Introduction
Hyzaar is a combination antihypertensive medication containing losartan potassium (an angiotensin II receptor blocker) and hydrochlorothiazide (a thiazide diuretic). This fixed-dose combination therapy is designed to provide complementary mechanisms of action for improved blood pressure control in patients who require multiple antihypertensive agents.
Mechanism of Action
Losartan component: Selectively blocks the angiotensin II type 1 (AT1) receptors, inhibiting the vasoconstrictor and aldosterone-secreting effects of angiotensin II. This results in vasodilation, reduced peripheral resistance, and decreased blood pressure. Hydrochlorothiazide component: Inhibits sodium reabsorption in the distal convoluted tubule of the nephron, promoting excretion of sodium and water. This reduces plasma volume and extracellular fluid volume, contributing to blood pressure reduction. The diuretic effect also produces a slight increase in plasma renin activity and aldosterone secretion.Indications
- Treatment of hypertension in patients who require multiple antihypertensive agents
- Not indicated for initial therapy of hypertension
- May be used as replacement therapy in patients already receiving both components separately
Dosage and Administration
Available formulations:- Hyzaar 50/12.5: 50 mg losartan/12.5 mg hydrochlorothiazide
- Hyzaar 100/12.5: 100 mg losartan/12.5 mg hydrochlorothiazide
- Hyzaar 100/25: 100 mg losartan/25 mg hydrochlorothiazide
- Renal impairment: Not recommended if CrCl <30 mL/min
- Hepatic impairment: Use with caution; not recommended in severe hepatic impairment
- Elderly: No initial dosage adjustment necessary, but monitor closely
- Pediatric: Safety and effectiveness not established
Pharmacokinetics
Absorption:- Losartan: Rapidly absorbed, bioavailability ~33%
- Hydrochlorothiazide: ~70% bioavailability
- Food does not significantly affect absorption
- Losartan: Protein binding ~98% (primarily albumin)
- Hydrochlorothiazide: Protein binding ~68%
- Both cross placenta and are excreted in breast milk
- Losartan: Converted to active metabolite E-3174 by CYP2C9 and CYP3A4
- Hydrochlorothiazide: Not significantly metabolized
- Losartan: Renal and biliary excretion; terminal half-life ~2 hours (6-9 hours for active metabolite)
- Hydrochlorothiazide: Renal excretion; half-life ~6-15 hours
Contraindications
- Hypersensitivity to any component
- Anuria
- History of angioedema related to previous ACE inhibitor or ARB therapy
- Concomitant use with aliskiren in patients with diabetes
- Severe renal impairment (CrCl <30 mL/min)
- Refractory hypokalemia, hyponatremia, or hypercalcemia
Warnings and Precautions
Fetal toxicity: Discontinue when pregnancy is detected due to risk of injury and death to developing fetus Hypotension: May occur in volume-depleted patients; correct volume depletion prior to administration Renal impairment: Monitor renal function; may cause acute renal failure in susceptible patients Electrolyte imbalances: Monitor potassium, sodium, magnesium, and calcium levels- Risk of hypokalemia with hydrochlorothiazide
- Risk of hyperkalemia with losartan
Drug Interactions
Potassium supplements/potassium-sparing diuretics: Increased risk of hyperkalemia Lithium: Decreased lithium clearance, increased lithium toxicity risk NSAIDs: May reduce antihypertensive effect and increase risk of renal impairment Other antihypertensives: Additive hypotensive effects Cholestyramine/colestipol: Reduced absorption of hydrochlorothiazide Digoxin: Thiazides may cause hypokalemia, increasing digoxin toxicity risk Oral hypoglycemics: Thiazides may alter glucose toleranceAdverse Effects
Common (≥1%):- Dizziness (3.5%)
- Upper respiratory infection (2.1%)
- Cough (1.8%)
- Fatigue (1.5%)
- Back pain (1.5%)
- Diarrhea (1.4%)
- Angioedema (<1%)
- Acute renal failure
- Severe hypotension
- Electrolyte imbalances
- Hepatotoxicity
- Rhabdomyolysis
- Blood dyscrasias
Monitoring Parameters
- Blood pressure regularly
- Renal function (BUN, creatinine) at baseline and periodically
- Electrolytes (potassium, sodium, magnesium, calcium) at baseline and periodically
- Liver function tests in patients with pre-existing liver disease
- Signs of fluid or electrolyte imbalance
- Serum uric acid levels (thiazides may increase uric acid)
Patient Education
- Take medication at the same time each day
- Report any signs of allergic reaction (swelling of face, lips, tongue, or throat)
- Monitor for dizziness, especially when standing up quickly
- Maintain regular follow-up appointments for blood pressure monitoring
- Report persistent dry cough, muscle pain, or weakness
- Use sun protection due to photosensitivity risk
- Avoid potassium supplements unless prescribed by healthcare provider
- Notify all healthcare providers about all medications being taken
- Immediately report if pregnancy is suspected or confirmed
References
1. FDA Prescribing Information: Hyzaar (losartan potassium-hydrochlorothiazide) Tablets 2. Whelton PK, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. J Am Coll Cardiol. 2018;71(19):e127-e248. 3. Burnier M. Angiotensin II type 1 receptor blockers. Circulation. 2001;103(6):904-912. 4. Sica DA. Diuretic-related side effects: development and treatment. J Clin Hypertens (Greenwich). 2004;6(9):532-540. 5. Elliott WJ. Double-blind comparison of eprosartan and enalapril on cough and blood pressure in unselected hypertensive patients. Eprosartan Study Group. J Hum Hypertens. 1999;13(6):413-417. 6. McInnes GT. Losartan/hydrochlorothiazide: a review of its use in essential hypertension. Drugs. 1998;56(5):871-893.