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Olmesartan + Hydrochlorothiazide

ARB · Antihypertensive

Also known as Olmezest H, Olmezox H, Olmesar H, Olmekem H

ARBAntihypertensiveATC C09DA08
CDSCO approvedATC C09DA08
Pharmacokineticsplasma · t hours
1.5hONSET1.5hPEAK12.5h9hDURATION
ONSET
1.5h · Olmesartan: ~1-2 hours. Hydrochlorothiazide: ~2 hours.
PEAK
1.5h · Olmesartan: 1-2 hours. Hydrochlorothiazide: 4-6 hours.
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

Treatment of essential hypertension in patients whose blood pressure is not adequately controlled on monotherapy or as initial therapy in patients likely to need multiple drugs to achieve their blood pressure goals.

Dosing

Adult
Initial dose is typically Olmesartan 20 mg/Hydrochlorothiazide 12.5 mg once daily orally. May be titrated up to a maximum of Olmesartan 40 mg/Hydrochlorothiazide 25 mg once daily. Common strengths available in India include 20/12.5 mg, 40/12.5 mg, and 40/25 mg.
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

Not recommended. Both olmesartan and hydrochlorothiazide are excreted in breast milk. Due to the potential for adverse effects on the infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Drug interactions

Aliskiren
Contraindicated
Textbook

Increased risk of hypotension, hyperkalemia, and renal impairment.

Avoid concomitant use.

Source: G&G 14e · p603

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

Other ARB drugs

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