Diosmin + Hesperidin

• Approved Indications:
• Chronic venous insufficiency (CVI), including symptoms such as leg heaviness, pain, swelling, and cramps
• Treatment and prevention of hemorrhoidal disease (acute and chronic hemorrhoids)
• Varicose veins and associated edema
• Post-thrombotic syndrome
• Off-label/Clinically Accepted Uses:
• Lymphedema management
• Microcirculatory disorders
• Adjunct therapy for venous ulcers and prevention of venous thromboembolism recurrence

• Route: Oral
• Adults:
• Typical dose ranges from 500 mg to 1000 mg of diosmin combined with 50 mg to 100 mg of hesperidin once or twice daily
• For chronic venous insufficiency: 1000 mg diosmin + 100 mg hesperidin once daily or divided doses
• For hemorrhoidal disease: initial higher doses (e.g., 2 tablets 3 times daily) during acute phase, followed by maintenance dosing
• Pediatrics:
• Safety and efficacy not established; use not routinely recommended
• Elderly:
• Use standard adult doses; monitor for tolerance and renal function
• Renal/Hepatic Impairment:
• No established dose adjustments; caution advised in severe impairment
• Administration Notes:
• Can be taken with or without food
• Maintain hydration during treatment

Diosmin and hesperidin are flavonoids that act synergistically to improve venous tone, reduce capillary permeability, and enhance lymphatic drainage. Diosmin inhibits the enzyme catechol-O-methyltransferase, leading to prolonged norepinephrine activity on the venous wall, resulting in venoconstriction and increased venous return. Both compounds exhibit antioxidant and anti-inflammatory effects by scavenging free radicals and inhibiting the release of inflammatory mediators such as prostaglandins and leukotrienes, thereby reducing vascular inflammation and edema.

• Absorption: Orally administered diosmin is converted to its aglycone, diosmetin, which is absorbed in the intestine. Hesperidin is hydrolyzed to hesperetin before absorption. Bioavailability is moderate due to metabolism by intestinal flora.
• Distribution: Both compounds bind moderately to plasma proteins and distribute primarily in plasma and vascular tissues.
• Metabolism: Extensive metabolism occurs in the liver and by gut microbiota, producing various metabolites with some pharmacological activity.
• Half-life: Diosmetin and hesperetin metabolites have elimination half-lives ranging from 8 to 11 hours.
• Elimination: Primarily renal excretion of metabolites; minor fecal elimination.
• Onset of Action: Clinical effects typically observed within days to weeks of therapy initiation.

• Pregnancy:
• Limited human data; animal studies do not indicate teratogenicity
• Use only if clearly needed and benefits outweigh risks
• Lactation:
• No data available; caution advised
• Potential low-level excretion into breast milk

• Primary Class: Phlebotropic agent (venotonic)
• Subclass: Flavonoid derivatives

• Known hypersensitivity to diosmin, hesperidin, or any excipients
• Severe renal or hepatic impairment (use caution)
• Pregnancy and lactation unless benefits outweigh risks

• Use cautiously in patients with a history of hypersensitivity reactions to flavonoids
• Monitor for rare allergic reactions
• Not recommended for children due to lack of safety data
• Discontinue if signs of hypersensitivity or severe adverse effects occur

• Common:
• Gastrointestinal disturbances: nausea, abdominal discomfort, diarrhea
• Headache
• Skin reactions: mild rash or pruritus
• Serious/Rare:
• Hypersensitivity reactions such as urticaria or angioedema (rare)
• Photosensitivity (rare)
• Typically well tolerated with mild and transient side effects

• No significant drug-drug interactions reported
• No known interactions with food or alcohol
• Caution when used concomitantly with anticoagulants or antiplatelet agents due to theoretical additive effects on bleeding risk

• Recent guidelines endorse diosmin + hesperidin as effective symptomatic treatment for chronic venous disease and hemorrhoidal disease
• Emphasis on use as adjunct therapy alongside compression therapy in venous insufficiency
• No recent major changes in dosing or safety profiles reported by regulatory bodies

• Store at 20°C to 25°C (68°F to 77°F)
• Protect from moisture and light
• Keep in tightly closed containers
• Keep out of reach of children
• Do not freeze