers and medicines. This will help protect the environment.

6. Contents of the container and additional information

Composition of Etoxysclerol 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 components (excipients) are: 96% ethanol, potassium dihydrogen phosphate, disodium hydrogen phosphate dihydrate, water for injections.

Appearance of the product and contents of the container

Etoxisclerol is a clear solution with a slight greenish-yellow tint. It is supplied as an injectable solution in a carton 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 20 mg/ml injectable solution. Package containing 5 ampoules of 2 ml each.

Marketing Authorization Holder and Manufacturing Responsible Party

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]

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

FERRER FARMA, S.A.

Av. Diagonal 549, 5th Floor,

08029 Barcelona (Spain)

Date of the most recent review of this leaflet: June 2023

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

This information is intended for healthcare professionals only

For more information, see the Summary of Product Characteristics.

Important precautions for use

-Sclerotherapy of varicose veins

• Etoxisclerol must be administered only 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 correct injection techniques.
• Prior to treatment, the healthcare professional must assess the patient's risk factors and inform them about the risks associated with this procedure. 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 circulation, bubbles, or particles reaching the right heart, the presence of a right-to-left shunt (e.g.: patent foramen ovale) may increase the likelihood of severe arterial adverse events. In patients with a history of migraine with aura, serious cerebrovascular events, or pulmonary hypertension, it is recommended to investigate for a right-to-left shunt (e.g.: patent foramen ovale) prior to sclerotherapy.
• In asymptomatic patients with a known right-to-left shunt (e.g.: patent foramen ovale), it is recommended to use smaller volumes and to 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 following extravasation; therefore, great care must be taken during intravenous needle placement, and it is important to use the minimum effective volume at each injection site.
• Sclerosing agents must never be injected intra-arterially, as this may cause severe necrosis potentially requiring amputation. In case of accidental intra-arterial injection, immediate vascular surgical treatment must be initiated.
• The use of any type of sclerosing agent in the facial area must be strictly evaluated, since intravascular injections may lead to negative pressure in the arteries and cause irreversible vision loss.
• In certain body areas such as the feet or malleolar region, the risk of inadvertent intra-arterial infiltration may be increased. Therefore, only small amounts and low concentrations should be used, with special care taken during this type of treatment.
• When treating great saphenous veins, the microfoam injection should be administered at a minimum distance of 8 to 10 cm from the saphenofemoral 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 joint.
• When Etoxisclerol is used in the form of microfoam, it is recommended to use disposable syringes with low silicone content, as this ensures better foam quality.

-Sclerotherapy treatment of hemorrhoids

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

Dosage

-Sclerotherapy treatment of varicose veins

Single and daily dosage

Adults and elderly

The dose of 2 mg/kg/day of lauromacrogol 400 should generally not be exceeded.

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

Concentration	Normal volume injected intravenously at appropriate puncture sites	Maximum total volume to be injected per day in a 70 kg patient	Maximum total volume to be injected per session (independent of patient weight)
	Liquid	Microfoam*	Liquid	Microfoam*
Etoxisclerol 30 mg/ml	up to 2 ml	up to 6 ml	4.6 ml	10 ml**

• The volume is the sum of the liquid plus the gas.

** In routine cases.

When Etoxisclerol 30 mg/mL is used in liquid form for sclerotherapy of medium and large varicose veins, and depending on the length of the segment to be treated, several injections may be administered, with a maximum of 2 mL of liquid per injection.

When Etoxisclerol 30 mg/mL is used as microfoam, up to 4 mL may be injected per puncture for treatment of the small saphenous vein, and up to 6 mL for treatment of the great saphenous vein.

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

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

Paediatric population

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

Method of administration

All injections must be administered intravenously; needle placement must be verified (e.g., by blood aspiration).

Regardless of the venous puncture technique (in a standing patient with a single cannula or in a seated patient with a syringe ready for injection), injections are normally performed with the leg in a horizontal position. Smooth-action disposable syringes suitable for sclerotherapy and needles of different diameters, depending on the indication, are recommended.

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

The sclerosant must be administered intravenously in small aliquots at multiple sites along the vein to be treated, either in liquid form or as microfoam. In the treatment of perforating veins, direct injection into the target vein is not recommended. The aim is to achieve optimal destruction of the vessel wall with the lowest necessary concentration of sclerosant to obtain a clinical effect. If the concentration is too high, necrosis or other adverse sequelae may occur.

Microfoam must be prepared immediately before use and administered by a physician adequately trained in the proper generation and administration of microfoam. The preparation of microfoam is described in section 6.6 of the Summary of Product Characteristics. Most techniques involve mixing the sclerosant and gas (e.g., sterile air) by repeated transfer between two syringes connected together.

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

Strict aseptic technique must be maintained during handling of Etoxisclerol.

Compression treatment following Etoxisclerol injection

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

After sclerotherapy with microfoam, the patient's leg should initially be kept 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 rather 5–10 minutes after injection.

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

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

Occasionally, thrombi may appear and may be removed by incision and thrombus evacuation.

-Sclerotherapy treatment of hemorrhoids

• For 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 is given. For the treatment of hemorrhoids located at the 11 o'clock position in men, the injected amount must not exceed 0.5 ml. Depending on the type of hemorrhoids, between 1 and 4 sessions may be required. The injection must be strictly submucosal and administered directly into the hemorrhoid or just above (cranial to) it in the tissue surrounding the hemorrhoid's feeding vessels.