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       #Post#: 492--------------------------------------------------
       (ACTRIMS/ECTRIMS) Bismuth subsalicylate may ease GI events due t
       o Tecfidera
       By: agate Date: September 22, 2014, 12:04 pm
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       Bismuth subsalicylate, AKA Pepto-Bismol.
       From DocGuide News, September 15, 2014:
       [quote]Bismuth Subsalicylate Eases Gastrointestinal Events
       Associated With Delayed-Release Dimethyl Fumarate
       By Brian Hoyle
       BOSTON -- Co-administration of bismuth subsalicylate (BS) and
       delayed-release dimethyl fumarate (DMF) in the first 4 weeks of
       an 8-week fumarate treatment can significantly reduce the
       severity and prevalence of flatulence and diarrhoea, according
       to research presented at the 30th European Committee for
       Treatment and Research in Multiple Sclerosis (ECTRIMS).
       If these results hold in larger studies, therapeutic compliance
       with a DMF regimen in patients with relapsing multiple sclerosis
       may be aided by the early inclusion of BS, stated Carlo
       Tornatore, MD, Georgetown University Hospital, Washington, DC,
       speaking here at a poster presentation on September 11.
       Phase 3 studies have established that delayed-release DMF is
       safe and effective in the treatment of relapsing-remitting
       multiple sclerosis; however, the benefits commonly are
       accompanied by gastrointestinal adverse events, including
       nausea, bloating, lower abdominal pain, diarrhoea, and
       flatulence, all of which may erode treatment compliance.
       Dr. Tornatore and colleagues randomised 175 healthy volunteers
       who all received an 8-week regimen of twice daily oral DMF (120
       mg or 240 mg for 4 weeks, followed by 240 mg for 4 weeks). The
       participants were randomised to a co-administration of either
       placebo (n = 87) or BS 524 mg (n = 88) during the first 4 weeks.
       Participants recorded symptoms during treatment using an
       electronic diary. Each diary was examined at weeks 2, 4, 6, and
       8, and participants received a follow-up phone call at week 10.
       The number of self-reported gastrointestinal adverse events was
       highest in the first week of treatment (50.0% for placebo, 55.7%
       for BS), and declined thereafter (26.6% for placebo, 21.3% for
       BS by week 8), with the weekly frequency being similar in both
       groups. During the 4 weeks of co-administration of placebo or BS
       with DMF, the prevalence of all gastrointestinal events and
       acute events was slightly higher in those receiving BS than in
       those receiving placebo. These rates were comparable to previous
       self-reported rates.
       The mean time from the beginning of treatment to the development
       of a gastrointestinal event was similar in the groups, and the
       first event tended to be reported as mild in both groups.
       When the data were parsed out according to the nature of the
       adverse events, however, a different picture emerged. The
       incidences of flatulence and diarrhoea in those receiving BS
       (38.6% and 36.4%, respectively) were much lower than in those
       receiving placebo (50.6% and 48.2%, respectively), but were not
       significantly different.
       The group receiving BS also displayed lower mean worst severity
       scores for flatulence (1.1 vs 1.8; least square mean difference
       0.7, 95% confidence interval [CI] 0.1 to 1.3) and diarrhoea (1.0
       vs 1.6; least square mean difference 0.6, 95% CI 0.0 to 1.2). BS
       was associated, however, with comparatively greater prevalence
       of lower abdominal pain (42.0% vs 38.8%) and bloating (40.9% vs
       37.6%).
       The number of symptomatic days and the duration of each symptom
       were comparable in the 2 groups, with the exception of bloating,
       which was appreciably longer in the placebo group (median
       duration approximately 12.5 hours) than the BS group (median
       duration approximately 8 hours).
       Participant rating of their symptoms as severe revealed a milder
       pattern in those receiving BS for flatulence (1.1% vs 5.9%) and
       diarrhoea (1.1% vs 9.4%), upper abdominal pain (0% vs 8.2%), and
       indigestion (0% vs 3.5%). Flushing of the skin was similar in
       both groups (about 70% in week 1 and declining steadily to week
       8 values of 45.8% and 32.5% in the placebo and BS group,
       respectively.
       Adverse events were reported by 146 of the 175 (83.4%)
       participants, including 72 (82.8%) in the placebo group and 74
       (84.1%) in the BS group. One participant in each group
       discontinued the study.
       The 2 groups were similar at baseline in age, gender proportion,
       race, body mass index, weight, and height.
       [Presentation title: Effect of bismuth subsalicylate on
       gastrointestinal events associated with delayed-release dimethyl
       fumarate: a double-blind, placebo-controlled study. Abstract
       P052][/quote]
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