After stopping lisinopril, how long should I wait before initiating losartan, particularly if the lisinopril was discontinued due to severe ACE‑inhibitor‑induced angioedema?

Switching from Lisinopril to Losartan: Timing and Safety Considerations

Direct Answer for Routine Switching

In routine clinical scenarios without angioedema, you can start losartan immediately after stopping lisinopril—no waiting period is required. 1

• A randomized controlled trial specifically evaluated immediate switching from captopril (an ACE inhibitor) to losartan in 177 hypertensive patients and found no clinically significant hypotension or adverse events requiring a washout period 1
• Within 12 hours of switching, only 3% of patients on losartan had systolic BP readings below 100 mmHg, which was not statistically different from those who continued ACE inhibitor therapy 1
• The study concluded that losartan was "effective and generally well tolerated when administered immediately after pretreatment with an ACE inhibitor" 1

Critical Exception: ACE Inhibitor-Induced Angioedema

If lisinopril was discontinued due to angioedema, you should NOT prescribe losartan or any other ARB—this is an absolute contraindication. 2, 3

Why ARBs Are Contraindicated After ACE Inhibitor Angioedema

• The American Heart Association explicitly states that another ARB should never be used if the patient had an allergic reaction (including angioedema) to an ACE inhibitor due to cross-reactivity risk 3
• The European Society of Cardiology advises against using ARBs in patients with a history of angioedema with ACE inhibitors 2
• Despite initial theories that ARBs would not cause angioedema (since they don't affect bradykinin metabolism), multiple case reports demonstrate that losartan can indeed cause angioedema 4, 5, 6
• Angioedema with losartan has been documented in patients with prior ACE inhibitor-induced angioedema, confirming cross-reactivity 5
• The reaction can occur anywhere from 24 hours to 16 months after starting losartan, and can recur even after initial resolution 4, 5

Alternative Medications After ACE Inhibitor Angioedema

If you need renin-angiotensin system blockade after ACE inhibitor angioedema, wait a minimum of 6 weeks, then consider cautiously reintroducing an ACE inhibitor—NOT an ARB. 3

• The American College of Cardiology and American Heart Association recommend a 6-week waiting period before considering ACE inhibitor rechallenge due to documented cross-reactivity patterns 3
• This counterintuitive recommendation reflects that ACE inhibitor angioedema may be idiosyncratic rather than purely bradykinin-mediated 6

For immediate blood pressure control without waiting, use calcium channel blockers or thiazide diuretics instead: 3

• Calcium channel blockers: Amlodipine 2.5-10 mg once daily is recommended by the American College of Cardiology for immediate BP control 3
• Thiazide diuretics: Chlorthalidone 12.5-25 mg once daily is an alternative, particularly for elderly patients or isolated systolic hypertension 3

Practical Initiation Protocol for Routine Switching (No Angioedema History)

When switching from lisinopril to losartan in standard clinical scenarios:

1. Day 1: Stop lisinopril, start losartan 50 mg once daily (or 25 mg if elderly/volume depleted) 7, 8
2. Week 1: Check renal function and potassium 7, 8
3. Weeks 2-4: Titrate to target dose of 100 mg daily if tolerated 8
4. Week 4: Recheck creatinine and potassium after dose increase 7, 8

Monitoring Parameters

• An initial creatinine rise of 10-20% is expected and acceptable, representing hemodynamic changes rather than kidney injury 2
• Progressive increases beyond 30% from baseline warrant discontinuation 2
• Monitor potassium closely, especially in patients with CKD or on potassium supplements 3, 8

Common Pitfalls to Avoid

Never combine losartan with an ACE inhibitor or direct renin inhibitor: 2, 8

• The American Heart Association explicitly advises against this combination due to increased risk of hyperkalemia, hypotension, and renal dysfunction 2
• The VALIANT trial showed that combining valsartan with captopril increased adverse events without improving survival 7

Do not use losartan in patients with bilateral renal artery stenosis: 2

• Angiotensin II is necessary for maintaining GFR when renal perfusion is compromised 2

Avoid in severe volume depletion states: 2

• Hold during severe dehydration, aggressive diuresis, or symptomatic hypotension 2