VENOSTOR 500 mg Film-coated tablets
Micronized purified flavonoid fraction
1. DENOMINATION
VENOSTOR 500 mg, film-coated tablet.
2. COMPOSITION
p. tablet
Micronized purified flavonoid fraction……………………………….500 mg
. Diosmin (90 %)…………………………………………………………..450 mg
. Flavonoids expressed as hesperidin (10 %)……………………. 50 mg
Excipients q.s. for one film-coated tablet.
HOW TO TAKE VENOSTOR™ (Diosmin+hesperidin) Tablets
Always take this medicine exactly as described in this manual or by your doctor or pharmacist. Check with your doctor or pharmacist if doubt.
The tablets should be taken up at mealtimes. The recommended dosage is:
Treatment of hemorrhoidal crisis
• 6 tablets per day for 4 days
• then 4 tablets per day for the next 3 days Treatment of disorders of the venous circulation and DMARD disease hemorrhoidal:
• 2 tablets per day
Do not take this medication for more than 3 months without consulting your doctor.
If you have taken more Diosmin+hesperidin that you should If you have used or taken too Diosmin+hesperidin immediately contact your doctor pharmacist or poison control center.
GOOD PRACTICES IN HEMORRHOID TREATMENT
Hemorrhoidal illness represents one of the most common medical conditions in man. The most recent statistics indicate a prevalence of about 25% in the adult population, and higher than 50% for those older than 50. However, the prevalence and incidence are most probably higher, considering the fact that, in certain patients, the illness begins in an asymptomatic fashion.
The origin of hemorrhoidal disease can be either mechanical or vascular (hemodynamic):
According to mechanical theory, the supportive structure of the hemorrhoidal plexus undergoes spontaneous involution which includes excessive laxity and leads to displacement of the internal hemorrhoids. Acute intrarectal or abdominal pressure are worsening factors.
Vascular factors are increasingly recognized as playing an important role in the development of hemorrhoidal disease through alterations of the vascular plexuses and dysfunction of the arteriovenous shunts, the effect of which are amplified, as above, by increased abdominal pressure.
Hemorrhoidal disease is often associated with inflammation. Therefore, the treatment of hemorrhoids has to achieve three objectives: to eliminate mechanical and local triggering factors, to reduce the inflammation, always present in acute manifestations and to reestablish optimal hemodynamic and microcirculatory conditions.
Eliminate mechanical and local triggering factors
To achieve the first objective it is necessary to observe certain lifestyle and dietary measures, which represent the basis of the treatment.
The dietary regime, above all, must include fiber-rich food and abundant liquids in order to ensure the regularity of the alvus and to maintain a soft consistency of the stools.
Mechanical laxatives, such as vaseline or liquid paraffin, can be utilized to this end, as well as avoiding consumption of stimulating drinks (tea, coffee), alcohol, and spices. Great care should be paid to personal hygiene and daily habits, avoiding smoking, a sedentary lifestyle, and a sitting position for prolonged periods of time.
There is doubt about the role of local treatment, which can be carried out through agents employed in various combinations: local anesthetics, anti-inflammatory drugs, lubricating substances, and substances with local venous tropism.
All these medicines have a favorable effect on clinical phenomenology, even if, up to now, studies have called into doubt their real effectiveness.
Reduce the inflammation
The second objective to achieve in the treatment of hemorrhoidal attacks is prevention of the inflammation. It has been demonstrated that metabolites of arachidonic acid (in particular prostaglandin and leukotrienes) levels are higher in the acute phase.1
Therefore, it is necessary to administer, in acute hemorrhoidal disease, substances able to antagonize the actions of the chemical mediators of the inflammation, including the kinins and the lymphokines, and to inhibit enzymatic activation of arachidonic acid.
Reestablish optimal hemodynamic and microcirculatory conditions
Hemodynamic and microcirculatory disorders lead to inflammation of the tissues and decrease of venous tone. The main inflammatory mediators involved are PGE-2 and TXA-2, whose levels are higher during attacks. The clinical manifestations of these disorders are pain and bleeding, which are very disabling in the patient’s9 daily life. The third objective consists therefore in opposing the PGE-2 and TXA-2 synthesis.
Venostor 500 mg IN THE TREATMENT OF HEMORRHOIDS
Venostor 500 mg provides complete efficacy in acute attacks
All symptoms are significantly improved from the second day of treatment.
A double-blind, placebo-controlled study was performed in 100 patients suffering from hemorrhoidal disease confirmed by proctoscopy, presenting an acute hemorrhoidal attack of up to 3 days, which had not been treated. The treatment lasted 7 days at the dosage of 6 tablets for 4 days and 4 tablets for 3 days.
A clinical examination was performed at D0 and D7, with an assessment of the symptoms and their improvement using a 4-point scale.
The results of this study demonstrated an overall improvement of the symptoms significantly higher in patients treated with Venostor 500 mg in comparison with the controls (P<0.001), which was already evident on the second day of treatment, but more marked at the end. The scores used to evaluate bleeding, pain, and itching resulted in a reduction in both groups on D7, but to a notably greater degree in patients treated with Venostor 500 mg (P<0.001); analogous results were observed regarding tenesmus, with a less relevant resolution percentage (Figure 1) and the objective clinical signs (proctitis). Also, the duration and intensity of the present crisis, compared with previously, were much more reduced in patients treated with flavonoids compared with the placebo group (P<0.001) (Figure 2).
Venostor 500 mg seems to offer a comprehensive pharmacological answer to all the needs of hemorrhoid treatment. Firstly, the flavonoids, including Venostor 500 mg, have been demonstrated to restain lysosome enzymes and interfere with enzymes involved in the flow of arachidonic acid, which causes inflammation.2
Venostor 500 mg has also demonstrated an antioxidant activity, which allows it to oppose free radicals,3 as well as a decreasing effect on the synthesis of PGE-2 and TXA-2 by the macrophage.4
All these effects result in a reduction of the pericapillar permeability,5 and an increase in the capillary resistance to blood extravasation in the interstitium.
The hemodynamic effect manifests itself through an increase in venous tone demonstrated both experimentally6 and clinically.7
Regarding clinical benefits, two recent studies have demonstrated the outstanding efficacy of Venostor 500 mg, both in acute and recurrent attacks.
If you forget to take VENOSTOR™ (Diosmin+hesperidin) tablets
Do not take a double dose to make up for the dose that you missed.
If you stop taking VENOSTOR™ (Diosmin+hesperidin) tablets
Your doctor will tell you how long you need to use VENOSTOR™ (Diosmin+hesperidin) tablets. Do not stop early treatment.
3. PHARMACEUTICAL FORM
Film-coated tablet.
4. CLINICAL DATA
4.1. INDICATIONS
– Treatment of symptoms related to venolymphatic insufficiency (heavy legs, pain, early morning restless legs),
– Treatment of functional symptoms related to acute hemorrhoidal attack.
4.2. DOSAGE AND METHOD OF ADMINISTRATION
– Usual dosage : 2 tablets daily in two divided doses, midday and evening at meal times.
– Acute hemorrhoidal attack : 6 tablets per day for the first 4 days, then 4 tablets per day for 3 days.
4.3. CONTRA-INDICATIONS
Not applicable
4.4. SPECIAL WARNINGS AND PRECAUTIONS FOR USE
Acute hemorrhoidal attack :
Administration of this medicine is no substitute for the specific treatment of other anal disorders. The treatment must be short-term. If the symptoms do not disappear rapidly, proctological examination should be performed and the treatment reviewed.VENOSTOR 500 mg 07.2005 2/3
4.5. DRUG INTERACTIONS AND OTHER FORMS OF INTERACTION
Not applicable
4.6. PREGNANCY AND LACTATION
Pregnancy :
Experimental studies in animals have not demonstrated any teratogenic effect in animals. Furthermore, no adverse effects have been reported to date in humans.
Lactation :
In the absence of data concerning excretion into breast milk, breast feeding is not recommended during treatment.
4.7. EFFECTS ON THE ABILITY TO DRIVE AND USE MACHINES
Not applicable
4.8. SIDE-EFFECTS
A few cases of minor gastrointestinal and neurovegetative disorders have been reported which did not require suspension of treatment.
4.9. OVERDOSAGE
Not applicable
5. PHARMACODYNAMIC PROPERTIES
5.1. PHARMACODYNAMIC PROPERTIES
Venotonic and vascular protector.
– Pharmacology
It is active upon the return vascular system in the following way :
. it reduces venous distensibility and stasis,
. in the microcirculation, it normalises capillary permeability and increases capillary resistance.
– Clinical pharmacology
Double blind controlled studies using methods by which the effects of the product on venous haemodynamics could be demonstrated and quantifed have confirmed the above pharmacological properties in man.
. Dose-effect relationship : a statistically significant dose-effect relationship was established with respect to venous plethysmographic parameters : capacitance, distensibility and rate of emptying. The optimum dose-effect ratio was obtained with 2 tablets.VENOSTOR 500 mg 07.2005 3/3
. Venous tonic activity : VENOSTOR 500 mg increases venous tone : venous occlusion plethysmography with a mercury stress gauge demonstrated a decrease in the rate of emptying.
. Microcirculatory activity : double-blind controlled studies showed a statistically significant difference between placebo and the drug. In patients presenting with signs of capillary fragility, VENOSTOR 500 mg increases capillary resistance, as measured by angiosterrometry.
– Clinical trials
Double-blind placebo-controlled trials have demonstrated the activity of the drug in phlebology, in the treatment of chronic venous insufficiency of the lower limbs (both functional and organic).
5.2. PHARMACOKINETICS PROPERTIES
In man, following oral administration of the substance containing 14C Diosmin :
– excretion is mainly faecal, a mean of 14% of the dose administered is excreted in the urine
– the elimination half-life is 11 hours.
– the drug is extensively metabolised as evidenced by the presence of various phenol acids in the urine.
5.3.PRECLINICAL SAFETY DATA
Not applicable.
The place of Venostor 500 mg in recent guidelines on the management of chronic venous disease
by F. Pitsch,France
FURTHER INFORMATION
• The active substance is a flavonoid fraction purified, micronized (500 mg) comprising 450 mg of Diosmin and 50 mg of expressed as hesperidin VENOSTOR™.
The other ingredients are: Sodium carboxymethyl starch, microcrystalline cellulose, gelatin, magnesium stearate, talc; titanium dioxide (E 171), glycerol, hypromellose, sodium lauryl sulfate, macrogol 6000, iron oxide yellow (E172), red iron oxide (E 172).
Aspect of VENOSTOR™ and contents of the pack
The tablets are film-coated, oval and salmon color.
Pack sizes:
Blister pack: 10 tablets / 30 tablet bottle
Box pack: 30 tablets