enalapril × hydrochlorothiazide

Synergistic BP reduction (a target combination in hypertension – even an enalapril/hydrochlorothiazide fixed-dose product exists). Hypovolemia can cause an abrupt BP drop and acute kidney injury at the first ACE-inhibitor dose. Hydrochlorothiazide shifts the RAAS toward activation, amplifying the first-dose ACE-inhibitor effect.

Start both at low doses. Confirm normovolemia before initiating the ACE inhibitor – hold the thiazide for 24–48 hours if needed. Check BP (including orthostatic measurement), creatinine, and potassium at 3–7 days.