Irbesartan, a nonpeptide tetrazole derivative, is an angiotensin II type 1 (AT1) receptor antagonist (also referred to as an angiotensin II receptor blocker [ARB]).1, 26
Irbesartan is used alone or in combination with other classes of antihypertensive agents in the management of hypertension.1, 26
Efficacy of irbesartan for the management of hypertension has been established by controlled studies of 8-12 weeks' duration in patients with mild to severe hypertension in outpatient settings.1, 3, 14, 15, 16, 17, 18, 22 Seven placebo-controlled studies have been conducted evaluating irbesartan as monotherapy in adult patients with hypertension.1 Compared to placebo, irbesartan, in doses of 150 or 300 mg once daily, was more effective in achieving decreases in systolic and diastolic blood pressure; placebo-subtracted reductions in trough blood pressure were 8-10/5-6 or 8-12/5-8 mmHg for irbesartan 150 or 300 mg, respectively.1 Trough-to-peak ratios for systolic and diastolic response with irbesartan ranged between 60-70%.1
Clinical studies have shown that the hypotensive effect of usual dosages of irbesartan in patients with mild to severe hypertension is comparable to or greater than that of usual dosages of losartan22 enalapril,17, 18, 23 or atenolol.16 Controlled trials have shown the addition of irbesartan to hydrochlorothiazide (in doses of 6.25, 12.5, or 25 mg) to result in additional dose-related reductions in blood pressure similar to that achieved with the same monotherapy doses of irbesartan.1
The principal goal of preventing and treating hypertension is to reduce the risk of cardiovascular and renal morbidity and mortality, including target organ damage.1200, 1300 The relationship between blood pressure and cardiovascular disease is continuous, consistent, and independent of other risk factors.1200, 1300 The higher the blood pressure, the more likely the development of coronary artery disease, heart failure, stroke, and chronic kidney disease across all ages and ethnic groups.1200, 1300 Each 20-mm Hg increment in systolic blood pressure or 10-mm Hg increment in diastolic blood pressure has been shown to double the risk of death from stroke, heart disease, or other vascular disease.171, 1200, 1300
Accurate blood pressure measurement in the office or clinic is essential for proper diagnosis and management of hypertension.1200, 1300, 1302 Out-of-office blood pressure measurements are recommended to confirm the diagnosis of hypertension.1200 Blood pressure categories range from normal to different grades/stages of hypertension and are intended to align therapeutic approaches with blood pressure levels.1300, 1302 According to most major guidelines, hypertension is diagnosed when systolic blood pressure is ≥140 mm Hg and/or diastolic blood pressure is ≥90 mm Hg as measured in the office or clinic.1300, 1302 Some guidelines consider a systolic blood pressure of 130-139 mm Hg and/or a diastolic blood pressure of 80-89 mm Hg to be stage 1 hypertension,1200 whereas other guidelines consider this a high-normal blood pressure; however, treatment recommendations are generally the same (nonpharmacologic therapy with consideration of pharmacologic therapy based on cardiovacular risk).1200, 1300, 1302
Comprehensive guidelines for the management of hypertension have been published by various authoritative groups.501, 1200, 1300, 1301, 1302 The first such guideline was published by the National Heart Lung and Blood Institute (NHLBI) in 1977, followed by a series of Joint National Committee (JNC) guidelines with JNC8 being the last iteration of these guidelines in 2014.501, 1200 The American College of Cardiology (ACC), American Heart Association (AHA), and other experts including the International Society of Hypertension (ISH) have published more recent clinical practice guidelines for the treatment of hypertension.1200, 1300, 1302 These guidelines all state that lifestyle/behavioral modifications (e.g., weight reduction in patients who are overweight or obese, dietary changes, sodium reduction, potassium supplementation, increased physical activity, moderation of alcohol intake, smoking cessation) are essential in the management of hypertension and should be implemented as first-line therapy to lower blood pressure and reduce total cardiovascular risk.1200, 1300, 1302 The decision whether to initiate antihypertensive drug therapy should be based on the office blood pressure level while also considering cardiovascular risk factors.1200, 1219, 1300, 1302 Most guidelines agree that antihypertensive drug treatment should be offered in addition to lifestyle modifications to patients with grade 2 (blood pressure 160-179/100-109 mm Hg) or grade 3 (systolic blood pressure ≥180/110 mm Hg) hypertension; however, there is some controversy regarding whether patients with grade 1 hypertension (blood pressure 140-159/90-99) should be treated with antihypertensive drug therapy.1200, 1300, 1302 Some guidelines recommend immediate drug treatment in patients with grade 1 hypertension (blood pressure 140-159/90-99) who have high cardiovascular risk or comorbid conditions (cardiovascular disease, chronic kidney disease, diabetes mellitus or hypertension-mediated organ damage) and a trial of lifestyle intervention first in those with low to moderate cardiovascular risk who do not have these comorbid conditions,1302 whereas other guidelines recommend that all hypertensive patients including those with grade 1 hypertension receive blood pressure-lowering treatment, irrespective of their cardiovascular risk.1300 In some guidelines, drug treatment is recommended in patients with blood pressure in the high-normal range (≥130/80 mm Hg) who have cardiovascular disease.1200, 1210, 1300
Current evidence-based practice guidelines for the management of hypertension in adults generally recommend the use of drugs from 4 classes of antihypertensive agents (angiotensin-converting enzyme [ACE] inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, and thiazide or thiazide-like diuretics); data from clinical outcome trials indicate that lowering blood pressure with any of these drug classes can reduce the complications of hypertension and provide similar cardiovascular risk reduction benefits. 501, 503, 1200, 1300, 1302 However, recommendations for initial drug selection and use in specific patient populations may vary across these guidelines.501, 503, 1200 This variability is due, in part, to differences in the guideline development process and the types of studies included in the evidence reviews (e.g., randomized controlled studies only versus a range of studies with different study designs).501, 503, 1200 Ultimately, choice of antihypertensive therapy should be individualized, considering the clinical characteristics of the patient (e.g., age, ethnicity/race, comorbid conditions, cardiovascular risk factors) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, costs).501, 503, 510, 1200, 1300, 1302 Angiotensin II receptor antagonists or ACE inhibitors may be particularly useful in the management of hypertension in patients with certain coexisting conditions such as diabetes mellitus or chronic kidney disease (CKD); angiotensin II receptor antagonists also may be preferred, generally as an alternative to ACE inhibitors, in hypertensive patients with heart failure or ischemic heart disease and/or following myocardial infarction (MI).1200 In patients with hypertension and compelling indications (e.g., CKD with albuminuria [urine albumin 300 mg/day or greater, or urine albumin: creatinine ratio of 300 mg/g or equivalent in the first morning void]), angiotensin II receptor antagonists are usually considered an alternative for ACE inhibitor-intolerant patients.1200, 1218 However, data indicate no difference in efficacy between ACE inhibitors and angiotensin II receptor antagonists with regard to blood pressure lowering and clinical outcomes (i.e., all-cause mortality, cardiovascular mortality, MI, heart failure, stroke, and end-stage renal disease).1200, 1218 Adverse events (e.g., cough, angioedema) leading to drug discontinuance occur more frequently with ACE inhibitor therapy than with angiotensin II receptor antagonist therapy.1218 Because of similar efficacy and a lower frequency of adverse effects, some experts believe that angiotensin II receptor antagonists should be used instead of an ACE inhibitor for the treatment of hypertension or hypertension with certain compelling indications.1218 Angiotensin II receptor antagonists may produce a smaller blood pressure response in hypertensive Black patients compared with non-Black patients.1 However, the combination of an ACE inhibitor or an angiotensin II receptor antagonist with a calcium-channel blocker or thiazide diuretic produces similar blood pressure lowering in Black patients as in other racial groups.1200 Other antihypertensive drugs such as beta blockers, direct vasodilators, alpha-1 blockers, loop diuretics, and aldosterone antagonists are available, but generally recommended as second-line agents or only in specific clinical situations.1200
Because most patients with hypertension will require at least 2 antihypertensive drugs to achieve adequate blood pressure control, use of single pill combinations are generally recommended when available.1302 Drug regimens with complementary activity, where a second antihypertensive agent is used to block compensatory responses to the first agent or affect a different pressor mechanism, can result in additive blood pressure lowering and are preferred.1200 Drug combinations that have similar mechanisms of action or clinical effects (e.g., the combination of an ACE inhibitor and an angiotensin II receptor antagonist) generally should be avoided.1200 Antihypertensive drug dosages should be adjusted and/or other agents substituted or added until goal blood pressure is achieved.1200 After initiation of antihypertensive drug therapy, a blood pressure goal of less than 130/80 mm Hg within 3 months is generally recommended if tolerated, but should be individualized.1200, 1301, 1302 While there is evidence from a randomized controlled study (SPRINT) demonstrating that intensive systolic blood pressure lowering (to <120 mm Hg) may be beneficial in patients with increased risk of cardiovascular disease, the study excluded patients with diabetes mellitus or prior stroke, and those younger than 50 years of age, which may decrease the generalizability of these findings.1210, 1219
Specific guidelines for the management of hypertension in pregnancy have been published by experts such as AHA and the American College of Obstetrics and Gynecologists (ACOG).1305, 1306 First-line oral antihypertensive drugs generally recommended in pregnant patients include labetalol, nifedipine (extended-release), or methyldopa.1200, 1302, 1305 Other oral dihydropyridine calcium-channel blockers such as nicardipine or amlodipine may also be considered.1302, 1304, 1305 In patients requiring immediate blood pressure lowering (i.e., eclampsia, HELLP [preeclampsia/hemolysis, elevated liver enzymes and low platelets]), IV labetalol, nicardipine, or magnesium sulfate may be used.1300, 1302 Renin-angiotensin system (RAS) blockers (e.g., ACE inhibitors, angiotensin receptor blockers, direct renin inhibitors) are contraindicated during pregnancy due to adverse fetal and neonatal outcomes.1200, 1300, 1302, 1305
The American Academy of Pediatrics (AAP) has published a clinical practice guideline for the management of high blood pressure in children and adolescents.1150 The guideline recommends calcium-channel blockers (e.g., nifedipine, amlodipine), ACE inhibitors, angiotensin II receptor antagonists, and thiazide diuretics for the initial management of hypertension in children requiring drug therapy.1150
Irbesartan is used in the treatment of diabetic nephropathy in patients with hypertension and type 2 diabetes with elevated serum creatinine and proteinuria (>300 mg/day).1
The current indication for irbesartan in hypertensive patients with type 2 diabetes mellitus and nephropathy is based principally on the results of a long-term multicenter, comparative, controlled trial ( Irbesartan Diabetic Nephropathy Trial [IDNT]).1, 43 A total of 1715 adult patients were randomized to treatment with either irbesartan, amlodipine, or placebo, with the dose titrated to a maintenance dose of 300 mg for irbesartan and 10 mg for amlodipine as tolerated.1, 43 Additional antihypertensive agents (diuretics, β-adrenergic blocking agents, peripheral α-adrenergic blocking agents, or central α2-adrenergic agonists) were used as needed in all treatment groups to achieve target blood pressure.1, 43 The primary composite end point was defined as a doubling of the baseline serum creatinine concentration, onset of end-stage renal disease (i.e., initiation of dialysis, renal transplantation, or a serum creatinine concentration of ≥6 mg/dL), or death.1, 43 Secondary endpoints included a composite of cardiovascular mortality and morbidity.1, 43 Among the study participants, 66.5% were male and 72.9% were <65 years of a 72, 13.3, 5, or 4.8% were white, Black, Asian, or Hispanic, respectively.1 After a mean of 2.6 years of follow-up, the primary composite end point occurred in 32.6, 39, or 41.1% of patients in the irbesartan, placebo, or amlodipine groups, respectively.1, 43 No difference was observed for secondary cardiovascular composite outcomes between the treatment groups, with 23.8, 22.6, or 25.3% of patients experiencing an event in the irbesartan, amlodipine, or placebo groups, respectively.43 Irbesartan was more effective in reducing proteinuria than placebo (27% reduction compared to placebo).1 Irbesartan was also associated with a 33% lower risk of doubling of serum creatinine concentration compared to placebo and a 37% lower risk of this outcome than amlodipine.43
The renoprotective effects of irbesartan were evaluated in a double-blind, randomized, placebo-controlled trial enrolling 590 adult patients with hypertension, type 2 diabetes, and microalbuminuria.48 Irbesartan was given in a dose of 150 or 300 mg once daily, with matching placebo.48 The primary outcome was time to first detection of overt nephropathy (overnight urinary albumin excretion >200 mcg/minute and ≥30% higher excretion than the baseline rate on at least 2 consecutive visits).48 After a median 2-year follow-up, diabetic nephropathy developed in 19 patients receiving irbesartan 150 mg, 10 patients receiving irbesartan 300 mg, and 30 patients receiving placebo.48
Guidelines from the Kidney Disease: Improving Global Outcomes (KDIGO) recommend initiation of an ACE inhibitor or angiotensin II receptor antagonist in patients with diabetes mellitus, hypertension, and moderately to severely elevated albuminuria (i.e., urine to creatinine ratio >30 mg/g).1600, 1630 Once initiated, these medications should be titrated to the maximum dosage tolerated.1600, 1630 In patients who have diabetes mellitus and albuminuria, but are normotensive†, ACE inhibitors or angiotensin II receptor antagonists may be considered.1600 Treatment with ACE inhibitors or angiotensin II receptor antagonists should be continued unless the serum creatinine concentration increases by >30% within the first month after initiation or following a dosage increase.1600
Current standards of care from the American Diabetes Association (ADA) and KDIGO provide similar management recommendations for patients with diabetes mellitus and CKD.1631 Treatment recommendations include optimization of glucose management and blood pressure control (<130/80 mmHg) to slow the progression of CKD.1631 For patients with diabetes mellitus and hypertension with moderate proteinuria (<300 mg/day), use of either an ACE inhibitor or an angiotensin II receptor antagonist is recommended.1631 For patients with severely increased proteinuria (≥300 mg/day), an ACE inhibitor or an angiotensin II receptor antagonist, given at maximally tolerated dosages, is strongly recommended to prevent progression of CKD and reduce the risk of cardiovascular events.1631 These agents are generally not recommended for primary prevention of CKD in patients with diabetes mellitus who are normotensive and have no evidence of CKD.1631
Angiotensin II receptor antagonists have also been used for the management of patients with nondiabetic CKD with moderate or severely increased albuminuria† (i.e., urinary albumin to creatinine ratio >30 mg/g) to prevent progression of CKD.1630 Once initiated, these medications should be titrated to the maximum dosage tolerated.1630 KDIGO guidelines state that angiotensin II receptor antagonists can also be considered in patients with CKD and normal to mildly increased albuminuria† (i.e., urinary albumin to creatinine ratio <30 mg/g) when other compelling indications (e.g., hypertension, heart failure, or low ejection fraction) are present.1630
Irbesartan has been used in the management of acute coronary syndrome (ACS)†, including non-ST-elevation ACS.1632, 1633
Current guidelines on the management of patients with ACS (including unstable angina, non-ST-segment elevation MI [non-STEMI], and STEMI) discuss treatment strategies for ACS (non-STEMI and STEMI), including the use of analgesics, antiplatelets/anticoagulants, and antilipemic agents.1633 In high-risk patients with ACS, an ACE inhibitor, angiotensin receptor antagonist, or a mineralocorticoid receptor antagonist may be recommended to reduce all-cause death and major adverse cardiovascular events.1633 A randomized, double-blind, double-dummy trial comparing irbesartan (150 or 300 mg) to enalapril (10 mg titrated to 20 mg) in 429 patients with non-ST-elevation ACS found no difference in change from baseline to 60 days in high-sensitivity C-reactive protein between the treatment groups.1632
Irbesartan is administered orally as tablets.1 Irbesartan is also commercially available as a fixed-combination tablet containing irbesartan and hydrochlorothiazide; see the full prescribing information for administration of this combination product.26
Since food does not affect the oral bioavailability of irbesartan, the manufacturer states that the drug can be taken without regard to meals.1
Irbesartan tablets should be stored at 25°C (excursions permitted between 15-30°C).1
Dosage of irbesartan must be individualized and adjusted according to blood pressure response.1
The manufacturer states that the recommended initial dosage of irbesartan in adults is 150 mg once daily in patients without depletion of intravascular volume;1 in adults with depletion of intravascular volume, the recommended initial dosage is 75 mg once daily.1 If blood pressure response is inadequate with the initial dosage, dosage may be increased as tolerated to a maximum of 300 mg once daily.1
For the management of diabetic nephropathy in adults with type 2 diabetes mellitus and hypertension, an elevated serum creatinine, and proteinuria (>300 mg/day), the recommended dosage of irbesartan is 300 mg once daily.1
The manufacturer states that some of the irbesartan dosages used in a clinical study did not effectively lower blood pressure in pediatric patients 6-16 years of age.1 In children 6-12 years of age, experts recommend an initial irbesartan dosage of 75 mg once daily and a maximum dosage of 150 mg once daily.1150 In children at least 13 years of age, experts recommend an initial irbesartan dosage of 150 mg once daily and a maximum dosage of 300 mg once daily.1150 These experts state that dosage may be increased every 2-4 weeks until blood pressure is controlled, the maximum dosage is reached, or adverse effects occur.1150
The manufacturer states that dosage adjustment of irbesartan is not necessary in patients with hepatic impairment.1
The manufacturer states that dosage modification of irbesartan is not necessary in adults with mild to severe renal impairment or on hemodialysis unless a patient with renal impairment is also volume-depleted.1
The manufacturer states that dosage adjustment in geriatric patients is not necessary.1
Fetal/Neonatal Morbidity and Mortality
A boxed warning about the risk of fetal harm is included in the prescribing information for irbesartan.1 Irbesartan may cause fetal harm when administered to a pregnant patient.1 Use of drugs that act on the renin-angiotensin system (RAS) during the second or third trimester of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death.1 Oligohydramnios caused by drugs that act on the RAS can result in fetal lung hypoplasia, skeletal deformations(including skull hypoplasia), anuria, hypotension, renal failure, and death.1 Discontinue irbesartan as soon as possible when pregnancy is detected.1 In the rare case that there is no appropriate alternative therapy, apprise the mother of the potential risk to the fetus.1 If irbesartan is used during pregnancy, perform serial ultrasound examinations to assess the intra-amniotic environment; if oligohydramnios is observed, consider alternative treatment.1 Oligohydramnios may not appear until after the fetus has sustained irreversible injury.1 Closely observe neonates who have been exposed to irbesartan in utero for signs of hypotension, oliguria, hyperkalemia, and other symptoms of renal impairment.1 If oliguria or hypotension occurs, support blood pressure and renal perfusion.1 Exchange transfusions or dialysis may be required.1
Other Warnings and Precautions
Hypotension in Volume or Salt-depleted Patients
Symptomatic hypotension may occur when irbesartan is initiated in patients with an activated RAS, such as volume- or salt-depleted patients (e.g., those receiving high doses of diuretics).1 Correct volume and/or salt depletion before initiation of irbesartan therapy or use a lower initial dosage.1
Changes in renal function, including acute renal failure, can be caused by drugs that inhibit the RAS.1 Patients whose renal function may depend in part on activity of the RAS (e.g., patients with renal artery stenosis, chronic kidney disease, severe heart failure, or volume depletion) may be at particular risk of developing acute renal failure or death while taking irbesartan.1 Monitor renal function periodically in these patients.1 Consider withholding or discontinuing irbesartan in patients who develop a clinically important reduction in renal function while receiving irbesartan.1
Intestinal angioedema has been reported in patients treated with angiotensin II receptor blockers, including irbesartan.1 Symptoms of intestinal angioedema included abdominal pain, nausea, vomiting, and diarrhea; symptoms resolved following discontinuation of the angiotensin II receptor blocker.1 If intestinal angioedema is diagnosed, discontinue irbesartan and initiate appropriate monitoring until symptom resolution occurs.1
When irbesartan is used in fixed combination with hydrochlorothiazide, the cautions, precautions, and contraindications associated with both drugs must be considered.26 Consult the full prescribing information for the fixed combination preparation for specific information.26
Irbesartan can cause fetal harm when administered to a pregnant woman.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions).1
Discontinue irbesartan as soon as possible when pregnancy is detected.1 In the rare case that there is no appropriate alternative therapy, apprise the mother of the potential risk to the fetus.1 If irbesartan is used during pregnancy, perform serial ultrasound examinations to assess the intra-amniotic environment; if oligohydramnios is observed, consider alternative treatment.1 Oligohydramnios may not appear until after the fetus has sustained irreversible injury.1 Closely observe neonates who have been exposed to irbesartan in utero for signs of hypotension, oliguria, hyperkalemia, and other signs of renal impairment.1 If oliguria or hypotension occurs, support blood pressure and renal perfusion.1 Exchange transfusions or dialysis may be required.1
Irbesartan is distributed into milk in rats; it is not known whether the drug is distributed into human milk or has any effects on the breast-fed infant or on milk production.1 Because of the potential risk in nursing infants, use of irbesartan in breast-feeding women is not recommended.1
Administration of irbesartan in dosages of up to 4.5 mg/kg once daily did not appear to effectively lower blood pressure in pediatric patients 6-16 years of age.1
Safety and efficacy of irbesartan in children <6 years of age have not been established.1
If oliguria or hypotension occurs in neonates with a history of in utero exposure to irbesartan, blood pressure and renal function should be supported; exchange transfusions or dialysis may be required.1
In hypertension studies involving 4925 patients, 18.5% of patients were ≥65 years of age and 3% were ≥75 years of age.1 No substantial differences in safety or efficacy of irbesartan monotherapy have been observed in geriatric patients relative to younger adults, but increased sensitivity cannot be ruled out.1
Following repeated oral administration, pharmacokinetics of irbesartan are not significantly affected in patients with mild to moderate cirrhosis of the liver.1
Pharmacokinetics of irbesartan are not altered in patients with renal impairment or on hemodialysis.1 Irbesartan is not removed by hemodialysis.1 Deterioration of renal function may occur in patients receiving irbesartan.1
The most common adverse effects occurring in patients receiving irbesartan for the treatment of diabetic nephropathy include hyperkalemia, dizziness, orthostatic dizziness, and orthostatic hypotension.1 Intestinal angioedema has also been reported.1
Irbesartan is metabolized principally by cytochrome P-450 (CYP) 2C9 isoenzyme.1 The drug does not substantially induce or inhibit CYP1A1, 1A2, 2A6, 2B6, 2D6, 2E1, or 3A4.1
Drugs Affecting Hepatic Microsomal Enzymes
A pharmacokinetic interaction (decreased irbesartan metabolism) is possible when irbesartan is used concomitantly with CYP2C9 substrates or inhibitors (e.g., nifedipine).1
Drugs that Increase Serum Potassium
Concomitant administration of irbesartan with drugs that increase serum potassium concentrations may result in hyperkalemia.1 Serum potassium concentrations should be monitored in such patients.1
Drugs that Block the Renin-Angiotensin System
Increased risk of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) are possible when irbesartan is used concomitantly with other drugs that block the renin-angiotensin system (e.g., angiotensin-converting enzyme [ACE] inhibitors, aliskiren); when irbesartan is used concomitantly with such drugs, blood pressure, renal function, and serum electrolyte concentrations should be monitored closely.1 The manufacturer states that most patients do not derive additional benefit from combination therapy with 2 renin-angiotensin system inhibitors compared with monotherapy.1 Concomitant use of irbesartan and aliskiren is contraindicated in patients with diabetes mellitus; in addition, such concomitant use should be avoided in patients with renal impairment (glomerular filtration rate [GFR] less than 60 mL/minute).1
Pharmacologic and/or pharmacokinetic interactions re unlikely when irbesartan is used concomitantly with digoxin.1
Pharmacokinetic interactions are unlikely when irbesartan is used concomitantly with hydrochlorothiazide.1
Elevations in lithium concentrations and lithium toxicity have been reported when irbesartan was used concomitantly with lithium.1 Serum lithium concentrations should be carefully monitored during such concomitant use.1
Decreased irbesartan metabolism has been observed in vitro when given with nifedipine; alteration of irbesartan pharmacokinetics were not observed in vivo when the drugs were administered concomitantly.1
Nonsteroidal Anti-inflammatory Agents
Deterioration of renal function is possible when irbesartan is used concomitantly with a nonsteroidal anti-inflammatory agent (NSAIA) in geriatric patients, volume-depleted patients (including those receiving concomitant diuretic therapy), or renally impaired patients; renal function should be monitored periodically in patients receiving concomitant therapy with irbesartan and NSAIAs, including selective cyclooxygenase-2 (COX-2) inhibitors.1
A pharmacologic interaction (attenuated hypotensive effects) is possible when angiotensin II receptor antagonists are used concomitantly with NSAIAs, including selective COX-2 inhibitors.1
Pharmacologic and/or pharmacokinetic interactions are unlikely when irbesartan is used concomitantly with warfarin.1
Irbesartan, a nonpeptide tetrazole derivative, is a specific competitive inhibitor of the angiotensin II receptor (type AT1) with a much greater affinity for the AT1 receptor than the AT2 receptor and no agonist activity.1 Through selective blockade of angiotensin II binding at the AT1 receptor, irbesartan blocks the physiologic actions of angiotensin II, including vasoconstrictor and aldosterone-secreting effects.1 Irbesartan does not inhibit angiotensin converting enzyme (ACE) or renin, and does not bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.1 A dose of irbesartan 150-300 mg inhibits angiotensin II pressor effects by 100% at 4 hours post-dose, with 40-60% inhibition persisting for 24 hours.1
Irbesartan is rapidly and completely absorbed following oral administration, with a bioavailability between 60-80%.1 Peak plasma concentrations generally occur at 1.5-2 hours following administration.1 Administration with a meal does not affect bioavailability.1 The pharmacokinetics of irbesartan are linear over its therapeutic dose range.1 Irbesartan is 90% protein bound, primarily to albumin and α1-acid glycoprotein.1 Distribution across the blood-brain barrier is weak.1 Following oral or IV administration, >80% of the circulating plasma radioactivity is attributable to unchanged irbesartan, with approximately 6% attributable to an inactive glucuronide conjugate metabolite.1 In vitro studies indicate that cytochrome P-450 (CYP)2C9 is primarily involved in the metabolism of irbesartan, with negligible metabolism by CYP3A4.1 The terminal half-life of irbesartan is 11-15 hours.1 After a single oral or IV dose, about 20% of radioactivity appears in urine; the remainder appears in the feces as irbesartan or its inactive metabolite.1 Elimination occurs via biliary and renal excretion.1 In studies of irbesartan in hypertensive patients, no differences in half-life or accumulation were observed based on sex; however, female patients had 11-44% higher plasma concentrations than males.1 Irbesartan AUC values are approximately 25% higher in Black patients compared to White patients; however, there is no difference between these groups in peak plasma concentrations.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets, film-coated | 75 mg* | Irbesartan Tablets | |
150 mg* | ||||
Irbesartan Tablets | ||||
300 mg* | Avapro® | Sanofi-Aventis | ||
Irbesartan Tablets |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets, film-coated | 150 mg with Hydrochlorothiazide 12.5 mg* | Sanofi-Aventis | |
Irbesartan and Hydrochlorothiazide Tablets | ||||
300 mg with Hydrochlorothiazide 12.5 mg* | Avalide® | Sanofi-Aventis | ||
Irbesartan and Hydrochlorothiazide Tablets |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
1. Sanofi-Aventis. Avapro® (irbesartan) tablets prescribing information. Bridgewater, NJ; 2025 May.
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14. Pool JL, Guthrie RM, Littlejohn T et al. Dose-related antihypertensive effects of irbesartan in patients with mild-to-moderate hypertension. Am J Hypertens. 1998;11:462-470.
15. Fogari R, Ambrosoli S, Corradi L, et al. 24-hour blood pressure control by once-daily administration of irbesartan assessed by ambulatory blood pressure monitoring. . J Hypertens. 1997;15:1511-1518.
16. Stumpe KO, Haworth D, Höglund C et al et al. Comparison of the angiotensin II receptor antagonist, irbesartan, and atenolol for the treatment of hypertension. J Hypertens . 1998; 7:31-37.
17. Larochelle P, Flack JM, Marbury, et al. Effects and tolerability of irbesartan versus enalapril in patients with severe hypertension. Am J Hypertens. 1997; 80:1613-1615.
18. Mimran A, Ruilope L, Kerwin L et al et al. A randomized, double-blind comparison of the angiotensin II receptor antagonist, irbesartan, with the full dose range of enalapril for the treatment of mild-to-moderate hypertension. J Hum Hypertens. 1998; 12(3): 203-208.
22. Kossler-Taub K, Littlejohn T, Elliott W et al. Comparative efficacy of two angiotensin II receptor antagonists, irbesartan and losartan, in mild-to-moderate hypertension. Am J Hypertens . 1998; 11:445-53. [PubMed 9607383]
23. Larochelle P, Flack JM, Marbury TC et al. Effects and tolerability of irbesartan versus enalapril in patients with severe hypertension. Am J Cardiol . 1997; 80:1613-5. [PubMed 9416950]
26. Sanfoi-aventis. Avalide® (irbesartan-hydrochlorothiazide) tablets prescribing information. Bridewater, NJ; 2025 May.
43. Lewis EJ, Hunsicker LG, Clarke WR et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med . 2001; 345:851-60. [PubMed 11565517]
48. Parving HH, Lehnert H, Bröchner-Mortensen J et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med . 2001; 345:870-6. [PubMed 11565519]
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503. Go AS, Bauman MA, Coleman King SM et al. An effective approach to high blood pressure control: a science advisory from the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention. Hypertension . 2014; 63:878-85. [PubMed 24243703]
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1150. Flynn J, Kaelber D, Baker-Smith C, et al. Clinical practice guidelines for screening and management of high blood pressure in children and adolescents. Pediatrics. 2017;140(3):e20171904.
1200. Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension . 2018; 71:el13-e115. [PubMed 29133356]
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