-          Improvement of symptoms associated with venolymphatic insufficiency: heavy legs, pain, primo-decubitus restlessness,

-          Supportive treatment for capillary fragility functional disorders,

-          Treatment of functional signs associated with haemorrhoidal crisis

Posology

-          Venous insufficiency: 1 tablet per day during a meal.

-          Haemorrhoidal crisis: 2 to 3 tablets per day during meals.

Pediatric population

The safety and efficacy of PHLEBODIA in children and adolescents aged less than 18 years have not yet been established.

Method of administration

Oral route.

This medicinal product contains an azo colouring agent (cochineal Red A) and may cause allergic reactions.

Haemorrhoidal crisis:

The administration of this product does not dispense patients from following specific treatments for other anal diseases.

The treatment must be short-term only.

If symptoms do not show signs of improvement rapidly, a proctological examination should be performed and the treatment should be revised.

No clinically relevant drug interaction has been reported to date with diosmin.

Pregnancy

There are no or limited amount of data from the use of diosmin in pregnant women.

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

As a precautionary measure, it is preferable to avoid the use of PHLEBODIA during pregnancy.

Breast-feeding

It is unknown whether diosmin or its metabolites are excreted in human milk. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from PHLEBODIA therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility

Reproductive toxicity studies did not show effects on fertility in male and female rats (see section 5.3).

No specific studies on the effects of diosmin on the ability to drive or use machines have been performed. Nevertheless, according to the global safety profile of diosmin, PHLEBODIA has no or negligible influence on the ability to drive and use machines.

The undesirable effects are listed according to the MedDRA classification of system organ classes and according to the frequency of occurrence as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000) and not known (cannot be determined from the available data).

*Gastrointestinal disorders rarely lead to treatment discontinuation.

To reports any side effect(s):

Saudi Arabia:

Other GCC States:   

No cases of overdose associated with adverse reactions were reported with PHLEBODIA administered alone.

Pharmacotherapeutic group: VASOPROTECTIVES/CAPILLARY STABILIZING AGENTS, ATC code: C05CA03 (cardiovascular system).

Venotonic and vasoprotective agent inducing venous constriction, increasing vascular resistance and reducing vascular permeability.

Various pharmacodynamic studies have been carried out to illustrate these properties.

In humans

Venotonic properties

-          Increase of the vasoconstrictive action of adrenaline, noradrenaline and serotonin on superficial veins of the hand or on an isolated saphenous vein.

-          Increase of venous tonus, demonstrated by measurement of venous capacitance using strain gauge plethysmography; reduction of the venous stasis.

-          The venoconstrictive effect is dose-related.

Reduction of mean venous pressure (in superficial system as well as in deep vein system), demonstrated by a double-blind study vs. placebo-controlled under Doppler control.

-          Increase of systolic and diastolic blood pressure in post-operative orthostatic hypotension.

-          Activity after saphenectomy.

Vasculoprotective properties

-          Increase of the capillary resistance which is related to the oral dose administered.

Absorption

After oral administration of PHLEBODIA, diosmin is metabolized to diosmetin by intestinal bacteria. Diosmetin is then absorbed and is found in the blood compartment as glucuroconjugates and sulfoconjugates. Diosmetin-3-O-glucuronide was shown to be a major diosmin’s metabolite.

The plasmatic concentration peak is reached between 12 and 15 hours after PHLEBODIA intake.

Distribution

In animals, the pharmacokinetic study on diosmin marked with carbon-14 showed a preferential radioactivity distribution in the vena cava and saphenous veins.

Elimination

In animals, the elimination is urinary (79%), faecal (11%) and biliary (2.4%), with evidence of an enterohepatic cycle.

In humans, diosmetin-3-O-glucuronide is found in the urine.

Non-clinical data from repeated toxicity, genotoxicity and reproductive toxicity studies did not reveal any particular risk for humans.

Talc, colloidal hydrophobic silica, micronised stearic acid, microcrystalline cellulose.

Film-coating: film-former agent (Sepifilm 002)*, colouring agent (Sepisperse AP 5523)**, Opaglos 6000***.

* Composition of film-former agent (Sepifilm 002): hypromellose, microcrystalline cellulose, macrogol 8 stearate type I.

** Composition of the colouring agent (Sepisperse AP 5523): propylene glycol, hypromellose, titanium dioxide, cochineal red A, black iron oxide, red iron oxide.

*** Composition of Opaglos 6000: carnauba wax, beeswax, shellac, ethanol dehydrated.

Not applicable.

Do not store above 30°C

PVC/Aluminium blister of 15 or 30 tablets.

Not all pack sizes may be marketed.

No special requirements.

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