How should I transition an adult patient from lisinopril to losartan, including the washout interval, starting dose, monitoring of renal function and potassium, and relevant contraindications?

Transition from Lisinopril to Losartan

Switch directly from lisinopril to losartan without a washout period, starting losartan 50 mg once daily the day after stopping lisinopril, and monitor renal function and potassium within 1–2 weeks. 1, 2

Direct Transition Protocol

No washout interval is required when switching from an ACE inhibitor to an ARB. Both drug classes act on the renin-angiotensin system through different mechanisms, and there is no pharmacologic reason to insert a gap between stopping one and starting the other. 1, 2

Starting Dose Selection

• Initiate losartan at 50 mg once daily on the day immediately following the last dose of lisinopril. 1, 2
• This starting dose is appropriate for most adults with hypertension or heart failure with reduced ejection fraction. 1, 2
• For patients with hepatic impairment, reduce the starting dose to 25 mg once daily due to approximately five-fold higher plasma concentrations. 2

Dose Titration Strategy

• Increase losartan to 100 mg once daily after 2–4 weeks if blood pressure remains ≥140/90 mmHg or heart failure symptoms persist. 1, 2
• For heart failure with reduced ejection fraction, the target dose is 100–150 mg daily based on outcomes data from the HEAAL trial, which demonstrated a 10% relative risk reduction at 150 mg versus 50 mg daily. 2
• Reassess blood pressure every 2–4 weeks during titration, aiming for a target of <130/80 mmHg within 3 months of therapy initiation. 2

Critical Monitoring Requirements

Renal Function and Electrolytes

• Check serum creatinine/eGFR and potassium within 1–2 weeks after switching to losartan. 1, 2
• A modest increase in serum creatinine of 0.1–0.3 mg/dL is expected and reflects hemodynamic alterations rather than true tubular injury; discontinuation is not required unless urinalysis shows evidence of acute tubular necrosis. 2
• Maximum acceptable creatinine increase is 50% or 266 μmol/L from baseline, with maximum acceptable serum potassium of 5.5 mmol/L. 1
• If creatinine increases by 100% or more, or reaches 310 μmol/L, discontinue losartan and seek specialist opinion. 1

Ongoing Surveillance

• After initial 1–2 week check, monitor potassium and renal function at 1 month, 3 months, then every 3–6 months if stable. 1, 2
• More frequent monitoring (every 1–2 weeks initially) is required for patients with:
  • Chronic kidney disease (eGFR <60 mL/min/1.73 m²) 2
  • Diabetes mellitus 2
  • Heart failure 1, 2
  • Baseline systolic blood pressure <80 mmHg 2
  • Concurrent use of potassium-sparing diuretics or NSAIDs 2

Absolute Contraindications to Losartan

• Pregnancy – Losartan causes serious fetal toxicity (renal dysfunction, oligohydramnios, skull hypoplasia, fetal death) and is contraindicated in all trimesters. 2
• History of angioedema with ARBs – Although less frequent than with ACE inhibitors, angioedema can occur with ARBs, particularly in patients who previously experienced ACE inhibitor-induced angioedema. 1, 2
• Severe bilateral renal artery stenosis – Use is contraindicated due to risk of acute renal failure. 1, 2
• Concurrent use with ACE inhibitors or direct renin inhibitors (aliskiren) – Dual RAAS blockade increases the risk of hyperkalemia, syncope, and acute kidney injury by 2–3-fold without added cardiovascular benefit. 1, 2

Special Populations and Dose Adjustments

Renal Impairment

• No dose adjustment is required for mild-to-moderate renal impairment (eGFR ≥30 mL/min/1.73 m²). 2
• For severe renal impairment (eGFR <30 mL/min), start at 25 mg once daily and titrate cautiously with close monitoring. 2
• Serial monitoring of serum electrolytes and renal function is mandatory, especially when losartan is used in conjunction with diuretics. 1

Elderly Patients (≥75 years)

• Initiate at a low dose (25–50 mg once daily) to reduce the risk of hypotension and renal insufficiency. 2
• Measure blood pressure in both sitting and standing positions (after 5 minutes seated, then at 1 minute and 3 minutes after standing) to detect orthostatic hypotension. 2
• Titrate more gradually (every 2–4 weeks rather than weekly) and monitor closely for symptomatic hypotension and orthostatic changes. 2

Heart Failure Patients

• Continue losartan during hospitalization for acute decompensation in the absence of hemodynamic instability or contraindications. 1
• Initiate losartan in stable patients prior to hospital discharge if not previously treated with an ARB. 1
• Target dose is 100–150 mg daily for heart failure with reduced ejection fraction. 1, 2

Common Pitfalls and How to Avoid Them

Medication Interactions

• Never combine losartan with an ACE inhibitor – The VALIANT trial demonstrated that dual RAAS blockade increased adverse outcomes without improving cardiovascular benefit. 1, 2
• Avoid NSAIDs – They blunt losartan's antihypertensive effect, worsen renal function, and dramatically increase hyperkalemia risk. 2
• Monitor lithium levels – Co-administration can precipitate lithium toxicity. 2
• Potassium supplements or potassium-sparing diuretics – Concomitant use markedly increases hyperkalemia risk, especially in chronic kidney disease. 2

Premature Discontinuation for Creatinine Rise

• Do not stop losartan for modest creatinine elevations (0.1–0.3 mg/dL) – This reflects expected hemodynamic changes, not acute tubular necrosis. 2
• Only discontinue if creatinine increases by 100% or more, or if urinalysis shows evidence of acute tubular injury. 1, 2

Inadequate Dose Titration

• Underdosing is widespread in clinical practice, with less than 25% of patients ever titrated to target doses. 2
• Higher doses of losartan provide greater benefits than lower doses, with little evidence that medium-range doses approximate the benefits of target doses. 2
• For heart failure, 150 mg daily was superior to 50 mg daily with a 10% relative risk reduction in death or heart failure hospitalization. 2

Combination Therapy Considerations

• If blood pressure remains uncontrolled on losartan 100 mg daily after 4–8 weeks, add hydrochlorothiazide 12.5–25 mg once daily. 1, 2
• The losartan + hydrochlorothiazide combination provides additive blood-pressure lowering; adding 12.5 mg HCTZ to losartan 50 mg produced a placebo-adjusted reduction of approximately 15.5 mmHg systolic / 9.2 mmHg diastolic. 2, 3
• Prefer single-pill fixed-dose combinations to improve adherence, which is markedly better than using separate pills. 2

Blood Pressure Targets

• Aim for <130/80 mmHg in most adults to reduce cardiovascular risk. 1, 2
• A minimum acceptable goal is <140/90 mmHg; lower targets provide additional cardiovascular protection when well tolerated. 2
• Reassess blood pressure every 2–4 weeks after switching to losartan, with the goal of reaching target within 3 months. 2