Moderate
Apixaban × Spironolactone
Direct oral anticoagulants (factor Xa inhibitors)×Potassium-sparing diuretics (mineralocorticoid receptor antagonists)
Mechanism
No direct pharmacokinetic interaction. In chronic kidney disease, spironolactone causes hyperkalaemia and apixaban exposure rises (partly renally cleared). Cumulative adverse event risk in reduced renal function.
Symptoms
Weakness, fatigue, arrhythmia (from hyperkalaemia), bleeding and bruising without trauma (from apixaban). Symptoms are more pronounced with creatinine clearance below 50 mL/min.
Management
With normal renal function, no dose change needed. At creatinine clearance 30–50 mL/min, check potassium and creatinine every 2–4 weeks. In severe CKD (clearance below 30 mL/min), stop spironolactone or switch to eplerenone with careful potassium monitoring.