Aethoxysklerol 1%

Chemische Fabrik Kreussler & Co. Aethoxysklerol 1% (amp.)
GmbH

Package leaflet: information for the user

Aethoxysklerol 1%, 10 mg/ml solution for injection
Lauromacrogol 400
Please read the entire leaflet carefully before using the medicine, because
it contains important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any questions, please consult your doctor or nurse.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or nurse. See section 4.

Contents of the leaflet

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

1. What Aethoxysklerol 1% is and what it is used for

Aethoxysklerol 1% is a sclerosing agent (sclerotherapy), intended for injection through a fine needle into the interior of a vein, causing fibrosis of its walls by means of lauromacrogol 400, previously also known as polidocanol or macrogol lauryl ether. This leads to closure and disappearance of the varicose vein. Aethoxysklerol 1% is used for sclerotherapy of varicose veins of the lower limbs.

2. Important information before using Aethoxysklerol 1%

When not to use Aethoxysklerol 1%:

• if the patient is allergic to lauromacrogol 400 or to any of the other components of this medicine (listed in section 6)
• if the patient has an acute, serious illness (particularly untreated)
• if the patient is immobilized
• if the patient has severe peripheral arterial obstructive disease (stage III and IV according to Fontaine classification)
• if the patient has thromboembolic disorders
• if the patient is at high risk of thrombosis (e.g. known hereditary predisposition to thrombosis or multiple risk factors such as use of hormonal contraceptives or hormone replacement therapy, obesity, smoking, or prolonged periods of immobilization)
• if sclerotherapy is to be performed with microfoam: if the patient has symptoms caused by a diagnosed heart defect (diagnosed, symptomatic left-to-right shunt).

Special precautions to be taken:

• in case of bronchial asthma and high predisposition to allergies
• in case of fever
• in patients with very poor general health condition
• in case of lower limb edema caused by fluid accumulation that cannot be treated with compression therapy
• in case of spider veins: arterial occlusion (stage II according to Fontaine classification)
• in case of inflammatory skin conditions at the site where sclerotherapy is to be performed
• in case of symptoms of microvascular occlusion, e.g. due to diabetes (microangiopathy), and reduced sensation (neuropathy)
• in patients with limited mobility. Sclerotherapy with microfoam:
• if the patient has a diagnosed heart defect, even if it does not cause any symptoms (diagnosed, asymptomatic left-to-right shunt)
• if the patient has previously experienced visual impairment or neurological disturbances (visual or neurological symptoms) after prior microfoam sclerotherapy.

Warnings and precautions
Before starting treatment with Aethoxysklerol 1%, consult a doctor or nurse. The medicine must not be administered intra-arterially due to the risk of causing necrosis, which may lead to amputation. In such a case, the patient must be urgently treated by a vascular surgeon. Administration of the product in the facial area may cause reversal of blood flow in the arteries and consequently lead to irreversible visual disturbances (blindness). In certain locations, e.g. in case of varicose veins around the ankle joint, the risk of accidental intra-arterial injection may be higher; therefore, only small amounts should be used, with extreme caution during administration.

Aethoxysklerol 1% and other medicines
Inform your doctor about all medicines currently or recently used, as well as any medicines you plan to use.
Tell your doctor about all recently used medicines, even those available without a prescription. The active substance lauromacrogol 400 is also used as a local analgesic (local anesthetic agent). Therefore, if used simultaneously with another anesthetic agent within 24 hours, there is a risk of increased effect, which may cause bradycardia.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult a doctor before using this medicine.
Aethoxysklerol 1% should not be used in pregnant women except in cases where it is absolutely necessary. There are no adequate data on the use of Aethoxysklerol 1% in pregnant women. Animal studies have not shown clear evidence of developmental abnormalities.
If sclerotherapy is necessary in breastfeeding women, breastfeeding should be interrupted for 2 to 3 days, as no human studies have been conducted on the passage of lauromacrogol 400 into breast milk.

Driving and operating machinery
This medicine does not affect the ability to drive or operate machinery.
The medicine contains 5% v/v ethanol (alcohol), i.e. up to 84 mg per dose, equivalent to 2 ml of beer or 0.83 ml of wine per dose. Harmful for individuals with alcohol-related disorders. This should be taken into account when administering to pregnant or breastfeeding women, children, and individuals in high-risk groups, such as patients with liver disease or epilepsy. The medicine contains less than 1 mmol (39 mg) of potassium per dose, meaning it is considered "potassium-free". The medicine contains less than 1 mmol (23 mg) of sodium per dose, meaning it is considered "sodium-free".

3. How to use Aethoxysklerol 1%

This medicine should always be used as directed by the physician. If in doubt, consult your doctor.

Aethoxysklerol 1% is used in sclerotherapy of nutritive vessels of telangiectasia (spider veins), in sclerotherapy of reticular varicose veins, and in sclerotherapy of small varicose veins.

This medicine may be administered in liquid form or as a standardized, homogeneous, microfoam, sticky microfoam.

Recommended dose

Depending on the size of the varicose veins being treated and the individual condition of each patient, the physician will decide on the appropriate treatment. In case of uncertainty, the smallest possible dose should be used.

The daily dose should not exceed 2 mg of lauromacrogol 400 per kg of body weight, meaning that for a patient weighing 70 kg, no more than 14 ml of 1% solution should be administered per day.

In routine cases, regardless of patient body weight and the concentration of lauromacrogol 400 used, the maximum recommended volume of microfoam per session and per day is 10 ml. Higher volumes of microfoam may be used following individual assessment of benefit-risk ratio.

In patients with a known history of drug hypersensitivity, during the first obliteration procedure, no more than 1 injection should be performed. In subsequent sessions, lauromacrogol 400 may be administered in several injections, not exceeding the maximum dose.

When using the medicine in sclerotherapy of central spider vein vessels, depending on the size of the area to be treated, 0.1 to 0.2 ml of Aethoxysklerol 1% solution is injected intravenously per injection.

When using the medicine in sclerotherapy of reticular varicose veins and small varicose veins, depending on the size of the varicose vein to be treated, 0.1 to 0.3 ml of Aethoxysklerol 1% solution in liquid form is injected intravenously per injection.

When using Aethoxysklerol 1% in microfoam form, for example in the treatment of feeding varicose veins (lateral veins), up to 4–6 ml of the medicine is injected per puncture. In the treatment of perforator varicose veins, 2–4 ml of the medicine is injected per puncture.

Methods of administration:

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

• Sclerotherapy of central spider veins and reticular varicose veins
  Injections of Aethoxysklerol 1% are usually performed with the leg placed in a horizontal position. Single-use syringes with smooth plunger movement are used. For telangiectasia, very fine needles (e.g., insulin needles) are used for injections. The puncture is performed tangentially, and the injection is administered slowly, maintaining the needle in an intravenous position.

• Sclerotherapy of small varicose veins
  Regardless of the method of venous puncture (in a standing patient with an infusion cannula or in a sitting patient with a syringe prepared for injection), the injection is usually performed with the leg placed horizontally.

For sclerotherapy, single-use syringes with smooth plunger movement and needles of various diameters, depending on the indication, are recommended.

During injection of the product in microfoam form, the lower limb may be placed horizontally or elevated approximately 30–45° above horizontal level. Direct puncture and injection into invisible veins should be performed under duplex ultrasound (USG) guidance. The needle should not be smaller than 25G.

Depending on the size of the varicose veins, multiple treatment sessions at one- or two-week intervals may be necessary.

• Note:
  Local thrombi that may form in some cases should be removed by puncturing and flushing them out.

• Compression after injection of Aethoxysklerol 1%
  After dressing the puncture site, a compression bandage or elastic compression stocking should be applied. After applying the dressing, the patient should walk for 30 minutes, preferably near the clinic.

Following sclerotherapy with liquid Aethoxysklerol, compression should be applied immediately after injection.

Following sclerotherapy with microfoam, the patient’s leg is initially immobilized for approximately 2–5 minutes. The Valsalva maneuver and muscle activation should be avoided during this time. Compression should not be applied immediately, but rather 5–10 minutes after injection.

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

To prevent slippage of the bandage, especially on the thigh or limbs with a conical shape, it is recommended to use an additional foam dressing underneath the proper compression dressing.

Successful sclerotherapy depends on careful and diligent post-procedural compression therapy.

Use in children
Aethoxysklerol is not indicated for use in children and adolescents.

Use of a dose higher than recommended of Aethoxysklerol 1%
If a dose higher than recommended is administered, local tissue necrosis may occur, especially after perivascular injection.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
The following adverse effects have been reported worldwide in connection with the use of lauromacrogol 400. In some cases, symptoms were troublesome but in most cases transient.
Since reports were usually based on spontaneous notifications, without reference to a defined patient population and without a control group, it is not possible to determine the exact frequency or establish a causal relationship with the administered medicine for each reported event. However, a rough estimation of frequency is possible based on long-term experience.
Local adverse effects (e.g. necrosis), particularly of the skin and deeper tissues (and rarely nerves), have been observed following accidental injection into surrounding tissue (perivascular injection). The occurrence of adverse effects is related to the dose and concentration of the administered medicine. Additionally, the following adverse effects have been observed:

Very rare (may occur in not more than 1 in 10,000 patients): anaphylactic shock, angioedema, generalized urticaria, asthma (asthma attacks), cerebral circulation disorders, hemiplegia, headache, migraine (rarely following foam sclerotherapy), local sensory disturbances (paraesthesia), reduced sensation in the oral cavity, loss of consciousness, dizziness, speech disorders, movement coordination disorders, disorientation, impaired vision (visual disturbances) (rarely following foam sclerotherapy), cardiac arrest, broken heart syndrome (stress-induced cardiomyopathy), palpitations, irregular heartbeat (tachycardia, bradycardia), pulmonary embolism, fainting, circulatory or cardiac collapse, vasculitis, dyspnea, chest discomfort (feeling of chest pressure), cough, taste disturbances, nausea, vomiting, excessive hair growth at the site of sclerotherapy, fever, sudden redness, malaise, weakness, blood pressure disturbances.

Rare (may occur in not more than 1 in 1,000 patients): deep vein thrombosis (possible association with underlying diseases), limb pain.

Uncommon (may occur in not more than 1 in 100 patients): thrombophlebitis, phlebitis, allergic dermatitis, contact urticaria, erythema, cutaneous allergic reactions, necrosis, sclerosis, swelling, nerve damage.

Common (may occur in not more than 1 in 10 patients): neovascularization (formation of blood vessels based on pre-existing vessels), haematomas, skin discoloration, bruising, pain (short-term at the site of sclerotherapy), thrombosis at the injection site (local blood clots within varicose veins).

Reporting of adverse effects
If any adverse effects occur, including any adverse effects not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse effects can be reported directly to the Department of Monitoring of Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C
02-222 Warszawa
tel.: 22 49-21-301
fax: 22 49-21-309
Website: https://smz.ezdrowie.gov.pl .
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Aethoxysklerol 1%

Keep the medicine out of the sight and reach of children.
Store below 25°C.
Do not use this medicine after the expiry date stated on the packaging.
The immediate packaging is intended for single use only.

6. Contents of the pack and other information

What Aethoxysklerol 1% contains
The active substance is lauromacrogol 400.
The other ingredients are: ethanol 96%, disodium phosphate dihydrate, potassium dihydrogen phosphate, water for injections.

What Aethoxysklerol 1% looks like and contents of the pack
The pack contains 5 ampoules. 1 ampoule of 2 ml contains 20 mg of lauromacrogol 400.

Marketing Authorisation Holder and Manufacturer
Chemische Fabrik Kreussler & Co. GmbH
Rheingaustr. 87-93
65203 Wiesbaden
Germany

For further information, please contact:
Alfasigma Polska Sp. z o.o.
Al. Jerozolimskie 96, 00-807 Warsaw
Tel: 22 824 03 64
email: [email protected]

Information intended exclusively for medical professionals:

Special warnings
Aethoxysklerol must be administered by a physician experienced in performing sclerotherapy procedures. Standardized foam for varicose vein sclerotherapy must be prepared according to instructions regarding appropriate methods.

Varicose vein sclerotherapy
Sclerosing medicinal products must never be injected into arteries, as this may cause severe tissue necrosis, potentially leading to the need for amputation. In the event of such occurrence, immediate contact with a vascular surgeon is required.

Indications for use in the facial area must be carefully evaluated due to all possible sclerosing agents, since intravascular injection may lead to reversal of pressure in the arteries and consequently to irreversible visual disturbances (blindness).

In certain body regions, such as the feet and ankles, the risk of inadvertent intra-arterial injection may be increased. Therefore, only small amounts of the medicinal product at low concentration should be used, and particular caution must be exercised during treatment.

Management of poisoning following incorrect administration of the medicinal product
a) Intra-arterial injection

1. Leave the cannula in place; if the cannula has already been removed, re-locate the puncture site
2. Inject 5 to 10 ml of local anesthetic without adrenaline
3. Administer heparin at a dose of 10,000 IU
4. Apply cotton wool and lower the ischemic limb
5. As a precaution, hospitalize the patient (vascular surgery department)

b) Perivenous injection
Depending on the amount and concentration of Aethoxysklerol injected subcutaneously, inject 5 to 10 ml of physiological saline at the injection site, mixed if possible with hyaluronidase. If the patient experiences severe pain, a local anesthetic (without adrenaline) may be administered.

Emergency management and corrective measures
Anaphylactic reactions
Anaphylactic reactions are rare but may be life-threatening. The physician providing medical care must be prepared to initiate emergency measures and have access to an appropriate emergency kit.
Treatment with β-blockers or angiotensin-converting enzyme (ACE) inhibitors may influence the course of emergency management in anaphylactic shock due to their effects on the circulatory system.