Proto-Venol (Capsules) Instructions for Use

Marketing Authorization Holder

Laboratoires Bouchara-Recordati (France)

Manufactured By

Beaufour Ipsen Industrie (France)

ATC Code

C05CA54 (Troxerutin in combination with other drugs)

Active Substances

Troxerutin (Rec.INN registered by WHO)

Ginkgo biloba (BP British Pharmacopoeia)

Heptaminol (Rec.INN registered by WHO)

Dosage Form

Proto-Venol

Capsules 14 mg+300 mg+300 mg: 30 pcs.

Dosage Form, Packaging, and Composition

Capsules hard gelatin, body – yellow, cap – green; capsule contents – partially compressed powder of light yellow color.

* containing a sum of flavonol glycosides 24% and a sum of terpene lactones 6%.

Excipients: colloidal silicon dioxide, magnesium stearate, capsule shell (colorant iron oxide yellow (E172), titanium dioxide (E171), gelatin), capsule cap (colorant iron oxide yellow (E172), indigo carmine (E132), titanium dioxide (E171), gelatin).

10 pcs. – blisters (3) – cardboard packs.

Clinical-Pharmacological Group

Venotonic drug

Pharmacotherapeutic Group

Angioprotective agent

Pharmacological Action

A combined agent used for venous circulation disorders, it has an angioprotective and venotonic action due to the synergistic effect of the three active substances.

Heptaminol hydrochloride has an analeptic effect on the cardiovascular system and enhances venous return.

Ginkgo biloba leaf dry extract has an antioxidant effect, has the ability to absorb free radicals, reduces platelet aggregation and improves microcirculation. It has an anti-inflammatory effect on cells causing the inflammatory process by suppressing the production of reactive oxygen and nitrogen species.

Troxerutin has an antioxidant effect on the endothelial membrane and an inhibitory effect on lipoxygenase, which leads to a decrease in capillary permeability, reduction of edema, reduction of local cell damage caused by free radicals, and limitation of adhesion of granulocytes and platelets to the venous endothelium. As a result of the action of troxerutin at the endothelial level, venous tone improves.

This agent increases venous tone and vascular resistance, enhances venous return, and also reduces capillary permeability, has local inhibitory properties against some allogeneic mediators (histamine, bradykinin, serotonin), lysosomal enzymes and free radicals responsible for inflammation and degradation of collagen fibers.

Pharmacokinetics

Heptaminol hydrochloride

When taken orally, it is well absorbed, has high bioavailability (80-90%). C_max is reached within 1.8 h. T_1/2 from plasma is 2.5-2.7 h. There is no metabolism, excretion occurs in urine within 24 h.

Ginkgo biloba leaf dry extract

Studies were conducted for lactone terpenes (ginkgolides A and B, bilobalide). When taken orally, they are well absorbed, have high bioavailability (80-90%). C_max is reached in 1-2 h. T_1/2 from plasma is 3-4 h for ginkgolide A, 4-6 h for ginkgolide B and 2-3 h for bilobalide.

Troxerutin

When taken orally, it is well absorbed. C_max is reached in 2-3 h. It is metabolized in the liver. Metabolism is slow, excretion occurs, mainly (65%), with bile and feces.

Indications

Symptomatic therapy of manifestations of chronic lymphovenous insufficiency (such as heaviness in the legs, leg pain, paresthesia); acute hemorrhoids.

ICD codes

Dosage Regimen

Administer orally with water.

For chronic lymphovenous insufficiency, take two capsules per day. Divide the dose into two intakes, one in the morning and one in the evening.

This provides a daily dose of 28 mg Ginkgo biloba extract, 600 mg heptaminol hydrochloride, and 600 mg troxerutin.

Continue treatment for a duration of one to three months.

For acute hemorrhoids, take four capsules per day. Divide the dose into two intakes, two capsules in the morning and two in the evening.

This provides a daily dose of 56 mg Ginkgo biloba extract, 1200 mg heptaminol hydrochloride, and 1200 mg troxerutin.

The treatment course for this indication is seven days.

If symptoms persist after this short course, discontinue use and seek a proctological examination.

Do not exceed the recommended daily dose.

The use of this combination in patients under 18 years of age is contraindicated.

Adverse Reactions

Nervous system disorders very rarely – headache.

Cardiac disorders frequency unknown – arterial hypertension.

Gastrointestinal disorders very rarely – pain in the upper abdomen, epigastric discomfort, nausea, diarrhea.

Skin and subcutaneous tissue disorders very rarely – anaphylactic reactions (angioedema, urticaria, skin itching, skin rash, allergic dermatitis).

Contraindications

Hypersensitivity to the components of the combination; peptic ulcer of the stomach and duodenum in the acute phase; chronic gastritis in the acute phase; acute myocardial infarction; acute cerebrovascular accident; hyperthyroidism; simultaneous administration with MAO inhibitors; pregnancy; breastfeeding period; age under 18 years.

With caution

Chronic renal failure (with long-term use); epilepsy; blood clotting disorders; simultaneous use of drugs that reduce blood clotting; simultaneous use with CYP3A4 substrates having a low therapeutic index; simultaneous use with P-glycoprotein substrates.

Use in Pregnancy and Lactation

The use of this combination is contraindicated during pregnancy and breastfeeding.

Use in Renal Impairment

With caution: chronic renal failure (with long-term use).

Special Precautions

Heptaminol hydrochloride

Patients with severe arterial hypertension should monitor blood pressure at the beginning of treatment.

Heptaminol may cause a positive reaction during anti-doping control in athletes.

Ginkgo biloba leaf extract

Patients with a predisposition to bleeding (hemorrhagic predisposition) and receiving concomitant anticoagulant and antiplatelet therapy should consult a doctor before taking this combination. While taking it, an increased predisposition to bleeding is possible. As a precaution during planned surgery, intake should be stopped 3-4 days before the operation.

The use of this combination may contribute to the occurrence of epileptic seizures in patients suffering from epilepsy.

Acute hemorrhoids: the use of this combination does not exclude the prescription of specific treatment for other diseases of the anal area. If symptoms do not disappear during the recommended short course of treatment (7 days), a proctological examination should be performed and treatment reviewed.

In case of venous circulation disorders of the lower extremities, the greatest effectiveness of treatment is noted if the patient follows a healthy lifestyle: avoid sun exposure, heat exposure, prolonged standing, excess weight; long walks and the use of suitable compression stockings contribute to the improvement of venous circulation.

Drug Interactions

Heptaminol hydrochloride

Simultaneous use with MAO inhibitors is contraindicated due to the risk of hypertensive crisis.

Ginkgo biloba leaf extract

Concomitant use of anticoagulants ( phenprocoumon, warfarin ) or antiplatelet drugs ( clopidogrel, acetylsalicylic acid and other NSAIDs ) may alter the effect of these drugs.

A drug interaction study with talinolol showed that Ginkgo biloba may inhibit P-glycoproteins at the intestinal level. This may increase the effect of P-glycoprotein-sensitive drugs in the intestine, such as dabigatran etexilate. When using drugs containing Ginkgo biloba and dabigatran concomitantly, precautions should be taken.

A drug interaction study with nifedipine showed that concomitant administration may increase the C_max of nifedipine in plasma and in some patients reach 100%, which may cause adverse reactions associated with nifedipine intake (dizziness, facial flushing with a feeling of heat).

Concomitant use with the drug efavirenz is not recommended; the plasma concentration of efavirenz may decrease due to induction of cytochrome CYP3A4.

Use is not recommended in patients constantly taking thiazide diuretics, anticonvulsants, as well as during treatment with gentamicin .

Troxerutin

When used concomitantly, it enhances the effect of ascorbic acid on the structure and permeability of the vascular wall.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Over-the-Counter

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.