4. Drug-Drug Interactions
Patient profiles will be assessed to identify those drug regimens which may result in clinically significant drug-drug interactions. Drug-drug interactions considered clinically relevant for ARBs are summarized in Table 4. Only those drug-drug interactions classified as clinical significance of contraindicated or those considered life-threatening which have not yet been classified will be reviewed.
| 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 | concurrent use is contraindicated in patients with diabetes mellitus. Administer drug combination cautiously; monitor serum potassium levels closely | major |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 | moderate |
| ACE inhibitors | eplerenone | increased risk of hyperkalemia as both agents decrease aldosterone levels | closely monitor serum potassium levels | major |
| 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 |
| ACE inhibitors | monoamine oxidase inhibitors | potential for additive hypotensive effects | monitor blood pressure closely, if drug combination utilized | moderate |
| 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 |
| 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 |
| ACE inhibitors | pregabalin | combined therapy may increase risk of developing life-threatening angioedema with respiratory compromise | observe patients closely if drug combination utilized | moderate |
| 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 |
| 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 |
| captopril | antacids | concurrent use may decrease gastrointestinal absorption of captopril | avoid concurrent use | major |
| 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 | moderate |