Etoxisclerol 10 mg/ml solution for injection

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Etoxisclerol 10 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; do not give it to others, even if they have the same symptoms as you, because it could harm them.
• If you experience any adverse reactions, consult your doctor, pharmacist or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

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 substance is lauromacrogol 400.

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

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

Do not use Etoxisclerol in sclerotherapy treatment of varicose veins

• 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 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 in sclerotherapy treatment of varicose veins with microfoam

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

Warnings and precautions

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

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

• If you have fever,
• If you suffer from respiratory distress attacks (bronchial asthma),
• If you have a strong predisposition to allergies,
• If your general health condition is poor,
• If you are undergoing sclerotherapy treatment for spider veins: in patients with arterial circulation disorders (arterial occlusive disease, 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 smallest blood vessels, for example due to diabetes (microangiopathy) and impaired sensitivity (neuropathy),
• If you have reduced mobility,
• If you suffer from frequent migraines.

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

• If you have a known opening in the interatrial septum of the heart, even if it does not cause 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 symptoms or neurological symptoms) following a previous sclerotherapy treatment with microfoam.

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 anaesthetics may increase the anaesthetic effect on the cardiovascular system.

Pregnancy, lactation and fertility

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

If you are pregnant, your doctor should not administer Etoxisclerol unless strictly necessary, as there is insufficient information regarding the use of Etoxisclerol in pregnant women. Animal studies did not show any evidence of teratogenic effects.

If treatment with Etoxisclerol is necessary 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 use of machines

No adverse effects on the ability to drive and use machines are known due to the use of Etoxisclerol.

Etoxisclerol contains ethanol, potassium, and sodium

This medicine 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 medicine is equal to 2 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 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 have alcohol addiction, 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 and is therefore considered essentially "sodium-free".

3. How to use Etoxisclerol

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

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

Depending on the size of the varicose vein to be treated and the individual patient's condition, your doctor will decide which treatment approach is appropriate. In case of doubt, the lowest possible dose should be chosen. Generally, the daily dose of 2 mg/kg of lauromacrogol 400 should not be exceeded.

In routine cases, a maximum volume of 10 ml of microfoam per session is recommended (the volume of microfoam corresponds to the sum of liquid and gas), regardless of the patient's body weight or the concentration of lauromacrogol 400.

To avoid a possible allergic reaction, especially in patients with a high predisposition to hypersensitivity reactions, it is recommended to administer only a small test dose of Etoxisclerol for the first treatment. Depending on the response, further 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 treatment with Etoxisclerol, you should follow your doctor's instructions. You may be advised to wear a compression bandage or compression stockings to help reduce inflammation and skin pigmentation.

Use in children

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.

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

4. Possible adverse effects

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

This section provides information on adverse reactions reported in association with the long-term use of the active substance. In some cases, these reactions were troublesome, but in most cases, they were only temporary. Since many of these reports were spontaneous, without reference to a defined 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.

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

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

• Frequent (may affect up to 1 in 10 people): appearance of previously invisible blood vessels in the treated area (neovascularization), bruising (hematoma), skin discoloration (hyperpigmentation), skin hemorrhage (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, skin redness (erythema), localized 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 concurrent medical condition), limb pain.

• Very rare (may affect up to 1 in 10,000 people): anaphylactic shock (a severe and sudden allergic reaction, with symptoms such as difficulty breathing, dizziness, and 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 sclerosing treatment with microfoam), local sensory disturbances (local paresthesia), reduced sensitivity or sensations in the mouth (oral hypoesthesia), 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-induced 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.

Reporting of adverse reactions

If you experience any type of adverse reaction, consult your doctor or pharmacist, even if it is a possible adverse reaction not listed in this leaflet. You may also report them directly through the Spanish Pharmacovigilance System for Human Medicinal Products: https://www.notificaram.es. By reporting adverse reactions, 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 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.

Medicines should 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 have any doubts, ask your pharmacist how to properly dispose of containers and medicines you no longer need. This will help protect the environment.

6. Contents of the container and additional information

Composition of Etoxisclerol 10 mg/ml

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

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

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

Appearance of the product and contents of the pack

Etoxisclerol is a clear solution with a slight greenish-yellow tint. 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. 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.

Marketing Authorization Holder and Manufacturing Responsibility

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 latest review of this leaflet: July 2020

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

• Etoxisclerol should 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 provider must evaluate the patient's risk factors and inform the patient 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 smallest effective volume at each injection site.
• Sclerosing agents must never be injected intra-arterially, as this may cause severe necrosis that could require amputation. In the event of accidental intra-arterial injection, immediate vascular surgical treatment must be instituted.
• The use of any sclerosant agent in the facial area must be strictly evaluated, as intravascular injections may lead to retrograde arterial flow and irreversible vision loss.
• In certain body areas, such as the feet or malleolar region, the risk of inadvertent intra-arterial injection may be increased. Therefore, only small amounts and low concentrations should be used, with particular care during such treatments.
• When treating the 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 toe dorsiflexion at 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.

Single and Daily Dose Regimen

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 and gas) per session is recommended, regardless of patient body weight or concentration of lauromacrogol 400. Larger volumes of microfoam may be administered 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.

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

** In routine cases.

When Etoxisclerol 10 mg/ml is used in liquid form for sclerotherapy of reticular veins and small varicose veins, several injections may be administered depending on the length of the segment to be treated, with a maximum of 0.3 ml of liquid per injection. For sclerotherapy of central veins in telangiectasias, up to 0.2 ml of liquid may be injected per puncture.

When Etoxisclerol 10 mg/ml is used as microfoam, for example for the treatment of varicose tributary veins, up to 4–6 ml of microfoam may be injected per puncture. For the treatment of perforating veins, up to 2–4 ml may be injected per puncture.

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 during subsequent treatment sessions, provided the maximum dose is not exceeded.

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

Paediatric population

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

Administration Method

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

Regardless of the venous puncture technique (in a standing patient with only a cannula or in a seated patient with a ready syringe), injections are typically performed with the leg in a horizontal position. Smooth-action disposable syringes are recommended for sclerotherapy, along with needles of different gauges 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 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 sclerosing agent must be administered intravenously in small aliquots at multiple points 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 goal is to achieve optimal destruction of the vessel wall with the lowest concentration of sclerosant necessary for 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 with gas (e.g., sterile air) by repeated transfers between two syringes connected together.

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

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

Compression Treatment Following Etoxisclerol Injection

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

After sclerotherapy with microfoam, the patient's leg is initially 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 require incision and evacuation for removal.