This combination tablet is indicated for the treatment of hypertension (high blood pressure).

Angiotensin-II, which is formed from angiotensin-I through the action of angiotensin-converting enzyme (ACE), is a potent vasoconstrictor and the main vasoactive hormone of the renin-angiotensin system. It plays a key role in the development of hypertension and also stimulates aldosterone secretion from the adrenal cortex. Olmesartan selectively blocks the binding of angiotensin-II to the AT1 receptor found in various tissues such as vascular smooth muscle and adrenal glands. By doing so, it inhibits the vasoconstrictor and aldosterone-secreting effects of angiotensin-II. In vitro studies show that olmesartan acts as a reversible and competitive antagonist of the AT1 receptor. It does not inhibit ACE, the enzyme responsible for converting angiotensin-I to angiotensin-II and breaking down bradykinin.

Hydrochlorothiazide is a thiazide diuretic that acts on the renal tubules to inhibit sodium and chloride reabsorption, leading to increased excretion of these electrolytes in nearly equal amounts. This diuretic effect reduces plasma volume, which increases plasma renin activity and aldosterone secretion, resulting in potassium loss and decreased serum potassium levels. Since the renin-aldosterone system is mediated by angiotensin-II, the use of an angiotensin-II receptor blocker like olmesartan helps counteract the potassium loss caused by hydrochlorothiazide.

Hypertension: The usual starting dose is 20/12.5 mg one tablet once daily. Dosing should be individualized. Depending on the blood pressure response, the dose may be titrated at intervals of 2-4 weeks to two tablets 40/25 once daily.

Olmesartan: No clinically significant drug interactions were observed when olmesartan medoxomil was co-administered with hydrochlorothiazide, digoxin, or warfarin in healthy subjects. Olmesartan is not metabolized by the cytochrome P450 system and does not affect P450 enzymes; therefore, interactions with drugs that inhibit, induce, or are metabolized by these enzymes are not expected.

Hydrochlorothiazide: When used together, the following interactions may occur:

• Alcohol, barbiturates, or narcotics: May increase orthostatic hypotension.
• Antidiabetic drugs (oral agents and insulin): Dose adjustment may be required.
• Other antihypertensive drugs: Additive blood pressure–lowering effect.
• Corticosteroids and ACTH: May reduce potassium levels further.
• Lithium: Increased risk of lithium toxicity.

This combination is contraindicated in patients with hypersensitivity to any component of the product. Due to hydrochlorothiazide, it is also contraindicated in patients with anuria or hypersensitivity to sulfonamide-derived drugs.

Common side effects include nausea, headache, dizziness, hyperuricemia, upper respiratory tract infection, and urinary tract infection. Other possible adverse effects include chest pain, back pain, peripheral edema, abdominal pain, dyspepsia, gastroenteritis, and diarrhea.

Safety during pregnancy and breastfeeding has not been established. The drug should be discontinued during pregnancy and lactation.

• Serum electrolytes should be monitored periodically to detect possible imbalances such as hypokalemia, hyponatremia, and hypochloremic alkalosis.
• Thiazide therapy may cause hyperuricemia in some patients.
• Caution is required in patients with impaired renal function.

Renal impairment: Usual dosing may be used if creatinine clearance is >30 mL/min. In severe renal impairment, loop diuretics are preferred; therefore, this combination is not recommended.
Hepatic impairment: No dose adjustment is required.
Pediatric use: Safety and efficacy have not been established.
Geriatric use: Limited data are available; elderly patients should generally be started with caution.

Olmesartan: Limited data are available. Overdose may cause hypotension and tachycardia. Supportive treatment is recommended.

Hydrochlorothiazide: Overdose may lead to electrolyte depletion such as hypokalemia, hypochloremia, and dehydration due to excessive diuresis. If digitalis is used, hypokalemia may worsen cardiac arrhythmias.

Combined antihypertensive preparations

Store in a cool, dry place, protected from light and moisture. Keep out of reach of children.