Normoven 1000

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT NORMOVEN 1000 (NORMOVEN 1000)

Composition:

Active substance: micronized purified flavonoid fraction (MPFF);

1 tablet contains 1000 mg of micronized purified flavonoid fraction, in the form of diosmin and hesperidin (the term "hesperidin" refers to a mixture of flavonoids: hesperidin, isorhoifolin, linarin, diosmetin) in a ratio of 9:1;

Excipients: microcrystalline cellulose, gelatin, magnesium stearate, sodium starch glycolate (type A), talc, purified water;

Coating: sodium lauryl sulfate; glycerin; Opadry II Orange film-coating mixture: (hypromellose (hydroxypropylmethylcellulose); lactose monohydrate; titanium dioxide (E 171); polyethylene glycol (macrogol); iron oxide yellow (E 172); iron oxide red (E 172)).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: oval-shaped, biconvex tablets, film-coated, ranging in color from light orange to light brown, with a score line on one side.

Pharmacotherapeutic group. Angioprotectives. Capillary-stabilizing agents.

Bioflavonoids. Diosmin, combinations. ATC code C05CA53.

Pharmacological properties.

Pharmacodynamics.

The medicinal product exerts a venotonic and angioprotective effect, reduces venous distensibility and venous stasis, improves microcirculation, decreases capillary permeability and increases their resistance, as well as enhances lymphatic drainage by increasing lymphatic outflow.

It is known that experimental studies in animals using the "ischemia/reperfusion" model have shown that administration of micronized purified flavonoid fraction is more effective in reducing vascular wall permeability and plasma extravasation compared to plain diosmin. This result is due to the protective effect on microcirculation provided by flavonoids such as hesperidin, diosmetin, linarin, and isorhoifolin, which are components of the fraction expressed as hesperidin. The reduction in vascular wall permeability and plasma extravasation observed with the use of micronized purified flavonoid fraction is more pronounced than that observed with plain diosmin or each flavonoid component administered separately. The aforementioned pharmacological properties have been confirmed in studies using methods capable of assessing the drug's impact on venous hemodynamics.

Dose–response relationship. A statistically significant dose-dependent effect of the medicinal product was established according to the following venous plethysmographic parameters: venous volume, venous distensibility, and venous outflow time. The optimal dose–response relationship was achieved with a daily dose of 1000 mg.

Venotonic activity. The drug increases venous tone: venous occlusion plethysmography demonstrated a reduction in venous outflow time.

Microcirculatory activity. It is known that studies have demonstrated a statistically significant difference between the drug and placebo. In patients with symptoms of capillary fragility, treatment increased capillary resistance, as determined by angio-stereometry.

The medicinal product also reduces leukocyte–endothelium interaction and leukocyte adhesion in postcapillary venules. This reduces the damaging effects of inflammatory mediators on venous walls and venous valve leaflets.

In clinical practice. It is known that studies have demonstrated the therapeutic efficacy of the drug in phlebology for the treatment of functional and organic chronic venous insufficiency of the lower limbs, as well as in proctology for the treatment of hemorrhoids.

Pharmacokinetics.

Elimination of the active substance occurs primarily via feces. On average, 14% of the administered dose is excreted in urine.

The elimination half-life is 11 hours.

The drug is actively metabolized, as confirmed by the presence of various phenolic acids in urine.

Clinical characteristics.

Indications.

Symptomatic treatment of venous and lymphatic insufficiency (leg heaviness, pain, nocturnal cramps, edema, trophic disorders, including varicose ulcers).

Symptomatic treatment of hemorrhoids.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients.

Interaction with other medicinal products and other forms of interaction.

No studies on interactions have been conducted. During post-marketing use of the drug, there have been no reports of any clinically significant interactions with medicinal products.

Special precautions for use

The use of this medicinal product in acute hemorrhoids does not replace specific therapy and does not preclude the treatment of other proctological diseases. If symptoms do not rapidly resolve during a short course of treatment, a proctological examination should be performed and the therapy re-evaluated.

In venous circulatory disorders, therapy combined with adherence to the following lifestyle recommendations is more effective:

• Avoid excessive sun exposure, prolonged standing, and excess body weight;
• Walk regularly and, in some cases, wear special compression stockings to improve circulation.

The medicinal product contains lactose and therefore should not be used in patients with rare hereditary forms of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption syndrome.

Use during pregnancy or breastfeeding

Pregnancy. Data on the use of micronized purified flavonoid fraction in pregnant women are lacking or limited in quantity.

Animal studies have not demonstrated a teratogenic effect.

As a precautionary measure, it is advisable to avoid using this medicinal product during pregnancy.

Breastfeeding. It is unknown whether the active substance or its metabolites pass into breast milk.

Risk to newborns/infants cannot be excluded.

The decision on whether to discontinue breastfeeding or to discontinue/abstain from treatment with this medicinal product should be made taking into account the benefit of breastfeeding for the child and the benefit of treatment for the mother.

Fertility. Reproductive toxicity studies in animals showed no effect on fertility.

Ability to affect reaction speed when driving or operating machinery

Studies on the effect of the flavonoid fraction on the ability to drive or operate machinery have not been conducted. However, based on the overall safety profile of the flavonoid fraction, Normoven 1000 has no effect or a negligible effect on this ability. If adverse reactions occur (see section "Adverse reactions"), caution is necessary.

Dosage and Administration.

For oral use. Intended for adult patients.

Venous-lymphatic insufficiency

The recommended dose is 1 tablet daily in the morning taken with food.

Haemorrhoidal disease

Treatment of acute haemorrhoidal attacks: 3 tablets daily for 4 days, followed by 2 tablets daily for the next 3 days. Take with food. The daily dose should be divided into 2–3 doses. Maintenance therapy: 1 tablet daily.

Duration of treatment

The duration of therapy should be determined by the physician depending on the indication and course of the disease.

Children

There are no data on the use of Normoven 1000 in children.

Overdose.

Symptoms: there is limited information on cases of overdose with this medicinal product. The most commonly reported adverse reactions in overdose were gastrointestinal reactions (such as diarrhoea, nausea, abdominal pain) and skin reactions (such as pruritus, rash).

Treatment: management of overdose should consist of symptomatic treatment.

Adverse Reactions

When using micronized purified flavonoid fraction, moderate-intensity adverse effects were observed, mainly affecting the gastrointestinal tract (diarrhea, dyspepsia, nausea, vomiting).

The adverse reactions listed below have been reported and are categorized by frequency as follows: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10,000, < 1/1000); very rare (< 1/10,000); frequency not known (cannot be estimated from the available data).

Nervous system disorders:
Rare: dizziness, headache, malaise.

Gastrointestinal disorders:
Common: diarrhea, dyspepsia, nausea, vomiting;
Uncommon: colitis;
Frequency not known*: abdominal pain.

Skin and subcutaneous tissue disorders:
Rare: pruritus, rash, urticaria;
Frequency not known*: isolated facial swelling, swelling of lips, eyelids, and in exceptional cases – Quincke's edema (angioedema).

Reporting of suspected adverse reactions.

Reporting of suspected adverse reactions after drug registration is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy via the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua

Shelf life. 3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25°C.

Keep out of reach and sight of children.

Packaging.

10 tablets in a blister; 3 blisters per carton.

10 tablets in a blister; 6 blisters per carton.

Availability. Over-the-counter (without prescription).

Manufacturer: JSC "KYIV VITAMIN PLANT".

Manufacturer's address and location of business operations:

38 Kopilivska Street, Kyiv, 04073, Ukraine.

Web-site: www.vitamin.com.ua