What is diosmin? How effective is it for treating conditions like hemorrhoids and venous leg ulcers? What are the potential side effects and precautions? Find answers to these questions and more in this detailed review.

Diosmina in English: A Comprehensive Overview

Diosmin is a naturally occurring flavonoid compound found primarily in citrus fruits. It has been studied for its potential therapeutic applications, particularly in the management of various circulatory and vascular disorders.

Uses and Effectiveness

Possibly Effective for:

• Hemorrhoids: Taking diosmin in high doses along with hesperidin (another plant compound) seems to reduce symptoms of hemorrhoids. Lower doses of diosmin combined with hesperidin and troxerutin also appear to be helpful.
• Venous leg ulcers: Taking diosmin with hesperidin and using compression dressings seems to aid in the healing of leg ulcers caused by poor circulation.

Insufficient Evidence for:

• Back pain: Early research suggests that taking diosmin for at least 8 weeks may decrease pain and reduce the need for rescue pain medication, similar to the effects of mannitol and dexamethasone.
• Chronic venous insufficiency (CVI): Some research indicates that taking diosmin may help reduce pain in people with CVI, but not all studies agree.
• Lymphedema: Taking diosmin with hesperidin may not reduce swelling of the arms following breast cancer surgery.
• Minor bleeding, bleeding gums, eye hemorrhage, liver protection, and varicose veins: More evidence is needed to determine the effectiveness of diosmin for these conditions.

Side Effects and Precautions

Side Effects

Diosmin is generally considered POSSIBLY SAFE for most people when taken by mouth in the short term. Potential side effects may include:

• Stomach pain
• Diarrhea
• Dizziness
• Headache
• Skin redness and hives
• Muscle pain
• Blood problems
• Altered heart rate

Precautions

Certain precautions should be taken when using diosmin:

• Pregnancy and breastfeeding: Not enough is known about the safety of diosmin during pregnancy and breastfeeding, so it’s best to avoid use.
• Bleeding disorders: Diosmin may worsen bleeding disorders, so it should be avoided if you have a bleeding disorder.

Interactions

Diosmin may interact with certain medications, potentially affecting how they are metabolized by the liver. Some potential interactions include:

• Chlorzoxazone (Parafon Forte, Paraflex): Diosmin may decrease the breakdown of chlorzoxazone, potentially increasing its effects and side effects.
• Diclofenac (Voltaren, others): Diosmin may decrease the breakdown of diclofenac, potentially increasing its effects and side effects.
• Medications broken down by the liver: Diosmin may decrease the liver’s ability to break down certain medications, potentially increasing their effects and side effects. Examples include celecoxib, diclofenac, fluvastatin, and warfarin.

Before taking diosmin, it’s important to inform your healthcare provider about any medications you are currently taking, as they can advise on the appropriate use and monitoring of diosmin to minimize the risk of interactions.

Dosing and Reviews

The appropriate dosage of diosmin can vary depending on the condition being treated and the individual’s response. It’s essential to follow the instructions provided by your healthcare provider or the product label.

Reviews of diosmin’s effectiveness and safety are generally positive, with some individuals reporting improved symptoms of hemorrhoids, venous leg ulcers, and other circulatory conditions. However, the quality and consistency of the evidence can vary, and more research may be needed to fully understand the potential benefits and risks of using diosmin.

Conclusion

Diosmin is a naturally occurring compound with potential therapeutic applications, particularly in the management of circulatory and vascular disorders. While it has shown promise in the treatment of hemorrhoids and venous leg ulcers, the evidence for its effectiveness in other conditions is still limited. It’s important to discuss the use of diosmin with your healthcare provider, taking into account the potential side effects and interactions, to determine if it’s the right option for your specific needs.

Overview, Uses, Side Effects, Precautions, Interactions, Dosing and Reviews

Overview

Diosmin is a chemical in some plants. It’s found mainly in citrus fruits.

Diosmin is most often used for hemorrhoids and leg sores caused by poor blood flow. It’s also used for other conditions, but there’s no strong evidence to support these uses.

Diosmin is often taken with hesperidin. Hesperidin is another plant chemical.

Diosmin might work by reducing swelling (inflammation) and restoring normal vein function. Diosmin also seems to have antioxidant effects.

Uses & Effectiveness ?

Possibly Effective for

• Hemorrhoids. Taking diosmin in high doses along with hesperidin seems to reduce symptoms of hemorrhoids. Taking diosmin in lower doses along with hesperidin plus troxerutin also seems to help. Taking diosmin in lower doses along with hesperidin seems to help prevent hemorrhoids from coming back.
• Leg sore caused by weak blood circulation (venous leg ulcer). Taking diosmin with hesperidin and using compression dressing seems to help heal leg ulcers caused by poor circulation.

Insufficient Evidence for

• Back pain. Early research shows that taking diosmin for at least 8 weeks decreases pain and might reduce the need to use rescue pain medicine similarly to receiving the standard medications mannitol and dexamethasone.
• Poor circulation that can cause the legs to swell (chronic venous insufficiency or CVI). Some research shows that taking diosmin may help to reduce pain by a small amount in people with CVI. But not all research agrees.
• Swelling in the arms or legs caused by damage to the lymph system (lymphedema). Taking diosmin with hesperidin might not reduce swelling of the arms following surgery for breast cancer.
• Minor bleeding.
• Bleeding gums.
• Bleeding (hemorrhage) in the eye.
• Preventing damage to the liver.
• Varicose veins.
• Other conditions.

More evidence is needed to rate the effectiveness of diosmin for these uses.

Side Effects

When taken by mouth: Diosmin is POSSIBLY SAFE for most people when used by mouth short-term. It can cause some side effects such as stomach pain, diarrhea, dizziness, headache, skin redness and hives, muscle pain, blood problems, and altered heart rate.

Special Precautions and Warnings

When taken by mouth: Diosmin is POSSIBLY SAFE for most people when used by mouth short-term. It can cause some side effects such as stomach pain, diarrhea, dizziness, headache, skin redness and hives, muscle pain, blood problems, and altered heart rate. Pregnancy and breast-feeding: Not enough is known about the use of diosmin during pregnancy and breast-feeding. Stay on the safe side and avoid use.

Bleeding disorders: Diosmin might make bleeding disorders worse. If you have a bleeding disorder, don’t use diosmin.

Interactions ?

Moderate Interaction

Be cautious with this combination

• The body breaks down chlorzoxazone (Parafon Forte, Paraflex) to get rid of it. Diosmin might decrease how quickly the body breaks down chlorzoxazone (Parafon Forte, Paraflex). Taking diosmin along with chlorzoxazone (Parafon Forte, Paraflex) might increase the effects and side effects of chlorzoxazone (Parafon Forte, Paraflex).

• The body breaks down diclofenac (Voltaren, others) to get rid of it. Diosmin might decrease how quickly the body breaks down diclofenac (Voltaren, others). Taking diosmin along with diclofenac (Voltaren, others) might increase the effects and side effects of diclofenac (Voltaren, others).

• Some medications are changed and broken down by the liver. Diosmin might decrease how quickly the liver breaks down some medications. Taking diosmin along with some medications that are broken down by the liver might increase the effects and side effects of these medications. Before taking diosmin, talk to your healthcare provider if you take any medications that are changed by the liver.
  
  
  Some medications that are changed by the liver include celecoxib (Celebrex), diclofenac (Voltaren), fluvastatin (Lescol), glipizide (Glucotrol), ibuprofen (Advil, Motrin), irbesartan (Avapro), losartan (Cozaar), phenytoin (Dilantin), piroxicam (Feldene), tamoxifen (Nolvadex), tolbutamide (Tolinase), torsemide (Demadex), warfarin (Coumadin), and others.

• Some medications are changed and broken down by the liver. Diosmin might decrease how quickly the liver breaks down some medications. Taking diosmin along with some medications that are broken down by the liver may increase the effects and side effects of these medications.
  
  
  Some medications changed by the liver include acetaminophen, chlorzoxazone (Parafon Forte), ethanol, theophylline, and anesthetics such as enflurane (Ethrane), halothane (Fluothane), isoflurane (Forane), and methoxyflurane (Penthrane).

• Some medications are moved by pumps in cells. Diosmin might make these pumps less active and increase the amount of some medications that get absorbed by the body. This might increase the amount of some medications in the body, which could lead to more side effects.
  
  
  Some medications that are moved by these pumps include some chemotherapeutic agents (etoposide, paclitaxel, vinblastine, vincristine, vindesine), antifungals (ketoconazole, itraconazole), protease inhibitors (amprenavir, indinavir, nelfinavir, saquinavir), h3 antagonists (cimetidine, ranitidine), some calcium channel blockers (diltiazem, verapamil), corticosteroids, erythromycin, cisapride (Propulsid), fexofenadine (Allegra), cyclosporine, loperamide (Imodium), quinidine, and others.

• Diosmin might slow blood clotting. Taking diosmin along with medications that also slow blood clotting might increase the chances of bruising and bleeding.
  
  Some medications that slow blood clotting include aspirin, clopidogrel (Plavix), diclofenac (Voltaren, Cataflam, others), ibuprofen (Advil, Motrin, others), naproxen (Anaprox, Naprosyn, others), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, warfarin (Coumadin), and others.

• The body breaks down carbamazepine (Tegretol) to get rid of it. Diosmin might decrease how quickly the body breaks down carbamazepine (Tegretol). Taking diosmin along with carbamazepine (Tegretol) might increase the effects and side effects of carbamazepine (Tegretol).

• Some medications including fexofenadine (Allegra) are moved by pumps in cells. Diosmin might make these pumps less active and increase how much of some medications get absorbed by the body. This might cause more side effects from some medications.

• Some medications are changed and broken down by the liver. Diosmin may decrease how quickly the liver breaks down some medications. Taking diosmin along with some medications may increase the effects and side effects of these medications. Before taking diosmin, talk to your health care provider if you are taking any medications that are changed by the liver.

  Some medications changed by the liver include lovastatin (Mevacor), ketoconazole (Nizoral), itraconazole (Sporanox), clarithromycin (Biaxin), erythromycin, cyclosporine (Neoral, Sandimmune), amlodipine (Norvasc), verapamil (Calan, Isoptin), diltiazem (Cardizem), estrogens, indinavir (Crixivan), fexofenadine (Allegra), triazolam (Halcion), alprazolam (Xanax), and many others.

Dosing

Diosmin is often taken in combination with hesperidin.

The following doses have been studied in scientific research:

ADULTS

BY MOUTH:

• For hemorrhoids: For treating hemorrhoids, 1350 mg of diosmin plus 150 mg of hesperidin twice daily for 4 days followed by 900 mg of diosmin and 100 mg of hesperidin twice daily for 3 days has been used. Also, 300 mg of diosmin, 300 mg of troxerutin, and 300 mg of hesperidin three times daily for 3 days, followed by two times daily for 2 days, and then once daily for 7 days has been used. Thereafter, 300 mg of diosmin, 300 mg of troxerutin, and 100 mg of hesperidin has been used daily for one month. Some researchers also try 600 mg of diosmin three times daily for 4 days, followed by 300 mg twice daily for 10 days, in combination with 11 grams of psyllium daily. However, this lower diosmin dose does not seem to be as effective.
• For leg ulcers caused by poor circulation (venous stasis ulcers): 900 mg of diosmin plus 100 mg of hesperidin daily has been used for up to 2 months.

View References

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CONDITIONS OF USE AND IMPORTANT INFORMATION: This information is meant to supplement, not replace advice from your doctor or healthcare provider and is not meant to cover all possible uses, precautions, interactions or adverse effects. This information may not fit your specific health circumstances. Never delay or disregard seeking professional medical advice from your doctor or other qualified health care provider because of something you have read on WebMD. You should always speak with your doctor or health care professional before you start, stop, or change any prescribed part of your health care plan or treatment and to determine what course of therapy is right for you.

This copyrighted material is provided by Natural Medicines Comprehensive Database Consumer Version. Information from this source is evidence-based and objective, and without commercial influence. For professional medical information on natural medicines, see Natural Medicines Comprehensive Database Professional Version.
© Therapeutic Research Faculty 2020.

Benefits, Dosage, Side Effects, and More

Diosmin is a flavonoid most commonly found in citrus fruits. Flavonoids are plant compounds that have antioxidant properties, which protect your body from inflammation and unstable molecules called free radicals (1, 2).

Diosmin was first isolated from the figwort plant (Scrophularia nodosa L.) in 1925 and has been used since 1969 as a natural therapy to treat various conditions, such as hemorrhoids, varicose veins, venous insufficiency, leg ulcers, and other circulatory issues (2).

It’s believed to help reduce inflammation and restore normal blood flow in people with venous insufficiency, a condition in which blood flow is impaired (2).

Today, diosmin is widely derived from another flavonoid called hesperidin, which is also found in citrus fruits — especially orange rinds (2).

Diosmin is often combined with micronized purified flavonoid fraction (MPFF), a group of flavonoids that includes disomentin, hesperidin, linarin, and isorhoifolin (3).

Most diosmin supplements contain 90% diosmin with 10% hesperidin and are labeled MPFF. In most cases, the terms “diosmin” and “MPFF” are used interchangeably (3).

This supplement is available over the counter in the United States, Canada, and some European countries. Depending on your location, it may be called Diovenor, Daflon, Barosmin, citrus flavonoids, Flebosten, Litosmil, or Venosmine (4, 5).

Diosmin is most widely used to treat blood vessel disorders, such as hemorrhoids and chronic venous insufficiency (CVI). Hemorrhoids are swollen veins located near the anus, while CVI refers to swollen, blocked veins in the legs (6, 7).

People may also take diosmin for other blood vessel disorders, including varicose veins, blood clots, retinal hemorrhage (bleeding in the retina of the eye), venous leg ulcers, and venous stasis (slow blood flow in the legs) (8, 9).

Research suggests that this compound may reduce inflammation in the veins and thus improve blood flow (2).

Hemorrhoids

Numerous studies suggest that diosmin helps treat internal and external hemorrhoids.

In a review of 24 studies in over 2,300 people, plant flavonoids like diosmin decreased hemorrhoid-related itchiness, bleeding, discharge, and other hemorrhoid symptoms (10).

Other studies reveal similar improvements in hemorrhoid symptoms. Additionally, diosmin has been shown to reduce recovery time following a hemorrhoidectomy, or surgical removal of hemorrhoids (3, 11, 12, 13).

Though these results are promising, most improvements are seen in people in the early stages of hemorrhoid disease. Overall, diosmin may not be as effective as other hemorrhoid treatments (11, 12, 14, 15).

Chronic venous disease

Chronic venous disease (CVD) is an umbrella term for conditions related to weak or diseased veins. These include CVI, varicose veins, spider veins, leg ulcers, and phlebitis — a condition in which the leg veins become swollen (16).

A 2012 review of 10 studies concluded that moderate evidence supports the use of MPFF (diosmin) to improve CVD symptoms, such as leg ulcers, edema, varicose veins, tingling sensation, general quality of life, and subjective pain ratings (16).

A 2016 review and 2018 meta-analysis supported these findings. Furthermore, they showed diosmin reduced leg heaviness, swelling, cramps, and restless leg syndrome (17, 18).

Diosmin treats CVD by reducing inflammation, improving the health of veins, and increasing blood and lymphatic circulation (3, 19, 20, 21).

Still, a 2017 study in 1,051 people noted that diosmin wasn’t as effective at treating CVD symptoms as other medications, such as Venoruton (Novartis) and Pycnogenol (pine bark extract). Other studies report similar findings (22, 23, 24).

Though diosmin may reduce symptoms of CVD, it’s best to speak to a healthcare professional before supplementing with it.

Back pain

In one study, 300 people reported minor improvements in back pain after taking 900 mg of diosmin 3 times daily for 2 weeks, followed by the same dose twice daily for 2 weeks, then a maintenance dose of 450 mg twice daily for 1 month (25).

However, compared with a control group taking mannitol and dexamethasone, diosmin was not more effective at reducing subjective back pain (25).

More research is needed to understand if diosmin aids back pain compared with more established treatments.

Other conditions

Some people take diosmin for other conditions, including lymphedema (swelling of the lymphatic system), varicocele (pain and enlargement of veins in the scrotum), minor bleeding, pelvic pain, and rosacea.

Diosmin is a known anti-inflammatory compound and may work to treat some of these inflammatory and circulation disorders.

Although small studies have shown some positive results for treating symptoms of lymphedema, varicocele, minor nasal bleeds, and pelvic pain, larger studies are needed before widespread recommendations can be made (26, 27, 28, 29).

Diosmin is generally recognized as a safe over-the-counter supplement.

Though rare, side effects of diosmin include stomach pain, diarrhea, headaches, dizziness, skin rash, hives, muscle pain, and — in severe cases — irregular heartbeat (30, 31).

If you experience any side effects after taking diosmin, discontinue use and speak with your healthcare provider. If you experience severe pain, severe diarrhea (10 or more loose stools in 24 hours), or an irregular heartbeat, seek medical attention immediately.

Diosmin is available over the counter in the United States, Canada, and certain European countries. It’s typically sold as micronized purified flavonoid fraction (MPFF), which usually contains 90% diosmin and 10% hesperidin.

The most common and well-researched supplement is Daflon 500 (450 mg diosmin, 50 mg hesperidin). It’s also known as Detralex in some regions. However, many other diosmin products are likely available in your local pharmacy and online.

Most diosmin products recommend taking one 500-mg supplement with food once in the morning and again in the evening for a total of 1,000 mg per day.

Under the guidance of a health professional, these dosage guidelines have been shown to be safe and effective for various conditions (16, 32, 33):

• Chronic venous disease: 1,000 mg per day for 3–6 months
• Hemorrhoids: 1,000–2,000 mg per day for 4 days, followed by 1,000 mg per day for 3 days
• Varicose veins: 1,000–2,000 mg per day for up to 6 months

Do not take diosmin for more than 3 months — or take more than the recommended dose on the label — unless instructed by your healthcare provider.

To date, there are no known cases of diosmin overdose or reports of toxicity.

Nonetheless, you should always follow the instructions on the label and speak to a healthcare professional to make sure it’s right for you.

Diosmin may interact with the following medications (34, 35, 36):

• anticoagulants (such as Warfarin)
• anticonvulsants (such as Carbamazepine and Phenytoin/Dilantin)
• antihistamines (such as Allegra)
• muscle relaxants (such as Chlorzoxazone)
• non-steroidal anti-inflammatory drugs (such as Voltaren, Motrin, Advil, and Aleve)
• acetaminophen (such as Tylenol)

Diosmin may inhibit various liver enzymes responsible for metabolizing the above medications. This can result in your medications working less effectively and may be dangerous for those with bleeding disorders by preventing proper blood clotting (34, 35, 36).

Diosmin may also interact with certain herbal supplements, including fenugreek, feverfew, garlic, ginger, ginkgo, ginseng, and turmeric, due to their involvement in blood thinning (34).

If you take any of these medications or supplements, be sure to speak to your healthcare provider before trying diosmin.

Be sure to store diosmin in a cool, dry environment, such as a medicine cabinet. Always read the label and avoid taking any supplements past their expiration date.

Due to a lack of safety research, women who are pregnant or breastfeeding should avoid taking diosmin.

Always speak with your healthcare provider before taking any supplements or medications.

Diosmin may worsen bleeding people with bleeding disorders. If you have any bleeding disorders, avoid this supplement unless instructed otherwise by your healthcare provider (30, 31).

Children and teenagers should avoid taking diosmin, as there is no available safety research in these age groups.

If you have any underlying conditions, such as diabetes, heart disease, and inflammatory bowel disease (IBD), it’s important to speak with a healthcare professional before taking diosmin.

Depending on your condition, a variety of other products or treatments may work as a suitable alternative to diosmin (7, 21, 37, 38):

• Hemorrhoids: high fiber diets, topical creams and suppositories, over-the-counter pain relievers (Advil, Motrin, Tylenol), prescription medications, injections, and surgical procedures like hemorrhoid removal or hemorrhoid stapling
• CVD (including varicose veins): over-the-counter pain relievers (Advil, Motrin, Tylenol), compression socks, exercise, Antistax (red vine leaf extract) or other supplements, prescription medications, sclerotherapy, laser or radiofrequency ablation, and surgical procedures like vein ligation

Though diosmin has been shown to aid these conditions, your healthcare provider may recommend a combination of treatments. For best results, always follow your healthcare provider’s recommendations.

Diosmin instructions for use: indications, contraindications, side effects – description Diosmin tab.

, cover. film coated, 600 mg: 5, 10, 15, 20, 25, 30, 40, 50, 60 or 100 pcs. (46631)

Phlebodia 600 mg: instruction, price, analogues | film-coated tablets Lab.

Innotech International

pharmacodynamics . A venotonic and angioprotector that improves venous outflow, increases vascular resistance and reduces their permeability, has anti-edematous and anti-inflammatory effects.

Phlebodia 600 increases the tone of small veins, thereby improving venous outflow and lymphatic drainage. Venous tone increases due to an increase in the tropism of parietal noradrenaline to vein myocytes (increases the synthesis and / or release of norepinephrine; inhibits the activity of catechol-O-methyltransferase; moderately reduces the activity of PDE). The vasoconstrictive effect of the drug concerns only the venous and lymphatic channels. The drug does not affect the tone of the arteries. In animals, Phlebodia 600 improves tissue trophism and microcirculation by reducing capillary permeability and increasing their resistance. The drug has a moderate antiplatelet and anti-inflammatory effect. In humans, the anti-inflammatory effect is realized due to anti-complementary activity, inhibition of the peroxide anion release reaction, and a decrease in the production of leukotrienes. 9The increase in capillary resistance is dose-dependent.

Pharmacokinetics . Absorption . After oral administration, diosmin is metabolized by intestinal bacteria to form diosmetin. Then diosmetin is absorbed and determined in the blood compartment in the form of glucuronide conjugates and sulfonic conjugates. It has been established that the main metabolite of diosmin is diosmetin-3-O-glucuronide.

Cmax _max in blood plasma is achieved 12-15 hours after taking the drug. 9in the kidneys, liver and lungs. In other tissues there is a small amount of the drug. Selective accumulation of diosmin in the walls of the veins reaches a maximum at 9 hours after ingestion and continues for the next 96 hours.

Derivation of . In animals, the drug is excreted in the urine (79%) and by enterohepatic circulation in the feces (11%) and bile (2.4%).

In humans, diosmin is excreted in the urine and is found as diosmetin-3-O-glucuronide. 9For acute hemorrhoids: 2-3 tablets per day during meals for 7 days. If symptoms of the disease persist after treatment of hemorrhoids, you should consult a doctor to correct the treatment. The maximum daily dose is 1800 mg (3 tablets).

hypersensitivity to the active substance or any of the excipients of the medicinal product.

from the gastrointestinal tract: often (≥1/100; <1/10) - abdominal pain; infrequently (≥1 / 1000; <1/100) - bloating, diarrhea, dyspepsia, nausea; rarely (≥1/10,000; <1/1000) - vomiting.

In rare cases, gastrointestinal disorders rarely lead to discontinuation of treatment.

To reduce the frequency of adverse reactions, the drug should be taken with food.

From the skin and subcutaneous tissue: infrequently (≥1/1000; <1/100) - allergic reactions such as rash, itching, urticaria, angioedema.

chronic venous and lymphatic insufficiency . This drug is most effective when a healthy lifestyle is followed. Avoid prolonged exposure to the sun and overheating, prolonged standing or sitting, lifting excess weight. Walking and in some cases wearing special medical support stockings contribute to the normalization of microcirculation and improve blood circulation.

Acute hemorrhoids . The use of the drug does not replace the specific therapy of other proctological diseases and does not interfere with the treatment of other diseases.

Treatment is carried out in a short course.

If symptoms persist after a short course, a proctological examination should be performed and the therapy reviewed.

This medicinal product contains cochineal red A (E124), which may cause allergic reactions.

Use during pregnancy or lactation . In the course of experimental studies in animals, no teratogenic effect of diosmin on the fetus was revealed. In clinical practice, there were no reports of any side effects in the treatment of pregnant women with the drug. Pregnant women should use the drug with caution. Before use, you should consult with your doctor. For the purpose of prevention, it is desirable to avoid the use of the drug during pregnancy.

Due to the lack of data on the penetration of the drug into breast milk, the use of this drug during lactation should be avoided. The decision to stop breastfeeding or discontinue/withdraw from treatment with Phlebodia 600 should be made taking into account the benefits of breastfeeding for the child and the benefits of therapy for the woman.

The ability to influence the reaction rate when driving vehicles or operating other mechanisms . No studies have been conducted on the effect of diosmin on the ability to drive vehicles or operate other mechanisms. Despite this, according to the safety profile of Diosmen in different countries of the world, Phlebodia 600 has little or no effect on the reaction rate when driving vehicles or operating other mechanisms.

Diosmin may enhance the vasoconstrictor effect of epinephrine, norepinephrine.

no cases of drug overdose have been reported.

in the original packaging at a temperature not exceeding 25 ° C, out of the reach of children. The active substance of the drug is diosmin. Released without a doctor’s prescription. Phlebodia 600 mg is prescribed to reduce the severity of symptoms due to lymphovenous insufficiency, such as a feeling of heaviness in the lower extremities, pain, trophic disorders; in the complex treatment of exacerbation of hemorrhoids; as an additional method of therapy for increased capillary fragility, microcirculation disorders (instruction of the Ministry of Health of Ukraine).

Diosmin

Diosmin (diosmetin 7-O-rutinoside) is a flavonoid (natural flavone hydroxy derivative) found in plants of the Rutaceae family, especially found in the pericarp of various citrus fruits (Imam F. et al., 2015). It was first isolated from the leaves of Scrophularia nodosa L. (Scrophulariaceae) in 1925 g., and currently it can also be obtained by dehydrogenation of another flavonoid – hesperidin. Diosmin has a wide range of biological properties, confirmed by numerous studies in vitro and in vivo . It acts as an antioxidant, antihyperglycemic, anti-inflammatory, antimutagenic and antiulcer agent (Silambarasan T. et al., 2012; Bogucka-Kocka A. et al., 2013).

Diosmin is now one of the most widely used natural compounds in the treatment of chronic venous insufficiency (CVI), a progressive disorder that affects an increasing number of people every year, due to its positive effect on the cardiovascular system. As a result of clinical studies, it was found that diosmin reduces the severity of pain and swelling in patients with CVI, as it improves lymphatic drainage and maintains microcirculation (Lyseng-Williamson K. A. et al., 2003; Batchvarov I. V. et al., 2010). It also increases capillary resistance, vascular tone and venous elasticity and reduces capillary filtration and capillary hyperpermeability (Perrin M. et al., 2011). Diosmin exhibits an anti-inflammatory effect by inhibiting the expression of pro-inflammatory cytokines by blocking the activation of NF-κB pathways (Imam F. et al., 2015). There was a regression of symptoms such as swelling, pain, a feeling of heaviness and pressure in the legs, as well as an improvement in the quality of life of patients with CVI (Maksimović Z.V. et al., 2008).

The antioxidant activity of diosmin may also have a significant effect on the relief of symptoms of CVI, as oxygen-free radicals released during inflammation can cause tissue damage and release of inflammatory mediators. It is known that prostaglandins and their analogs isoprostanes are considered as biomarkers of oxidative stress (Davi G. et al., 1999; Prasain J. K. et al., 2013). For example, elevated levels of both compounds have been reported in patients with cardiovascular disease (Petrosino T. et al., 2014).

Urgency

The prevalence and incidence of chronic and acute venous disease in the world is very high in both industrialized and developing countries. Currently, chronic venous diseases of the lower extremities are an integral part of the deadly angiopandemic of the third millennium. Today, the frequency of the most severe cases with a progressive stage of venous insufficiency in the population has increased by 2 times. Among venoactive (venoactive) drugs, a micronized purified fraction of the flavonoid diosmin is widely prescribed. Compression sclerotherapy, liquid or foam, is a safe and effective invasive treatment for telangiectasias, reticular varices, and saphenous varicose veins. Direct oral anticoagulants are one of the therapeutic and prophylactic options for deep vein thrombosis (DVT) and venous thromboembolism (VTE), however, there are restrictions on use for patients with malignant neoplasms and during pregnancy. The most effective is triple simultaneous prevention. Thrombosis of superficial veins more than 5 cm long is also an indication for anticoagulant therapy (Gavorník R. et al., 2015).

Oxidative stress plays an important role in the pathophysiology of many human diseases, while antioxidants prevent the development of various adverse symptoms. Diosmin is a natural flavonoid used in disorders of the vascular system, especially in CVI, and plays a significant role in alleviating the symptoms of this pathology. The study examined the effect of diosmin treatment on isoprostane levels in plasma samples from patients with CVI. Qualitative analysis was performed using high performance liquid chromatography followed by detection spectrometry (LC-MS). A statistically significant decrease in the content of isoprostane after 3 months of treatment was observed in the study group; however, the most significant changes were found in patients who smoke (Marcin Feldo et al., 2018).

Chronic venous insufficiency

CVI is defined as morphological and functional disorders of the venous system, manifested by varicose veins (structural changes in the vein wall), venous leg ulcers, edema or skin changes. The primary stage of the disease is the result of increased and persistent venous hypertension, caused mainly by reflux due to malfunction of the venous valves. Increases hydrostatic pressure and blood flow in capillaries. This causes the adhesion of leukocytes to the capillary endothelium and initiates an inflammatory reaction. Consequently, the capillaries become permeable to fluid, which causes the formation of edema (Perrin M., Ramelet A. A., 2011).

CVI first appears as an increase in venous tension (venous hypertension or high blood pressure in the veins) with or without reflux (Kurz, 1999). Depending on the cause, CVI can be congenital, primary (with an undetermined cause), or secondary (post-thrombotic, post-traumatic, or other causes). Depending on the pathophysiology, the development of the disease may be due to occlusion (blocked veins), reflux, or both. Finally, this may depend both on the superficial or deep venous system, and on perforation anomalies (Porter T.M., 1995).

CVI is an important cause of discomfort and inability to work, as a result of which the quality of life is reduced. The prevalence of this pathology has not been clearly recorded because there are few studies available today, and those that are available do not have the full amount of necessary information. Some studies do not cover the entire pathological spectrum and focus only on varicose veins or ulcers, while others do not use the standard characteristics of the disease, but refer to many different diagnostic criteria (Nicolaides A., 2000). As a result, the prevalence of the disease was estimated in the range of 1–50% (Stanhope J. M., 1975; Van den Oever, 1998). One study showed an annual incidence of 2.6% in women and 1.9% in men (Brand, 1988).

The causes of cardiovascular disease are unknown, although they are associated with the expansion and deformation of the veins, as well as a violation of the normal functioning of the valves of the veins. Trophic skin diseases and venous ulcers result from severe varicose veins (Carpentier, 2000). Varicose veins have a multifactorial origin associated with advanced age and possibly lifestyle (sedentary lifestyle), pregnancy and hereditary factors, and obesity. The risk of ulcers may be increased due to trauma and previous episodes of deep vein thrombosis (clinical or subclinical) (Scott, 1995).

Clinical manifestations of CVI vary depending on the stage of the disease and may include a feeling of heaviness in the limbs, paresthesia (tingling), convulsions, pain, edema (swelling), varicose veins, skin pigmentation, varicose ulcers, and signs of skin atrophy.

Surgery, sclerotherapy, and sequential mechanical compression are generally considered the preferred treatments. Nevertheless, pharmacological treatments are often used, including phlebotonic drugs. Although phlebotonics are dispensed from pharmacies in some countries, they are not widely available in others. For example, in Spain, some phlebotonics are not used for CVI, while a number of other phlebotonics, such as diosmin, are used, but the period of their use is limited to 2-3 months during an exacerbation of the disease. Phlebotonics are a heterogeneous group of drugs used to treat chronic venous insufficiency. Most of these drugs are naturally occurring flavonoids extracted from plants. Synthetic products with flavonoid-like properties are also used for venous diseases. They are known as phlebotonics (venoactive) drugs. Phlebotonics affect macrocirculation, for example they can improve venous tone (Tsouderos, 1991), and microcirculation parameters, for example, reduce capillary permeability (Behar, 1988).

However, there are doubts about the clinical efficacy and safety of phlebotonics. As a result of some studies, it was found that the risk of agranulocytosis is associated with drugs in this group (Kaufman, 1991; Ibañez, 2000). It is for this reason that it is especially necessary to conduct an objective and thorough assessment of the effectiveness of phlebotonics (Martinez M. J. et al., 2005).

CVI is accompanied by a pronounced inflammatory response, which is believed to lead to the development and progression of the disease. Although compression therapy has long been a standard treatment, recent research confirms that flavonoid treatment may also be beneficial. The purpose of one of the reviews is to summarize information about the effect of plant flavonoids on the inflammatory process and the immune response through the inhibition of important regulatory enzymes. As a result of research, it was found that this effect is due to the inhibition of key enzymes involved in the biosynthesis of prostaglandin (ie, lipoxygenase (an iron-containing enzyme), phospholipase and COX) by flavonoids. Flavonoids also inhibit phosphodiesterases involved in cell activation. Much of this effect is associated with the biosynthesis of protein cytokines, which mediate the adhesion of circulating leukocytes to injury sites. Protein kinases are another class of regulatory enzymes that are affected by flavonoids. Kinase inhibition is associated with the competitive binding of flavonoids to ATP at one of the catalytic sites of the enzyme. These modes of inhibition provide the mechanisms by which flavonoids inhibit inflammation. Therefore, it is assumed that this class of substances can be effective in the treatment of CVI (Manthey J.A., 2000).

Therapy of hemorrhoids

Several theories about the etiopathogenesis and physiopathology of hemorrhoids have been proposed so far. From a physiopathological point of view, the vascular factor is of particular importance, which, in turn, is influenced by mechanical factors that disrupt the venous backflow. As evidence of a hemorrhoidal crisis characterized by local swelling, pain and bleeding, the use of bioflavonoid preparations is considered the first choice. During the study, purified diosmin was used at a dose of 2 tablets of 450 mg 2 r / day for the first 7 days, and then 1 tablet 1 r / day for 2 months. The study was conducted in a group consisting of 66 patients with primary hemorrhoids of the 1st–4th degree. The results obtained confirmed the effectiveness of diosmin in reducing the severity of pain and bleeding in the 1st week of therapy: 79and 67% (diosmin and placebo groups, respectively). At the 2nd week, the indicators were 98 and 86%, respectively. Tolerability of diosmin was excellent: this characteristic of the drug allows doctors to widely prescribe diosmin in the complex therapy of hemorrhoids, as well as in preparing the patient for further treatment (Diana G. et al., 2000).

Conclusion

Despite the high level of development of modern angiology and vascular surgery, the problem of CVI, which complicates the course of various venous diseases, apparently does not tend to be solved, which requires a constant search for optimization of methods of treatment and rehabilitation of patients with the aforementioned syndrome. Particular attention should be paid to the endothelial state in CVI and the possibilities of correcting endothelial dysfunction using bioflavonoids, in particular diosmin (Kalinin R.E. et al., 2015).

One such drug is Phlebodia 600 mg (diosmin), which increases the tone of small veins, thereby improving venous outflow and lymphatic drainage. The vasoconstrictive effect of the drug concerns only the venous and lymphatic channels. The drug does not affect the tone of the arteries. Phlebodia 600 mg improves tissue trophism and microcirculation by reducing capillary permeability and increasing their resistance.