- Treatment of symptoms related to chronic venous insufficiency (heavy legs, pain, nocturnal leg cramps).

- Treatment of functional symptoms related to acute or permanent hemorrhoidal complaints.

- 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.

Children and adolescents

The safety and efficacy of Capillo in children and adolescents is not demonstrated. There are no studies available.

Patients with impaired kidney and liver function

There are no special dosing guidelines for patients with hepatic impairment and impaired renal function.

Elderly patients

There are no special dosing guidelines for elderly patients.

The tablets are swallowed whole with plenty of liquid at meal times.

The treatment is preferably carried out over a few months

The use of this drug in the symptomatic treatment of acute hemorrhoidal Complaints do not exclude the therapy of other anal conditions. Should not the symptoms cured quickly, a proctological examination is recommended and the treatment should be checked.

Uncommonly severe discomfort occurs, especially on one leg that runs through Swelling, discoloration of the skin, feeling of tension or heat and pain,

a doctor should be consulted immediately. It can be symptoms of a Vein thrombosis related to the underlying venous insufficiency.

No interaction studies were performed. however, it was under the extraordinarily large experience regarding the safety profile of Capillo 500 mg .

No Drug interaction reported.

Pregnancy

Data from a limited number of exposed pregnancies show no adverse effects on pregnancy or on the health of the fetus or the Newborns.

Further relevant epidemiological data are currently not available.

Animal studies show no direct or indirect harmful effects on pregnancy, embryonic / fetal development; Childbirth or postnatal development (see section 5.3).

When prescribing to pregnant women, the benefit / risk ratio should be carefully weighed, preferable to avoid the use of CAPILLO during pregnancy.

Lactation

It is not known if the flavonoid fraction passes into breast milk. The excretion of Flavonoid fraction in breast milk has not been studied in animal studies. In deciding whether the breastfeeding continues or continue the therapy with Capillo, should the Benefits of breastfeeding for the child or therapy with Capillo for the patient to be weighed.

Fertility

Reproductive toxicity studies have shown no effect on male or female fertility.

 (see section 5.3).

No studies on the effects of the flavonoid fraction on the Driving and using machines.

However, considering the overall safety profile of the flavonoid fraction, Capillo 500 mg has a negligible influence on these abilities.

Summary of safety profile

The side effects reported with Capillo in clinical trials were of light intensity. These mainly concerned gastrointestinal complaints (diarrhea, dyspepsia, Nausea, vomiting).

Tabulated list of adverse reactions

The following adverse reactions have been reported and ranked according to the following frequencies: Very

common (≥1 / 10); common (≥1 / 100 to <1/10); occasionally (≥1 / 1,000 to <1/100); rarely (≥1 / 10,000 to

<1 / 1.000); very rare (<1 / 10,000); not known (frequency based on available data can not be estimated).

* Post marketing surveillance

To report any side effects

National Pharmacovigilance &amp; Drug Safety Centre (NPC)

•                  Fax: +966-11-205-7662

•                  Toll free phone: 8002490000

•                  E-mail: npc.drug@sfda.gov.sa

•                  Website: www.sfda.gov.sa/npc

No cases of overdoses were reported.

The large therapeutic range of the product indicates a negligible risk of intoxication out.

Pharmacotherapeutic group: Venotonic and vascular protector: bioflavonoids

ATC code: C05CA53

Ø 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.

Ø 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.

· Venous tonic activity: DAFLON® 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, DAFLON® 500 mg increases capillary resistance, as measured by angiosterometry.

Ø 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).

The studies were conducted after oral administration of the drug with 14C-labeled diosmin and after a single oral dose of Capillo 500 mg to healthy volunteers.

Absorption:

After single oral administration of 14C-radiolabelled Capillo, the Absorption (relative to total urinary excretion) 58%.

Distribution:

Based on concentration measurements of total diosmetin in plasma single oral administration of 500 mg Capillo-micronized flavonoid fraction, which is 90% Diosmin and 10% other flavonoids - expressed as hesperidin - will be the maximum Plasma concentrations reached within 12 hours (range: 8-24 hours).

Metabolism:

Diosmin is metabolized in the enterocytes to its aglycone diosmetin, which among its circulating glucurono derivatives and various phenolic acids, including Hippuric acid, is transformed.

Elimination:

In the first 24 hours, elimination is mainly via the urine

single oral administration, with 31% of the oral dose excreted during this period.

The total excretion is complete (109 +/- 23%), with 58 +/- 20% of the urinary dose and 51 +/-

24% of the dose is recovered in the faeces (the majority of fecal excretion is after 24 Reached hours).

Based on concentration measurements of total diosmetin in plasma after single oral Administration of 500 mg Capillo, the elimination half-life is about 13 +/- 5 hours.

General and specific animal studies have no significant evidence of toxicity given.

The oral dose was 180 times higher than the usual therapeutic dose for humans

In mice, rats or monkeys no toxic or lethal effects and caused no unusual behavior or biological, anatomical or histological changes. Studies in rats and rabbits showed neither an embryotoxic nor a teratogenic effect.

There is no change in fertility occurred.

In vitro and in vivo tests showed no mutagenic potential.

Maize starch

Croscarmellose Sodium

Crospovidone

Povidone

Magnesium Stearate

Hypromellose

Polyethylene Glycol

Glycerin

Titanium dioxide

Iron Oxide Yellow

Iron Oxide Red

Not applicable.

Store below 30°C

Store in the original Carton.

Capillo 500mg Film Coated Tablets packed in PVC-Aclar Clear / Alu blister as a pack of “10” tablets per blister and 30 tablets per box (three blister’s).

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