There are several medications that are contraindicated, should be avoided, or require close monitoring if they are concomitantly used with angiotensin receptor blockers (ARBs).1-9
Angiotensin Converting Enzyme Inhibitors (ACEI). Concomitant use of the antihypertensive class of medicine angiotensin converting enzyme inhibitor (ACEI) and ARBs should be avoided.1-9 It can result in hypotension, hyperkalemia, and renal impairment. If combined, close monitoring of blood pressure, electrolyte concentrations, and renal function is recommended. The 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults states that using an ARB with and ACEI or other renin inhibitor is potentially harmful.10 It explicitly says this is NOT recommended as antihypertensive therapy for adults. [Strong-HARM Recommendation (Level A)].
Aliskiren. Concomitant use of the antihypertensive renin blocker aliskiren (Tekturna) and ARBs should be avoided.1-9,11 It can result in hypotension, hyperkalemia, and renal impairment. If combined, close monitoring of blood pressure, electrolyte concentrations, and renal function is recommended. Concomitant use is contraindicated in people with diabetes mellitus.1-9,11,12 Concomitant use should be avoided in people with renal impairment (glomerular filtration rate less than 60 mL/minute). The 2017 Guideline states that Aliskiren should not be used in combination with ARBs or ACEIs [Strong-HARM Recommendation (Level A)].10
Lithium. Concomitant use with ARBs increases serum lithium concentrations and result in lithium toxicity.1-9
Nonsteroidal Anti-inflammatory Agents (NSAIDs). Concomitant use of NSAIDs, including selective cyclooxygenase-2 inhibitors, and ARBs can cause renal impairment, including acute renal failure, in people who are geriatric, volume-depleted (including people on diuretics), or have renal function impairment.1-9 Renal function should be monitored if coadministration occurs. Effects are usually reversible. Antihypertensive effects of ARBs may be attenuated when NSAIDs are also taken.
Potassium-sparing Diuretics. Concomitant use potassium supplements and potassium-containing salt substitutes and ARBs can increase the risk of hyperkalemia.2,3,5,8,9,13 Some doctors suggest avoiding coadministration.9,13
Potassium Supplements and Potassium-containing Salt Substitutes. Concomitant use of potassium-sparing diuretics (such as, amiloride, spironolactone, or triamterene) and ARBs can increase the risk of hyperkalemia.2,3,5,8,9,13 Some doctors suggest avoiding coadministration.9,13
Digoxin. It is recommended that serum digoxin concentrations be monitored when telmisartan therapy is initiated, adjusted, or discontinued in patients stabilized on digoxin.4,9,14,15 Coadministration may cause increased plasma digoxin concentrations.4,9,15 Dosing adjustments may be needed.16
Interactions that may affect dosing that doctors should be aware of include:*
Colesevelam hydrochloride: Olmesartan should be administered at least four hours before a colesevelam hydrochloride dose.7,17 Concurrent administration of the bile acid sequestering agent colesevelam hydrochloride lowers the systemic exposure of olmesartan by 39%. This is ameliorated by staggering administration of the two drugs.17
Drugs That Inhibit Hepatic Transport Systems
In vitro data suggest that valsartan is a substrate of organic anion transporter protein (OATP) 1B1 (hepatic uptake transporter) and multidrug resistance protein MRP2 (hepatic efflux transporter).5,9,18 Use of valsartan concomitantly with inhibitors of OATP 1B1 (e.g., cyclosporine, rifampin) or MRP2 (e.g., ritonavir) may result in significantly increased systemic exposure to valsartan.
*These are not included in the patient text as they won't affect patient medication decision making.
- Teveten [package insert]. North Chicago, IL: AbbVie Inc.; 2014.
- Edarbi [package insert] Atlanta, GA: Arbor Pharmaceuticals, LLC; 2016.
- Cozaar [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp; 2015.
- Micardis [package insert] Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2014.
- Diovan [package insert]East Hanover, NJ: Novartis Pharmaceuticals Corp; 2017.
- Avapro [package insert] Bridgewater, NJ: Sanofi-Aventis U.S. LLC; 2016.
- Benicar [package insert] Parsippany, NJ: Daiichi Sankyo, Inc; 2009.
- Atacand [package insert] Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2016.
- AHFS Drug Information. Gerald K. McEvoy PD, ed. 24:32.08 Angiotensin II Receptor Antagonists. 59th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2017.
- Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a reportof the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension 2017.
- New warning and contraindication for blood pressure medicines containing aliskiren (Tekturna). FDA Drug Safety Communication. U.S. Food & Drug Administration; 2012.
- Parving HH, Brenner BM, McMurray JJ, et al. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med 2012; 367 (23): 2204-2213.
- JC FPS. Focus on Azilsartan: A next-generation angiotensin II receptor blocker for the treatment of hypertension. Formulary 2010; 45: 342-349.
- McClellan KJ, Markham A. Telmisartan. Drugs 1998; 56 (6): 1039-1044; discussion 1045-1036.
- Stangier J, Su CA, Hendriks MG, et al. The effect of telmisartan on the steady-state pharmacokinetics of digoxin in healthy male volunteers. J Clin Pharmacol 2000; 40 (12 Pt 1): 1373-1379.
- Israili ZH. Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension. J Hum Hypertens 2000; 14 Suppl 1: S73-86.
- He L, Wickremasingha P, Lee J, et al. The effects of colesevelam HCl on the single-dose pharmacokinetics of glimepiride, extended-release glipizide, and olmesartan medoxomil. J Clin Pharmacol 2014; 54 (1): 61-69.
- Yamashiro W, Maeda K, Hirouchi M, Adachi Y, Hu Z, Sugiyama Y. Involvement of transporters in the hepatic uptake and biliary excretion of valsartan, a selective antagonist of the angiotensin II AT1-receptor, in humans. Drug Metab Dispos 2006; 34 (7): 1247-1254.