ACE inhibitors are contraindicated in combination with a neprilysin inhibitor. They should not be administered within 36 hours of switching to or from the nepriltsin inhibitor sacubitril/valsartan. Patients taking these medicines together may be at increased risk for angioedema.
ACE inhibitors should not be co-administered with aliskiren in patients with diabetes.1-14
The following drug interactions are not contraindications, but manufacturers recommend they be carefully considered and patients using both therapies concomitantly be monitored by a doctor.
Dual Blockade of the Renin-Angiotensin System (RAS) – Taking angiotensin receptor blockers or aliskiren with ACE inhibitors is associated with increased risk of hypotension, hyperkalemia, and changes in renal function including acute renal failure. Most patients receiving a combination of these drugs do not get any additional benefit compared to monotherapy. In general, combining renin-angiotensin system inhibitors should be avoided. Co-administering aliskiren with ACE inhibitors should be avoided in patients with renal impairment (glomerular filtration rate <60 mL/min).
Diuretics – Patients on diuretics, especially those who have recently started diuretic therapy, may experience an excessive reduction of blood pressure after starting to take an ACE inhibitor. ACE inhibitors can attenuate potassium loss caused by thiazide-type diuretics, increasing the risk of hyperkalemia.
Nonsteroidal Anti-Inflammatory Agents (NSAIDs) – In elderly patients, volume-depleted, or with compromised renal function, coadministration of NSAIDs (including selective cyclooxygenase-2 inhibitors) with ACE inhibitors may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Antihypertensive effects of ACE inhibitors may be attenuated by NSAIDs.
Mammalian Target of Rapamycin (mTOR) Inhibitors – Patients receiving coadministration of an ACE inhibitor and mTOR inhibitor (e.g. temsirolimus, sirolimus, everolimus) or a neprilysin inhibitor may be at increased risk of angioedema.
Lithium – Lithium toxicity has been reported in patients receiving lithium with ACE inhibitors. The condition was usually reversible upon discontinuation of lithium or the ACE inhibitor.
Gold – Nitritoid reactions with symptoms including facial flushing, nausea, vomiting, and hypotension have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and also taking ACE inhibitors. 1-14
Antidiabetics – Taking benazepril, lisinopril, or trandolapril with antidiabetic medicines including insulins and oral hypoglycemic agents may increase the risk of hypoglycemia.1,7-9, 14
Vasodilators – The manufacturer of captopril recommends discontinuing the use of drugs such as nitroglycerin or other nitrates for management of angina if possible before starting captopril. The effect of concomitant use of vasodilators in patients using captopril for heart failure has not been rigorously studied by manufacturers.2
Sympathetic Nervous System – Captopril should be used with caution in combinations with agents affecting sympathetic activity such as ganglionic blocking agents or adrenergic neuron blocking agents due to the potential effect on the sympathetic nervous system.2
Antacids – Fosinopril should be taken 2 hours apart from antacids. A clinical pharmacology study found that coadministration of an antacid (aluminum hydroxide, magnesium hydroxide, and simethicone) with fosinopril reduced serum levels and urinary excretion of fosinoprilat as compared with fosinopril administered alone, suggesting antacids may impair absorption of fosinopril.6
Tetracycline – Coadministration of quinapril with tetracycline reduced absorption of tetracycline by about 28-37%, possibly due to the high magnesium content in quinapril tablets. This interaction should be considered if co-prescribing quinapril with tetracycline or other drugs that interact with magnesium.12
A systematic review examined drug interactions and contraindications of herbal and dietary supplements on hypertension medication.15 The following herbal supplements were found to be contraindicated for use among patients with hypertension: American ginseng, Asian ginseng, bitter orange, ginkgo, goldenseal, mate, and Siberian ginseng. Potassium supplements can also increase the risk of hyperkalemia in patients taking ACE inhibitors or diuretics. Another systematic review found that the herbal products Irish moss, kelp, and licorice may increase the effects of all antihypertensives.16
- Lotensin [package insert]. Parsippany, NJ: Validus Pharmaceuticals LLC; 2019.
- Capoten [package insert]. Chestnut Ridge, NY: Par Pharmaceutical; 2017.
- Epaned [package insert]. Wilmington, MA: Azurity Pharmaceuticals, Inc.; 2020.
- Vasotec [package insert]. Bridgewater, NJ: Bausch Health US LLC; 2018.
- Enalaprilat [package insert]. Lake Forest, IL: Hospira, Inc.; 2021.
- Monopril [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2003.
- Qbrelis [package insert]. Wilmington, MA: Azurity Pharmaceuticals, Inc.; 2020.
- Prinivil [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp.; 2021.
- Zestril [package insert]. Morristown, NJ: Almatica Pharma LLC; 2020.
- Univasc [package insert]. Smyrna, GA: USB, Inc; 2012.
- Aceon [package insert]. Cincinnati, OH: Patheon Pharmaceuticals, Inc.; 2017.
- Accupril [package insert]. New York, NY: Parke Davis, Pfizer; 2021.
- Altace [package insert]. New York, NY: Pfizer Laboratories; 2022.
- Mavik [package insert]. Whippany, NJ: Halo Pharmaceutical Inc.; 2017.
- Cicardi M, Aberer W, Banerji A, et al. Classification, diagnosis, and approach to treatment for angioedema: consensus report from the Hereditary Angioedema International Working Group. Allergy 2014; 69 (5): 602-616.