What is the recommended protocol for transitioning from lisinopril (Angiotensin-Converting Enzyme (ACE) inhibitor) to losartan (Angiotensin II Receptor Blocker (ARB))?

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Transitioning from Lisinopril to Losartan

You can switch directly from lisinopril to losartan without any washout period, starting losartan the day after stopping lisinopril. Unlike the transition from an ACE inhibitor to an ARNI (which requires a 36-hour washout), switching from an ACE inhibitor to an ARB does not require any waiting period and can be done immediately 1.

Dosing Strategy for the Transition

Initial Losartan Dose Selection

  • If the patient is on low-dose lisinopril (≤10 mg daily): Start losartan at 25-50 mg once daily 1.

  • If the patient is on moderate-to-high dose lisinopril (20-40 mg daily): Start losartan at 50 mg once daily 1.

  • The target dose of losartan for most indications is 50-100 mg once daily, with 100 mg being the maximum recommended daily dose 1, 2, 3.

Titration Schedule

  • Reassess blood pressure, renal function (creatinine/eGFR), and potassium within 1-2 weeks after initiating losartan 1.

  • If blood pressure remains ≥140/90 mmHg after 1 month on losartan 50 mg, increase to 100 mg once daily 4.

  • Titration can occur every 2-4 weeks based on blood pressure response and tolerability 1.

Monitoring Parameters

Critical Laboratory Values to Check

  • Baseline (before switch): Serum creatinine, eGFR, and potassium 1.

  • 1-2 weeks post-switch: Repeat creatinine, eGFR, and potassium 1.

  • Acceptable changes: An initial rise in creatinine of 10-20% is expected and represents hemodynamic changes rather than kidney injury 5.

  • Concerning changes requiring intervention: A rise in serum creatinine >30% from baseline warrants holding the medication and reassessing 5.

Blood Pressure Monitoring

  • Check blood pressure (including orthostatic measurements) at 1-2 weeks, then monthly until controlled 1.

  • Patients with systolic blood pressure <80 mmHg, low serum sodium, diabetes mellitus, or impaired renal function require particularly close surveillance 1.

Common Clinical Scenarios

Why Patients Switch from Lisinopril to Losartan

The most common reason for switching is ACE inhibitor-induced cough, which occurs in a few percent of patients and can be a cause of discontinuation 2. Studies demonstrate that the incidence of cough with losartan therapy in patients who had cough with ACE inhibitors is similar to placebo (17-29% vs 25-35% placebo) and dramatically lower than continuing lisinopril (62-69%) 2.

Angioedema is another indication for switching, though it is much less frequent with ARBs than ACE inhibitors 1. However, rare cases of cross-reactivity exist where patients develop angioedema to both ACE inhibitors and subsequently to ARBs 1.

Special Populations Requiring Dose Adjustment

  • Severe renal impairment (eGFR <30 mL/min/1.73 m²): Consider starting at a lower dose (25 mg daily), though losartan is not removed by hemodialysis 1, 3.

  • Volume depletion or aggressive diuresis: Ensure adequate volume status before initiating losartan to avoid hypotension 1, 5.

  • Elderly patients (≥75 years): May start at lower doses (25 mg daily) due to increased risk of hypotension 1.

Critical Pitfalls to Avoid

Do Not Combine ACE Inhibitors and ARBs

Never overlap lisinopril and losartan therapy. Combining two RAS blockers (ACE inhibitor and ARB) is explicitly not recommended and increases risks of hypotension, renal dysfunction, and hyperkalemia without providing additional cardiovascular benefit 1, 6, 7.

Contraindications to Losartan

  • Pregnancy: Losartan, like all ARBs, is contraindicated in pregnancy due to serious fetal toxicity when given in the second and third trimesters 3.

  • Bilateral renal artery stenosis: ARBs can cause acute renal failure in this setting 5.

  • History of angioedema with ARBs: Absolute contraindication 5.

Drug Interactions

Losartan has a favorable drug-drug interaction profile with no clinically relevant interactions with hydrochlorothiazide, warfarin, or digoxin 3. However, monitor potassium closely when combining with aldosterone antagonists (spironolactone, eplerenone) or potassium-sparing diuretics due to additive hyperkalemia risk 1.

Adding Additional Antihypertensive Therapy

If blood pressure remains uncontrolled on losartan 100 mg daily:

  • First-line addition: Combine with a thiazide/thiazide-like diuretic or dihydropyridine calcium channel blocker, preferably as a single-pill combination 1.

  • Second-line addition: If still uncontrolled on three drugs (ARB + CCB + diuretic), consider adding spironolactone 1.

  • Do not add a second ARB or combine with an ACE inhibitor 1, 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Clinical pharmacokinetics of losartan.

Clinical pharmacokinetics, 2005

Guideline

When to Hold Irbesartan Due to Renal or Cardiovascular Risks

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Angiotensin II Receptor Blocker Combination Therapy

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Maximum Dose of Angiotensin Receptor Blockers (ARBs)

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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