What is Hyzaar (losartan and hydrochlorothiazide)?

What is Hyzaar?

Hyzaar is a fixed-dose combination antihypertensive medication containing losartan potassium (an angiotensin II receptor blocker/ARB) and hydrochlorothiazide (a thiazide diuretic), indicated for the treatment of hypertension and for stroke risk reduction in patients with hypertension and left ventricular hypertrophy. 1

Composition and Mechanism

• Losartan is the first angiotensin II receptor antagonist that specifically blocks angiotensin II at AT-1 receptors, preventing vasoconstriction and aldosterone secretion 2
• Hydrochlorothiazide (HCTZ) is a thiazide diuretic that reduces blood volume through sodium and water excretion 2
• The combination works through complementary pharmacologic mechanisms, providing additive antihypertensive effects with potentially fewer adverse effects than higher doses of either component alone 2

Clinical Indications

• Primary hypertension treatment, including as initial therapy in severe hypertension 1
• Stroke risk reduction specifically in patients with hypertension and documented left ventricular hypertrophy 1
• The combination is particularly useful when monotherapy with either component fails to achieve adequate blood pressure control 3

Evidence-Based Efficacy

• The combination of losartan 50 mg with hydrochlorothiazide 12.5 mg produces the greatest blood pressure reduction (17.2 mmHg systolic and 13.2 mmHg diastolic), with effects appearing additive 2
• Approximately 78% of patients treated with losartan 50 mg plus HCTZ 12.5 mg achieve excellent or good antihypertensive response (diastolic BP <90 mmHg or ≥10 mmHg reduction) 2
• The peak-to-trough ratio ranges from 62% to 85%, indicating smooth 24-hour blood pressure control with once-daily dosing 2

Cardiovascular Outcomes Data

• In the LIFE study, losartan-based therapy (where the vast majority of patients received hydrochlorothiazide in addition to losartan) demonstrated superior cardiovascular outcomes compared to atenolol-based therapy, primarily through reduced stroke risk 4
• The beneficial effect was particularly pronounced in diabetic patients, showing statistically significant reductions in all-cause mortality 4
• Losartan-based therapy also reduced the incidence of new-onset diabetes mellitus compared to beta-blocker therapy 1

Role in Treatment Guidelines

• The ARB plus thiazide diuretic combination represents an evidence-based two-drug regimen recommended by international guidelines 5
• When blood pressure remains uncontrolled on this combination, guidelines recommend adding a calcium channel blocker (typically amlodipine) as the third agent, creating the preferred triple therapy regimen 5
• An inhibitor of the renin-angiotensin-aldosterone system (such as losartan) should be part of the pharmacological combination when treating hypertensive patients, particularly those with diabetes 4

Pharmacokinetic Profile

• No clinically significant pharmacokinetic interaction exists between losartan and hydrochlorothiazide when administered together 6
• The geometric mean AUC ratio is 1.02 for both losartan and its active metabolite E-3174, confirming no interference between the two components 6
• Coadministration is well tolerated with maintained bioavailability of both agents 6

Safety and Tolerability

• The most common adverse effects (≥4% incidence) include headache, asthenia/fatigue, dizziness, sinusitis, and upper respiratory infection, occurring at rates only slightly greater than placebo 2
• The combination may reduce HCTZ-induced metabolic disorders, particularly offering benefits for patients with hyperuricemia 3
• Renal function should be monitored when instituting losartan, especially considering the risk of deterioration in the presence of renal artery stenosis 4

Common Pitfalls to Avoid

• Do not combine losartan with ACE inhibitors, as dual renin-angiotensin system blockade increases risks of hyperkalemia and renal dysfunction without mortality benefit 5, 7
• Monitor serum potassium levels when using this combination, as both components can affect potassium homeostasis (HCTZ causes hypokalemia while losartan may cause hyperkalemia) 5
• Be aware that thiazide diuretics are associated with increased risk of developing type 2 diabetes, though this risk is mitigated when combined with ARBs like losartan 4

Practical Prescribing Considerations

• The fixed-dose combination improves treatment adherence compared to taking separate tablets through simplified once-daily dosing 7, 3
• Available formulations include various dose combinations to allow titration based on blood pressure response 1
• The combination provides a logical choice for patients requiring dual therapy to achieve blood pressure targets 3