Irbesartan

Brand Names: Irbesartan

Drug Class: Angiotensin 2 Receptor Blocker

Overview

11 DESCRIPTION Irbesartan is an angiotensin II receptor (AT 1 subtype) antagonist. Irbesartan is a non-peptide compound, chemically described as a 2-butyl-3-[ p -( o -1 H -tetrazol-5‑ylphenyl)benzyl]-1,3-diazaspiro[4.4]non-1-en-4-one. Its empirical formula is C 25 H 28 N 6 O, and the structural formula: Irbesartan is a white to off-white crystalline powder with a molecular weight of 428.5.

Mechanism of Action

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 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 primary vasoactive hormone of the renin-angiotensin system, and an important component in the pathophysiology of hypertension. It also stimulates aldosterone secretion by the adrenal cortex. Irbesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively binding to the AT 1 angiotensin II receptor found in many tissues (e.g., vascular smooth muscle, adrenal gland). There is also an AT 2 receptor in many tissues, but it is not involved in cardiovascular homeostasis.

Indications

  • 1 INDICATIONS AND USAGE Irbesartan tablets are an angiotensin II receptor blocker (ARB) indicated for: Treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. ( 1.1 ) Treatment of diabetic nephropathy in hypertensive patients with type 2 diabetes, an elevated serum creatinine, and proteinuria. ( 1.2 ) 1.1 Hypertension Irbesartan tablets are indicated for the treatment of hypertension, to lower blood pressure.

Common Doses

  • 300 mg
  • 150 mg
  • 75 mg

Dosage

2 DOSAGE AND ADMINISTRATION Indication Dose Hypertension ( 2.2 ) 150 to 300 mg once daily Diabetic Nephropathy ( 2.3 ) 300 mg once daily 2.1 General Considerations Irbesartan tablets may be administered with other antihypertensive agents and with or without food. 2.2 Hypertension The recommended initial dose of irbesartan tablets is 150 mg once daily. The dosage can be increased to a maximum dose of 300 mg once daily as needed to control blood pressure [see Clinical Studies (14.1) ]. 2.

Black Box Warning

WARNING: FETAL TOXICITY When pregnancy is detected, discontinue irbesartan tablets as soon as possible [see Warnings and Precautions ( 5.1 ) and Use in Specific Populations ( 8.1 )]. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus [see Warnings and Precautions ( 5.1 ) and Use in Specific Populations ( 8.1 ) ]. WARNING: FETAL TOXICITY See full prescribing information for complete boxed warning. When pregnancy is detected, discontinue irbesartan tablets as soon as possible. ( 5.1 , 8.

Contraindications

  • 4 CONTRAINDICATIONS Irbesartan tablets are contraindicated in patients who are hypersensitive to any component of this product. Do not coadministrate aliskiren with irbesartan tablets in patients with diabetes. Hypersensitivity to any component of this product. ( 4 ) Coadministration with aliskiren in patients with diabetes. ( 4 )

Side Effects

  • 6 ADVERSE REACTIONS The following important adverse reactions are described elsewhere in the labeling: Hypotension in Volume or Salt-Depleted Patients [see Warnings and Precautions (5.2) ] Impaired Renal Function [see Warnings and Precautions (5.3) ] Nephropathy in type 2 diabetic patients: The most common adverse reactions which were more frequent than placebo were hyperkalemia dizziness, orthostatic dizziness, and orthostatic hypotension. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Solco Healthecare US LLC. at 1-866-257-2597 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.

Interactions

  • 7 DRUG INTERACTIONS Lithium: Risk of lithium toxicity. ( 7 ) Nonsteroidal Anti-inflammatory Drugs (NSAIDs) and COX-2 inhibitors: Increased risk of renal impairment. Reduced antihypertensive effects. ( 7 ) Dual blockade of the renin-angiotensin system: Increased risk of renal impairment, hypotension, and hyperkalemia. ( 7 ) 7.1 Agents Increasing Serum Potassium Coadministration of irbesartan tablets with other drugs that raise serum potassium levels may result in hyperkalemia, sometimes severe. Monitor serum potassium in such patients. 7.