Table 4: ACE Inhibitor Drug-Drug Interactions
| Target Drug | Interacting Drug | Interaction | Recommendation | Clinical Significance Level # |
|---|---|---|---|---|
| ACE inhibitors | aliskiren | potential for additive hypotensive effects; increased hyperkalemia risk with this drug combination as both decrease serum aldosterone levels | administer drug combination cautiously; monitor serum potassium levels closely | moderate (DrugReax) 3-moderate (CP) |
| ACE inhibitors | angiotensin II receptor blockers | potential for enhanced pharmacologic/ adverse effects (e.g., hypotension, hyperkalemia, changes in renal function) as both agents block renin-angiotensin-aldosterone system | avoid combination; if concurrent therapy necessary, monitor blood pressure, potassium and renal function and observe for adverse events | major (DrugReax) 2-major (CP) |
| ACE inhibitors | antidiabetic agents | potential for enhanced hypoglycemic effects due to improved insulin sensitivity by ACE inhibitors | closely monitor blood glucose levels; reduced antidiabetic doses may be necessary | moderate (DrugReax) 3-moderate (CP) |
| ACE inhibitors | azathioprine | increased risk of anemia, leukopenia with drug combination; mechanism unknown | avoid combination, if possible; if combined therapy necessary, monitor for myelosuppression | major (DrugReax) 2-major (CP) |
| lisinopril | clozapine | potential for increased serum clozapine levels and enhanced pharmacologic, adverse effects; lisinopril may decrease clozapine renal elimination through unknown mechanism | assess clinical response, monitor serum clozapine levels if drug combination utilized | 3-moderate (CP) |
| ACE inhibitors | cyclosporine | increased risk of acute renal failure, hyperkalemia with drug combination due to ACE inhibition, which causes decreased angiotensin II and aldosterone | closely monitor renal function and serum potassium levels | moderate (DrugReax) 3-moderate (CP) |
| ACE inhibitors | entecavir | potential for increased entecavir serum levels and enhanced pharmacologic/ adverse effects due to ACE inhibitor effects on renal function |
monitor for increased adverse events if drug combination is administered | 3-moderate (CP) |
| ACE inhibitors | eplerenone | increased risk of hyperkalemia as both agents decrease aldosterone levels | closely monitor serum potassium levels | 2-major (CP) |
| ACE inhibitors | lithium | potential for increased serum lithium levels and enhanced pharmacologic, toxic effects, possibly due to decreased lithium clearance | avoid combination, if possible; if drug combination necessary, monitor serum lithium levels and observe for signs of lithium toxicity | moderate (DrugReax) 3-moderate (CP) |
| ACE inhibitors | monoamine oxidase inhibitors | potential for additive hypotensive effects | monitor blood pressure closely, if drug combination utilized | 3-moderate (CP) |
| ACE inhibitors | NSAIDs, salicylates, COX-2 inhibitors | potential for decreased antihypertensive effects, increased renal impairment risk (especially in patents dependent on renal prostaglandins for perfusion), with combined therapy due to inhibition of prostaglandin synthesis | monitor blood pressure, renal function, and clinical status if drug combination utilized; low-dose aspirin less likely to reduce ACE inhibitor antihypertensive, cardioprotective effects | moderate (DrugReax) 3-moderate (CP) |
| ACE inhibitors | potassium-sparing diuretics, potassium salts | ACE inhibitors reduce aldosterone concentrations, resulting in increased potassium concentrations; increased hyperkalemia risk with drug combination due to additive pharmacologic effects | monitor serum potassium levels and signs/symptoms of hyperkalemia if drug combination administered; patients with renal failure, diabetes, advanced age may be at increased risk; use combination cautiously in heart failure patients | major (DrugReax) 2-major (CP) |
| ACE inhibitors | pregabalin | combined therapy may increase risk of developing life-threatening angioedema with respiratory compromise | observe patients closely if drug combination utilized | 2-major (CP) |
| ACE inhibitors | sacubitril/ valsartan (Entresto®) | concurrent administration may result in angioedema due to inhibition of bradykinin degradation | avoid drug combination; monitor blood pressure, renal function, and electrolytes if combined therapy is utilized | contraindicated (DrugReax) 1-contraindicated (CP) |
| ACE inhibitors | trimethoprim | co-administration may increase risk of additive hyperkalemia due to decreased aldosterone synthesis by ACE inhibitor and potassium-sparing effect on distal nephron by trimethoprim | monitor serum potassium levels and monitor patients for signs/symptoms of hyperkalemia if drug combination administered | moderate (DrugReax) 2-major (CP) |
| trandolapril/verapamil | flibanserin (Addyi®) | verapamil (CYP3A4 inhibitor) and flibanserin (CYP3A4 substrate) administered concurrently may result in increased serum flibanserin levels with resultant severe hypotension, syncope, sedation | avoid combined use; if adjunctive use necessary, discontinue CYP3A4 inhibitor for at least 2 weeks before initiating/reinitiating flibanserin therapy, or discontinue flibanserin at least 2 days before starting/restarting CYP3A4 inhibitor therapy | contraindicated (DrugReax) 1-severe (CP) |
| trandolapril/verapamil | colchicine | colchicine is p-glycoprotein (P-gp) and CYP3A4 substrate; adjunctive use may result in increased colchicine serum concentrations and enhanced pharmacologic/ adverse effects due to P-gp and CYP3A4 inhibition by verapamil | avoid concurrent use; if combined use necessary, observe for serious colchicine adverse effects, including neuromuscular toxicity, and adjust colchicine dosages | contraindicated (DrugReax) 2-major (CP) |
| trandolapril/verapamil | dofetilide (Tikosyn®) | concomitant administration may result in increased cardiotoxicity risk (e.g., torsades de pointes, QT interval prolongation, cardiac arrest) due to increased dofetilide absorption/serum levels | combined use is contraindicated | contraindicated (DrugReax) 1-severe (CP) |
Legend:
- *Clinical Pharmacology