Instructions for use Flebaven 500 film-coated tablets 500 mg blister No. 60
Composition
active ingredient: diosmin;
1 tablet contains 500 mg of micronized diosmin;
Excipients: polyvinyl alcohol, croscarmellose sodium, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: brownish-yellow, biconvex, film-coated, capsule-shaped tablets.
Pharmacotherapeutic group
Angioprotectors. Bioflavonoids. Capillary stabilizing agents. Diosmin. ATX code C05C A03.
Pharmacological properties
Pharmacodynamics
Mechanism of action
Venotonic activity
Diosmin reduces venous distensibility and reduces venous stasis. Diosmin increases venous tone and therefore reduces blood capacity, distensibility and stasis: venous occlusion mercury plethysmography shows a reduction in venous emptying time.
The end effect is to reduce venous hypertension in patients with vein diseases.
Microcirculatory activity
Diosmin reduces capillary permeability and increases capillary resistance. It also has an anti-inflammatory effect by affecting prostaglandin synthesis. Controlled double-blind clinical trials have shown a statistically significant difference between diosmin and placebo. In patients with capillary fragility, treatment with diosmin increases capillary resistance and reduces clinical manifestations. After administration of 1 g of diosmin daily, compared with placebo, a decrease in capillary permeability was also observed, as determined using technetium-labeled albumin or plethysmography.
Pharmacodynamic effects
The pharmacological activity of diosmin in humans has been confirmed in controlled double-blind clinical studies, as well as by objective and quantitative methods of studying the effect of the active substance on venous hemodynamics.
Effect on the lymphatic system
Diosmin stimulates lymphatic activity, improving interstitial space drainage and increasing lymphatic flow. Administration of 1 g of diosmin daily reduces lymphatic capillary diameter and intralymphatic pressure, improving the number of functioning lymphatic capillaries in patients with severe chronic venous insufficiency without ulcers.
Clinical efficacy and safety
Controlled double-blind clinical studies demonstrate the therapeutic activity of the drug for the treatment of signs and symptoms of established chronic venous disease and for the treatment of acute hemorrhoidal disease.
Pharmacokinetics
Absorption
After oral administration, diosmin is rapidly hydrolyzed in the intestine by intestinal flora and absorbed as its aglycone derivative, diosmetin. The oral bioavailability of micronized diosmin is approximately 60%.
Distribution
The volume of distribution of diosmetin is 62.1 L, indicating extensive tissue distribution.
Biotransformation
Diosmetin is extensively metabolized to phenolic acids or their glycine conjugates, which are excreted in the urine. In humans, the predominant metabolite found in urine is m-hydroxy-phenylpropionic acid, which is mainly excreted in the conjugated form. Metabolites found in smaller amounts include phenolic acids corresponding to 3-hydroxy-4-methoxybenzoic acid and 3-methoxy-4-hydroxyphenylacetic acid.
Breeding
Elimination of micronized diosmin is relatively rapid, with approximately 34% of the radiolabeled 14C-diosmin dose being excreted in the urine and feces within the first 24 hours and approaching 86% within the first 48 hours. Approximately half of the dose is excreted in the feces as unchanged diosmin or diosmetin, while these two compounds are not excreted in the urine.
The half-life of diosmetin showed a mean value of 31.5 hours, ranging from 26 to 43 hours.
Indication
Symptomatic treatment of chronic venolymphatic insufficiency (heaviness in the legs, pain, night cramps, edema, trophic disorders, including varicose ulcers). Symptomatic treatment of hemorrhoids.
Contraindication
Hypersensitivity to the active substance or any excipient.
Interaction with other medicinal products and other types of interactions
Interaction studies have not been conducted. Despite extensive post-marketing experience with diosmin, no interactions with other drugs have been reported to date.
Application features
The use of this medicinal product for acute hemorrhoids does not replace specific therapy and does not interfere with the treatment of other proctological diseases. If the symptoms do not disappear quickly during a short course of treatment, a proctological examination should be performed and the therapy reviewed.
In cases of venous circulation disorders, it is more effective to combine therapy with adherence to the following lifestyle recommendations:
Particular attention should be paid if the patient's condition worsens during treatment. This may manifest as skin inflammation, phlebitis, subcutaneous induration, severe pain, skin ulcers or atypical symptoms (e.g. sudden swelling of one or both legs).
Flebaven® is ineffective in reducing swelling of the lower extremities caused by heart, liver, or kidney disease.
Ability to influence reaction speed when driving vehicles or other mechanisms
No studies on the effects of diosmin on the ability to drive or use machines have been conducted. However, based on the overall safety profile, diosmin has no or negligible influence on this ability.
Use during pregnancy or breastfeeding
Pregnancy
Pregnant women should use Flebaven® with caution. Consult a doctor before use.
Studies have not revealed any teratogenic effects of the drug; no side effects have been reported.
Breast-feeding
Due to the lack of data on its penetration into breast milk, use during breastfeeding should be avoided.
Fertility
Reproductive toxicity studies in animals showed no effect on fertility.
Method of administration and doses
For oral use.
For adults. Tablets should be taken with meals.
Chronic venolymphatic insufficiency
The recommended dose is 2 tablets per day, taken once or divided into 2 doses. The duration of treatment is at least 4–5 weeks.
Hemorrhoid disease
Treatment of acute hemorrhoid episodes: 6 tablets per day for 4 days, then 4 tablets per day for the next 3 days. The daily dose should be divided into 2-3 doses. Maintenance therapy - 2 tablets per day.
The duration of treatment is determined by the doctor depending on the indication for use and the course of the disease (see the section "Peculiarities of use").
Children
There are no data on the use of diosmin in children.
Overdose
No cases of overdose have been reported.
Adverse reactions
During clinical studies, side effects of moderate intensity were observed with the use of diosmin, mainly from the gastrointestinal tract (diarrhea, dyspepsia, nausea, vomiting).
The following adverse reactions have been reported and are classified according to frequency: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10000, < 1/1000); very rare (< 1/10000); frequency unknown (cannot be estimated from the available information).
| Classification by organ systems | Frequency | Adverse reaction |
| From the nervous system | Rarely | Dizziness
Headache
Malaise |
| Gastrointestinal tract | Often | Diarrhea
Dyspepsia
Nausea
Vomiting |
| Infrequently | Colitis | |
| Frequency unknown | Pain in the abdominal area | |
| Skin and subcutaneous tissue disorders | Rarely | Itch
Rash
Urticaria |
| Frequency unknown* | Localized swelling of the face, lips, eyelids. In exceptional cases - Quincke's edema | |
* Post-marketing surveillance data.
Reporting of suspected adverse reactions.
Reporting of suspected adverse reactions after the marketing authorisation of a medicinal product is of great importance. This allows for continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions via the national reporting system.
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 25 °C in the original packaging to protect from moisture.
Keep out of reach of children.
Packaging
15 tablets in a blister; 4 blisters in a cardboard box.
Vacation category
Without a prescription.
Producer
KRKA, dd, Novo mesto, Slovenia/ KRKA, dd, Novo mesto, Slovenia
Location of the manufacturer and its business address
Smarjeska cesta 6, 8501 Novo mesto, Slovenia.
