DEERFIELD, IL – Lubiprostone, marketed as Amitiza by Sucampo Pharmaceuticals Inc. and its partner Takeda Pharmaceuticals USA Inc., has been approved by the Food and Drug Administration (FDA) as the first oral treatment for opioid-induced constipation in adults with chronic noncancer pain.
The drug is a specific activator of ClC-2 chloride channels in the intestinal epithelium, and, through activation of apical ClC-2 channels in the intestinal epithelium, bypasses the antisecretory action of opiates.The new approval came after a Supplemental New Drug Application that received a priority review. The drug already is approved in the United States for the treatment of chronic idiopathic constipation in adults, also at a dose of 24 μg twice daily, and irritable bowel syndrome with constipation in women 18 years of age and older at a dose of 8 μg twice daily.
FDA approval was based on results from 12-week, Phase 3 studies in patients taking opioids, including morphine, oxycodone and fentanyl for chronic noncancer pain and a long-term open-label safety study. Two of the Phase 3 studies met the overall efficacy endpoint, although a third study did not, according to a Sucampo press release.
The manufacturer points out that the effectiveness of the drug in patients taking diphenylheptane opioids, such as methadone, hasn’t been established and that concomitant use of these opioids might interfere with its effectiveness.
Opioid-induced constipation is a common adverse effect of long-term opioid use because the binding of opioids to peripheral opioid receptors in the gastrointestinal (GI) tract results in absorption of electrolytes, such as chloride, with a subsequent reduction in small intestinal fluid. Activation of enteric opioid receptors also results in abnormal GI motility.