Long-Term Safety and Efficacy of Lubiprostone in Opioid-induced Constipation in Patients with Chronic Noncancer Pain.

Abstract

Chronic opioid analgesic use often causes opioid-induced constipation (OIC). This open-label extension study evaluated the safety and efficacy of lubiprostone, a chloride channel (ClC-2) activator, for treatment of OIC in patients with chronic noncancer pain. Adults with OIC were enrolled from two 12-week, placebo-controlled, double-blind studies and received lubiprostone 24μg twice daily for up to 9months. OIC was defined as <3 spontaneous bowel movements (SBMs)/week during the 2-week baseline period, of which ≥25% were characterized by hard to very hard stool consistency, subjectively incomplete evacuation, and/or moderate or worse straining. Inclusion criteria required consistent treatment with full opioid agonists ≥30days prior to screening and throughout the study. All 439 patients who received lubiprostone were analyzed for safety and efficacy. Overall, 24.6% of patients reported treatment-related adverse events (AEs), most commonly nausea (5.0%), diarrhea (4.6%), headache (1.6%), and vomiting (1.4%). No treatment-related serious AEs were reported. Nausea and diarrhea each led to study discontinuation in 5 patients (1.1%); 2 cases each of nausea and diarrhea were rated as severe. Rescue medication usage decreased from month 1 (33.0%) to month 9 (18.6%). Mean weekly SBM frequency (1.4) was significantly increased from baseline at all months (P<0.001, range 4.9 to 5.3). Straining, abdominal bloating, abdominal discomfort, stool consistency, constipation severity, and bowel habit regularity were significantly improved from baseline at all months (P<0.001). Lubiprostone treatment was well tolerated and improved symptoms and signs of OIC in this 9-month, open-label study of patients with chronic noncancer pain.