Can Angiotensin-Converting Enzyme (ACE) inhibitors cause pancreatitis?

From the Guidelines

ACE inhibitors can cause pancreatitis, although it is a rare side effect, and the exact mechanism is not fully understood, but it may involve localized angioedema of pancreatic tissue or changes in bradykinin metabolism. The risk of pancreatitis appears to be highest within the first few months of starting treatment with ACE inhibitors, such as lisinopril, enalapril, captopril, and ramipril. If you're taking an ACE inhibitor and experience symptoms such as severe abdominal pain radiating to your back, nausea, vomiting, or fever, you should seek immediate medical attention as these could indicate pancreatitis.

Key Considerations

• The provided evidence does not directly address the relationship between ACE inhibitors and pancreatitis, but it highlights the importance of careful patient selection and monitoring when prescribing ACE inhibitors, particularly in patients with a history of pancreatitis or other risk factors 1.
• The benefits of ACE inhibitors in reducing morbidity and mortality in patients with heart failure and other conditions often outweigh the rare risk of pancreatitis, but alternative medications like angiotensin receptor blockers (ARBs) may be considered for patients with a history of pancreatitis.
• Patients should never stop taking their ACE inhibitor without consulting their healthcare provider, as abrupt withdrawal can lead to clinical deterioration.

Monitoring and Management

• Patients taking ACE inhibitors should be closely monitored for signs and symptoms of pancreatitis, such as severe abdominal pain, nausea, vomiting, and fever.
• If pancreatitis is suspected, the patient should seek immediate medical attention, and the healthcare provider should consider alternative medications or adjust the treatment plan as needed.
• The use of ACE inhibitors should be carefully weighed against the potential risks and benefits in each individual patient, taking into account their medical history, current health status, and other factors.

From the Research

Association between ACE Inhibitors and Pancreatitis

• ACE inhibitors have been associated with an increased risk of pancreatitis in some studies 2, 3, 4.
• The mechanism of ACE inhibitor-induced pancreatitis is thought to be related to ductal obstruction and fluid retention due to angioedema effects 2.
• Multiple dose changes within a short period of time can lead to acute drug-induced pancreatitis (DIP), in addition to classic DIP caused by steady-state doses 2.
• Some studies have reported a dose-dependent relationship between ACE inhibitors and pancreatitis, with higher daily doses increasing the risk of acute pancreatitis 4.

Epidemiological Studies

• A retrospective cohort study found no significant association between ACE inhibitor use and acute pancreatitis in the elderly 5.
• A case-control study found an increased risk of acute pancreatitis associated with ACE inhibitor use, particularly in the first 6 months of therapy 4.
• Another study reported a patient who developed acute pancreatitis shortly after taking lisinopril and hydrochlorothiazide, highlighting the potential risk of ACE inhibitors in causing pancreatitis 6.

Clinical Implications

• Clinicians should consider discontinuing ACE inhibitors in patients with pancreatitis of no identifiable source 3.
• The use of ACE inhibitors should be carefully evaluated in patients with a history of pancreatitis or those at high risk of developing pancreatitis 2, 4.