Package Leaflet: Information for the User

Etoxisclerol 10 mg/ml injectable solution

Lauromacrogol 400

Read this leaflet carefully before you start using 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; do not give it 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.

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. Storage of Etoxisclerol

6. Contents of the pack and additional information

Etoxisclerol is a sclerosant whose active principle is lauromacrogol 400.

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

Do not 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 muststay in bedor 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 opening 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 a severe predisposition to allergies,
• If your general state of health is poor,
• If you are about to undergo sclerosing treatment of spider veins: in patients with arterial circulation disorders (arterial occlusive disease, Fontaine stage II),
• If you have swollen legs due to fluid accumulation (edema) and cannot be relieved by compression,
• If you have skin inflammation 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 opening 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, lactation, 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 not enough information available on the use of Etoxisclerol in pregnant women. Animal studies did not show any evidence of malformations.

If treatment with Etoxisclerol 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 to breast milk.

Driving and operating machinery

No adverse 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 medication contains 84.00 mg of alcohol (ethanol) in each 2 ml ampoule, equivalent to 5% (v/v). The amount of alcohol in one ampoule of this medication is equivalent to 2 ml 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 affect 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 an 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 essentially "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 both in liquid form and as a microfoam (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 what 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 that a maximum volume of 10 ml of microfoam (the volume of microfoam corresponds to the sum of the liquid and the gas) be administered 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, generally, repeated sessions (2 to 4 on average) are needed.

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.

Use in Children

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, phone 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.

This section informs about 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, 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 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 in the skin and tissue near the varicose vein (and, in rare cases, in nerves), when treating leg varices after accidental injections in the tissue near the same. 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):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 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), broken heart syndrome (stress cardiomyopathy), irregular or rapid 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), chest pressure sensation, 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 about possible adverse effects that do not appear in this prospectus. You can also report them directly through theSpanish System for the Pharmacovigilance of Medicines for Human Use: https://www.notificaram.es.By reporting adverse effects, you can contribute to providing more information about the safety of this medicine.

This medication does not require any special temperature for conservation.

Keepthis medicationout of 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.

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

Composition of Etoxisclerol 10 mg/ml

• The active principle is lauromacrogol 400.
• Each ml of injectable solution contains 10 mg of lauromacrogol 400.

Each ampoule of 2 ml of injectable solution contains 20 mg of lauromacrogol 400.

• The other components (excipients) are: ethanol 96%, dihydrogen phosphate of potassium, dihydrate of sodium hydrogen phosphate, 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 20 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)

Last review date of this prospectus: July 2020

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/

For more information, see the Technical Data Sheet.

Important precautions for use

• Etoxisclerolshould be administered only 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 a 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, therefore, 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 it may cause severe necrosis that may require amputation. In case 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 into 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 joint.
• When using Etoxisclerol in the form of microfoam, it is recommended to use disposable syringes with low silicone content, as it 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 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 10 mg/ml in liquid form for sclerotherapy of reticular veins and small varices, and depending on the length of the segment to be treated, several injections with a maximum of 0.3 ml of liquid per injection may be administered. For sclerotherapy of central telangiectasias, up to 0.2 ml of liquid per puncture may be injected.

When using Etoxisclerol 10 mg/ml in microfoam, for example, for the treatment of varicose veins, up to 4-6 ml of microfoam per puncture may be injected. For the treatment of perforating veins, up to 2-4 ml per puncture 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 often required.

Pediatric population

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

Administration form

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

Regardless of the venous puncture technique (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.

For telangiectasias, very fine needles (e.g. insulin needles) are used. The puncture is performed tangentially and the injection is administered slowly.

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 an ultrasound.The puncture should not be performed with a needle smaller than 25G.

The sclerosant must be administered intravenously 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 main 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 the Technical Data Sheet.The majority of 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 ofEtoxisclerol.

Treatment with compression after injection of Etoxisclerol

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.