Amitiza

LubiprostoneSUCAMPO/TAKEDAChloride 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).

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.