Eluxadoline is a mixed µ-opioid receptor and ?-opioid receptor agonist and d-opioid receptor antagonist, approved for the treatment of irritable bowel syndrome with diarrhea (IBS-D).
Dr Brooks Cash and colleagues from Alabama, USA evaluated the safety and tolerability of eluxadoline 75 and 100mg twice daily (BID) in one Phase 2 (IBS-2001) and two Phase 3 (IBS-3001 and IBS-3002) studies.
Adults with IBS-D were randomized to placebo or eluxadoline BID for 12 (IBS-2001), 26 (IBS-3002), or 52 (IBS-3001) weeks.
Safety data were pooled.
Adverse events were assessed, with special focus on opioid-related adverse events, including suspected sphincter of Oddi spasm events.
The research team included 2,776 patients in the enrolled set.
The team reported that the safety set comprized 2,814 patients, based on actual treatments received.
The most frequent adverse events in the placebo and eluxadoline 75 and 100?mg groups were constipation, and nausea.
The team observed that discontinuation due to constipation was uncommon.
There were 10 SOS events that occurred in eluxadoline-treated patients, manifesting as acute abdominal pain with elevated aminotransferases or lipase, or pancreatitis; all occurred in patients without a gallbladder.
The researchers observed that 8 of these events occurred with the higher dose of eluxadoline, within 1 week of initiation of therapy, and all resolved with eluxadoline discontinuation.
The team found that there were 5 events independently adjudicated as pancreatitis not associated with SOS, three of which were associated with heavy alcohol use.
Dr Brooks' team comments, "Eluxadoline was well tolerated in Phase 2 and 3 trials, with constipation and nausea the most common adverse events."
"Consistent with the known adverse effects of opioid agonists, clinically apparent SOS events were observed in eluxadoline-treated patients."
"All occurred in patients without a gallbladder and the majority were observed in patients on the higher dose of eluxadoline, suggesting a possible association."