ARBI 300MG TABLET

Indications

• Hypertension
• Diabetic nephropathy in patients with type 2 diabetes

Dosage

Children: Refer to BNF for Children for specific dosing information.

Adults: Initially 75–150 mg once daily, may be increased to 300 mg once daily if tolerated.

Mechanism of action

Irbesartan prevents angiotensin II binding to the AT1 receptor in tissues such as vascular smooth muscle and the adrenal gland. It binds to the AT1 receptor with over 8500 times more affinity than to the AT2 receptor. By blocking angiotensin II from binding, irbesartan induces vascular smooth muscle relaxation and inhibits aldosterone secretion, which together lower blood pressure. This action counteracts the vasoconstrictive and sodium-retaining effects of angiotensin II.

Pharmacodynamics

Irbesartan is an effective angiotensin receptor blocker that lowers blood pressure and has a wide therapeutic index. It is well-tolerated at doses up to 900 mg daily, although typical therapeutic doses range from 150 mg. Its long half-life allows for once-daily dosing, making it convenient for patient adherence.

Pharmacokinetics

Irbesartan is well absorbed following oral administration, with peak plasma concentrations occurring within 1-2 hours. It undergoes extensive hepatic metabolism, primarily by glucuronidation, and is excreted via the urine and feces. The elimination half-life is approximately 11 hours, which supports its once-daily dosing regimen. Renal impairment may necessitate cautious use, especially in patients with creatinine clearance less than 30 mL/min.

Contra-indications

• Hypersensitivity to irbesartan or any of the excipients
• Severe hepatic impairment
• Bilateral renal artery stenosis or stenosis in a solitary kidney

Adverse effects

• Dizziness
• Fatigue
• Hypotension
• Angioedema
• Elevated blood urea or creatinine
• Hyperkalemia
• Gastrointestinal disturbances

Interactions

• Irbesartan and bulevirtide: Unknown (affects efficacy)
• Other antihypertensive agents may have additive effects
• Non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the antihypertensive effect of irbesartan

Precautions

• Caution in patients with a history of angioedema
• Monitor renal function in patients with renal impairment
• Use with caution in patients with diabetes or heart failure

Pregnancy

Irbesartan is contraindicated during pregnancy due to potential harm to the fetus, particularly in the second and third trimesters.

Breast-feeding

Caution is advised as it is not known if irbesartan is excreted in human milk.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Irbesartan 75 mg tablets
• Irbesartan 150 mg tablets
• Irbesartan 300 mg tablets
• Oral suspension (special order)

Mechanism of action

Irbesartan prevents angiotensin II binding to the AT₁ receptor in tissues like vascular smooth muscle and the adrenal gland. Irbesartan and its active metabolite bind the AT₁ receptor with 8500 times more affinity than they bind to the AT₂ receptor. Irbesartan's prevention of angiotensin II binding causes vascular smooth muscle relaxation and prevents the secretion of aldosterone, lowering blood pressure. Angiotensin II would otherwise bind to the AT₁ receptor, inducing vasoconstriction and aldosterone secretion, raising blood pressure. 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.

Pharmacodynamics

Irbesartan is an angiotensin receptor blocker used to treat hypertension and diabetic nephropathy. It has a long duration of action as it is usually taken once daily and a wide therapeutic index as doses may be as low as 150mg daily but doses of 900mg/day were well tolerated in healthy human subjects.