ABSTRACT
The paper describes a case report of a patient with a significant history of opioid-induced dysfunction of the sphincter of Oddi, who required morphine sulfate to manage oral mucositis pain, and who was successfully treated with concomitant oral naloxegol (Moventig: Kyowa Kirin, Galashiels, UK).
Subject(s)
Analgesics, Opioid/adverse effects , Morphinans/therapeutic use , Morphine/adverse effects , Narcotic Antagonists/therapeutic use , Polyethylene Glycols/therapeutic use , Spasm/chemically induced , Spasm/drug therapy , Sphincter of Oddi Dysfunction/drug therapy , Administration, Oral , Carcinoma, Squamous Cell/complications , Humans , Male , Middle Aged , Morphinans/administration & dosage , Mucositis/complications , Mucositis/drug therapy , Narcotic Antagonists/administration & dosage , Pain/complications , Pain/drug therapy , Polyethylene Glycols/administration & dosage , Sphincter of Oddi Dysfunction/chemically induced , Sphincter of Oddi Dysfunction/physiopathology , Tonsillar Neoplasms/complicationsABSTRACT
OBJECTIVES: Eluxadoline is a mixed µ-opioid receptor (OR) and κ-OR agonist and δ-OR antagonist, approved for the treatment of irritable bowel syndrome with diarrhea (IBS-D). This analysis evaluated the safety and tolerability of eluxadoline 75 and 100 mg twice daily (BID) in one Phase 2 (IBS-2001) and two Phase 3 (IBS-3001 and IBS-3002) studies. METHODS: Adults with IBS-D (Rome III criteria) were randomized to placebo or eluxadoline (75 or 100 mg) BID for 12 (IBS-2001), 26 (IBS-3002), or 52 (IBS-3001) weeks. Safety data were pooled. Adverse events (AEs) were assessed, with special focus on opioid-related AEs, including suspected sphincter of Oddi spasm (SOS) events. RESULTS: 2,776 patients were included in the enrolled set; the safety set comprised 2,814 patients, based on actual treatments received. The most frequent AEs in the placebo and eluxadoline 75 and 100 mg groups were constipation (2.5, 7.4, and 8.1%, respectively) and nausea (5.0, 8.1, and 7.1%, respectively); discontinuation due to constipation was uncommon (0.3, 1.1, and 1.5%, respectively). Ten SOS events (10/1,839; 0.5%) occurred in eluxadoline-treated patients, manifesting as acute abdominal pain with elevated aminotransferases or lipase, or pancreatitis; all occurred in patients without a gallbladder. Eight of these events occurred with the higher dose of eluxadoline, within 1 week of initiation of therapy, and all resolved with eluxadoline discontinuation. There were five events independently adjudicated as pancreatitis not associated with SOS, three of which were associated with heavy alcohol use. CONCLUSIONS: Eluxadoline was well tolerated in Phase 2 and 3 trials, with constipation and nausea the most common AEs. 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.
