Teveten

Generic Name: Eprosartan Mesylate
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

Warning(s)

  • May cause fetal and neonatal morbidity and mortality if used during pregnancy.1 30 50 51 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  • If pregnancy is detected, discontinue as soon as possible.1 30 51

Introduction

Angiotensin II receptor (AT1) antagonist.1 2 7 14

Uses for Teveten

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).1 2 5 7 9 25 26 27 28 29

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One of several preferred initial therapies in hypertensive patients with chronic kidney disease, diabetes mellitus, or heart failure.44

Can be used as monotherapy for initial management of uncomplicated hypertension; however, thiazide diuretics are preferred by JNC 7.44

Diabetic Nephropathy

First-line agent in the treatment of diabetic nephropathy in hypertensive patients with type 2 diabetes mellitus.

CHF

Second-line agent in the treatment of CHF; should be used only in those intolerant of ACE inhibitors.

Teveten Dosage and Administration

General

Hypertension

  • Fixed-combination eprosartan/hydrochlorothiazide tablets should not be used for initial treatment of hypertension.30

Administration

Oral Administration

Administer orally once or twice daily without regard to meals.1 2 30

Dosage

Available as eprosartan mesylate; dosage expressed in terms of eprosartan.1 30

Adults

Hypertension
Monotherapy
Oral

Initially, 600 mg once daily in adults without intravascular volume depletion.1 7 Adjust dosage at approximately monthly intervals (more aggressively in high-risk patients) to achieve BP control.44

Usual dosage: 400–800 mg daily, given in 1 dose or 2 divided doses; limited experience with higher dosages.1 30

If effectiveness diminishes toward end of dosing interval in patients treated once daily, consider increasing dosage or administering drug in 2 divided doses.1 2 7

Combination Therapy
Oral

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.30

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.30

Special Populations

Hepatic Impairment

No initial dosage adjustment necessary.1 30

Renal Impairment

No initial dosage adjustment generally is necessary in patients with moderate or severe renal impairment; maximum 600 mg daily.1 30

Eprosartan/hydrochlorothiazide fixed combination not recommended in patients with anuria.30

Geriatric Patients

No initial dosage adjustment necessary.1

Volume- and/or Salt-Depleted Patients

Correct volume and/or salt depletion prior to initiation of therapy or initiate therapy under close medical supervision.1 30

Cautions for Teveten

Contraindications

  • Known hypersensitivity to eprosartan or any ingredient in the formulation.1 7 8

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

Possible fetal and neonatal morbidity and mortality when used during pregnancy.1 30 51 (See Boxed Warning.) Such potential risks occur throughout pregnancy, especially during the second and third trimesters.51

Also may increase the risk of major congenital malformations when administered during the first trimester of pregnancy.50 51

Discontinue as soon as possible when pregnancy is detected, unless continued use is considered lifesaving.50 51 Nearly all women can be transferred successfully to alternative therapy for the remainder of their pregnancy.13

Hypotension

Possible symptomatic hypotension, particularly in volume- and/or salt-depleted patients (e.g., those treated with diuretics or undergoing dialysis).1 30 (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 30

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

Sensitivity Reactions

Anaphylactoid reactions and/or angioedema possible;1 3 8 not recommended in patients with a history of angioedema associated with or unrelated to ACE inhibitor or angiotensin II receptor antagonist therapy.10 132

General Precautions

Renal Effects

Possible oliguria, progressive azotemia and, rarely, acute renal failure and/or death in patients with severe CHF.1 30

Increases in BUN and Scr possible in patients with unilateral or bilateral renal artery stenosis.1 30

Use of Fixed Combinations

When used in fixed combination with hydrochlorothiazide, consider the cautions, precautions, and contraindications associated with hydrochlorothiazide.30

Specific Populations

Pregnancy

Category C (1st trimester); Category D (2nd and 3rd trimesters).1 30 (See Boxed Warning.)

Lactation

Distributed into milk in rats; not known whether eprosartan is distributed into human milk.1 30 Discontinue nursing or the drug.1 30

Pediatric Use

Safety and efficacy not established.1 7 30

Geriatric Use

BP reduction with eprosartan monotherapy was slightly less in patients ≥65 years of age compared with younger patients.1 BP responses were similar in geriatric and younger patients receiving fixed-combination eprosartan/hydrochlorothiazide tablets.30 No substantial differences in safety relative to younger adults.1 30

Hepatic Impairment

Use with caution.1

Renal Impairment

Use with caution.1

Deterioration of renal function may occur.1 30 (See Renal Effects under Cautions.)

Use of eprosartan in fixed combination with hydrochlorothiazide is not recommended in patients with anuria.30

Blacks

BP reduction may be smaller in black patients compared with nonblack patients; use in combination with a diuretic.1 5 7

Common Adverse Effects

Upper respiratory tract infection, rhinitis, pharyngitis, cough, viral infection, urinary tract infection, abdominal pain, injury, arthralgia, fatigue, depression, dizziness,30 headache,30 back pain,30 hypertriglyceridemia.1 2 7

Interactions for Teveten

Not metabolized by CYP isoenzymes.1 30 Does not inhibit CYP1A, 2A6, 2C9/8, 2C19, 2D6, 2E, or 3A in vitro.1 30

Drugs Affecting Hepatic Microsomal Enzymes

Pharmacokinetic interactions with inhibitors or inducers of CYP2C9 or CYP3A unlikely.1 2

Specific Drugs

Drug

Interaction

Comment

Digoxin

Pharmacokinetic interaction unlikely1 2

Diuretics, potassium-sparing (e.g., amiloride, spironolactone, triamterene)

Possible additive hyperkalemic effects30

Concomitant use not recommended30

Fluconazole

Pharmacokinetic interaction unlikely1 2

Glyburide

Pharmacologic interaction unlikely1 2

Hydrochlorothiazide

Pharmacokinetic interaction unlikely1 2 30

Additive hypotensive effects2

Ketoconazole

Pharmacokinetic interaction unlikely1 30

Nifedipine, extended-release

Interaction unlikely1

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

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

Possible reduced antihypertensive effects1

Monitor renal function periodically1

Potassium supplements and potassium-containing salt substitutes

Possible additive hyperkalemic effect30

Concomitant use not recommended30

Ranitidine

Pharmacokinetic interaction unlikely1 2

Warfarin

Pharmacologic interaction unlikely1 2

Teveten Pharmacokinetics

Absorption

Bioavailability

Peal plasma concentration generally achieved 1–2 hours after oral administration in fasting state.1 Absolute bioavailability is about 13%.1 30

Onset

Following a single oral dose, onset of antihypertensive effect evident within 1–2 hours.1 During chronic therapy, maximum antihypertensive effects generally achieved after 2–3 weeks.1 30

Food

Food delays absorption.1 30

Special Populations

In male patients with hepatic impairment, AUC after a single 100-mg oral dose increased by approximately 40%.1 30

In patients with moderate or severe renal impairment, AUC increased by 70–90% and peak plasma concentration increased by 30–50%.1

Distribution

Extent

Crosses the placenta and is distributed in the fetus in animals.1 30

Distributed into milk in rats; not known whether distributed into human milk.1 30

Plasma Protein Binding

Approximately 98%.1 30

Elimination

Metabolism

Not metabolized by CYP isoenzymes.1 2 30

No pharmacologically active metabolites detected.1 7

Elimination Route

Eliminated by biliary and renal excretion, mainly as unchanged drug.1 2 30

Half-life

Approximately 20 hours following multiple oral doses.1

Special Populations

Poorly removed by hemodialysis.1 30

Stability

Storage

Oral

Tablets

20–25°C.1 30

Actions

  • Blocks the physiologic actions of angiotensin II, including vasoconstrictor and aldosterone-secreting effects.1 30

  • Does not interfere with response to bradykinins and substance P.1 30

  • Does not share the ACE inhibitor common adverse effect of dry cough.1 30

Advice to Patients

  • Risks of use during pregnancy.1 30 50 51

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1 30

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (including salt substitutes containing potassium).1 30

  • Importance of informing patients of other important precautionary information.1 30 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Eprosartan Mesylate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

400 mg (of eprosartan)

Teveten

Abbott

600 mg (of eprosartan)

Teveten

Abbott

Eprosartan Mesylate Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

600 mg (of eprosartan) with Hydrochlorothiazide 12.5 mg

Teveten HCT

Abbott

600 mg (of eprosartan) with Hydrochlorothiazide 25 mg

Teveten HCT

Abbott

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Teveten 400MG Tablets (ABBOTT): 30/$90.99 or 90/$250.97

Teveten 600MG Tablets (ABBOTT): 30/$119.99 or 90/$323.97

Teveten HCT 600-12.5MG Tablets (ABBOTT): 30/$120.99 or 90/$335.97

Teveten HCT 600-25MG Tablets (ABBOTT): 30/$109.98 or 90/$309.98

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions December 23, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

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

References

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5. Anon. Drugs for hypertension. Med Lett Drugs Ther. 2001; 43:17-22. [PubMed 11242494]

6. Anon. Consensus recommendations for the management of chronic heart failure. On behalf of the membership of the advisory council to improve outcomes nationwide in heart failure. Part II. Management of heart failure: approaches to the prevention of heart failure. Am J Cardiol. 1999; 83:9-38A.

7. Biovail Pharmaceuticals. Morrisville, NC: Personal communication.

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50. Cooper WO, Hernandez-Diaz S, Arbogast PG et al. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med. 2006; 354:2443-51. [PubMed 16760444]

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121. Sipahi I, Debanne SM, Rowland DY et al. Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials. Lancet Oncol. 2010; 11:627-36. [PubMed 20542468]

122. Nissen SE. Angiotensin-receptor blockers and cancer: urgent regulatory review needed. Lancet Oncol. 2010; 11:605-6. [PubMed 20542469]

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126. Food and Drug Administration. FDA drug safety communication: No increase in risk of cancer with certain blood pressure drugs-angiotensin receptor blockers (ARBs). Rockville, MD; 2011 Jun 2. Available from FDA website. Accessed 2011 Jun 15.

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128. ARB Trialists Collaboration. Effects of telmisartan, irbesartan, valsartan, candesartan, and losartan on cancers in 15 trials enrolling 138,769 individuals. J Hypertens. 2011; 29:623-35. [PubMed 21358417]

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132. Howes LG, Tran D. Can angiotensin receptor antagonists be used safely in patients with previous ACE inhibitor-induced angioedema? Drug Saf. 2002; 25:73-6.

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