Case Report
Acute Pancreatitis Following a Single Dose of Codeine Phosphate: A Case Report
Noor Obeid1*, Lucy Fletcher2 and Ian CC King1
1Department of General Surgery, Queen Victoria Hospital, UK
2Department of General Surgery, Royal Victoria Infirmary, UK
*Corresponding author: Noor Obeid, Department of General Surgery, Queen Victoria Hospital, East Grinstead, UK
Published: 26 Sep, 2016
Cite this article as: Obeid N, Fletcher L, King ICC. Acute
Pancreatitis Following a Single Dose
of Codeine Phosphate: A Case Report.
Ann Clin Case Rep. 2016; 1: 1146.
Abstract
Several drugs have previously been implicated to cause acute pancreatitis. We report the rare case of codeine induced acute pancreatitis. A 43-year-old woman developed the symptoms and clinical signs of acute pancreatitis 90 minutes after the ingestion of codeine phosphate. The diagnosis was proved both biochemically and radiologically which excluded other potential causes. The likely underlying pathophysiology is codeine-induced spasm of the sphincter of oddi.
Introduction
Acute Pancreatitis (AP) is a serious and potentially life threatening condition with a risk of morbidity and rates of mortality seen between 1.9% - 18.8% [1]. The most common causes are gallstones, alcohol and trauma however other aetiologies such as drugs are important to consider when patients present with acute pancreatitis and whilst prescribing medications [2]. It is estimated that between 0.3% - 5.3% of cases of AP are caused by drugs [2]. A number of drugs have been reported to cause AP, including sodium valproate, clomipramine, azathioprine and simvastatin, various antibiotics and steroids [3]. We present the extremely unusual case of AP following ingestion of codeine phosphate.
Case Presentation
A 43-year-old female attended the emergency department with severe epigastric pain radiating
through to her back. Symptoms developed approximately ninety minutes after the ingestion of 30mg
of codeine phosphate, which she had taken for pain caused by acute sinusitis. There was no history
of gallstones, alcohol excess or abdominal trauma. The patient’s past medical history included a
previous perianal fistula and haemophilia, of which she was a carrier. She did not take any regular
medications. Examination revealed a dehydrated and tachycardic patient with severe tenderness
to palpation in the epigastrium with no guarding, peritonism or organomegaly. Laboratory tests
showed an elevated serum amylase 395 U/L, a white cell count of 15.0, neutrophils 12.0, CRP
54. Serum lipids were within normal range. Abdominal ultrasound scan showed no evidence of
cholelithiasis or common bile duct dilation, the pancreas had a normal appearance.
The epigastric pain lasted approximately three hours and was relieved with morphine and
intravenous fluids. The patient was diagnosed with codeine-induced acute pancreatitis, and
monitored overnight prior to discharge the following day with antibiotics for her sinusitis. A second
serum amylase performed 4 weeks later had returned to normal (<120 U/L) further supporting the
diagnosis.
Discussion
A medication, specifically codeine phosphate, was the causative factor in this patient’s acute
pancreatitis. Pancreatitis inducing drugs are classified into four categories (I-IV). Class I and II
drugs are most likely to cause acute pancreatitis; codeine is included within class I [4].
Codeine has recently been recognised as a cause of acute pancreatitis and only limited number
cases have been published to date. These cases have all been documented in patients who have
previously had a cholecystectomy. Hastier et al. [5] have noted this occurrence twice, the first being
in 1996 where they reported a case of pancreatitis after a patient ingested 60mg of codeine [4].
The second paper was in 2000 where they reported on a four patient series of codeine-induced
pancreatitis [4,6]. In 2010 Torres et al. [7] published a case of codeine-induced pancreatitis in a
patient one hour after ingesting a combination of 500mg acetaminophen and 30mg codeine [4]. The most recent paper on this topic was by Turkmen et al. [4] in 2015 in
which they reported a case of drug induced pancreatitis in a patient
with a previous cholecystectomy. The patient developed symptoms of
pancreatitis 60 minutes after taking 30mg of codeine for mild muscle
aches.
It has been suggested that the pathophysiology of codeineinduced
pancreatitis is likely due to constriction of the sphincter of
Oddi which has been demonstrated to be induced by subcutaneous
injection with therapeutic doses of codeine and morphine [8]. Positive
re-challenge has previously been documented further proving
codeine as a cause for AP [5]. Further oral challenge of codeine in this
index patient was not performed due to ethical reasons. The majority
of previous case reports are very similar to the case described above
with onset of symptoms approximately 1-3 hours post ingestion of
codeine [6]. Studies have shown that injection of therapeutic doses
of opioid cause rapid onset of constriction of the sphincter of Oddi,
lasting for approximately two hours which correlates with reported
symptoms [9].
AP should be considered as a potential side effect when
prescribing codeine particularly in patients who has previously
undergone cholecystectomy [7]. These patients are possibly more
likely to suffer from codeine associated AP due to smooth-muscle
hyperplasia or fibrosis increasing sphincter of Oddi spasm postcholecystectomy
[7]. However, in contrast to the majority of previous
reports our case shows that codeine induced AP is not exclusive to the
post-cholecystectomy patient population.
In conclusion we have identified a case of codeine induced AP
in a middle-aged woman. Similar cases should be more regularly
reported to understand more accurately incidence and improve
education on this condition. Increasing the awareness of codeine as a
cause of AP, will enable clinicians to make a more informed decision
when prescribing codeine in preventing this condition. Prescribing
codeine as a form of analgesia in patients presenting with AP should be done with care so as not to exacerbate the existing condition. In
future medical professionals should be mindful of the association
of codeine and AP when patients present clinically, biologically and
radiologically with AP.
References
- de Beaux AC, Palmer KR, Carter DC. Factors influencing morbidity and mortality in acute pancreatitis; an analysis of 279 cases. Gut. 1995; 37: 121- 126.
- Barreto SG, Tiong L, Williams R. Drug-induced acute pancreatitis in a cohort of 328 patients. A single-centre experience from Australia. JOP. 2011; 12: 581-585.
- Andersen V, Sonne J, Andersen M. Spontaneous reports on drug-induced pancreatitis in Denmark from 1968 to 1999. Eur J Clin Pharmacol. 2001; 57: 517-521.
- Turkmen S, Buyukhatipoglu H, Suner A, Apucu HG, Ulas T. Prior cholecystectomy predisposes to acute pancreatitis in codeine-prescribed patients. Int J Crit Illn Inj Sci. 2015; 5: 114-115.
- Hastier P, Demarquay JF, Maes B, Caroli-Bosc FX, Dumas R, Delmont J, et al. Acute pancreatitis induced by codeine-acetaminophen association: a case report with positive rechallenge. Pancreas. 1996; 13: 324-326.
- Hastier P, Buckley MJ, Peten EP, Demuth N, Dumas R, Demarquay JF, et al. A new source of drug-induced acute pancreatitis: codeine. Am J Gastroenterol. 2000; 95: 3295-3298.
- Torres D, Parrinello G, Trapanese C, Licata G. Sudden Severe abdominal pain after a single low dose of paracetamol/codeine in a cholecystectomized patient: learning from a case report. Am J Ther. 2010; 17: e133-e134.
- Hastier P, Longo F, Buckley M, Chichmanian RM, Delmont JP. Pancreatitis induced by codeine: a case report with positive rechallenge. Gut. 1997; 41: 705-706.
- Roberts-Thomson IC, Toouli J. Abnormal responses to morphineneostigmine in patients with undefined biliary type pain. Gut. 1985; 26: 1367-1372.