Lubiprostone
SUCAMPO/TAKEDA
Chloride channel activator approved for chronic constipation
By increasing intestinal fluid secretion, lubiprostone increases motility in the intestine, thereby increasing the passage
of stool and alleviating symptoms associated with constipation. Lubiprostone was approved on January 31, 2006, for the treatment
of chronic idiopathic constipation (CIC) in adults.
Efficacy. The efficacy of lubiprostone in the treatment of CIC was evaluated in a dose-finding, double-blind, parallel-group, placebo-controlled
phase 2 study of 127 patients with CIC. The patients were randomized to receive placebo or lubiprostone 24, 48, or 72 mcg/d.
The primary efficacy variable in the study was the daily average number of spontaneous bowel movements (SBMs). The study demonstrated
that all patients who received lubiprostone experienced a noticeable improvement in clinical response. There was no statistically
significant improvement in clinical response beyond a total daily dose of 24 mcg. In 2 identical, double-blind, placebo-controlled
studies, 479 patients with CIC were randomized to receive 4 weeks of either lubiprostone 24 mcg/bid or placebo. The primary
end point of the studies was the SBM frequency following initiation of double-blind treatment. Patients receiving lubiprostone
had a higher frequency of SBMs than patients receiving placebo during all 4 weeks of the study. At Week 4 of Study 1, patients
in the lubiprostone group experienced a mean change in SBM rate from baseline of 3.9±4.6 versus 1.3±2.5 for patients in the
placebo group. Similarly, at Week 4 of Study 2, patients in the lubiprostone group experienced a mean change in SBM rate from
baseline of 4.1±4.8 versus 1.9±2.7 for patients in the placebo group. In both studies, lubiprostone treatment demonstrated
increases in the percentage of patients who experienced SBMs within the first 24 hours after administration when compared
with placebo (56.7% vs 36.9% in Study 1 and 62.9% vs 31.9% in Study 2).
Safety. Patients with symptoms suggestive of mechanical gastrointestinal obstruction should be evaluated prior to initiating lubiprostone
treatment. Lubiprostone may cause nausea. Food may be administrated concomitantly with the drug to reduce the symptoms of
nausea. Lubiprostone should not be administered to patients who have severe diarrhea, and patients should be aware of the
possible occurrence of diarrhea during treatment. The most common adverse events associated with lubiprostone therapy are
nausea and diarrhea. Dosing. The recommended dose of lubiprostone is 24 mcg taken twice daily orally with food. Physicians and patients should periodically
assess the need for continued therapy.
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Posted 2008-02-16 07:58:17.0
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