OLMESARTAN MEDOXOMIL AND HYDROCHLOROTHIAZIDE

Clinical safety rating: avoid

NSAIDs may diminish the antihypertensive effect Lithium levels may be increased Use in pregnancy can cause injury and death to the developing fetus.

How it works

Olmesartan medoxomil is an angiotensin II receptor blocker (ARB) that selectively inhibits angiotensin II binding to AT1 receptors, reducing vasoconstriction and aldosterone secretion. Hydrochlorothiazide is a thiazide diuretic that inhibits sodium and chloride reabsorption in the distal convoluted tubule, increasing diuresis and lowering blood pressure.

What the body does with it

Metabolism	Olmesartan medoxomil is a prodrug that is rapidly hydrolyzed to active olmesartan by esterases in the gastrointestinal tract and liver. Olmesartan is not metabolized by CYP450 enzymes. Hydrochlorothiazide is not extensively metabolized; most is excreted unchanged in urine.
Excretion	Olmesartan: ~60% renal, ~35% fecal. Hydrochlorothiazide: ~70% renal (unchanged), ~30% biliary/fecal.
Half-life	Olmesartan: terminal half-life ~10–15 hours; no accumulation. Hydrochlorothiazide: terminal half-life ~6–15 hours; prolonged in renal impairment.
Protein binding	Olmesartan: >99% bound (mainly albumin). Hydrochlorothiazide: ~68% bound (albumin).
Volume of Distribution	Olmesartan: ~17 L (~0.24 L/kg for 70 kg). Hydrochlorothiazide: ~3–4 L/kg (extensive tissue distribution).
Bioavailability	Olmesartan: ~26% (oral); prodrug medoxomil cleaved to active form. Hydrochlorothiazide: ~65–70% (oral).
Onset of Action	Oral: olmesartan onset 1–2 h; hydrochlorothiazide onset 2 h; combined effect within 2–4 h.
Duration of Action	Olmesartan: 24 h (dosing once daily). Hydrochlorothiazide: 6–12 h, but combined effect up to 24 h with repeated dosing.

Classification & Brands

Dosing & administration

Oral, one tablet once daily. Starting dose: Olmesartan medoxomil 20 mg / hydrochlorothiazide 12.5 mg. Titrate up to maximum 40 mg / 25 mg daily as needed.

Dosage form	TABLET
Renal impairment	Contraindicated if GFR <30 mL/min/1.73 m². For GFR 30-60 mL/min/1.73 m², use with caution; avoid thiazide diuretics if severe renal impairment. No dose adjustment needed for GFR ≥60 mL/min/1.73 m².
Liver impairment	Child-Pugh Class A and B: No dose adjustment. Child-Pugh Class C: Not recommended due to limited data; use with caution.
Pediatric use	Not approved for pediatric patients <18 years of age. Safety and efficacy not established.
Geriatric use	Start at lowest dose (20/12.5 mg once daily). Monitor renal function and electrolytes more frequently. Titrate slowly based on blood pressure response and tolerability.

Use during pregnancy

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

Clinical note

NSAIDs may diminish the antihypertensive effect Lithium levels may be increased Use in pregnancy can cause injury and death to the developing fetus.

FDA category	Contraindicated
Breastfeeding	Hydrochlorothiazide excreted in breast milk in low amounts; olmesartan not studied, but other ARBs have minimal excretion. M/P ratio unknown. Use caution, especially in neonates, due to potential renal effects.
Teratogenic Risk	First trimester: Potential risk based on drugs acting on renin-angiotensin system. Second and third trimesters: Fetal renal dysfunction, oligohydramnios, skull ossification defects, hypotension, and death. Hydrochlorothiazide may cause fetal or neonatal jaundice, thrombocytopenia.

Warnings & precautions

■ FDA Black Box Warning

WARNING: FETAL TOXICITY - Drugs acting directly on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected.

Side Effect Profile

Common Effects	Dizziness Weakness Headache Tiredness Edema swelling Chest pain
Serious Effects

Absolute Contraindications

["Anuria (with hydrochlorothiazide component)","Hypersensitivity to olmesartan, hydrochlorothiazide, or sulfonamide-derived drugs","Pregnancy (2nd and 3rd trimesters)","Severe renal impairment (CrCl < 30 mL/min) as fixed-dose combination","Concomitant use with aliskiren in patients with diabetes mellitus"]

Clinical Precautions

Precautions

["Hypotension in volume- or salt-depleted patients","Renal function impairment: Monitor serum creatinine and potassium","Electrolyte imbalances: Hyponatremia, hypokalemia, hypomagnesemia","Fetal/neonatal morbidity and mortality","Exacerbation of systemic lupus erythematosus","Acute angle-closure glaucoma (rare with hydrochlorothiazide)","Non-melanoma skin cancer risk (photosensitivity with hydrochlorothiazide)"]

Drug interactions

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OLMESARTAN MEDOXOMIL AND HYDROCHLOROTHIAZIDE

Clinical safety rating: avoid

NSAIDs may diminish the antihypertensive effect Lithium levels may be increased Use in pregnancy can cause injury and death to the developing fetus.

How it works

What the body does with it

Metabolism	Olmesartan medoxomil is a prodrug that is rapidly hydrolyzed to active olmesartan by esterases in the gastrointestinal tract and liver. Olmesartan is not metabolized by CYP450 enzymes. Hydrochlorothiazide is not extensively metabolized; most is excreted unchanged in urine.
Excretion	Olmesartan: ~60% renal, ~35% fecal. Hydrochlorothiazide: ~70% renal (unchanged), ~30% biliary/fecal.
Half-life	Olmesartan: terminal half-life ~10–15 hours; no accumulation. Hydrochlorothiazide: terminal half-life ~6–15 hours; prolonged in renal impairment.
Protein binding	Olmesartan: >99% bound (mainly albumin). Hydrochlorothiazide: ~68% bound (albumin).
Volume of Distribution	Olmesartan: ~17 L (~0.24 L/kg for 70 kg). Hydrochlorothiazide: ~3–4 L/kg (extensive tissue distribution).
Bioavailability	Olmesartan: ~26% (oral); prodrug medoxomil cleaved to active form. Hydrochlorothiazide: ~65–70% (oral).
Onset of Action	Oral: olmesartan onset 1–2 h; hydrochlorothiazide onset 2 h; combined effect within 2–4 h.
Duration of Action	Olmesartan: 24 h (dosing once daily). Hydrochlorothiazide: 6–12 h, but combined effect up to 24 h with repeated dosing.

Classification & Brands

Dosing & administration

Oral, one tablet once daily. Starting dose: Olmesartan medoxomil 20 mg / hydrochlorothiazide 12.5 mg. Titrate up to maximum 40 mg / 25 mg daily as needed.

Dosage form	TABLET
Renal impairment	Contraindicated if GFR <30 mL/min/1.73 m². For GFR 30-60 mL/min/1.73 m², use with caution; avoid thiazide diuretics if severe renal impairment. No dose adjustment needed for GFR ≥60 mL/min/1.73 m².
Liver impairment	Child-Pugh Class A and B: No dose adjustment. Child-Pugh Class C: Not recommended due to limited data; use with caution.
Pediatric use	Not approved for pediatric patients <18 years of age. Safety and efficacy not established.
Geriatric use	Start at lowest dose (20/12.5 mg once daily). Monitor renal function and electrolytes more frequently. Titrate slowly based on blood pressure response and tolerability.

Use during pregnancy

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

Clinical note

NSAIDs may diminish the antihypertensive effect Lithium levels may be increased Use in pregnancy can cause injury and death to the developing fetus.

FDA category	Contraindicated
Breastfeeding	Hydrochlorothiazide excreted in breast milk in low amounts; olmesartan not studied, but other ARBs have minimal excretion. M/P ratio unknown. Use caution, especially in neonates, due to potential renal effects.
Teratogenic Risk	First trimester: Potential risk based on drugs acting on renin-angiotensin system. Second and third trimesters: Fetal renal dysfunction, oligohydramnios, skull ossification defects, hypotension, and death. Hydrochlorothiazide may cause fetal or neonatal jaundice, thrombocytopenia.

Warnings & precautions

■ FDA Black Box Warning

WARNING: FETAL TOXICITY - Drugs acting directly on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected.

Side Effect Profile

Common Effects	Dizziness Weakness Headache Tiredness Edema swelling Chest pain
Serious Effects

OLMESARTAN MEDOXOMIL AND HYDROCHLOROTHIAZIDE

How it works

What the body does with it

Classification & Brands

Dosing & administration

Use during pregnancy

Warnings & precautions

Side Effect Profile

Absolute Contraindications

Clinical Precautions

Drug interactions

OLMESARTAN MEDOXOMIL AND HYDROCHLOROTHIAZIDE

How it works

What the body does with it

Classification & Brands

Dosing & administration

Use during pregnancy

Warnings & precautions

Side Effect Profile

Absolute Contraindications

Clinical Precautions

Drug interactions

Clinical Tips & Counseling