Can Hydrochlorothiazide (HCTZ) cause pancreatitis?

Hydrochlorothiazide and Pancreatitis

Yes, hydrochlorothiazide (HCTZ) can cause acute pancreatitis, though it is a relatively uncommon adverse effect that should be considered in patients presenting with abdominal pain while on this medication.

Evidence for HCTZ-Induced Pancreatitis

Hydrochlorothiazide has been documented in multiple case reports as a potential cause of acute pancreatitis:

• A recent case report (2025) described a 58-year-old female patient who experienced recurrent episodes of acute pancreatitis that resolved after discontinuation of HCTZ, with no recurrence during follow-up 1
• Another report documented a fatal case of necrotizing pancreatitis associated with hydrochlorothiazide and lisinopril therapy in a 49-year-old man 2
• A case of acute pancreatitis was reported in a 33-year-old woman just 10 days after starting irbesartan/HCTZ combination therapy 3

Mechanism and Risk Assessment

The exact mechanism by which HCTZ induces pancreatitis is not fully understood. However, some important considerations include:

• Drug-induced acute pancreatitis (DIAP) is relatively uncommon, accounting for approximately 0.1-2% of all acute pancreatitis cases 4
• HCTZ-induced pancreatitis appears to be dose-dependent, with higher doses more commonly associated with this adverse effect 3
• The risk may be increased when HCTZ is combined with other medications that affect the renin-angiotensin system, such as ACE inhibitors or ARBs 3, 2

Clinical Implications

When managing patients on HCTZ who develop symptoms suggestive of pancreatitis:

1. Maintain high clinical suspicion: Consider HCTZ as a potential cause in patients presenting with abdominal pain, especially when other common causes (gallstones, alcohol) have been excluded
2. Prompt discontinuation: If HCTZ-induced pancreatitis is suspected, the medication should be discontinued immediately
3. Monitor for resolution: Symptoms typically resolve and serum amylase/lipase levels normalize within days after discontinuation
4. Avoid rechallenge: Patients with confirmed HCTZ-induced pancreatitis should avoid future use of this medication

Alternative Antihypertensive Options

For patients who have experienced HCTZ-induced pancreatitis but require antihypertensive therapy:

• Consider calcium channel blockers like amlodipine, which have not been strongly associated with pancreatitis 5
• ACE inhibitors or ARBs may be used, but caution is warranted as there are also case reports of pancreatitis with these medications 3, 2
• Loop diuretics may be an alternative in patients requiring diuretic therapy, particularly in those with reduced renal function (eGFR <30 mL/min/m²) 5

Conclusion

While HCTZ-induced pancreatitis is uncommon, it represents a potentially serious adverse effect that clinicians should be aware of. Prompt recognition and discontinuation of the medication are essential for management, and alternative antihypertensive strategies should be implemented for affected patients.