HYZAAR

Clinical safety rating: caution

Comprehensive clinical and safety monograph for HYZAAR (HYZAAR).

How it works

Hyzaar is a combination of losartan potassium, an angiotensin II receptor blocker (ARB), and hydrochlorothiazide, a thiazide diuretic. Losartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively antagonizing the AT1 receptor, reducing peripheral resistance. Hydrochlorothiazide inhibits the sodium-chloride symporter in the distal convoluted tubule, increasing excretion of sodium and water, thereby reducing plasma volume.

What the body does with it

Metabolism	Losartan is primarily metabolized by CYP2C9 and CYP3A4 to its active carboxylic acid metabolite (E-3174). Hydrochlorothiazide is not metabolized and is excreted unchanged in urine.
Excretion	Losartan: ~50% renal (4% unchanged, 50% as active metabolite E-3174), ~50% biliary/fecal. Hydrochlorothiazide: >95% renal (unchanged).
Half-life	Losartan: terminal t1/2 1.5–2.5 h; active metabolite E-3174: 6–9 h, clinical effect persists ~24 h. Hydrochlorothiazide: 5.6–14.8 h (prolonged in renal impairment).
Protein binding	Losartan: 98.7% (albumin, alpha-1 acid glycoprotein). E-3174: 99.8%. Hydrochlorothiazide: 40–68% (albumin).
Volume of Distribution	Losartan: ~34 L (0.5 L/kg). E-3174: ~12 L. Hydrochlorothiazide: 3–4 L/kg (extensive tissue distribution).
Bioavailability	Losartan: oral ~33% (extensive first-pass metabolism). Hydrochlorothiazide: oral 65–75%.
Onset of Action	Oral: losartan antihypertensive effect within 1 week, maximal effect at 3–6 weeks; hydrochlorothiazide diuresis begins 2 h, peak at 4–6 h.
Duration of Action	Losartan: 24 h (once-daily dosing). Hydrochlorothiazide: 6–12 h (diuretic effect). Clinical BP reduction sustained over 24 h with combination.

Classification & Brands

Dosing & administration

Hyzaar (losartan 50 mg / hydrochlorothiazide 12.5 mg) orally once daily. May increase to 1 tablet of losartan 100 mg / hydrochlorothiazide 25 mg once daily if needed.

Dosage form	TABLET
Renal impairment	Contraindicated in anuria. For CrCl 30-50 mL/min: no adjustment needed. For CrCl less than 30 mL/min: not recommended (loop diuretics preferred).
Liver impairment	Mild to moderate hepatic impairment (Child-Pugh class A or B): initiate losartan at 25 mg once daily; use combination product only if titrated on individual components. Severe hepatic impairment (Child-Pugh class C): contraindicated.
Pediatric use	Not indicated for children under 18 years of age. Safety and efficacy not established.
Geriatric use	Start at lowest dose (losartan 50 mg / hydrochlorothiazide 12.5 mg once daily). Monitor renal function and electrolytes; increased risk of hypotension and electrolyte imbalance.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for HYZAAR (HYZAAR).

Breastfeeding	Losartan and hydrochlorothiazide are excreted in human milk in low amounts; M/P ratio not established for losartan. Due to potential for adverse effects in nursing infants (e.g., hypotension, electrolyte disturbances), use is not recommended during breastfeeding.
Teratogenic Risk	First trimester: Limited data; potential risk of congenital malformations cannot be excluded. Second and third trimesters: Fetal renal dysfunction, oligohydramnios, skull ossification defects, hypotension, and anuria. Exposure after 20 weeks gestation is associated with severe fetal and neonatal morbidity.

Warnings & precautions

■ FDA Black Box Warning

WARNING: FETAL TOXICITY - When pregnancy is detected, discontinue Hyzaar as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Anuria (hydrochlorothiazide component)","Hypersensitivity to losartan, hydrochlorothiazide, or sulfonamide-derived drugs","Pregnancy (particularly second and third trimesters)","Severe renal impairment (CrCl <30 mL/min)"]

Clinical Precautions

Precautions

["Hypotension in volume- or salt-depleted patients","Impaired renal function including acute renal failure","Electrolyte imbalances (hyperkalemia, hyponatremia)","Hypersensitivity reactions (angioedema)","Acute angle-closure glaucoma (hydrochlorothiazide component)","Fetal/neonatal morbidity and mortality (see black box warning)","Exacerbation of systemic lupus erythematosus (hydrochlorothiazide)"]

Clinical Tips & Counseling

Drug interactions

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HYZAAR

Clinical safety rating: caution

Comprehensive clinical and safety monograph for HYZAAR (HYZAAR).

How it works

What the body does with it

Metabolism	Losartan is primarily metabolized by CYP2C9 and CYP3A4 to its active carboxylic acid metabolite (E-3174). Hydrochlorothiazide is not metabolized and is excreted unchanged in urine.
Excretion	Losartan: ~50% renal (4% unchanged, 50% as active metabolite E-3174), ~50% biliary/fecal. Hydrochlorothiazide: >95% renal (unchanged).
Half-life	Losartan: terminal t1/2 1.5–2.5 h; active metabolite E-3174: 6–9 h, clinical effect persists ~24 h. Hydrochlorothiazide: 5.6–14.8 h (prolonged in renal impairment).
Protein binding	Losartan: 98.7% (albumin, alpha-1 acid glycoprotein). E-3174: 99.8%. Hydrochlorothiazide: 40–68% (albumin).
Volume of Distribution	Losartan: ~34 L (0.5 L/kg). E-3174: ~12 L. Hydrochlorothiazide: 3–4 L/kg (extensive tissue distribution).
Bioavailability	Losartan: oral ~33% (extensive first-pass metabolism). Hydrochlorothiazide: oral 65–75%.
Onset of Action	Oral: losartan antihypertensive effect within 1 week, maximal effect at 3–6 weeks; hydrochlorothiazide diuresis begins 2 h, peak at 4–6 h.
Duration of Action	Losartan: 24 h (once-daily dosing). Hydrochlorothiazide: 6–12 h (diuretic effect). Clinical BP reduction sustained over 24 h with combination.

Classification & Brands

Dosing & administration

Hyzaar (losartan 50 mg / hydrochlorothiazide 12.5 mg) orally once daily. May increase to 1 tablet of losartan 100 mg / hydrochlorothiazide 25 mg once daily if needed.

Dosage form	TABLET
Renal impairment	Contraindicated in anuria. For CrCl 30-50 mL/min: no adjustment needed. For CrCl less than 30 mL/min: not recommended (loop diuretics preferred).
Liver impairment	Mild to moderate hepatic impairment (Child-Pugh class A or B): initiate losartan at 25 mg once daily; use combination product only if titrated on individual components. Severe hepatic impairment (Child-Pugh class C): contraindicated.
Pediatric use	Not indicated for children under 18 years of age. Safety and efficacy not established.
Geriatric use	Start at lowest dose (losartan 50 mg / hydrochlorothiazide 12.5 mg once daily). Monitor renal function and electrolytes; increased risk of hypotension and electrolyte imbalance.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for HYZAAR (HYZAAR).

Breastfeeding	Losartan and hydrochlorothiazide are excreted in human milk in low amounts; M/P ratio not established for losartan. Due to potential for adverse effects in nursing infants (e.g., hypotension, electrolyte disturbances), use is not recommended during breastfeeding.
Teratogenic Risk	First trimester: Limited data; potential risk of congenital malformations cannot be excluded. Second and third trimesters: Fetal renal dysfunction, oligohydramnios, skull ossification defects, hypotension, and anuria. Exposure after 20 weeks gestation is associated with severe fetal and neonatal morbidity.