NAME OF THE MEDICINAL PRODUCT

Lyoton 1000 gel 1000 IU/g

Lioton 1000 Gel 1000 IU/g

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

1 g of gel contains 1000 IU of heparin sodium.

Excipients with known action:

methyl parahydroxybenzoate and propyl parahydroxybenzoate as preservatives.

Bitter orange blossom oil and lavender oil as fragrances containing citral, citronellol, coumarin, d-limonene, farnesol, geraniol and linalool.

For the full list of excipients, see section 6.1.

3. MEDICINAL FORM

Gel

4. CLINICAL DATA

Therapeutic indications

Treatment of superficial vein diseases such as varicose syndromes and related complications: phlebothrombosis, thrombophlebitis, superficial periphlebitis, varicose ulcers.

Postoperative varicophlebitis, a condition after saphenectomy.

Traumas and contusions, infiltrates and localized edema, subcutaneous hematomas. Injuries and sprains of the muscle-tendon and capsule-ligament structures.

4.2 Dosage and method of administration

Application to the skin: one to three times a day, 3-10 cm of gel is applied to the affected skin area and gently rubbed.

Pediatric population

Due to limited experience and lack of data, it should not be used in children.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in point 6.1.

Lioton 1000 gel should not be used on areas with bleeding, on open wounds or on mucous membranes, as well as on infected areas in the presence of purulent processes.

4.4 Special warnings and precautions for use

The use of Lioton 1000 gel in the presence of hemorrhages should be considered carefully. This medicine contains methyl parahydroxybenzoate and propyl parahydroxybenzoate as preservatives. This can cause allergic reactions (possibly the delayed type).

This medicine contains flavors with citral, citronellol, coumarin, d-limonene, farnesol,

geraniol and linalool. Citral, citronellol, coumarin, d-limonene, farnesol, geraniol and linalool can cause allergic reactions.

4.5 Interaction with other medicinal products and other forms of interaction

Administration of heparin may further increase prothrombin time in patients receiving oral anticoagulants.

4.6 Fertility, pregnancy and breastfeeding

There are no specific data on the use of the medicinal product during pregnancy and breastfeeding.

4.7 Effects on the ability to drive and use machines

Lyoton 1000 gel does not affect the ability to drive and operate machinery.

4.8 Adverse drug reactions

Allergic reactions to heparin when applied to the skin are very rare. However, in isolated cases, hypersensitivity reactions such as reddening of the skin and itching may occur, which usually disappear quickly after discontinuation of treatment.

Reporting of suspected adverse reactions

Post-marketing reporting of suspected adverse reactions is important. This allows continued monitoring of the benefit/risk ratio of the medicinal product. Healthcare professionals are required to report any suspected adverse reaction through a national reporting system:

Executive Agency for Medicines, 8 Damyan Gruev Street

1303 Sofia

Phone: +35 928903417

website: www.bda.bg

4.9 Overdose

To date, no cases of overdose have been described. In case of occurrence, the effect of heparin can be neutralized with protamine sulfate.

5. PHARMACOLOGICAL DATA

Pharmacodynamic properties

Pharmacotherapeutic group: Antivaricose agents, heparin and heparinoids for local use, ATC C05BA03.

Experimental pharmacological data indicate that Lioton 1000 gel applied to the skin has significant anti-edematous, anti-granulomatous, anti-exudative, anti-inflammatory and anticoagulant activity.

5.2 Pharmacokinetic properties

Pharmacokinetic studies in rats have shown that heparin is available in plasma for up to 24 hours after administration, with peak levels reached after 8 hours. Excretion is mainly through the kidneys. Application on the skin of Lioton 1000 gel does not cause

any changes in blood coagulation parameters in humans.

5.3 Preclinical safety data

Short-term toxicological studies in mice and rats have shown that Lioton 1000 gel has very low subcutaneous (sc) and intraperitoneal (ip) toxicity (LD50 2000 mg/kg). Subchronic and chronic treatment by application to the skin has also shown good local and systemic tolerability of the medicinal product.

6. PHARMACEUTICAL DATA

List of excipients

Carbomer 940

Methyl parahydroxybenzoate Propyl parahydroxybenzoate Ethanol

Bitter orange blossom oil (contains linalool, d-limonene, geraniol, citral, citronellol and farnesol)

Lavender oil (contains linalool, d-limonene, geraniol and coumarin) Trolamine

Purified water

6.2 Incompatibilities

Not applicable.

6.3 Expiry Date

Five years

6.4 Special storage conditions

To be stored below 25 °C.

6.5 Type and contents of packaging

Cardboard box containing a tube of 30 g, 50 g or 100 g of gel. Not all types of packaging can be put on sale.

6.6 Special precautions for disposal

There are no special disposal requirements.

Any unused medicinal product or waste materials derived from it should be disposed of in accordance with local requirements.

7. HOLDER OF THE USE PERMIT

A.MENARINI Industrie Farmaceutiche Riunite srl Via Sette Santi 3

Florence, Italy

8. USE PERMIT NUMBER

9600341