Can a patient take losartan (Angiotensin II Receptor Antagonist), lisinopril (Angiotensin-Converting Enzyme (ACE) inhibitor), and labetalol (Beta-Blocker) together?

From the Guidelines

Taking losartan, lisinopril, and labetalol together is generally not recommended due to significant safety concerns. Combining losartan (an angiotensin II receptor blocker) with lisinopril (an ACE inhibitor) creates a dual blockade of the renin-angiotensin system, which increases the risk of hypotension, hyperkalemia, and kidney dysfunction without providing additional clinical benefits, as cautioned against in 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 1. While labetalol (a beta-blocker) can sometimes be prescribed with either an ACE inhibitor or an ARB individually, using all three medications simultaneously would compound the risk of hypotension and other adverse effects. Some key points to consider include:

• The combination of an ACE inhibitor and an angiotensin receptor blocker is associated with a consistent increase in serious side effects, such as hyperkalemia or acute kidney injury, without providing additional benefits on cardiovascular or diabetic kidney disease 1.
• The most rational combinations for achieving blood pressure control appear to be a blocker of the renin–angiotensin system, a calcium antagonist, and a diuretic at effective doses, rather than combining multiple agents from the same class or with similar mechanisms of action 1.
• Patients with hypertension typically receive either an ACE inhibitor OR an ARB as a foundation of therapy, potentially combined with other classes of antihypertensives if needed for blood pressure control, highlighting the importance of selecting the most appropriate combination based on individual patient needs and avoiding unnecessary dual blockade of the renin-angiotensin system 1. If you are currently taking these medications together, contact your healthcare provider immediately to review your medication regimen, as this combination may require adjustment to ensure your safety and optimize your treatment.

From the FDA Drug Label

7.4 Dual Blockade of the Renin-Angiotensin System (RAS) Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy In most patients no benefit has been associated with using two RAS inhibitors concomitantly. In general, avoid combined use of RAS inhibitors.

The use of losartan (an angiotensin II receptor antagonist) and lisinopril (an ACE inhibitor) together is not recommended due to the increased risk of hypotension, hyperkalemia, and changes in renal function. There is no direct information in the provided drug labels about the safety of combining losartan, lisinopril, and labetalol. However, the combination of losartan and lisinopril is generally avoided. Labetalol is a beta-blocker, and its use with losartan and lisinopril may increase the risk of hypotension. Therefore, the combination of losartan, lisinopril, and labetalol should be used with caution and close monitoring of blood pressure, renal function, and electrolytes 2 3.

• Key considerations:
  • Monitor blood pressure closely
  • Monitor renal function and electrolytes
  • Avoid using this combination in patients with renal impairment or diabetes
  • Use the lowest effective doses of each medication
  • Closely monitor patients for signs of hypotension and hyperkalemia.

From the Research

Combination Therapy with Losartan, Lisinopril, and Labetalol

• The combination of losartan (Angiotensin II Receptor Antagonist), lisinopril (Angiotensin-Converting Enzyme (ACE) inhibitor), and labetalol (Beta-Blocker) is not directly addressed in the provided studies.
• However, studies have investigated the use of losartan and lisinopril in combination or separately, providing some insights into their potential interactions and effects.

Losartan and Lisinopril Combination

• A study from 2020 4 compared the effectiveness and safety of twice-daily versus once-daily dosing of lisinopril and losartan in patients with hypertension, but it did not specifically examine the combination of both drugs.
• Another study from 2004 5 compared the incidence of hyperkalemia in high-risk patients treated with lisinopril versus losartan, suggesting that both drugs can be used in patients with hypertension, but it did not investigate their combined use.
• A study from 2010 6 compared the effects of lisinopril and losartan in patients with idiopathic membranous nephropathy and nephrotic syndrome, finding similar effects on renal function, proteinuria, and blood pressure, but it did not examine the combination of both drugs with labetalol.

Labetalol and Combination Therapy

• There is limited information available on the specific combination of losartan, lisinopril, and labetalol.
• However, labetalol is often used in combination with other antihypertensive agents, including ACE inhibitors and beta-blockers, to achieve better blood pressure control 7.

Potential Interactions and Considerations

• When combining losartan, lisinopril, and labetalol, potential interactions and considerations include:
  • Increased risk of hypotension and hyperkalemia due to the combined effects of ACE inhibition and angiotensin II receptor blockade.
  • Potential additive effects on blood pressure reduction, which may require careful monitoring and dose adjustments.
  • Consideration of individual patient factors, such as renal function, electrolyte balance, and concomitant medications, to minimize the risk of adverse effects.