Dioxel

450 mg/50 mg film-coated tablet: Brown, elliptical, biconvex, plain on both sides.
Each film-coated tablet contains: Micronized purified flavonoid fraction 500 mg (Equivalent to 450 mg diosmin + 50 mg hesperidin).
900 mg/100 mg film-coated tablet: Peach colored oval shaped film-coated tablet having break line on one side.
Each film-coated tablet contains: Diosmin IHS 900 mg, Hesperidin IHS 100 mg.

Pharmacology: Pharmacodynamics: Micronized purified flavonoid fraction (MPFF) is an oral phlebotropic and vascular protective agent consisting of 90% diosmin and 10% hesperidin. It increases venous tone, improves lymphatic drainage and protects the microcirculation from inflammatory processes and apoptosis. By decreasing the expression of some endothelial adhesion molecules, MPFF inhibits the activation, migration and adhesion of leukocytes at the capillary level. This leads to a reduction in the release of inflammatory mediators such as oxygen-free radicals, prostaglandins and thromboxane resulting in a decrease in capillary hyperpermeability.
Pharmacokinetics: Diosmin is rapidly transformed in the intestine by intestinal flora and absorbed as its aglycone, diosmetin, after oral administration.
A study compared the absorption of a single oral dose of radiolabelled MPFF [500 mg tablets containing trace amounts (about 25 nCi) of ¹⁴C-diosmin] with that of nonmicronized diosmin in 12 healthy male volunteers. Results showed that about half of an oral 500 mg dose of radiolabelled MPFF was absorbed within 48 hours of administration. Since unabsorbed diosmin was not excreted in the urine, absorption was evaluated based on the urinary elimination of radioactivity. Reduction in the particle size of diosmin led to a significant increase in absorption; mean gastrointestinal absorption of micronized ¹⁴C-diosmin was significantly greater than with nonmicronized ¹⁴C-diosmin (57.9 vs. 32.7% during 0 to 168 hours postdose; p=0.004).
The time to peak plasma concentration of diosmetin is 1 hour and plasma concentrations decrease slowly after 2 hours; diosmetin is still detectable after 48 hours. The mean volume of distribution of diosmetin is 62.1 liters.
Diosmetin is rapidly and extensively degraded to phenolic acids or their glycine conjugate derivates, which are eliminated in the urine. The predominant metabolite in man is 3-hydroxy-phenylpropionic acid which is mainly eliminated in its conjugated form. Metabolites found in smaller amounts include other phenolic acids corresponding to 3-hydroxy-4-methoxybenzoic acid, 3-methoxy-4-hydroxyphenylacetic acid and 3,4-dihydroxybenzoic acid. It is possible that unidentified metabolites may be responsible for the pharmacological activity of diosmin.
Elimination of micronized diosmin is relatively rapid with ≈34% of the radiolabelled dose of ¹⁴C-diosmin excreted in the urine and feces over the first 24 hours and ≈86% over the first 48 hours. Unmetabolized diosmin and diosmetin are not excreted in the urine. The cumulative excretion of the dose in the urine and feces was 100%. About half of the dose was eliminated in the feces as unchanged diosmin and diosmetin.

This medicine is a venotonic (it increases venous tone) and a vasculoprotector (it increases resistance in small blood vessels). It is recommended for treating venous circulation disorders or symptoms related to venolymphatic insufficiency (swollen legs, pain, early morning restless legs) and for treating functional symptoms related to acute hemorrhoidal attack.

450 mg/50 mg film-coated tablet: See table.

Click on icon to see table/diagram/image

900 mg/100 mg film-coated tablet: Venous insufficiency: 1 tablet daily, at mealtime. Hemorrhoidal attack: The recommended dose is 3 tablets per day for 4 days and then 2 tablets per day for the next 3 days, at mealtimes.
Must be taken orally, by mouth.
If patient misses a dose, do not double the dose. Take the usual dose.
Seek medical attention immediately if the patient has taken more than the recommended dosage.

No cases of overdose have been reported. If patient has taken more than the recommended dose, consult the doctor or pharmacist immediately. An overdose of this medicine can make side effects worse.

Do not take Diosmin + Hesperidin film-coated tablet: If allergic (hypersensitive) to micronized purified flavonoid fraction or any of the other ingredients.

Venous circulation disorders: This treatment is at its most effective when combined with a healthy lifestyle.
Avoid exposure to the sun, heat, standing for too long, excess weight.
Walking, and wearing appropriate stockings when applicable, promote blood circulation.
Hemorrhoidal attack: 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.
If the hemorrhoid disorder persists for more than 15 days, it is essential to consult a doctor or health care provider.
Taking or using other medicines, herbal or dietary supplements: Tell the doctor, health care provider or pharmacist if the patient is taking or has recently taken any other medicines, including medicines obtained without a prescription.
Taking Diosmin + Hesperidin film-coated tablet with food and drink: Not applicable.
Driving and using machines: Not applicable.

Pregnancy: If patient is discovered to be pregnant during treatment, or if pregnant & is planning to take this medicine, ask the doctor or health care provider for advice.
Breast-feeding: Breast-feeding is inadvisable for the duration of the treatment, due to the absence of data on the passage of the medicine into breast milk. Ask the doctor, health care provider or pharmacist for advice before taking any medicine.

450 mg/50 mg film-coated tablet: Autonomic: Anxiety, cramps, drowsiness, feeling of discomfort, headache, hypotension, insomnia, palpitation, tiredness, vertigo.
Gastrointestinal: Abdominal pain, diarrhea, dyspepsia, epigastric pain, gastric discomfort, nausea, vomiting.
900 mg/100 mg film-coated tablet: Like all medicines, this medicine can cause side effects, although not everybody gets them.
The frequency of the possible undesirable effects listed as follows is defined using the following system: Very common (affects more than 1 user out of 10); Common (affects 1 to 10 users out of 100); Uncommon (affects 1 to 10 users out of 1,000); Rare (affects 1 to 10 users out of 10,000); Very rare (affects less than 1 user out of 10,000); Frequency not known (cannot be estimated from the available data).
Nervous system disorders: Rare: dizziness, headaches, discomfort.
Gastrointestinal disorders: Common: diarrhea, dyspepsia (indigestion), nausea, vomiting.
Uncommon: colitis.
Frequency not known: abdominal pain.
Skin and subcutaneous tissue disorders: Rare: rash, pruritus (itching), urticaria (hives).
Frequency not known: isolated face, eyelids, and lips edema.
Exceptionally, Quincke's edema (angioedema).

No cases of drug interaction have been reported since the marketing of the product.
Food and drink: Not applicable. However, in order to avoid possible interactions between various drugs, always tell the doctor or the pharmacist about any other treatment the patient is receiving.

Store at temperatures not exceeding 30°C.

Anorectal Preparations / Phlebitis & Varicose Preparations

C05CA53 - diosmin, combinations ; Belongs to the class of bioflavonoids used as capillary stabilizing agents.

Non-Rx