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Irbesartan (Monograph)

Brand name: Avapro
Drug class: Angiotensin II Receptor Antagonists
VA class: CV805
Chemical name: 2-Butyl-3-[[2′(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-yl]methyl]-1,3-diazaspiro[4.4]non-1-en-4-one
Molecular formula: C25H28N6O3S•½C4H4 O4
CAS number: 138402-11-6

Medically reviewed by Drugs.com on Oct 26, 2023. Written by ASHP.

Warning

  • May cause fetal and neonatal morbidity and mortality if used during pregnancy.1 26 71 72 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  • If pregnancy is detected, discontinue as soon as possible.1 26 72

Introduction

Angiotensin II receptor (AT1) antagonist (i.e., angiotensin II receptor blocker, ARB).1 2 4 5 6 21 22 23

Uses for Irbesartan

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).1 2 3 4 5 6 14 15 16 17 18 21 22 23 1200

Angiotensin II receptor antagonists are recommended as one of several preferred agents for the initial management of hypertension according to current evidence-based hypertension guidelines; other options include ACE inhibitors, calcium-channel blockers, and thiazide diuretics.501 502 503 504 1200 While there may be individual differences with respect to recommendations for initial drug selection and use in specific patient populations, current evidence indicates that these antihypertensive drug classes all generally produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.501 502 503 504 1200 1213

Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).501 502 503 504 515 1200 1201

A 2017 ACC/AHA multidisciplinary hypertension guideline classifies BP in adults into 4 categories: normal, elevated, stage 1 hypertension, and stage 2 hypertension.1200 (See Table 1.)

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:e13-115.

Individuals with SBP and DBP in 2 different categories (e.g., elevated SBP and normal DBP) should be designated as being in the higher BP category (i.e., elevated BP).

Table 1. ACC/AHA BP Classification in Adults1200

Category

SBP (mm Hg)

DBP (mm Hg)

Normal

<120

and

<80

Elevated

120–129

and

<80

Hypertension, Stage 1

130–139

or

80–89

Hypertension, Stage 2

≥140

or

≥90

The goal of hypertension management and prevention is to achieve and maintain optimal control of BP.1200 However, the BP thresholds used to define hypertension, the optimum BP threshold at which to initiate antihypertensive drug therapy, and the ideal target BP values remain controversial.501 503 504 505 506 507 508 515 523 526 530 1200 1201 1207 1209 1222 1223 1229

The 2017 ACC/AHA hypertension guideline generally recommends a target BP goal (i.e., BP to achieve with drug therapy and/or nonpharmacologic intervention) <130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk.1200 In addition, an SBP goal of <130 mm Hg is recommended for noninstitutionalized ambulatory patients ≥65 years of age with an average SBP of ≥130 mm Hg.1200 These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.1200 1202 1210

Previous hypertension guidelines generally have based target BP goals on age and comorbidities.501 504 536 Guidelines such as those issued by the JNC 8 expert panel generally have targeted a BP goal of <140/90 mm Hg regardless of cardiovascular risk and have used higher BP thresholds and target BPs in elderly patients501 504 536 compared with those recommended by the 2017 ACC/AHA hypertension guideline.1200

Some clinicians continue to support previous target BPs recommended by JNC 8 due to concerns about the lack of generalizability of data from some clinical trials (e.g., SPRINT study) used to support the current ACC/AHA hypertension guideline and potential harms (e.g., adverse drug effects, costs of therapy) versus benefits of BP lowering in patients at lower risk of cardiovascular disease.1222 1223 1224 1229

Consider potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs when deciding a patient’s BP treatment goal.1200 1220 1229

For decisions regarding when to initiate drug therapy (BP threshold), the 2017 ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors.1200 1207 ASCVD risk assessment recommended by ACC/AHA for all adults with hypertension.1200

ACC/AHA currently recommend initiation of antihypertensive drug therapy in addition to lifestyle/behavioral modifications at an SBP ≥140 mm Hg or DBP ≥90 mm Hg in adults who have no history of cardiovascular disease (i.e., primary prevention) and a low ASCVD risk (10-year risk <10%).1200

For secondary prevention in adults with known cardiovascular disease or for primary prevention in those at higher risk for ASCVD (10-year risk ≥10%), ACC/AHA recommend initiation of antihypertensive drug therapy at an average SBP ≥130 mm Hg or an average DBP ≥80 mm Hg.1200

Adults with hypertension and diabetes mellitus, chronic kidney disease (CKD), or age ≥65 years are assumed to be at high risk for cardiovascular disease; ACC/AHA state that such patients should have antihypertensive drug therapy initiated at a BP ≥130/80 mm Hg.1200

In stage 1 hypertension, experts state that it is reasonable to initiate drug therapy using the stepped-care approach in which one drug is initiated and titrated and other drugs are added sequentially to achieve the target BP.1200 Initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes recommended in adults with stage 2 hypertension and average BP >20/10 mm Hg above BP goal.1200

Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to angiotensin II receptor antagonists.501 504 1200 However, the combination of an ACE inhibitor or an angiotensin II receptor antagonist with a calcium-channel blocker or thiazide diuretic produces similar BP lowering in black patients as in other racial groups.1200

Angiotensin II receptor antagonists or ACE inhibitors may be particularly useful in hypertensive patients with diabetes mellitus or CKD; angiotensin II receptor antagonists also may be preferred, as an alternative to ACE inhibitors, in hypertensive patients with heart failure or ischemic heart disease and/or post-MI.501 502 504 523 524 527 534 535 536 543 1214 1215

Diabetic Nephropathy

Management of diabetic nephropathy manifested by elevated Scr and proteinuria (urinary protein excretion >300 mg daily) in patients with type 2 diabetes mellitus and hypertension.1

A recommended agent in the management of patients with diabetes mellitus and persistent albuminuria who have modestly elevated (30–300 mg/24 hours) or higher (>300 mg/24 hours) levels of urinary albumin excretion; slows rate of progression of renal disease in such patients.49 51 52 53 535 536 1232

Heart Failure

Angiotensin II receptor antagonists have been used in the management of heart failure† [off-label].524 528 800

Because of their established benefits, ACE inhibitors have been the preferred drugs for inhibition of the renin-angiotensin-aldosterone (RAA) system in patients with heart failure and reduced left ventricular ejection fraction (LVEF); 524 however, some evidence indicates that therapy with an ACE inhibitor (enalapril) may be less effective than angiotensin receptor-neprilysin inhibitor (ARNI) therapy (e.g., sacubitril/valsartan) in reducing cardiovascular death and heart failure-related hospitalization.701 702 703 800

Angiotensin II receptor antagonists may be used as an alternative for those patients in whom an ACE inhibitor or ARNI is inappropriate.524 800

ACCF, AHA, and the Heart Failure Society of America (HFSA) recommend that patients with chronic symptomatic heart failure and reduced LVEF (NYHA class II or III) who are able to tolerate an ACE inhibitor or angiotensin II receptor antagonist be switched to therapy containing an ARNI to further reduce morbidity and mortality.800

Irbesartan Dosage and Administration

General

BP Monitoring and Treatment Goals

Administration

Oral Administration

Administer orally once daily without regard to meals.1 21

Dosage

Pediatric Patients

Hypertension
Oral

Children 6–12 years of age: Initially, 75 mg once daily recommended by experts; dosage may be increased every 2–4 weeks until BP controlled, maximum dosage reached (150 mg once daily), or adverse effects occur.1150

Children ≥13 years of age: Initially, 150 mg once daily recommended by experts; dosage may be increased every 2–4 weeks until BP controlled, maximum dosage reached (300 mg once daily), or adverse effects occur.1150

Adults

Hypertension
Irbesartan Therapy
Oral

Manufacturer recommends initial dosage of 150 mg once daily in adults without intravascular volume depletion.1 In adults with depletion of intravascular volume, the usual initial dosage is 75 mg once daily.1 24

Usual dosage: 150–300 mg once daily;1 1200 no additional therapeutic benefit with higher dosages or with twice-daily dosing.1

Irbesartan/Hydrochlorothiazide Fixed-combination Therapy
Oral

Manufacturer states fixed-combination preparation can be used for initial treatment of hypertension in patients who are likely to need multiple drugs to achieve their BP goals.26 Consider potential benefits and risks of initiating therapy with the fixed combination.26

If BP is not adequately controlled by monotherapy with irbesartan or hydrochlorothiazide, can switch to fixed-combination tablets (irbesartan 150 mg and 12.5 mg hydrochlorothiazide; then irbesartan 300 mg and hydrochlorothiazide 12.5 mg), administered once daily.26 Can increase dosage to irbesartan 300 mg and hydrochlorothiazide 25 mg daily, if needed, to control BP.26

In patients receiving fixed-combination tablets as initial therapy, the usual starting dosage is irbesartan 150 mg and hydrochlorothiazide 12.5 mg once daily.26 May increase dosage after 1–2 weeks of therapy to a maximum of irbesartan 300 mg and hydrochlorothiazide 25 mg once daily.26

Diabetic Nephropathy
Oral

Initial dosage of 75 mg once daily used in clinical trial.1 Increase dosage to target maintenance dosage of 300 mg once daily.1 No data available on effects of lower dosages.1

Special Populations

Hepatic Impairment

No initial dosage adjustments necessary.1 26

Renal Impairment

No initial dosage adjustments necessary.1 26

Irbesartan/hydrochlorothiazide fixed combination not recommended in patients with severe renal impairment.26

Geriatric Patients

No initial dosage adjustments necessary.1 26

Volume- and/or Salt-depleted Patients

Correct volume and/or salt depletion prior to initiation of therapy or initiate therapy using lower initial dosage (75 mg once daily).1 24 26 Fixed-combination tablets containing irbesartan and hydrochlorothiazide are not recommended as initial therapy in patients with intravascular volume depletion.26

Detailed Irbesartan dosage information

Cautions for Irbesartan

Contraindications

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

Possible reduction in fetal renal function and increase in fetal and neonatal morbidity and mortality when drugs that act on the renin-angiotensin system (e.g., angiotensin II receptor antagonists, ACE inhibitors) are used during the second and third trimesters of pregnancy.1 26 (See Boxed Warning.) Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations.1 26 Potential neonatal effects include skull hypoplasia, anuria, hypotension, renal failure, and death.1 26

Discontinue irbesartan as soon as possible when pregnancy is detected, unless continued use is considered lifesaving.1 72 Nearly all women can be transferred successfully to alternative therapy for the remainder of their pregnancy.13

Sensitivity Reactions

Anaphylactoid reactions and/or angioedema possible;1 26 not recommended in patients with a history of angioedema associated with or unrelated to ACE inhibitor or angiotensin II receptor antagonist therapy.544 545 73

Other Warnings and Precautions

Hypotension

Possible symptomatic hypotension, particularly in volume- and/or salt-depleted patients (e.g., those receiving diuretics or undergoing dialysis).1 26 (See Volume- and/or Salt-depleted Patients under Dosage and Administration.)

Transient hypotension is not a contraindication to additional doses; may reinstate therapy cautiously after BP is stabilized (e.g., with volume expansion).1 26

Malignancies

In July 2010, FDA initiated a safety review of angiotensin II receptor antagonists after a published meta-analysis found a modest but statistically significant increase in risk of new cancer occurrence in patients receiving an angiotensin II receptor antagonist compared with control.120 121 123 126 However, subsequent studies, including a larger meta-analysis conducted by FDA, have not shown such risk.126 127 128 129 Based on currently available data, FDA has concluded that angiotensin II receptor antagonists do not increase the risk of cancer.126

Renal Effects

Possible oliguria, progressive azotemia, and, rarely, acute renal failure and/or death in patients with severe heart failure.1 26

Increases in BUN and Scr possible in patients with renal artery stenosis, CKD, or volume depletion.1 26

Use of Fixed Combinations

When used in fixed combination with hydrochlorothiazide, consider the cautions, precautions, and contraindications associated with hydrochlorothiazide.26

Specific Populations

Pregnancy

Category D.1 26 (See Boxed Warning.)

May cause fetal and neonatal morbidity and mortality when administered to a pregnant woman.1 26 Discontinue as soon as possible when pregnancy is detected.1 26 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1 26 Discontinue nursing or the drug.1 26

Pediatric Use

If oliguria or hypotension occurs in neonates with a history of in utero exposure to irbesartan, support BP and renal function; exchange transfusions or dialysis may be required.1 26 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Dosages of up to 4.5 mg/kg once daily did not appear to effectively lower BP in pediatric patients 6–16 years of age.1 Not studied in children <6 years of age.1

Safety and efficacy of the fixed-combination preparation containing irbesartan and hydrochlorothiazide not established.26

Geriatric Use

No substantial differences in safety or efficacy of irbesartan monotherapy or fixed-combination containing irbesartan and hydrochlorothiazide relative to younger adults, but increased sensitivity cannot be ruled out.1 26

Renal Impairment

Use with caution.1

Deterioration of renal function may occur.1 26 (See Renal Effects under Cautions.)

Use of irbesartan in fixed combination with hydrochlorothiazide is not recommended in patients with severe renal impairment.26

Black Patients

BP reduction may be smaller in black patients than in patients of other races.1 26 69 70 1200 (See Hypertension under Uses.)

Common Adverse Effects

Diarrhea, dyspepsia/heartburn, fatigue in patients with hypertension; also, dizziness, orthostatic dizziness, and orthostatic hypotension in patients with diabetic nephropathy.1

Drug Interactions

Metabolized principally by CYP2C9.1 26 Does not substantially induce or inhibit CYP1A1, 1A2, 2A6, 2B6, 2D6, 2E1, or 3A4.1 26

Drugs Affecting Hepatic Microsomal Enzymes

Potential pharmacokinetic interaction (decreased irbesartan metabolism) with CYP2C9 inhibitors.1 26

Specific Drugs

Drug

Interaction

Comments

ACE Inhibitors

Increased risk of renal impairment, hyperkalemia, and hypotension1 26

Generally avoid concomitant use1 26

Monitor BP, renal function, and electrolytes if used concomitantly1 26

Aliskiren

Increased risk of renal impairment, hyperkalemia, and hypotension1 26 550

Generally avoid concomitant use1 26

Monitor BP, renal function, and electrolytes if used concomitantly1 26 550

Concomitant use contraindicated in patients with diabetes mellitus1 26 550

Avoid concomitant use in patients with GFR<60 mL/minute1 26 550

Angiotensin II receptor antagonists

Increased risk of renal impairment, hyperkalemia, and hypotension1 26

Generally avoid concomitant use1 26

Monitor BP, renal function, and electrolytes if used concomitantly1 26

Digoxin

Pharmacologic and/or pharmacokinetic interactions unlikely1 26

Diuretics, potassium-sparing

Possible hyperkalemia1 26

Monitor serum potassium concentrations1 26

Hydrochlorothiazide

Pharmacokinetic interactions unlikely1 26

Additive hypotensive effects1 26

Lithium

Elevations in lithium concentrations and lithium toxicity reported1 26

Carefully monitor serum lithium concentrations 1 26 `

Nifedipine

Decreased irbesartan metabolism in vitro; alteration of irbesartan pharmacokinetics not observed in vivo1 26

NSAIAs, including selective cyclooxygenase-2 (COX-2) inhibitors

Possible deterioration of renal function in geriatric, volume-depleted, or renally impaired patients1 26

Possible reduced antihypertensive effects1

Monitor renal function periodically1

Salt substitutes, potassium-containing

Possible hyperkalemia1 26

Monitor serum potassium concentrations1 26

Tolbutamide

Possible decreased irbesartan metabolism26

Warfarin

Pharmacologic and/or pharmacokinetic interaction unlikely1 26
Irbesartan drug interactions (more detail)

Irbesartan Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentration generally achieved 1.5–2 hours after oral dose.1 Absolute bioavailability is about 60–80%.1 26

Onset

Antihypertensive effect evident within 2 weeks, with maximum BP reduction after 2–4 weeks.1 26

Food

Food does not affect bioavailability.1 26

Distribution

Extent

Crosses the placenta and is distributed in the fetus in animals.1 26

Crosses the blood-brain barrier poorly, if at all, in animals.1 15

Distributed into milk in rats; not known whether distributed into human milk.1 26

Plasma Protein Binding

90% (principally albumin and α1-acid glycoprotein).1 26

Elimination

Metabolism

Undergoes hepatic metabolism by glucuronide conjugation and oxidation (principally by CYP2C9) to inactive metabolites.1 26

Elimination Route

Eliminated in urine and feces (via bile).1 26

Half-life

Terminal elimination half-life: 11–15 hours.1

Special Populations

Not removed by hemodialysis.1 26 Pharmacokinetics not substantially altered by hemodialysis or renal impairment.1 26

Stability

Storage

Oral

Tablets

15–30°C.1 26

Actions

Advice to Patients

Preparations

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.

Irbesartan

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

75 mg

Avapro

Sanofi-Aventis

150 mg

Avapro

Sanofi-Aventis

300 mg

Avapro

Sanofi-Aventis
Irbesartan Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

150 mg with Hydrochlorothiazide 12.5 mg

Avalide

Sanofi-Aventis

300 mg with Hydrochlorothiazide 12.5 mg

Avalide

Sanofi-Aventis

AHFS DI Essentials™. © Copyright 2024, Selected Revisions November 5, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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