AETHOXYSKLEROL Solution for injection Ref.[27688] Active ingredients: Polidocanol

Aethoxysklerol should only be administered by healthcare professionals experienced in sclerotherapy and the required preparation techniques.

Sclerotherapy of varicose veins should be used with caution in the following situations:

• In patients with asymptomatic but known patent foramen ovale (PFO), it is recommended to use smaller volumes and avoid Valsalva manoeuvre in the minutes after injection.
• In patients that suffered from visual or neurological symptoms (e.g. migraine) after previous microfoam sclerotherapy, it is recommended that the patients should lie down for a longer time and avoid Vaslava manoeuvre in the minutes after injection. Use smaller volumes in these patients.
• Patients showing the symptoms of a fever (febrile state).
• Patients with bronchial asthma or a known strong predisposition to allergies.
• When treating telangiectasias in patients with arterial occlusive disease (Fontaine stage II).
• The presence of leg oedema if it cannot be influenced by compression.
• Inflammatory skin disease in the area of treatment.
• Patients showing symptoms of microangiopathy or neuropathy
• Patients with reduced mobility.
• Anticoagulation is not a contraindication to sclerotherapy. In general, special care should be taken in patients using anticoagulation medication.

Pre-procedure evaluation

Before treatment, the healthcare professional should investigate patient’s risk factors and inform them about the risks of the technique.

A thorough pre-procedure evaluation for valvular competency should be carried out as appropriate.

Sclerotherapy should not be undertaken if significant valvular incompetence is suspected following the evaluation.

Follow-up

The healthcare professional should see the patient again in the weeks after treatment to perform a clinical efficacy and safety evaluation. Patients should have post-treatment follow-up of sufficient duration to assess for the development of deep vein thrombosis. Adequate post-treatment compression may decrease the incidence of deep vein thrombosis.

Improper administration when treating varicose veins

Sclerosants must never be injected intra-arterially because this can cause severe necrosis which may necessitate amputation. A vascular surgeon must be called in immediately if any such incident occurs.

In certain body regions such as in the foot or malleolar region, the risk of inadvertent intra-arterial injection may be increased. Therefore, in these regions only small amounts should be used in low concentrations with particular care.

Adverse effects, including tissue necrosis, may occur following extravasation, therefore it is important to exercise extreme care in intravenous needle placement and use the minimal effective volume at each injection site.

Management of local toxicity after improper administration when treating varicose veins

a) Intra-arterial injection

1. Leave cannula in place; if already removed, relocate the puncture site and aspirate blood and the remaining sclerosing solution back into the syringe
2. Inject 5-10 ml of a local anaesthetic, without the addition of adrenaline
3. Start with anticoagulation e.g. by injection of 5,000 IU heparin or equivalents (if possible, into the affected artery; otherwise i.v.)
4. Pack the ischaemic leg in wadding and lower
5. Hospitalise the patient as a precaution (vascular surgery)

b) Extravenous injection

Depending on the quantity and concentration of Aethoxysklerol injected extravenously, inject 5 to 10 ml of physiological saline, if possible combined with hyaluronidase, at the application site. If the patient is in severe pain, a local anaesthetic (without adrenaline) may be injected.

Emergency measures and antidotes

Anaphylactic reactions

Anaphylactic reactions are very rare, but potentially life-threatening situations. The attending doctor should be prepared for emergency measures and have a suitable emergency kit available. Therapy with beta blockers or ACE (angiotensin converting enzyme) inhibitors may influence emergency procedures for anaphylactic shock because of their cardiovascular effects.

Stress cardiomyopathy and cardiac arrest

Stress cardiomyopathy (Tako Tsubo) and cardiac arrest have been very rarely reported following Aethoxysklerol sclerotherapy. Patients complaining of chest pain or discomfort during or after the procedure should be promptly investigated and monitored. All patients should also be made aware of this possible adverse event and advised to immediately seek medical advice in case of any symptoms.

Excipients with known effect

All Aethoxysklerol products contain:

• 5% (v/v) ethanol which may be harmful for those sufferng from alcoholism or undergoing treatment of alcoholism with Disulfiram. To be taken into account in pregnant or breast-feeding women, children and high risk groups such as patients with liver disease or epilepsy.
• Potassium, but less than 1 mmol (39 mg) potassium per ampoule, i.e. essentially ‘potassium-free’.
• Sodium, but less than 1 mmol (23 mg) sodium per ampoule, i.e. essentially ‘sodium-free’.

Lauromacrogol 400 is a local anaesthetic. When combined with other anaesthetics, there is a risk of an additive effect of these anaesthetics on the cardiovascular system.

Pregnancy

Safety for use in pregnancy has not been established. Studies in animals showed reproductive toxicity, but no teratogenic potential (see section 5.3).

Treatment should be postponed until after childbirth.

Aethoxysklerol should be used only when clearly needed for symptomatic relief and when the potential benefits outweigh the potential hazards to the fetus.

Breast-feeding

It is not known whether lauromacrogol 400 is excreted in human milk. Caution should be exercised when used in nursing mothers. If sclerotherapy is necessary during breast-feeding, it is advisable to suspend breast-feeding for 2-3 days.

Fertility

It is not known whether lauromacrogol 400 affects fertility.

No negative effects on the ability to drive and use machines are known for Aethoxysklerol.

The most commonly reported side effects are temporary in most cases and include short-term injection site pain, injection site intravaricose blood clots and temporary skin discolouration after treatment.

Local adverse reactions (e.g. necrosis), especially of the skin and of the underlying tissue (and, in rare cases, of the nerves), were observed when treating varicose veins in the leg after inadvertent injection into the surrounding tissue (paravenous injection). The risk increases with increasing Aethoxysklerol concentrations and volumes.

The most serious side effects reported in patients receiving lauromacrogol 400 are anaphylactic shock, pulmonary embolism, cerebrovascular accident, stress cardiomyopathy (Tako Tsubo) and cardiac arrest.

The adverse events are categorised according to MedDRA (Medical Dictionary for Regulatory Activities) and listed by system organ class. The frequencies seen below estimated from published data and spontaneous reports and are defined using the following convention: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).

Immune system disorders

Very rare: anaphylactic shock, angioedema, urticaria (generalised), asthma (asthmatic attack)

Nervous system disorders

Very rare: cerebrovascular accident (stroke, transient ischaemic attack (TIA)), hemiparesis, headache, migraine, paraesthesia (local), hypoaesthesia oral, loss of consciousness, confusional state, aphasia, ataxia, dizziness.

Rare: migraine (when using sclerosing microfoam).

Eye disorders

Very rare (‘rare’ when using sclerosing microfoam): visual impairment (visual disturbance)

Cardiac disorders

Very rare: cardiac arrest, palpitations, stress cardiomyopathy (Tako Tsubo)

Vascular disorders

Common: neovascularisation, haematoma

Uncommon: thrombophlebitis superficial, phlebitis

Rare: deep vein thrombosis

Very rare: pulmonary embolism, syncope vasovagal, circulatory collapse, vasculitis

Respiratory, thoracic and mediastinal disorders

Very rare: dyspnoea, chest discomfort, cough

Gastrointestinal disorders

Very rare: dysgeusia, nausea, vomiting

Skin and subcutaneous tissue disorders

Common: skin hyperpigmentation, ecchymosis

Uncommon: dermatitis allergic, urticaria contact, skin reaction, erythema

Very rare: hypertrichosis (in the area of sclerotherapy)

Musculoskeletal and connective tissue disorders

Rare: pain in extremity

General disorders and administration site conditions

Common: injection site pain (short-term), injection site thrombosis (local intravaricose blood clots)

Uncommon: necrosis of skin and tissues, induration, swelling

Very rare: pyrexia, hot flush, asthenia, malaise

Investigations

Very rare: blood pressure abnormal, heart rate abnormal (tachycardia, bradycardia)

Injury, poisoning and procedural complications

Uncommon: nerve injury

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme.

Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.