Hydrochlorothiazide and Irbesartan

AVALIDE ® (irbesartan and hydrochlorothiazide) tablets are indicated for the treatment of hypertension. AVALIDE may be used in patients whose blood pressure is not adequately controlled on monotherapy. AVALIDE may also be used as initial therapy in patients who are likely to need multiple drugs to achieve their blood pressure goals. The choice of AVALIDE as initial therapy for hypertension should be based on an assessment of potential benefits and risks. Patients with stage 2 (moderate or severe) hypertension are at relatively high risk for cardiovascular events (such as strokes, heart attacks, and heart failure), kidney failure, and vision problems, so prompt treatment is clinically relevant.

Irbesartan Angiotensin II is a potent vasoconstrictor formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the RAS and also stimulates aldosterone synthesis and secretion by adrenal cortex, cardiac contraction, renal resorption of sodium, activity of the sympathetic nervous system, and smooth muscle cell growth. Irbesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively binding to the AT 1 angiotensin II receptor. There is also an AT 2 receptor in many tissues, but it is not involved in cardiovascular homeostasis. Irbesartan is a specific competitive antagonist of AT 1 receptors with a much greater affinity (more than 8500-fold) for the AT 1 receptor than for the AT 2 receptor, and no agonist activity.

General Considerations Maximum effects within 2 to 4 weeks after dose change. Renal impairment: Not recommended for patients with severe renal impairment (creatinine clearance <30 mL/min). Hypertension Initiate with 150/12.5 mg. Titrate to 300/12.5 mg then 300/25 mg if needed. Replacement therapy: May be substituted for titrated components.

AVALIDE is contraindicated in patients who are hypersensitive to any component of this product. Because of the hydrochlorothiazide component, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs. Do not coadminister aliskiren with AVALIDE in patients with diabetes. Hypersensitivity to any component of this product. Anuria. Hypersensitivity to sulfonamide-derived drugs.

Boxed warning (fetal toxicity): When pregnancy is detected, discontinue AVALIDE as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. Hypotension: Correct volume depletion prior to administration. Impaired renal function. Thiazide diuretics may cause an exacerbation or activation of systemic lupus erythematosus. Acute angle-closure glaucoma, acute myopia, and choroidal effusion.

Most common adverse events (≥5% on AVALIDE and more often than on placebo) are dizziness, fatigue, and musculoskeletal pain.

NSAIDs and selective COX-2 inhibitors: Can reduce diuretic, natriuretic of diuretic, may lead to increased risk of renal impairment and reduced antihypertensive effect. Monitor renal function periodically. Dual blockade of the renin-angiotensin system: Increased risk of renal impairment, hypotension, and hyperkalemia. Antidiabetic drugs: Dosage adjustment of antidiabetic may be required. Cholestyramine and colestipol: Reduced absorption of thiazides. Lithium: Increases in serum lithium concentrations and lithium toxicity. Carbamazepine: Increased risk of hyponatremia.

Store at 25°C (77°F), excursions permitted to 15°C–30°C (59°F–86°F).