Eprosartan

Class: Angiotensin II Receptor Antagonists
VA Class: CV805
Chemical Name: (E)-α-[[2-butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5-yl]methyl-ene]-2-thiophenepropanoic acid monomethanesulfonate
Molecular Formula: C₂₃H₂₄N₂O₄S•CH₄
CAS Number: 144143-96-4
Brands: Teveten

Medically reviewed by Drugs.com on Feb 8, 2022. Written by ASHP.

Introduction

Angiotensin II receptor (AT₁) antagonist (i.e., angiotensin II receptor blocker, ARB).

Uses for Eprosartan

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).

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 preferred options include ACE inhibitors, calcium-channel blockers, and thiazide diuretics. 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.

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).

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

Source: 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).

The goal of hypertension management and prevention is to achieve and maintain optimal control of BP. 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.

The 2017 ACC/AHA hypertension guideline generally recommends a target BP goal (i.e., BP to achieve with drug therapy and/or nonpharmacologic intervention) of <130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk. 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. These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.

Other hypertension guidelines generally have based target BP goals on age and comorbidities. 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 patients compared with those recommended by the 2017 ACC/AHA hypertension guideline.

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 2017 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.

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.

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

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%).

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.

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. Individualize drug therapy in patients with hypertension and underlying cardiovascular or other risk factors.

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. 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.

Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to angiotensin II receptor antagonists. 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.

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.

Diabetic Nephropathy

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.

Heart Failure

Angiotensin II receptor antagonists have been used in the management of heart failure†.

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); 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.

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

No additional therapeutic benefit when angiotensin II receptor antagonist used in combination with an ACE inhibitor.

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.

Eprosartan Dosage and Administration

General

BP Monitoring and Treatment Goals

• Monitor BP regularly (i.e., monthly) during therapy and adjust dosage of the antihypertensive drug until BP controlled.

• If unacceptable adverse effects occur, discontinue drug and initiate another antihypertensive agent from a different pharmacologic class.

• If adequate BP response not achieved with a single antihypertensive agent, either increase dosage of single drug or add a second drug with demonstrated benefit and preferably a complementary mechanism of action (e.g., calcium-channel blocker, thiazide diuretic). Many patients will require ≥2 drugs from different pharmacologic classes to achieve BP goal; if goal BP still not achieved, add a third drug.

Administration

Oral Administration

Administer orally once or twice daily without regard to meals.

Dosage

Available as eprosartan mesylate; dosage expressed in terms of eprosartan.

Adults

Hypertension

Eprosartan Therapy

Oral

Manufacturer recommends initial dosage of 600 mg once daily as monotherapy in adults without intravascular volume depletion.

Usual dosage: Manufacturer states 400–800 mg daily, given in 1 dose or 2 divided doses; limited experience with higher dosages. Some experts state 600–800 mg daily, given in 1 dose or 2 divided doses.

If effectiveness diminishes toward end of dosing interval in patients treated once daily, consider increasing dosage or administering drug in 2 divided doses.

Eprosartan/Hydrochlorothiazide Fixed-combination Therapy

Oral

Manufacturer states fixed-combination preparation should not be used for initial antihypertensive therapy.

If BP is not adequately controlled by monotherapy with eprosartan or hydrochlorothiazide, can switch to fixed-combination tablets (eprosartan 600 mg and hydrochlorothiazide 12.5 mg; then eprosartan 600 mg and hydrochlorothiazide 25 mg) administered once daily.

If BP response diminishes toward the end of the dosing interval during once daily administration, increase dosage of the fixed-combination tablets to eprosartan 600 mg and hydrochlorothiazide 25 mg daily or add eprosartan 300 mg each evening.

Special Populations

Hepatic Impairment

No initial dosage adjustment necessary.

Renal Impairment

No initial dosage adjustment generally is necessary in patients with moderate or severe renal impairment; maximum 600 mg daily.

Eprosartan/hydrochlorothiazide fixed combination not recommended in patients with anuria.

Geriatric Patients

No initial dosage adjustment necessary.

Volume- and/or Salt-Depleted Patients

Correct volume and/or salt depletion prior to initiation of therapy or initiate therapy under close medical supervision.

Cautions for Eprosartan

Contraindications

• Known hypersensitivity to eprosartan or any ingredient in the formulation.

• Concomitant use of eprosartan and aliskiren in patients with diabetes mellitus. (See Specific Drugs under Interactions.)

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

Possible fetal and neonatal morbidity and mortality when used during pregnancy. (See Boxed Warning.) Such potential risks occur throughout pregnancy, especially during the second and third trimesters.

Also may increase the risk of major congenital malformations when administered during the first trimester of pregnancy.

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

Sensitivity Reactions

Facial edema reported with eprosartan; anaphylactoid reactions and/or angioedema reported with other angiotensin II receptor antagonists. Eprosartan not recommended in patients with a history of angioedema associated with or unrelated to ACE inhibitor or angiotensin II receptor antagonist therapy.

Other Warnings and Precautions

Hypotension

Possible symptomatic hypotension, particularly in volume- and/or salt-depleted patients (e.g., those treated with diuretics or undergoing dialysis). (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).

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. However, subsequent studies, including a larger meta-analysis conducted by FDA, have not shown such risk. Based on currently available data, FDA has concluded that angiotensin II receptor antagonists do not increase the risk of cancer.

Renal Effects

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

Increases in BUN and S_cr possible in patients with unilateral or bilateral renal artery stenosis.

Use of Fixed Combinations

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

Specific Populations

Pregnancy

Category D. (See Boxed Warning.)

Lactation

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

Pediatric Use

Safety and efficacy not established.

Geriatric Use

BP reduction with eprosartan monotherapy was slightly less in patients ≥65 years of age compared with younger patients. BP responses were similar in geriatric and younger patients receiving fixed-combination eprosartan/hydrochlorothiazide tablets. No substantial differences in safety relative to younger adults.

Hepatic Impairment

Use with caution.

Renal Impairment

Use with caution.

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

Use of eprosartan in fixed combination with hydrochlorothiazide is not recommended in patients with anuria.

Black Patients

BP reduction may be smaller in black patients than in patients of other races. (See Hypertension under Uses.)

Common Adverse Effects

Upper respiratory tract infection, rhinitis, pharyngitis, cough, viral infection, urinary tract infection, abdominal pain, injury, arthralgia, fatigue, depression, dizziness, headache, back pain, hypertriglyceridemia.

Interactions for Eprosartan

Not metabolized by CYP isoenzymes. Does not inhibit CYP1A, 2A6, 2C9/8, 2C19, 2D6, 2E, or 3A in vitro.

Drugs Affecting Hepatic Microsomal Enzymes

Pharmacokinetic interactions with inhibitors or inducers of CYP2C9 or CYP3A unlikely.

Specific Drugs

Eprosartan Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentration generally achieved 1–2 hours after oral administration in fasting state. Absolute bioavailability is about 13%.

Onset

Following a single oral dose, onset of antihypertensive effect evident within 1–2 hours. During chronic therapy, maximum antihypertensive effects generally achieved after 2–3 weeks.

Food

Food delays absorption.

Special Populations

In male patients with hepatic impairment, AUC after a single 100-mg oral dose increased by approximately 40%.

In patients with moderate or severe renal impairment, AUC increased by 70–90% and peak plasma concentration increased by 30–50%.

Distribution

Extent

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

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

Plasma Protein Binding

Approximately 98%.

Elimination

Metabolism

Not metabolized by CYP isoenzymes.

No pharmacologically active metabolites detected.

Elimination Route

Eliminated by biliary and renal excretion, mainly as unchanged drug.

Half-life

Approximately 20 hours following multiple oral doses.

Special Populations

Poorly removed by hemodialysis.

Stability

Storage

Oral

Tablets

20–25°C.

Actions

• Blocks the physiologic actions of angiotensin II, including vasoconstrictor and aldosterone-secreting effects.

• Does not interfere with response to bradykinins and substance P.

• Does not share the ACE inhibitor common adverse effect of dry cough.

Advice to Patients

• Risks of use during pregnancy.

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (including salt substitutes containing potassium).

• Importance of informing patients of other important precautionary information. (See Cautions.)

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.

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