Parenteral troxerutin and carbazochrome combination in the treatment of post-hemorrhoidectomy status: a randomized, double-blind, placebo-controlled, phase IV study.

Flavonoids, such as troxerutin, have been shown to be safe and effective agents for the treatment of chronic venous insufficiency. The fixed combination between troxerutin 150 mg and carbazochrome 1.5 mg (Fleboside ampoules) was previously shown to have a good efficacy and safety profile in non-surgical patients with acute uncomplicated hemorrhoids. The purpose of this randomized, double-blind, placebo-controlled study was to investigate the efficacy and tolerability of the active combination in the treatment of post-hemorrhoidectomy patients. 30 patients were randomized to receive one of two treatments: troxerutin 150 mg and carbazochrome 1.5 mg, or placebo, i.m. 3 ml ampoules twice a day for five consecutive days after the surgical procedure, starting from the day of surgery. Efficacy parameters were assessed as follows: at baseline (T1), after the first administration (T2; day of surgery), the second day after the surgical procedure (T3), and the fifth day after the surgical procedure (T4); hemorrhoidal symptoms based on a visual analogue scale (VAS): pain, discharge, bleeding, inflammation, and pruritus; analgesic intake, if any; time to restore a physiological defecation; edema evaluation (based on a four-point scale: 0 = absent; 1 = mild; 2 = moderate; 3 = severe); camera pictures taken at T1 and T4 (in selected patients); and blood coagulation tests. Analysis between treatment groups revealed a highly significant difference at T3 and T4 for the total VAS score (p = 0.007 and p = 0.001, respectively) in favor of the active combination treatment. A statistically significant difference was also observed for bleeding and pruritus at T3 and for these two parameters and both inflammation and edema at T4 (p < 0.001) in favor of the active combination group. No adverse events were reported. Neither the active combination nor placebo affected blood coagulation tests. We conclude that intramuscular administration of the fixed combination of troxerutin 150 mg and carbazochrome 1.5 mg is effective, well tolerated and superior to placebo in improving hemorrhoidal and post-surgical symptoms during the five days following surgery.

Effect of bioflavonoids (trihydroxyethylrutin and disodium flavodate) in vitro on neutrophil reactive oxygen production and phagocytic ability assessed by flow cytometry.

Neutrophil granulocytes have been described as agents of defence and destruction. The effect of two flavonoid compounds (trihydroxyethylrutin and disodium flavodate) on the phagocytic ability and generation of reactive oxygen radicals of neutrophils was studied at concentrations of 5 mg/l, 50 mg/l and 100 mg/l. Flow cytometry was used to study phagocytic ability by measuring uptake of fluorescein-labelled bacteria. The generation of reactive oxygen intermediates was estimated by means of a CD16 phycoerythrin-conjugated mouse anti-human monoclonal antibody. In vitro trihydroxyethylrutin (THET) and disodium flavodate (DF) treatment reduced reactive oxygen production (DF at 5 mg/l--40%, at 50 mg/l--71% and at 100 mg/l--82%; THET at 5 mg/l--53%, at 50 mg/l--88%, at 100 mg/l--93%; all p < 0.001). This was rapidly reversible after plasma exchange. Both flavonolds did not affect neutrophil phagocytic ability. We conclude that THET and DF could decrease oxidative tissue damage by neutrophils. A beneficial effect in peripheral vein disease could be anticipated from these results.