Aliskiren
Contraindicated
Textbook
Increased risk of hypotension, hyperkalemia, and renal impairment.
Avoid concomitant use.
Source: G&G 14e · p603
Drug reference
Olmesartan + Hydrochlorothiazide
ARB plus thiazide diuretic fixed-dose combination. · Antihypertensive
Also known as Olmezest H, Olmezox H, Olmesar H, Olmekem H
ARB plus thiazide diuretic fixed-dose combination.AntihypertensiveATC C09DA08
CDSCO approvedATC C09DA08
- ONSET
- 1.5h · Olmesartan: ~1-2 hours. Hydrochlorothiazide: ~2 hours.
- PEAK
- 1.5h · Olmesartan: 1-2 hours. Hydrochlorothiazide: 4-6 hours.
- t½
- 12.5h · Olmesartan: 10-15 hours. Hydrochlorothiazide: 5.6-14.8 hours.
- DURATION
- 9h · Olmesartan: 24 hours. Hydrochlorothiazide: 6-12 hours.
EXCRETION
—
not curated
INTERACTIONS
12 major
incl. contraindicated
PREGNANCY
Category D (especially in the 2nd and 3rd trimesters due to potential for fetal injury and death from the ARB component).
FDA category + note
Top interactionssee all 12 →
- AliskirenContraindicatedTextbookG&G 14e · p603
- Sacubitril ValsartanContraindicatedTextbookG&G 14e · p602
- Angiotensin Converting Enzyme InhibitorsSevereTextbookHarrison 22e · p2396
- BenazeprilSevereTextbookG&G 14e
Mechanism
Olmesartan is an angiotensin II receptor blocker (ARB) that selectively blocks the binding of angiotensin II to the AT1 receptor, inhibiting vasoconstriction and aldosterone secretion. Hydrochlorothiazide is a thiazide diuretic that increases the excretion of sodium and chloride, and subsequently water, by inhibiting their reabsorption in the distal convoluted tubule. The combination provides additive blood pressure reduction through complementary mechanisms. Combination rationale: This fixed-dose combination leverages the complementary actions of an ARB and a thiazide diuretic to achieve greater blood pressure reduction than either agent alone. Olmesartan counters the diuretic-induced activation of the renin-angiotensin-aldosterone system, while hydrochlorothiazide enhances the antihypertensive effect. This synergistic approach also often improves patient compliance due to fewer pills.
Indications
US BENICAR HCT label: BENICAR HCT is indicated for hypertension and is not indicated for initial therapy.
Dosing
- Adult
- US BENICAR HCT: after inadequate olmesartan monotherapy, start 40/12.5 mg once daily; after inadequate HCTZ monotherapy or HCTZ dose-limiting adverse effects, start 20/12.5 mg once daily. May titrate to 40/25 mg once daily.
- Pediatric
- Safety and efficacy have not been established in pediatric patients; therefore, it is not recommended.
- Renal adjustment
- Not recommended for patients with severe renal impairment (creatinine clearance <30 mL/min). In patients with moderate renal impairment (CrCl 30-60 mL/min), use with caution and monitor closely.
- Hepatic adjustment
- Contraindicated in severe hepatic impairment. Use with caution and consider lower initial doses in patients with mild to moderate hepatic impairment.
- Geriatric
- No specific dose adjustment is generally required; however, caution is advised, and renal function should be monitored due to potential age-related decline in renal function.
- Max dose
- Olmesartan 40 mg/Hydrochlorothiazide 25 mg once daily.
Pharmacokinetics
Onset
Olmesartan: ~1-2 hours. Hydrochlorothiazide: ~2 hours.
Peak effect
Olmesartan: 1-2 hours. Hydrochlorothiazide: 4-6 hours.
Duration
Olmesartan: 24 hours. Hydrochlorothiazide: 6-12 hours.
Half-life
Olmesartan: 10-15 hours. Hydrochlorothiazide: 5.6-14.8 hours.
Bioavailability
Olmesartan: Approximately 26%. Hydrochlorothiazide: Approximately 60-80%.
Protein binding
Olmesartan: >99%. Hydrochlorothiazide: 40-68%.
Metabolism
Olmesartan: Minimal hepatic metabolism. Hydrochlorothiazide: Not metabolized, excreted unchanged.
Excretion
Olmesartan: Biliary/fecal (50-60%) and renal (30-40%) as unchanged drug. Hydrochlorothiazide: Primarily renal (unchanged).
Contraindications
- Anuria
- Hypersensitivity to olmesartan, hydrochlorothiazide, or other sulfonamide-derived drugs
- Severe renal impairment (creatinine clearance <30 mL/min)
- Severe hepatic impairment
- Biliary obstruction
- Refractory hypokalemia, hyponatremia, hypercalcemia and symptomatic hyperuricemia
- Second and third trimesters of pregnancy
- Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment (GFR <60 mL/min/1.73 m2)
Side effects
Common
DizzinessFatigueHeadacheNauseaUpper respiratory tract infectionHyperuricemiaHypokalemiaCough
Serious
- Angioedema
- Symptomatic hypotension
- Renal dysfunction/failure
- Electrolyte imbalances (e.g., severe hyponatremia, hypokalemia, hypomagnesemia, hypercalcemia)
- Acute myopia and secondary angle-closure glaucoma
- Pancreatitis
- Skin reactions (e.g., Stevens-Johnson syndrome)
Pregnancy & lactation
Pregnancy
Category D (especially in the 2nd and 3rd trimesters due to potential for fetal injury and death from the ARB component).
Lactation
US BENICAR HCT label: Human milk excretion of olmesartan is unknown; thiazides appear in human milk. Decide whether to discontinue nursing or BENICAR HCT based on maternal clinical need and potential infant risk.
Drug interactions
Sacubitril Valsartan
Contraindicated
Textbook
Potentially excessive hypotension, increased risk of adverse effects.
Do not use in conjunction with other ARBs.
Source: G&G 14e · p602
Angiotensin Converting Enzyme Inhibitors
Severe
Textbook
Greater incidence of acute kidney injury (AKI) and adverse cardiac events.
The combination of these two classes should be avoided.
Source: Harrison 22e · p2396
Benazepril
Severe
Textbook
Increased worsening of renal function, hypotension, syncope, and hyperkalemia without increased efficacy.
Not recommended for the treatment of hypertension. Previous studies indicate more harm than benefit.
Source: G&G 14e
Captopril
Severe
Textbook
Increased worsening of renal function, hypotension, syncope, and hyperkalemia without increased efficacy.
Not recommended for the treatment of hypertension. Previous studies indicate more harm than benefit.
Source: G&G 14e
Enalapril
Severe
Textbook
Increased worsening of renal function, hypotension, syncope, and hyperkalemia without increased efficacy.
Not recommended for the treatment of hypertension. Previous studies indicate more harm than benefit.
Source: G&G 14e
Enalaprilat
Severe
Textbook
Increased worsening of renal function, hypotension, syncope, and hyperkalemia without increased efficacy.
Not recommended for the treatment of hypertension. Previous studies indicate more harm than benefit.
Source: G&G 14e
Fosinopril
Severe
Textbook
Increased worsening of renal function, hypotension, syncope, and hyperkalemia without increased efficacy.
Not recommended for the treatment of hypertension. Previous studies indicate more harm than benefit.
Source: G&G 14e
Imidapril
Severe
Textbook
Greater incidence of acute kidney injury (AKI) and adverse cardiac events.
The combination of these two classes should be avoided.
Source: Harrison 22e · p2396
Lisinopril
Severe
Textbook
Increased worsening of renal function, hypotension, syncope, and hyperkalemia without increased efficacy.
Not recommended for the treatment of hypertension. Previous studies indicate more harm than benefit.
Source: G&G 14e
Moexipril
Severe
Textbook
Increased worsening of renal function, hypotension, syncope, and hyperkalemia without increased efficacy.
Not recommended for the treatment of hypertension. Previous studies indicate more harm than benefit.
Source: G&G 14e
Perindopril
Severe
Textbook
Increased worsening of renal function, hypotension, syncope, and hyperkalemia without increased efficacy.
Not recommended for the treatment of hypertension. Previous studies indicate more harm than benefit.
Source: G&G 14e
Related guidelines
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Partially reviewed; remaining content unreviewed·Updated: 2026-09-11