Swissmedic Vigilance News

Among those cases in which drug causality was retained,
five out of the seven patients had at least
one comorbidity predisposing them to the onset of
pancreatitis, and five out of seven had at least one
risk factor for acute or drug-induced pancreatitis.
In three cases, the suspected drugs were classified
in category Ia according to Wolfe et al. (2020), i.e.
at least one case report with a positive rechallenge,
consistent latency and other causes having been
ruled out. In one case the suspected drug was classified
in category II. Finally, the suspected drugs in
the last three cases were not included in the classification
tables for assessing the association with
drug-induced pancreatitis (4–6).
Discussion
As mentioned in the introduction, cases of druginduced
pancreatitis are rare. Their progression is
usually benign, but they can become life-threatening
in isolated cases. Therefore, a knowledge of
those drugs capable of triggering pancreatitis can
be useful for clinicians and enable them to identify
this rare aetiology and, most importantly, refrain
from re-administer the implicated drugs to their
patients.
In February 2023, drug-induced pancreatitis was also
the subject of a new section, "Pharmacovigilance in
the spotlight", published on the Swissmedic website
(7). This section presents three case reports involving
isotretinoin (class II), azathioprine (class Ia)
and semaglutide (not classified) (4). It serves as a
reminder that this adverse drug reaction should be
considered in the differential diagnosis as a possible
cause of acute pancreatitis.
The determination of drug causality in cases of
pancreatitis can be complex to establish. Similar to
other adverse drug reactions, it involves an exclusion
diagnosis, and it is advisable to first rule out
other potential causes such as biliary (gallstones) or
alcoholic aetiology, paying particular attention to
their frequency (1). A biliary origin should be suspected,
particularly if the transaminase levels are
abnormal. In elderly patients, obstruction of the
pancreatic ducts by a tumour should be considered,
although this scenario is rare. In young patients, an
infectious origin should be explored systematically.
Other aetiological causes that should also be taken
into account include hypertriglyceridaemia, autoimmune
factors, hyper/hypocalcaemia, a malignant
tumour, a genetic cause, a complication of endoscopic
retrograde cholangiopancreatography, and
trauma (8).
Alongside the aetiological investigations, the
chronology of the symptoms in relation to the
start of the implicated drug, the clinical outcome
upon discontinuation and the results of biological
tests are also useful in establishing the diagnosis. It
should be noted, however, that a latency of several
months does not rule out a drug-related aetiology.
The drugs implicated in the cases reported to RPVC
Geneva include treatments that are commonly
known to be associated with the onset of acute
pancreatitis, such as metronidazole, paracetamol/
codeine and valproate, as well as ceftriaxone, although
the acknowledged association with the
latter is considered to be less strong. The three
other cases involve anti-diabetic drugs that were
recently placed on the market and that are therefore
not yet included in the various classification
systems: semaglutide (a glucagon-like peptide 1
analogue [GLP1]), empagliflozin and dapagliflozin
(sodium-glucose transport protein 2 inhibitors
[SGLT-2]), although it should be noted that drugs
belonging to the same classes – liraglutide and
canagliflozin – are already classified in category Ic.
In fact, several case reports involving the use of
GLP-1 receptor agonists can be found in the literature
(9–13), and acute pancreatitis is listed as an
uncommon adverse reaction (≥1/1,000,