Fibrovein

Package leaflet: Information for the patient

Fibrovein, 0.2%, 0.5%, 1%, and 3%, solution for injection
Sodium tetradecyl sulfate
Please read all of this leaflet carefully before 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 further questions, please consult your doctor or nurse.
If you experience any serious adverse reactions, including any adverse reactions not listed in this leaflet, inform your doctor or nurse immediately.
See section 4.

Table of contents

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

1. What Fibrovein is and what it is used for

Fibrovein contains the active substance sodium tetradecyl sulfate.
Fibrovein is available in various concentrations and is used in the treatment of varicose veins, large, medium, and small dilated blood vessels, and spider veins.
The active substance belongs to a group of medicines known as sclerosing agents. Sclerosing agents are chemical substances which, when injected into a diseased vein, cause swelling of its inner lining and adhesion of its walls. Blood flow through the vein becomes impossible, and eventually fibrosis (scar tissue formation) occurs. After several weeks, the vein usually becomes no longer visible.
Fibrovein is intended for use in adults only.

2. Important information before using Fibrovein

When not to use Fibrovein:

• if the patient has a known allergy to sodium tetradecyl sulphate or to any of the other ingredients of this medicine (listed in section 6), or if the patient has an allergic disease;
• if the patient is unable to walk for any reason or is seriously ill;
• if the patient is at risk of developing blood clots in the venous system due to:
• inherited blood disorders, such as thrombophilia;
• use of hormonal contraceptives or hormone replacement therapy;
• significant obesity;
• smoking;
• prolonged immobilization;
• if the patient has recently experienced blood clots in superficial or deep veins, or in the lungs;
• if the patient has recently undergone surgery;
• if the patient has varicose veins caused by tumours located in the pelvic area or abdominal cavity, unless the tumour has been removed;
• if the patient has an uncontrolled systemic disease such as diabetes, hyperthyroidism, asthma, blood abnormalities, blood infection, recent skin disorders, or breathing difficulties;
• if the patient has swelling or redness of the skin, which is warm or tender to touch (phlebitis);
• if the patient has any infection;
• if the patient has a progressive tumour;
• if the patient has abnormal closure of the deep vein valves (valvular insufficiency);
• if the patient has an arterial embolism;
• if the patient has acute inflammation of the leg veins (acute phlebitis);
• if the patient has a symptomatic heart defect (only when using the sclerosant in foam form).

Warnings and precautions
Before starting treatment with Fibrovein, discuss with the doctor if:
the patient has allergies to any foods or medications, or has any other allergies; in such cases, the patient should consult the doctor, who may administer a test dose 24 hours before further treatment;
the patient has previously experienced blood clots in superficial or deep veins, or in the lungs;
the patient has a symptomatic heart defect (in case of foam sclerosant use).
the patient has migraines;
the patient has venous disorders in the legs, associated with a chronic condition causing tissue swelling (lymphedema). Fibrovein may increase local pain and inflammation for several days or weeks;
the patient has a history of pulmonary hypertension;
the patient has experienced a transient ischemic attack (TIA), stroke, or serious cerebrovascular event;
the patient has been diagnosed with arterial or venous disease (atherosclerosis);
the patient has been diagnosed with blood clots and inflammation of arteries and veins in hands and feet (Buerger's disease);
the patient has breathing difficulties controlled with medication (asthma).
Fibrovein must only be administered by a physician. According to national guidelines, it may be administered under a physician's supervision by appropriately trained medical personnel experienced in venous anatomy and familiar with proper injection techniques. Before the injection, the physician may assess the function of the patient's venous valves.
Before the procedure, the physician will ask the patient several questions about their health and provide information about potential adverse effects associated with the procedure.
During treatment
The physician will monitor the patient during and after sclerotherapy for hypersensitivity reactions (redness, itching, coughing) or neurological symptoms (visual disturbances, migraines, tingling, or numbness).
The physician will schedule a follow-up visit for the patient.
Children and adolescents
The safety and efficacy of Fibrovein in children and adolescents have not been established.
Fibrovein and other medicines
If the patient is taking hormonal contraceptives (so-called "the pill") or using hormone replacement therapy, there may be an increased risk of developing venous blood clots (see “When not to use Fibrovein”). Inform the doctor or nurse about this.
Inform the doctor or nurse about all medicines currently or recently taken, as well as any medicines the patient plans to take, including those available without a prescription.
Pregnancy and breastfeeding
The patient must inform the doctor if:
she is pregnant or suspects she may be pregnant;
she plans to become pregnant;
she is breastfeeding.
The safety of Fibrovein during pregnancy has not been established. Fibrovein should not be used in pregnant women unless clearly necessary. The doctor will decide whether Fibrovein treatment is appropriate for the patient.
It is unknown whether Fibrovein passes into breast milk. If the patient is breastfeeding, the doctor will decide whether Fibrovein is suitable for her.
Driving and operating machinery
After administration of Fibrovein, to reduce the risk of inflammation and skin discoloration, the doctor may recommend appropriate bandaging of the legs and/or wearing compression stockings, which may affect the ability to drive.
Fibrovein contains sodium, potassium, and benzyl alcohol
This medicine contains:
less than 1 mmol (23 mg) of sodium per vial/ampoule, meaning the medicine is considered "sodium-free";
less than 1 mmol (39 mg) of potassium per vial/ampoule, meaning the medicine is considered "potassium-free";
40 mg of benzyl alcohol in each 2 ml ampoule or 100 mg of benzyl alcohol in each 5 ml vial, equivalent to 20 mg/ml. Benzyl alcohol may cause allergic reactions. If the patient is pregnant, breastfeeding, or has liver or kidney disease, consult a doctor or pharmacist. This is because large amounts of benzyl alcohol may accumulate in the body, potentially causing adverse effects (so-called "metabolic acidosis").

3. How to use Fibrovein

Do not attempt to self-inject the Fibrovein medication. Treatment must always be administered by an experienced physician trained in proper injection techniques.
The treatment involves very careful and slow injection of the medication using the finest needles available into diseased veins, enabling removal of blood from them. The medication may be manually mixed using two syringes and a three-way stopcock to create a mixture with air and produce a foam, which helps remove blood from larger veins. In such cases, the medication must be administered by a physician trained in proper techniques for producing and administering the medication in foam form.
When treating invisible varicose veins of the lower limbs and for foam sclerotherapy, the procedure should be performed under ultrasound (USG) guidance.
The physician will decide which concentration of Fibrovein to use and which areas to treat. Recommended doses:
Adults and elderly patients

• 0.1 ml to 2 ml of Fibrovein per injection. The physician may administer up to a maximum of 10 ml of the three lower concentrations of Fibrovein, but no more than 4 ml when using the highest concentration.

Due to limitations regarding the maximum daily dose of sclerosing agent, it may be necessary to repeat the procedure several times.
After completion of treatment with Fibrovein, follow your physician's instructions. The physician may recommend appropriate bandaging of the legs and/or wearing compression stockings to reduce the risk of inflammation and skin discoloration.
If you have any further doubts regarding the use of this medication, consult your physician or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Serious adverse reactions may occur. Treatment with Fibrovein must be discontinued
and you should immediately contact your doctor or go to the nearest hospital emergency department
if any of the following symptoms occur:

Uncommon (may occur in up to 1 in 100 people)

• Blood clots in deep veins (deep vein thrombosis, most likely due to the underlying disease). Symptoms include pain, swelling, and tenderness in one leg (usually in the calf), severe pain in the affected area, increased warmth of the skin in the area of the clot or redness of the skin, particularly at the back of the leg below the knee.

Rare (may occur in up to 1 in 1,000 people)

• Local necrosis of skin tissue or, less frequently, nerves. Symptoms include pain, change in skin colour (redness), swelling or fluid accumulation, blisters on the skin (which may be filled with clear fluid or blood), dark red, purple or black skin discolouration, abnormal sensations (tingling, pricking, burning), numbness or loss of sensation.

Very rare (may occur in up to 1 in 10,000 people)

• The most serious adverse reaction is a severe allergic reaction (anaphylactic shock), which may cause difficulty breathing or a sudden drop in blood pressure leading to a feeling of fainting or loss of consciousness. Anaphylactic shock is rare but may be fatal; therefore, appropriate treatment must be administered immediately if it occurs.
• Arterial blockage caused by a blood clot, which may lead to:

o stroke or interruption of blood supply to the brain or eye (transient ischaemic attack).
Symptoms may include weakness, numbness or paralysis of the face, arm or leg,
usually on one side of the body, slurred or distorted speech or difficulty
understanding others, blindness in one or both eyes or double vision.
o pulmonary embolism. Symptoms may include sudden shortness of breath, sudden, sharp chest
pain which may worsen during deep breathing or coughing, rapid heartbeat or increased
respiratory rate.
To protect patients from this very rare adverse reaction, this medicine must not be used in patients
with an increased risk of developing blood clots in veins and arteries (risk of thrombosis).

• Circulatory failure. Symptoms may include feeling tired, dizziness, fainting, chest pain, shortness of breath, weakness, dizziness, vomiting and palpitations.
• Tissue necrosis following accidental intra-arterial injection. Symptoms may vary depending on the amount of medicine injected, the site of injection, and the speed of receiving medical assistance. They may range from pain without long-term damage to loss of large areas of tissue, including the foot, which may necessitate amputation of the limb.

Other adverse reactions that may occur include:
Very common (may occur in more than 1 in 10 people):

• Superficial phlebitis.

Common (may occur in up to 1 in 10 people)

• Pain or burning (short-term at the injection site);
• Skin pigmentation;
• Dilation of subcutaneous capillaries at the injection site (so-called matting).

Uncommon (may occur in up to 1 in 100 people):

• Local allergic or non-allergic skin reactions, e.g. redness, itching, rash or swelling;
• Visual disturbances;
• Migraine.

Rare (may occur in up to 1 in 1,000 people):

• Cough, shortness of breath, feeling of tightness/pressure in the chest;
• Burning, tingling, pricking or itching of the skin;
• Headache, feeling faint;
• Disorientation, dizziness, loss of consciousness.

Very rare (may occur in up to 1 in 10,000 people):

• Fever, hot flushes, red itchy skin (urticaria);
• Nausea, vomiting, diarrhoea, sensation of a swollen or enlarged tongue, dry mouth;
• Phlebitis.

Reporting of adverse reactions
If any adverse symptoms occur, including any adverse symptoms not listed
in this leaflet, inform your doctor or nurse. Adverse reactions can be
reported directly to the Department of Monitoring Adverse Drug Reactions
of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products,
Al. Jerozolimskie 181 C, 02-222 Warsaw, Tel.: +48 22 49 21 301, Fax: +48 22 49 21 309,
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps to provide more information on the safety of this medicine.

5. How to store Fibrovein

Keep this medicine out of the sight and reach of children.
There are no special requirements regarding storage temperature.

• Do not freeze.
• Store vials and ampoules in the outer carton to protect from light.
• Do not use this medicine after the expiry date stated on the cardboard box after "Expiry date (EXP)". The expiry date refers to the last day of the stated month.

For single use only. The contents of the container should be used immediately after opening.
Any unused or leftover medicine must be discarded.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Fibrovein contains
The active substance is sodium tetradecyl sulfate.
For the 0.2% concentration:
Each ml of injection solution contains 2 mg of sodium tetradecyl sulfate.
Each 5 ml vial contains 10 mg of sodium tetradecyl sulfate.
For the 0.5% concentration:
Each ml of injection solution contains 5 mg of sodium tetradecyl sulfate.
Each 2 ml ampoule contains 10 mg of sodium tetradecyl sulfate.
For the 1% concentration:
Each ml of injection solution contains 10 mg of sodium tetradecyl sulfate.
Each 2 ml ampoule contains 20 mg of sodium tetradecyl sulfate.
For the 3% concentration:
Each ml of injection solution contains 30 mg of sodium tetradecyl sulfate.
Each 2 ml ampoule contains 60 mg of sodium tetradecyl sulfate.
Each 5 ml vial contains 150 mg of sodium tetradecyl sulfate.
Other ingredients are: benzyl alcohol (20 mg/ml), disodium phosphate dodecahydrate, potassium dihydrogen phosphate, water for injections, sodium hydroxide (for pH adjustment). See section 2 "Fibrovein contains sodium and potassium".

What Fibrovein looks like and contents of the pack
Fibrovein is a solution for injection contained in glass ampoules or vials. The solution is clear, colourless, sterile, and free from visible solid particles.
Fibrovein, 0.2%: pack contains 2, 5 or 10 vials of 5 ml.
Fibrovein, 0.5%: pack contains 5 ampoules of 2 ml.
Fibrovein, 1%: pack contains 5 ampoules of 2 ml.
Fibrovein, 3%: pack contains 5 ampoules of 2 ml or 2, 5 or 10 vials of 5 ml.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer:
Marketing Authorisation Holder:
STD Pharmaceutical (Ireland) Limited
Block 1, Blanchardstown Corporate Park, Ballycoolen Road, Blanchardstown, Dublin 15
D15 AKK1, Ireland
+353 1588 6916

Manufacturer:
Medipha Sante
Les Fjords-Immeuble Oslo
19 Avenue de Norvege
91953 Courtaboeuf CEDEX
France
Chemische Fabrik Kreussler & Co. GmbH
Rheingaustrasse 87-93
65203 Wiesbaden,
Germany

This medicinal product is authorised in the European Economic Area countries under the following names:
Bulgaria, Czech Republic, France, Germany, Fibrovein
Ireland, Netherlands, Poland, Romania
Austria, Spain Veinfibro

Other sources of information:
Detailed information on this medicinal product is available on the website of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
www.urpl.gov.pl

Information intended exclusively for medical professionals:

Fibrovein, 0.2%, solution for injection
Fibrovein, 0.5%, solution for injection
Fibrovein, 1%, solution for injection
Fibrovein, 3%, solution for injection
Additional information regarding this product is available in the Summary of Product Characteristics (SmPC).

Dosage and method of administration

Dosage
The medicinal product Fibrovein is intended for intravenous use only. Depending on the size and severity of venous lesions, different concentrations are required. Spider veins should be treated only with the 0.2% concentration, and reticular veins with 0.5%. The 1% concentration is most effective for small and medium varicose veins, while the 3% concentration is indicated for larger venous lesions. The size of non-visible varicose veins should be determined under ultrasound (USG) guidance.

The sclerosing agent should be administered intravenously in small, equal portions along the course of the diseased vein. Fibrovein at concentrations of 0.2% and 0.5% should be administered in liquid form. Fibrovein at concentrations of 1% and 3% may be administered either as a liquid sclerosing agent or as a mixture of the sclerosant with air (foam formulation), according to the description provided in the table below. The goal of the procedure is to achieve optimal destruction of the vessel wall using the minimal effective concentration of sclerosant necessary for successful treatment. Excessively high concentrations of the medicinal product may lead to tissue necrosis or other complications.

Adults

*Sum of fluid and air volume
In cases where particular caution is indicated, it is recommended to perform a sensitivity test by administering to the patient 0.25 to 0.5 ml of the medicinal product Fibrovein and observing the patient for several hours, followed by administration of a second or higher dose.
The procedure often requires repetition (on average, patients require 2 to 4 additional procedures) due to the limited dose that can be applied during a single procedure. To protect the patient against an allergic reaction, at the beginning of each procedure it is recommended to administer a small test dose of the medicinal product Fibrovein.

Fibrovein, 1% and 3% solution for injection
When administering the sclerosing agent in foam form
Foam intended for treatment of larger veins can be prepared using the medicinal product Fibrovein at concentrations of 1% and 3%. The foam must be prepared immediately before administration. It must be administered to the patient by a physician adequately trained in proper techniques for producing and administering the medicinal product in foam form. Ideally, foam sclerotherapy should be performed under ultrasound (USG) guidance.

Fibrovein, 0.2% solution for injection
For spider veins, the smallest possible needles (e.g., 30 G) should be used for injection, and the medicinal product should be injected slowly to allow blood removal from the treated venous vessels. The treatment of spider veins may also employ the so-called air-block technique involving additional air injection.

Elderly patients
There are no special dosage recommendations.

Children and adolescents
The safety and efficacy of the medicinal product Fibrovein in children and adolescents have not been established. Data are lacking.

Method of administration
Below are instructions for preparing the foam. The method described is the Tessari technique. Other techniques (e.g., DSS, Easyfoam, Sterivein) may also be used.
Strict aseptic conditions must be maintained when preparing the Fibrovein medicinal product for administration.
The Fibrovein medicinal product is intended for single use and parenteral administration. After opening the vial or ampoule, the product should be used immediately, and any unused solution should be discarded.
Visual inspection for the presence of particulate matter should be performed before use. If the solution contains particulate matter, it should not be used.
Ideally, foam sclerotherapy should be performed under ultrasound (USG) control. In such cases, the product must be administered by a physician adequately trained in proper techniques for producing and administering the medicinal product in foam form.

Pharmaceutical incompatibilities
This medicinal product should not be mixed with heparin.
Do not mix the medicinal product with other medicinal products, as compatibility studies have not been conducted.

Special warnings and precautions for use
The Fibrovein medicinal product should be administered exclusively by a physician; however, if national guidelines permit, it may be administered under physician supervision by appropriately qualified medical personnel who have experience in venous system anatomy, diagnosis and treatment of venous diseases, and knowledge of proper injection techniques.
Allergic reactions, including anaphylactic shock, have been reported; therefore, the physician administering this product should be prepared to initiate anti-shock treatment.
During the procedure, the physician must have immediate access to emergency resuscitation equipment.
Due to the need for special caution, the patient should be treated in a hospital setting.
Serious local adverse reactions, including tissue necrosis, may occur following extravasation; therefore, particular care should be taken during needle insertion, and the minimal effective dose should be injected at each injection site. The solution should be injected slowly.
Particular care must be taken to avoid injecting the solution into an artery, as this may cause tissue necrosis, potentially leading to limb amputation.
Special caution is required when performing injections in the foot and above and below the malleolus (malleolus) due to the risk to one of the arteries. Compression should be applied when treating smaller veins, as the likelihood of pigmentation may be greater if blood extravasation occurs at the injection site.

Foam preparation and injection preparation
General recommendations
Foam quality depends on specific conditions:

• Concentration of the product: Foam can only be prepared using sodium tetradecyl sulfate at concentrations from 1% to 3%.
• Fluid-to-air ratio: Usually, this ratio is 1 volume of liquid to 3 to 4 volumes of air.
• Number of transfers between syringes: The physician should follow the number of transfers specified for each technique.
• Macroscopic consistency of the foam: The foam quality should be checked outside the syringe before administration. The foam should be uniform, soft, and cohesive, without visible large bubbles. If the foam contains large bubbles, it should be discarded and a new batch prepared.
• Total foam preparation time: Foam preparation should take approximately 10 seconds from the first to the last transfer of fluid between syringes.
• Maximum time between foam preparation and injection: The sclerosant foam must be used within sixty seconds after preparation. After sixty seconds, any unused foam remnants must be discarded. If needed, additional foam should be prepared.

Foam preparation (Tessari technique)
Strict aseptic conditions must be maintained during foam preparation.
To produce foam, 1 ml of liquid sclerosant is drawn into one sterile syringe and 3 ml or 4 ml of sterile air into a second sterile syringe. Air should be drawn into the syringe through a 0.2 μm sterilizing filter, ensuring its sterility. The syringes are connected using a sterile three-way tap/connector (Fig. 1). When preparing foam, Luer Lock syringes are recommended, and eye protection should be worn. Connecting a syringe with a Luer slip fitting to a three-way tap under pressure may fail, resulting in uncontrolled product leakage.
After connecting the syringes, the sclerosant/air mixture is dynamically transferred approximately 20 times between the syringes through the three-way connector until a uniform, smooth consistency foam is obtained (Figs. 2 and 3).
The syringe containing the foam is then disconnected from the connector, and intravenous injection is immediately performed using this syringe to deliver the foam into the vessel (Fig. 4).
The sclerosant foam must be used within sixty seconds of preparation. After sixty seconds, any unused foam remnants must be discarded. If needed, additional foam should be prepared.
Foam quality should be checked before administration. The foam should have a uniform consistency, be white in color, and not contain visible large bubbles to the naked eye.

Excipients
This medicinal product contains:

• less than 1 mmol (23 mg) of sodium per vial/ampoule, meaning the medicine is considered "sodium-free".
• less than 1 mmol (39 mg) of potassium per vial/ampoule, meaning the medicine is considered "potassium-free".
• 40 mg of benzyl alcohol in each 2 ml ampoule or 100 mg of benzyl alcohol in each 5 ml vial, corresponding to 20 mg/ml. Benzyl alcohol may cause allergic reactions. It may cause metabolic acidosis during pregnancy, breastfeeding, or in cases of liver or kidney disease.