Page 27 - Delaware Medical Journal - March 2017
P. 27
CASE REPORT
Importantly, there were no episodes of acute pancreatitis in the control/placebo group.9 The phase III clinical trials included a
total of 2,428 patients who were randomly assigned to twice daily doses of placebo,
75 mg, or 100 mg of eluxadoline. Acute
in the treatment arm (two in the 75 mg eluxadoline group and three in the 100 mg eluxadoline group) and none in the placebo acute pancreatitis, one was associated with spasm of the sphincter of Oddi, another with biliary sludge, and the remaining three were associated with alcohol consumption. In addition to acute pancreatitis, eight patients developed severe abdominal pain consistent with SOD. Interestingly, all nine patients who developed SOD had a previous history of cholecystectomy.8
Since FDA approval of eluxadoline for treatment of IBS-D, we know of no reported cases of pancreatitis associated with the use of this drug. We report a case of eluxadoline-related acute pancreatitis described, outside of phase III clinical trials.
CASE REPORT
We present a 38-year-old woman with history of cholecystectomy, vitamin D headaches, and IBS-D who presented with bilateral lower quadrant abdominal pain and a two-year history of diarrhea. In the past, Loperamide and Dicyclomine provided mild symptomatic relief. Her symptoms were further evaluated with upper and lower endoscopy with random small bowel and colon biopsies, all of which were normal. Subsequently, she was started on eluxadoline 100 mg twice daily. The following day, she presented
to the emergency department with
severe epigastric abdominal pain and nausea. Physical exam was notable for severe epigastric tenderness to palpation. Notable initial lab tests included lipase (1080 units/L), amylase (725 units/L),
AST (1310 units/L), ALT (915 units/L), alkaline phosphatase (264 units/L) and total bilirubin (1.8 mg/dL). She was diagnosed with acute pancreatitis and managed with supportive care. Eluxadoline was held at
the time of admission. She denied other prescription or over-the-counter medications (including acetaminophen), recent alcohol consumption, or tobacco use. There were
no recorded episodes of hypotension,
and renal function was normal, lowering suspicion for ischemic liver injury. Further evaluation for acute pancreatitis and elevated liver enzymes revealed normal serum calcium, triglyceride, ethanol, and acetaminophen levels. An acute viral hepatitis panel and anti-nuclear antibody were also normal. A right upper quadrant ultrasound demonstrated a common bile duct measuring 4mm, with no discrete hepatic lesions. Therefore, we presume that acute pancreatitis was most likely caused by eluxadoline. Her hospital course was uncomplicated. Over the next four days, liver enzymes normalized and symptoms progressively improved. Eluxadoline was discontinued at the time of discharge home.
DISCUSSION
We describe a case of eluxadoline- associated pancreatitis due to SOD.
Our patient had a previous history of cholecystectomy and developed pancreatitis
is worth mentioning again that patients who had cholecystectomy in the IBS 3001 and 3002 trials were at greater risk of SOD-related severe abdominal pain
or acute pancreatitis.8 Eluxadoline is a μ-opioid receptor agonist that has a similar mechanism of action to other opioids, including codeine and morphine. Opiates are listed among medications presumed to cause drug-induced pancreatitis.10 Hastier
et al. published a case series of four patients who developed acute pancreatitis after codeine ingestion, and all four patients had a history of cholecystectomy.11
There has been an effort in the past to delineate the effect of μ-agonists on sphincter of Oddi physiology. The principal effect of narcotics on the sphincter of Oddi is an increase in phasic wave frequency. Sphincter of Oddi manometry has shown
the sphincter of Oddi occurs during
the relaxation phase of the sphincter. Because narcotics decrease the sphincter’s pancreatic secretions into the duodenum
is decreased, resulting in stasis in the biliary system, causing elevation of biliary pressure.12 Interestingly, this escalation
in biliary pressure is more pronounced
with absence of the gallbladder. It has
been shown that administration of opioids increases biliary pressure in opossums subjected to cholecystectomy, but this effect is not seen in their counterparts
with intact gallbladders.13 Tanaka et al. injected morphine to stimulate sphincter
of Oddi spasm in seven patients pre- and post-cholecystectomy. The result of this study exhibited no augmentation of biliary pressure in the former, but discrete increase in biliary pressure in the latter group. One possible explanation for this observation is that the gallbladder acts as a low pressure reservoir of the biliary tract and absorbs extra pressure in the bile duct that is created as a result of sphincter of Oddi contraction. Presumably, after cholecystectomy, there
is loss of this pressure reservoir, leading to
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