Bortezomib-Induced Acute Pancreatitis

Bouraoui Elouni
1
, Chaker Ben Salem
2
, Michelle Zamy
1
,
Jaballah Sakhri
3
, Kamel Bouraoui
2
, Michel Biour
1
1
Pharmacovigilance Regional Center, Saint Antoine Hospital. Paris, France.
2
Department of Clinical Pharmacology, Faculty of Medicine of Sousse;
3
Department of Surgery,
Farhat Hached University Hospital. Sousse, Tunisia
Dear Sir:
Bortezomib is the first proteasome inhibitor approved
by the Food and Drug Administration (FDA) and
indicated for patients with multiple myeloma refractory
to at least one prior therapy [1].
The most common adverse effects of bortezomib
include hematological toxicities (especially transient
thrombocytopenia), gastrointestinal disturbances,
peripheral neuropathy, fatigue, fever, dyspnea, rash,
and myalgia [2]. We herein present the first case of
acute pancreatitis induced by bortezomib.
A 58-year-old female was treated with vincristine,
doxorubicin, and dexamethasone for a myeloma. She
had no history of dyslipidemia or alcohol abuse. In
relation to the relapse of the myeloma, two doses of
bortezomib (1.3 mg/m2) were administered
intravenously at a 4-day time interval. Concomitant
medications in our patient included dexamethasone,
levothyroxine for hypothyroidism, and paracetamol.
Two days later, she presented because of abdominal
pain of medium intensity localized in the epigastrium
for which she was hospitalized. On admission, the
patient had normal vital signs without fever.
Abdominal examination revealed only mild epigastric
tenderness. There was no rigidity or guarding. There
were no palpable abdominal masses. The remainder of
the examination was normal. A laboratory work-up
showed a normal blood cell count and did not
demonstrate hypertriglyceridemia, hypercholesterolemia
or hypercalcemia. A liver test, renal function, serum
electrolytes and blood sugars were all normal. The
determination of pancreatic enzymes revealed that
serum lipase was high at 493 IU/L (reference range: 0-
200 IU/L) but serum amylase was normal at 67 IU/L
(reference range: 0-110 IU/L). Serology of infectious
agents (hepatitis A, B, C, varicella zoster virus,
cytomegalovirus, Epstein-Barr virus, human immuno-
deficiency virus, echovirus and Coxsackie viruses)
were negative. On such basis, pancreatitis was
suspected. Abdominal ultrasonography revealed a
morphologically normal pancreas; there were neither
peripancreatic fluid collections and nor biliary
dilatation. Abdominal computed tomography (CT) did
not show cystic or tumor lesions. An MRI-
cholangiopancreatography examination revealed no
hepatobiliary abnormalities including stones, and
confirmed the abdominal ultrasonography and CT
findings. Her lipase level four days after the last
bortezomib administration had dropped slightly to 419
IU/L, and it was close to the normal level (256 IU/L)
after another four days. At this time, the patient became
asymptomatic. All the biologic values were within the
normal range. Concomitant medications including
dexamethasone and levothyroxin had not been stopped.
Ten days after the last administration, the patient
received bortezomib again. A few hours later, she
developed abdominal pain with hyperlipasemia at 477
IU/L. The bortezomib was stopped immediately with
the diagnosis of acute pancreatitis. The patient
improved quickly after bortezomib withdrawal and
serum lipase levels decreased to normal (145 IU/L) six
days after the last administration. According to the
Naranjo probability scale, bortezomib-induced acute
pancreatitis was probable [3].
Although many drugs have been suspected of causing
pancreatitis, they are a relatively rare cause with an
estimated incidence of only 0.1-2% [4]. The
pathogenesis of drug-induced pancreatitis is not clear,
but it may be caused by an allergic response or by a
direct toxic effect [5]. In our case, the diagnosis was
based on the exclusion of potential medical causes,
such as pancreatic malformation, diabetes,
Received March 2nd, 2010 - Accepted March 4th, 2010
Key words bortezomib; Drug toxicity; Pancreatitis
Correspondence Bouraoui Elouni
Centre de Pharmacovigilance, Hôpital Saint-Antoine, 75571 Paris
cedex 12, France
Phone: +33-1.4347.5469; Fax: +33-1.430.7071
E-mail: elounibouraoui@yahoo.fr
Document URL http://www.joplink.net/prev/201005/10.html

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JOP. J Pancreas (Online) 2010 May 5; 11(3):275-276.
JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 11, No. 3 - May 2010. [ISSN 1590-8577]
276
dyslipidemia, alcoholism, infectious agents, the
resolution of clinical and biological signs when the
bortezomib was withdrawn and evidence of a positive
rechallenge. Recently, the beneficial effects of
bortezomib in acute experimental pancreatitis have
been reported. These effects of the drug seem to be
mediated by the inhibition of nuclear factor kappa B
activation and induction of heat shock protein synthesis
[6]. Despite this possible anti-inflammatory effect in
acute experimental pancreatitis, one should not exclude
bortezomib as a possible cause of acute pancreatitis.
Until now, no case of pancreatitis related to bortezomib
has been published in the international literature and a
search of OVIDSP (http://ovidsp.tx.ovid.com/),
PubMed/MEDLINE
(http://www.ncbi.nlm.nih.gov/
sites/entrez) and EMBASE (http://www.embase.com)
have also not revealed any previous case reports of
pancreatitis associated with bortezomib. In conclusion,
clinicians should be aware that acute pancreatitis may
occur in patients taking bortezomib.
Conflict of interest None
References
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