When can the dose of losartan (angiotensin II receptor antagonist) be increased for uncontrolled hypertension?

Losartan Dose Titration for Uncontrolled Hypertension

The dose of losartan should be increased from 50 mg to 100 mg once daily when blood pressure remains uncontrolled (≥140/90 mmHg) after 2-4 weeks of treatment at the initial dose. 1

Initial Dosing and Titration Protocol

• Starting dose for most patients is 50 mg once daily 1
• Lower starting dose of 25 mg is recommended for patients with possible intravascular depletion (e.g., those on diuretic therapy) 1
• After 2-4 weeks on the initial dose, assess blood pressure control 2
• If blood pressure remains ≥140/90 mmHg, increase to the maximum dose of 100 mg once daily 1
• Allow 2-4 weeks between dose adjustments to fully assess the effect of each dose 2

Evidence Supporting Dose Titration

The FDA-approved labeling for losartan indicates that doses of 50 mg, 100 mg, and 150 mg once daily provide statistically significant systolic/diastolic mean decreases in blood pressure compared to placebo, ranging from 5.5-10.5/3.5-7.5 mmHg 1. Clinical studies have demonstrated that:

• The 10 mg and 25 mg doses produce some effect at peak but small and inconsistent 24-hour responses 1
• 50-100 mg doses provide significant and consistent blood pressure reduction 1
• The 100 mg dose may provide additional benefit in patients not adequately controlled on 50 mg 1

When to Consider Combination Therapy

If blood pressure remains uncontrolled despite maximum losartan dose (100 mg daily):

• Add a calcium channel blocker (e.g., amlodipine 5 mg) or a thiazide-like diuretic (e.g., hydrochlorothiazide 12.5 mg) 2
• The addition of hydrochlorothiazide 12.5 mg to losartan 50 mg once daily has been shown to result in placebo-adjusted blood pressure reductions of 15.5/9.2 mmHg 1
• For patients with heart failure with reduced ejection fraction, the target dose of losartan is 150 mg daily for maximum clinical benefit 2

Monitoring and Safety Considerations

• Monitor blood pressure every 2-4 weeks during dose adjustments 2
• Check renal function and potassium levels before and after significant dose increases, especially in patients with:
  • Chronic kidney disease
  • Bilateral renal artery stenosis
  • Concomitant use of potassium-sparing diuretics 2
• Asymptomatic hypotension is not a reason to avoid dose titration, as the clinical benefits of reaching target doses outweigh the risks 3
• The most dramatic decreases in blood pressure with losartan typically occur with the initial dose; subsequent changes with each dosing increment are comparatively smaller 3

Special Populations

• In patients with mild-to-moderate hepatic impairment, start with 25 mg once daily 1
• For patients with heart failure with reduced ejection fraction, guidelines recommend titrating to maximally tolerated doses of ARBs, with a target dose of 100 mg daily for losartan 3
• For patients with left ventricular hypertrophy, the dose can be increased to 100 mg once daily based on blood pressure response 1

Common Pitfalls to Avoid

1. Inadequate dose titration: Many physicians fail to uptitrate to target doses due to concerns about tolerability, but medium-range doses may not provide the full benefits of target doses 3

2. Premature discontinuation: Temporary side effects like mild dizziness upon standing can often be managed through patient education rather than dose reduction 3

3. Failure to recognize the importance of target doses: The target doses of losartan for heart failure (100 mg daily) are typically higher than those commonly used for hypertension in general practice 3

4. Not allowing sufficient time between dose adjustments: Allow at least 2-4 weeks to fully assess the effect of each dose before further titration 2