Drug Interactions Between Omeprazole and Chlorthalidone
Direct Answer
There are no clinically significant drug interactions between omeprazole and chlorthalidone, and these medications can be safely co-administered without specific monitoring beyond standard electrolyte surveillance for thiazide diuretics.
Rationale and Evidence
Absence of Direct Interaction
Omeprazole and chlorthalidone do not share metabolic pathways or mechanisms that would create clinically meaningful interactions. 1
Omeprazole is primarily metabolized through hepatic CYP2C19 and CYP3A4 enzymes, with its main drug interaction concerns involving medications that require these pathways for activation or clearance (such as clopidogrel). 1, 2, 3
Chlorthalidone is a thiazide-like diuretic that works at the distal convoluted tubule and does not undergo significant hepatic metabolism via cytochrome P450 enzymes. 1, 4, 5
The pharmacokinetic profile of chlorthalidone (extremely long half-life of 40-60 hours, large volume of distribution, elimination by tubular secretion) does not overlap with omeprazole's metabolism or mechanism of action. 4, 5
Separate Clinical Considerations
While these drugs don't interact with each other, each has independent monitoring requirements:
For Chlorthalidone:
- Check electrolytes (particularly potassium and sodium) and renal function within 4 weeks of initiation or dose escalation. 1
- Monitor for hypokalemia, hyponatremia (especially in elderly patients), hyperuricemia, and glucose intolerance. 1, 4
- Chlorthalidone at 25 mg is more potent than hydrochlorothiazide 50 mg and may be effective even in advanced CKD (eGFR <30 mL/min/1.73 m²). 1, 5
For Omeprazole:
- The primary concern with omeprazole is its interaction with clopidogrel (if prescribed), not with chlorthalidone. 1, 6
- Omeprazole can alter absorption of pH-dependent medications (like ketoconazole) and increase digoxin absorption through P-glycoprotein inhibition. 2, 3, 7
Clinical Bottom Line
Co-prescribe omeprazole and chlorthalidone without concern for drug-drug interaction. Follow standard monitoring protocols for each medication independently: electrolytes and renal function for chlorthalidone 1, and consideration of alternative PPIs only if the patient is also taking clopidogrel 6.