DIOSMIN
 0.0 OVERVIEW
 A. Diosmin is a flavone derivative with phlebotropic properties.
 B. DOSING INFORMATION: Oral doses of diosmin 450 milligrams (mg) twice daily (in
combination with hesperidin 50 mg) are used in the treatment of chronic venous insufficiency,
hemorrhoids, venous leg ulcers, and upper limb lymphedema secondary to conventional
therapy of breast cancer. Topical application two or three times daily is used for treatment of
hemorrhoids, ankle edema and venous leg ulcers.
 C. PHARMACOKINETICS: After oral administration, diosmin is well absorbed and is excreted
mainly in the feces. The mean elimination half-life is 11 hours.
 D. CAUTIONS: Diosmin is well tolerated. Adverse effects, which include gastrointestinal and
autonomic disorders, are rare and mild.
 E. CLINICAL APPLICATIONS: Diosmin is used in the treatment of chronic venous insufficiency,
hemorrhoids, ankle edema, venous leg ulcers, premenstrual syndrome, microangiopathy in
diabetic patients and upper limb lymphedema secondary to conventional therapy of breast
cancer. The chemopreventive effects of diosmin in combination with hesperidin have been
tested in experimental studies.
3. ADULT:
 a. The symptomatic effect of diosmin 450 milligrams (mg)/hesperidin 50 mg (Daflon(R)) twice daily over a
period of 1 or 2 months in the treatment of chronic venous insufficiency has been reported by various
double-blind trials (Laurent et al, 1988; Tsouderos, 1989; Cospite & Dominici, 1989; Geroulakos &
Nicolaides, 1994; Belcaro et al, 1995). These studies, many of which were placebo-controlled, have
reported significant improvement in the diosmin group for functional symptoms (sensation of heaviness,
weakness, heat or burning leg pain, night cramps, paresthesia), edema or swelling of the feet and/or
ankles, redness or cyanosis. Diosmin was superior to placebo for increasing venous tone regardless of
venous insufficiency type, including functional venous insufficiency. Side effects have been rarely
reported.
 b. The safety of diosmin/hesperidin 450/50 milligrams during one year of continuous administration was
assessed in a prospective study of 215 outpatients with chronic venous insufficiency. Functional
symptoms quickly improved and improvement was maintained throughout the year of study. Tolerability
and safety of treatment was demonstrated by the rarity and mildness of adverse effects and the lack of
changes in laboratory parameters (Guillot et al, 1989).
Mobic (Meloxicam)
3.3.5 GASTROINTESTINAL
 A. GASTROINTESTINAL EFFECTS
 1. SUMMARY: Gastrointestinal adverse effects have occurred in up to 32% of patients treated
with meloxicam; the incidence of serious events (eg, ulceration) has been 0.2% or less in
available studies. Meloxicam may be better tolerated than piroxicam, diclofenac, and naproxen.
 2. Gastrointestinal disturbances are the most common adverse events seen during oral
meloxicam therapy, occurring in 17 to 32% of patients treated with 7.5 or 15 mg once daily
(Noble & Balfour, 1996; Prouse et al, 1996; Anon, 1996). Although the lower dose has been
slightly better tolerated, this difference is not statistically or clinically significant. The
gastrointestinal tolerability of meloxicam has been generally superior to that of piroxicam,
naproxen, and diclofenac; however, up to 15% of patients have required discontinuation of
meloxicam therapy due to gastrointestinal complications (Noble & Balfour, 1996; Prouse et al,
1996).
 3. In a pooled analysis of double-blind trials (total n=3,727), ABDOMINAL PAIN, DYSPEPSIA,
and upper gastrointestinal events were all observed in less than 8% of patients receiving
meloxicam 7.5 or 15 mg daily; the incidence of severe gastrointestinal events was
approximately 2%, with gastrointestinal perforation, ulcer, or bleeding occurring in 0.1% treated
with 7.5 mg daily and 0.2% treated with 15 mg daily. Approximately 4% of patients discontinued
therapy due to gastrointestinal complications. Incidences for most of these events, as well as
total gastrointestinal events, were significantly higher with piroxicam 20 mg daily, diclofenac 100
mg daily (sustained-release), and naproxen 750 to 1000 mg daily; exceptions were for upper
gastrointestinal adverse effects (similar in frequency with piroxicam and meloxicam) and
perforation/ulcer/bleeding (no significant difference between diclofenac and meloxicam) (Noble
& Balfour, 1996). It should be noted that some differences favoring meloxicam barely achieved
statistical significance (eg, dyspepsia and incidence of discontinuing therapy compared to
piroxicam), and may not prove clinically relevant.