Hemorrhoid flare-ups – Heavy legs – Micronized flavonoids

For whom: Adults
Pregnancy: Not authorized / not recommended
Breastfeeding: Not authorized / not recommended
Form: Tablets

Presentation / What it is for

Flavonoids 1000 mg Zentiva is a vasoprotective medicine indicated for the treatment of symptoms of chronic venous insufficiency of the lower limbs, such as:

• Heavy legs and swelling

• Pain

• Night-time leg cramps

It is also indicated for the treatment of symptoms of acute hemorrhoid flare-ups, such as:

• Pain

• Bleeding

• Swelling in the anal area

This Zentiva medicine increases venous tone and improves the resistance of small blood vessels.

Composition (What’s in Flavonoids Zentiva 1000 mg tablets?)

Each tablet contains the following active substances:

• Micronized flavonoids: 1000 mg

  • as diosmin: 900 mg

  • other flavonoids expressed as hesperidin: 100 mg

Other ingredients (excipients):

• Tablet core: microcrystalline cellulose (type 102), gelatin, corn starch, talc, magnesium stearate.

• Film coating:

  • Opadry II orange 85F230113: partially hydrolyzed poly(vinyl alcohol), titanium dioxide, macrogol 3350, talc, yellow iron oxide, red iron oxide

  • Opadry EZ clear 254U590005: maltodextrin, talc, guar galactomannan, hypromellose, partially hydrolyzed poly(vinyl alcohol), medium-chain triglycerides

Dosage and method of administration (Advice)

This medicine is supplied as film-coated tablets. Treatment is for adults only.
Take by mouth only, with meals.

For chronic venous insufficiency

• Take 1 tablet once daily for 2 months.

• After that, if symptoms persist and justify it, treatment can be continued for an additional 2 months.

• For venous insufficiency, treatment should be combined with a healthy lifestyle.

• If there is no improvement or symptoms worsen after 6 weeks, consult your doctor.

For an acute hemorrhoid flare-up

• First 4 days: take 1 tablet three times daily (3 tablets per day).

• Next 3 days: take 1 tablet twice daily (2 tablets per day).

• Treatment duration is limited to a short period (7 days).

• If symptoms do not resolve after 7 days, consult your doctor.

Precautions for use (Advice)

• This medicine is for adults only.

• Do not take this medicine if you are allergic to the active substance or any of the other ingredients.

• Tell your doctor or pharmacist if you are taking any other medicines.

• Zentiva Flavonoids 1000 mg is not recommended during pregnancy or breastfeeding.

Additional suggestion

For venous insufficiency, consider Class 2 compression socks, such as Thuasne Venoflex (cotton).

Pack size

1 box of 18 film-coated tablets

Please read the following full disclosure before purchasing or taking this product.

SUMMARY OF PRODUCT CHARACTERISTICS

ANSM – Last updated: 07/01/2025

1. NAME OF THE MEDICINAL PRODUCT

FLAVONOIDS ZENTIVA CONSEIL 1000 mg, film-coated tablet

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Micronized flavonoids ................................................................................. 1000 mg

In the form of:

• Diosmin ...................................................................................................... 900 mg

• Other flavonoids expressed as hesperidin ............................................... 100 mg

Per one film-coated tablet.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Film-coated tablet.

Oval, orange-brown film-coated tablets with rounded edges, scored on both sides, measuring 23.4 ± 0.3 mm in length, 8.4 ± 0.3 mm in width, and 7.0–8.2 mm in thickness.
The score line is intended only to facilitate swallowing and does not divide the tablet into equal doses.

4. CLINICAL PARTICULARS

4.1. Therapeutic indications

FLAVONOIDS ZENTIVA CONSEIL is indicated in adults for:

Treatment of chronic venous insufficiency of the lower limbs when the following functional symptoms are present:

• heavy legs and swelling;

• pain;

• nocturnal leg cramps.

Symptomatic treatment of acute hemorrhoidal attacks.

4.2. Posology and method of administration

Posology

Adults

Chronic venous insufficiency
The usual dose is 1 tablet once daily for 2 months.
Treatment may be continued for an additional 2 months if persistence of symptoms justifies it.

Acute hemorrhoidal attacks

• During the first 4 days, the daily dose is 3 tablets, i.e.

  • 1 tablet three times daily, or

  • 1 tablet taken once, followed by 2 tablets taken together once daily.

• During the following 3 days, the recommended daily dose is 2 tablets, i.e.

  • 1 tablet twice daily.

For this indication, FLAVONOIDS ZENTIVA CONSEIL should be used only for a short duration (7 days) (see section 4.4).

Pediatric population

The safety and efficacy of FLAVONOIDS ZENTIVA CONSEIL in children and adolescents under 18 years of age have not been established. Therefore, use in the pediatric population is not recommended.

Hepatic and/or renal impairment

The safety and efficacy of micronized flavonoids have not been studied in patients with renal or hepatic impairment. To date, no data are available to justify dose adjustment in these subgroups.

Elderly

The safety and efficacy of micronized flavonoids have not been studied in elderly patients. To date, no data are available to justify dose adjustment in this subgroup.

Method of administration

Oral use. Tablets should be taken with meals.

4.3. Contraindications

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

4.4. Special warnings and precautions for use

Use of this medicinal product for the symptomatic treatment of acute hemorrhoidal attacks does not replace specific treatments for rectal disorders. Treatment duration must be limited to a short period (7 days). If symptoms persist after short-term treatment, a proctological examination should be performed and treatment reassessed.

For the treatment of chronic venous insufficiency, optimal benefit is achieved through an appropriate lifestyle. Prolonged exposure to sunlight, prolonged standing, and excess weight should be avoided. Walking and the use of compression stockings may help improve lower-limb circulation.

Careful monitoring is recommended if the condition worsens during treatment. This may manifest as skin inflammation, vein inflammation, subcutaneous induration, severe pain, skin ulcers, or atypical symptoms (e.g., sudden swelling of one or both legs).

FLAVONOIDS ZENTIVA CONSEIL is not effective in reducing lower-limb edema caused by heart, liver, or kidney disease.

4.5. Interaction with other medicinal products and other forms of interaction

No interaction studies have been conducted. Extensive post-marketing experience has revealed no interactions between micronized flavonoids and other medicinal products.

4.6. Fertility, pregnancy and lactation

Pregnancy

No data are available on the use of micronized flavonoids in pregnant women.
Animal studies have shown no direct or indirect harmful effects on reproduction (see section 5.3).
As a precautionary measure, use of FLAVONOIDS ZENTIVA CONSEIL during pregnancy should be avoided.

Breastfeeding

It is unknown whether the active substance/metabolites are excreted in human breast milk. A risk to newborns/infants cannot be excluded. A decision must be made whether to discontinue breastfeeding or discontinue/abstain from treatment, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

Fertility

Reproductive toxicity studies showed no effect on male or female rat fertility (see section 5.3). No clinical data are available regarding the effects of micronized flavonoids on fertility.

4.7. Effects on ability to drive and use machines

Effects on the ability to drive and use machines have not been studied. However, based on its overall safety profile, FLAVONOIDS ZENTIVA CONSEIL has no or negligible influence on the ability to drive and use machines.

4.8. Undesirable effects

Summary of the safety profile

Moderate adverse reactions, mainly gastrointestinal events (nausea, vomiting, diarrhea, dyspepsia), have been reported in clinical studies with micronized flavonoids.

Tabulated list of adverse reactions

Frequency categories: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000); not known (cannot be estimated from available data).

Nervous system disorders

• Rare: headache, dizziness, malaise

Gastrointestinal disorders

• Common: nausea, vomiting, diarrhea, dyspepsia

• Uncommon: colitis

• Not known*: abdominal pain

Skin and subcutaneous tissue disorders

• Rare: rash, pruritus, urticaria

Immune system disorders

• Not known*: isolated edema of the face, lips, and eyelids associated with hypersensitivity reactions; in exceptional cases, angioedema

* Post-marketing experience.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization is important. It allows continued monitoring of the benefit-risk balance. Healthcare professionals should report suspected adverse reactions via the national reporting system:
Agence nationale de sécurité du médicament et des produits de santé (ANSM) – Regional Pharmacovigilance Centers
Website: https://signalement.social-sante.gouv.fr/

4.9. Overdose

Experience with overdose of micronized flavonoids is limited. The most frequently reported adverse events include gastrointestinal disorders (diarrhea, nausea, abdominal pain) and skin disorders (pruritus, rash).

5. PHARMACOLOGICAL PROPERTIES

5.1. Pharmacodynamic properties

Pharmacotherapeutic group: capillary-active agents, bioflavonoids
ATC code: C05CA53

Mechanism of action
FLAVONOIDS ZENTIVA CONSEIL reduces venous distensibility and venous stasis. At the microcirculatory level, it normalizes capillary permeability and strengthens capillary resistance.

Pharmacodynamic effects

Dose-effect relationship
A statistically significant dose-effect relationship has been established for venous plethysmographic parameters (capacitance, distensibility, and emptying time). The optimal dose-effect ratio is achieved with 1 tablet.

Venotonic activity
Venous occlusion plethysmography demonstrated a reduction in venous emptying time.

Microcirculatory activity
Double-blind controlled studies demonstrated a statistically significant difference versus placebo. In patients with capillary fragility, micronized flavonoids increased capillary resistance measured by angiostereometry.

Clinical efficacy and safety
Double-blind, placebo-controlled clinical trials demonstrated the efficacy of micronized flavonoids in treating chronic venous insufficiency of the lower limbs and acute hemorrhoidal attacks.

5.2. Pharmacokinetic properties

Absorption
After oral administration, micronized diosmin and hesperidin are rapidly converted in the intestinal lumen into diosmetin and hesperetin, which are absorbed as such. Peak plasma concentrations of diosmetin are reached after 1–3 hours, and hesperetin after approximately 5 hours.

Distribution
In systemic circulation, diosmetin and hesperetin are bound to plasma proteins, mainly human serum albumin.

Biotransformation
The drug is extensively metabolized, as evidenced by the presence of various phenolic acids in urine.

Elimination
In humans, following oral administration of carbon-14-labeled diosmin, excretion is mainly fecal; on average, 14% of the administered dose is excreted in urine.
Elimination half-life is 11 hours.

5.3. Preclinical safety data

Acute administration in mice, rats, and monkeys of oral doses up to 180 times the human therapeutic dose caused neither toxicity nor mortality. No behavioral, biological, anatomical, or histological alterations were observed. Studies in rats and rabbits showed no embryotoxic or teratogenic effects, and fertility was not affected. In vitro and in vivo studies did not indicate mutagenic potential.

6. PHARMACEUTICAL PARTICULARS

6.1. List of excipients

Tablet core:
Microcrystalline cellulose (type 102), gelatin, corn starch, talc, magnesium stearate.

Film coating:
Opadry II orange 85F230113: partially hydrolyzed polyvinyl alcohol, titanium dioxide, macrogol 3350, talc, yellow iron oxide, red iron oxide.
Opadry EZ clear 254U590005: maltodextrin, talc, guar galactomannan, hypromellose, partially hydrolyzed polyvinyl alcohol, medium-chain triglycerides.

6.2. Incompatibilities

Not applicable.

6.3. Shelf life

3 years.

6.4. Special precautions for storage

No special storage conditions required.

6.5. Nature and contents of container

18, 30, 36, or 60 film-coated tablets in PVC/Aluminium blister packs, in a cardboard box.
Not all pack sizes may be marketed.

6.6. Special precautions for disposal and handling

Any unused medicinal product or waste material should be disposed of in accordance with local regulations.

7. MARKETING AUTHORIZATION HOLDER

ZENTIVA FRANCE
35 Rue du Val de Marne
75013 Paris
France

8. MARKETING AUTHORIZATION NUMBER(S)

• 34009 302 747 0 5: 18 tablets (PVC/Aluminium blister)

• 34009 302 747 2 9: 30 tablets (PVC/Aluminium blister)

• 34009 550 959 6 5: 36 tablets (PVC/Aluminium blister)

• 34009 550 959 7 2: 60 tablets (PVC/Aluminium blister)

9. DATE OF FIRST AUTHORIZATION / RENEWAL

[To be completed by the marketing authorization holder]

10. DATE OF REVISION OF THE TEXT

[To be completed by the marketing authorization holder]

11. DOSIMETRY

Not applicable.

12. INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS

Not applicable.

CONDITIONS OF PRESCRIPTION AND SUPPLY

Medicinal product not subject to medical prescription.