IRBESARTAN- irbesartan tablet
Roxane Laboratories, Inc.
WARNING: FETAL TOXICITY
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When pregnancy is detected, discontinue Irbesartan Tablets as soon as possible.
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Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. See WARNINGS: Fetal Toxicity.
DESCRIPTION
Irbesartan is an angiotensin II receptor (AT1 subtype) antagonist.
Irbesartan is a non-peptide compound, chemically described as a 2-butyl-3-[p -(o -1H -tetrazol-5-ylphenyl)benzyl]-1,3-diazaspiro[4.4]non-1-en-4-one.
Its empirical formula is C25 H28 N6 O, and the structural formula:
Irbesartan is a white to off-white crystalline powder with a molecular weight of 428.5. It is a nonpolar compound with a partition coefficient (octanol/water) of 10.1 at pH of 7.4. Irbesartan is slightly soluble in alcohol and methylene chloride and practically insoluble in water.
Irbesartan Tablets, USP are available for oral administration in unscored tablets containing 75 mg, 150 mg, or 300 mg of irbesartan USP. Inactive ingredients include: colloidal silicon dioxide, croscarmellose sodium, lactose, magnesium stearate, and microcrystalline cellulose.
CLINICAL PHARMACOLOGY
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 principal pressor agent of the renin-angiotensin system (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 AT1 angiotensin II receptor. There is also an AT2 receptor in many tissues, but it is not involved in cardiovascular homeostasis.
Irbesartan is a specific competitive antagonist of AT1 receptors with a much greater affinity (more than 8500-fold) for the AT1 receptor than for the AT2 receptor and no agonist activity.
Blockade of the AT1 receptor removes the negative feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and circulating angiotensin II do not overcome the effects of irbesartan on blood pressure.
Irbesartan does not inhibit ACE or renin or affect other hormone receptors or ion channels known to be involved in the cardiovascular regulation of blood pressure and sodium homeostasis. Because irbesartan does not inhibit ACE, it does not affect the response to bradykinin; whether this has clinical relevance is not known.