Drug information of Irbesartan

Mechanism of effect

Irbesartan is a nonpeptide tetrazole derivative and an angiotensin II antagonist that selectively blocks the binding of angiotensin II to the AT₁ receptor. Angiotensin II stimulates the adrenal cortex to synthesize and secrete aldosterone, which decreases the excretion of sodium and increases the excretion of potassium. Angiotensin II also acts as a vasoconstrictor in vascular smooth muscle. Irbesartan, by blocking the binding of angiotensin II to the AT₁ receptor, promotes vasodilation and decreases the effects of aldosterone. The negative feedback regulation of angiotensin II on renin secretion is also inhibited, but the resulting rise in plasma renin concentrations and consequent rise in angiotensin II plasma concentrations do not counteract the blood pressure–lowering effect that occurs. The action of ARBs is different from ACE inhibitors, which block the conversion of angiotensin I to angiotensin II, meaning that the production of angiotensin II is not completely inhibited, as the hormone can be formed via other enzymes.

Pharmacodynamic

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. Irbesartan's inhibition of angiotensin II binding to the AT1 receptor leads to multiple effects including vasodilation, a reduction in the secretion of vasopressin, and reduction in the production and secretion of aldosterone. The resulting effect is a decrease in blood pressure.

Unlike ACE inhibitors, irbesartan and other ARBs do not interfere with response to bradykinins and substance P, which allows for the absence of adverse effects that are present in ACE inhibitors (eg. dry cough).

Pharmacokinetics

Bioavailability: 60-80%

Onset: 1-2 hr (peak effect)

Duration: 24 hr

Peak plasma time: 1.5-2 hr

Protein bound: 90%

Vd: 53-93 L

Metabolism

Metabolized by hepatic CYP2C9 and minimally by CYP3A4

Metabolites: Irbesartan glucuronide conjugate (inactive)

Half-life: 11-15 hr

Renal clearance: 3-3.5 mL/min

Total body clearance: 157-176 mL/min

Excretion: Feces (80%), urine (20%)

Drug indications

Hypertension , Diabetic Nephropathies

Dosage

Adult

Hypertension

150 mg/day PO initially; may be increased to 300 mg/day PO

Hypovolemia: 75 mg/day PO initially

Nephropathy in Type 2 Diabetes

75-300 mg/day PO

Pediatric

Hypertension

<6 years: Safety and efficacy not established

6-12 years: 75 mg/day PO initially; not to exceed 150 mg/day            

>12 years: 150 mg/day PO initially; may be increased to 300 mg/day PO

Drug contraindications

Hypersensitivity

Side effects

Diarrhea , vertigo , tiredness

Interactions

Drospirenone , Canagliflozin , Benazepril , Spironolactone , Lisinopril , Captopril , Amiloride , potassium citrate , Trimethoprim , Aliskiren , Moexipril , quinapril , Potassium iodide , sulfamethoxazole+trimethoprim , Triamterene , Fosinopril , Ramipril , Trandolapril , Perindopril , Treprostinil , Angiotensin II

Alerts

Angioedema, volume-depletion, severe congestive heart failure (CHF), hepatic or renal impairment, hypertrophic cardiomyopathy, aortic or mitral valve stenosis, surgery or anesthesia

Use with caution in renal artery stenosis; avoid in bilateral renal artery stenosis

Risk of hypotension or hyperkalemia

Dual blockade of the renin-angiotensin system with ARBs, angiotensin-converting enzyme (ACE) inhibitors, or aliskiren is associated with increased risk of hypotension, hyperkalemia, and altered renal function (including acute renal failure) in comparison with monotherapy

Risk of heart failure-related morbidity; concomitant treatment with ACE inhibitors and beta-adrenergic agents is not recommended

Black Box Warnings

Discontinue as soon as possible when pregnancy is detected; drug affects renin-angiotensin system, causing oligohydramnios, which may result in fetal injury or death

Points of recommendation

• Tell all of your health care providers that you take irbesartan. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how irbesartan affects you.
• To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
• Have your blood pressure checked often. Talk with your doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• If you are taking a salt substitute that has potassium in it, a potassium-sparing diuretic, or a potassium product, talk with your doctor.
• If you are on a low-salt or salt-free diet, talk with your doctor.
• If you are taking lithium, talk with your doctor. You may need to have your blood work checked more closely while you are taking it with irbesartan.
• If you are taking irbesartan and have high blood pressure, talk with your doctor before using OTC products that may raise blood pressure. These include cough or cold drugs, diet pills, stimulants, ibuprofen or like products, and some natural products or aids.
• Talk with your doctor before you drink alcohol.
• Be careful in hot weather or while being active. Drink lots of fluids to stop fluid loss.
• Tell your doctor if you have too much sweat, fluid loss, throwing up, or loose stools. This may lead to low blood pressure.

• Take with or without food.
• Take irbesartan at the same time of day.
• Keep taking irbesartan as you have been told by your doctor or other health care provider, even if you feel well.
• To gain the most benefit, do not miss doses.
• Drink lots of noncaffeine liquids unless told to drink less liquid by your doctor.

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

Related drugs

Telmisartan , Azilsartan , Candesartan , Losartan , Valsartan , Eprosartan , Olmesartan