Bisoprolol Fumarate

Class: beta-Adrenergic Blocking Agents
VA Class: CV100
Chemical Name: 2-Propanol, 1 - (4 - ((2 - (1 - methylethoxy)ethoxy)methyl)phenoxy) - 3 - ((1 - methylethyl)amino),(±),(E) - 2 - butenedioate (2:1) (salt)
Molecular Formula: C₁₈H₃₁NO₄•½C₄H₄O₄
CAS Number: 104344-23-2
Brands: Zebeta, Ziac

Introduction

β₁-selective adrenergic blocking agent

Uses for Bisoprolol Fumarate

Hypertension

Management of hypertension as monotherapy or in combination with other classes of antihypertensive agents.^{1 2 3 4 5 6 7 18 21}

One of several preferred initial therapies in hypertensive patients with heart failure, postmyocardial infarction, ischemic heart disease, and/or diabetes mellitus.⁴⁴

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

CHF

Management of mild to moderately severe (NYHA class II or III) heart failure of ischemic or cardiomyopathic origin† in conjunction with cardiac glycosides, diuretics, and ACE inhibitors.^{22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38}

Bisoprolol, carvedilol, and extended-release metoprolol succinate have been shown to be effective in reducing the risk of death in patients with chronic heart failure; however, these positive findings should not be considered indicative of β-adrenergic blocking agent class effect.⁵⁵

Bisoprolol Fumarate Dosage and Administration

General

• 
  

  Individualize dosage according to patient response and tolerance.^{3 18}

  
  


• 
  

  If long-term therapy is discontinued, reduce dosage gradually over a period of about 1–2 weeks.^{1 2 20} (See Abrupt Withdrawal of Therapy under Cautions.)

  
  

Administration

Oral Administration

Administer orally;^{1 2 3 4 5 6 7} absorption does not appear to be affected by food.^{1 2 3 4 6 7}

Dosage

Available as bisoprolol fumarate; dosage expressed in terms of the fumarate.^{1 2 3}

Pediatric Patients

Hypertension†

Combination Therapy

Oral

Some experts state that the initial dosage of the commercially available fixed-combination tablets (containing 2.5 mg of bisoprolol fumarate and 6.25 mg of hydrochlorothiazide) is 1 tablet daily.⁵² If needed, dosage may be increased to the fixed-combination preparation containing 10 mg of bisoprolol fumarate and 6.25 mg of hydrochlorothiazide administered once daily.⁵²

Adults

Hypertension

Monotherapy

Oral

Initially, 2.5–5 mg once daily.^{1 3 5 18 21 44}

Increase dosage gradually up to 20 mg daily.^{1 2 3 18}

Bisoprolol/Hydrochlorothiazide Combination Therapy

Oral

Patients in whom BP is not adequately controlled by monotherapy with bisoprolol fumarate 2.5–20 mg daily or those who respond adequately to a hydrochlorothiazide dosage of 50 mg daily, but potassium loss is problematic, can switch to a fixed-combination preparation containing bisoprolol and hydrochlorothiazide.^{2 3}

Initial use of fixed-combination preparations generally is not recommended, adjust by administering each drug separately, then use the fixed combination if optimum maintenance dosage corresponds to the drug dosages in the combination preparation.^{18 19}

Alternatively, may initiate daily therapy with the fixed-combination preparation containing bisoprolol fumarate 2.5 mg and hydrochlorothiazide 6.25 mg daily.^{2 3 21}

CHF†

Oral

Initially, 1.25 mg daily⁴⁰ for 2–4 weeks or less in adults with mild to moderately severe heart failure.^{22 30}

If tolerated, increase to 2.5 mg daily for 2–4 weeks; subsequent dosages can be doubled every 2–4 weeks.^{22 30}

If deterioration (usually transient) occurs during titration, increase dosage of concurrent diuretic⁴⁰ and decrease dosage of β -blocker or temporarily discontinue β -blocker.⁴⁰ Do not continue dosage titration until symptoms of worsening heart failure have stabilized.⁴⁰ Initial difficulty in dosage titration should not preclude subsequent attempts to successfully titrate the dosage.⁴⁰

Reduce dosage in patients with CHF who experience symptomatic bradycardia (e.g., dizziness) or 2nd or 3rd degree heart block.⁴⁰

Prescribing Limits

Pediatric Patients

Hypertension†

Combination Therapy

Oral

Some experts state that the maximum dosage of bisoprolol fumarate in fixed combination with hydrochlorothiazide is 10 mg of bisoprolol fumarate and 6.25 mg of hydrochlorothiazide (i.e., 1 tablet of the 10/6.25-mg fixed combination) daily.⁵²

Adults

Hypertension

Monotherapy

Oral

Maximum is 20 mg daily.^{1 2 3 18} However, JNC 7 currently recommends a lower maximum dosage of 10 mg daily.⁴⁴

Combination Therapy

Oral

Dosage of bisoprolol/hydrochlorothiazide fixed combination generally should not exceed bisoprolol fumarate 20 mg and hydrochlorothiazide 12.5 mg (i.e., 2 tablets of the 10/6.25-mg fixed combination) daily.^{2 3}

CHF†

Oral

Maximum recommended by ACC and AHA: 10 mg once daily.⁴⁰

Special Populations

Hepatic Impairment

Hepatitis or Cirrhosis

Initially 2.5 mg once daily.¹

Increase dosage with caution.^{1 3}

Renal Impairment

Cl_cr <40 mL/minute

Initially 2.5 mg daily.¹

Increase dosage with caution.^{1 3}

Discontinue bisoprolol/hydrochlorothiazide fixed combination if progressive renal impairment develops.²

Cl_cr <20 mL/minute per 1.73 m²

Generally, maximum 10 mg once daily.^{4 6 8 a}

Hemodialysis

Apparently not removed by dialysis; supplemental dose is not required after dialysis.^{1 3}

Geriatric Patients

Dosage adjustment not required unless appreciable renal or hepatic impairment is present.^{1 2}

Bronchospastic Disease

Initially, 2.5 mg daily;^{1 3} use the possible lowest dosage.¹

Cautions for Bisoprolol Fumarate

Contraindications

• 
  

  Patients with sinus bradycardia, heart block greater than first degree, cardiogenic shock, or overt cardiac failure.^{1 2}

  
  


• 
  

  Hypersensitivity to bisoprolol fumarate, any ingredient in the formulation, or sulfonamides.²

  
  

Warnings/Precautions

Warnings

Cardiac Failure

Possible precipitation of CHF.^{1 2}

Avoid use in overt CHF;^{1 2} may use cautiously in patients with well-compensated heart failure (e.g., those controlled with cardiac glycosides and/or diuretics).^{1 2}

Adequate treatment (e.g., with a cardiac glycoside and/or diuretic) and close observation recommended if signs or symptoms of impending cardiac failure occur; if cardiac failure continues, discontinue therapy, gradually if possible.^{1 2 22 40}

Abrupt Withdrawal of Therapy

Abrupt discontinuance of therapy is not recommended as it may exacerbate symptoms or precipitate MI or ventricular arrhythmias in patients with CAD.^{1 2} Gradually decrease dosage over 1–2 weeks and monitor patients carefully.^{1 2 3 18 19 20 21} If manifestations of withdrawal (exacerbation of angina or hypotension) occur, increase dosage or reinstitute therapy, at least temporarily.^{1 2 3 18}

Peripheral Vascular Disease

Possible precipitation or aggravation of symptoms of arterial insufficiency; use with caution.^{1 2}

Bronchospastic Disease

Generally should not be used in patients with bronchospastic disease,^{1 2} but may be used with caution in such patients who do not respond to or cannot tolerate alternative treatment.^{1 2}

Administer the lowest effective dosage (initially 2.5 mg once daily);^{1 2} a bronchodilator (e.g. a β₂-adrenergic agonist) should be available.^{1 2}

Major Surgery

Use with caution in patients undergoing major surgery involving general anesthesia.^{1 2} Use particular care if anesthetics that depress the myocardium (e.g., cyclopropane, ether, trichloroethylene) are used.^{1 2} (See Myocardial depressant general anesthetics under Interactions.)

Diabetes and Hypoglycemia

Possible decreased signs and symptoms of hypoglycemia (e.g., tachycardia).^{1 2}

Use with caution in patients with diabetes mellitus receiving hypoglycemic drugs.^{1 2}

Thyrotoxicosis

Signs of hyperthyroidism (e.g., tachycardia) may be masked.^{1 2} Possible exacerbation of hyperthyroidism or precipitation of thyroid storm if therapy is abruptly withdrawn; carefully monitor patients having or suspected of developing thyrotoxicosis.^{1 2}

General Precautions

History of Anaphylactic Reactions

Possible increased reactivity to repeated, accidental, diagnostic, or therapeutic challenges with a variety of allergens while taking β-blockers.^{1 2} Such patients may be unresponsive to usual doses of epinephrine.^{1 2}

Other Precautions

Shares the toxic potentials of β-blockers; observe the usual precautions of these agents.^{1 2} In addition, when used in fixed-combination with hydrochlorothiazide, consider the cautions, precautions, and contraindications associated with thiazide diuretics.^{1 2}

Specific Populations

Pregnancy

Category C.^{1 2}

Lactation

Not known whether bisoprolol fumarate is distributed into human milk.^{1 2} Use with caution.¹

Pediatric Use

Safety and efficacy not established in children;^{1 2} however, some experts recommend the use of bisoprolol fumarate/hydrochlorothiazide fixed combination in hypertensive children (1–17 years of age).⁵²

Geriatric Use

Safety and efficacy profiles in geriatric individuals are similar to those in younger adults.^{1 2}

Hepatic Impairment

In patients with hepatitis or cirrhosis, reduce initial dosage and adjust dosage cautiously.^{1 3} (See Hepatic Impairment under Dosage and Administration).

Renal Impairment

Cl_cr <40 mL/minute: threefold increase in half-life;^{1 2} reduce initial dosage and adjust dosage cautiously.^{1 3} (See Renal Impairment under Dosage and Administration).

Common Adverse Effects

Fatigue, headache, diarrhea, peripheral edema, and upper respiratory tract infection.^{1 2}

Interactions for Bisoprolol Fumarate

Not metabolized by isoenzyme CYP2D6.

Specific Drugs

Drug	Interaction	Comments
β-Adrenergic blocking agents		Do not use with other β- blockers1 2
Catecholamine-depleting drugs (e.g., reserpine, guanethidine)	Possible additive effects with concurrent use1 2	Monitor closely for excessive decreases in sympathetic activity1 2
Calcium-channel blocking agents (e.g., verapamil, diltiazem])	Potential for additive negative effects on AV nodal conduction	Use with caution1 2
Cimetidine	No clinically important pharmacokinetic interaction1 2
Clonidine	β-Adrenergic blockade may exacerbate rebound hypertension which may occur following clonidine discontinuance a	Discontinue β-blockers several days before withdrawal of clonidine 1 2
Digoxin	No clinically important pharmacokinetic interaction
Disopyramide	Potential for additive negative effects on AV nodal conduction1 2	Use with caution1 2
Myocardial depressant general anesthetics (e.g., ether, cyclopropane, trichloroethylene)	Increased risk of hypotension and heart failure1 2	Use with caution1 2 41
Rifampin	Potential for increased clearance and decreased elimination half-life of bisoprolol1 2	Initial dosage adjustments of bisoprolol are not necessary1 2
Thiazide diuretics	No clinically important pharmacokinetic interaction1 2
Warfarin	No effect on prothrombin time with stable warfarin dosage1 2

Bisoprolol Fumarate Pharmacokinetics

Absorption

Bioavailability

About 80%.^{1 2}

Onset

In healthy individuals, decreased tachycardia (exercise- and isoproterenol-induced) occurs within 1–4 hours.^{1 2}

Duration

In normal individuals, decreased tachycardia generally persists for 24 hours.^{1 2}

Food

Food does not appear to affect absorption.¹

Distribution

Extent

Not known whether distributed into human milk.^{1 2}

Plasma Protein Binding

About 30%.^{1 2}

Elimination

Metabolism

Not metabolized by CYP2D6.^{1 2}

20% first-pass metabolism.^{1 2}

Elimination Route

Excreted in urine as unchanged drug (50%) and as inactive metabolites; less than 2% excreted in feces.^{1 2}

Half-life

9–12 hours.^{1 2}

Special Populations

In patients with cirrhosis, half-life is more variable and substantially prolonged (range: 8.3–21.7 hours).^{1 2}

In renal impairment (Cl_cr <40 mL/minute): threefold increase in half-life.¹ (See Renal Impairment under Dosage and Administration.)

In geriatrics, half-life slightly increased due to decreased renal function.^{1 2}

Stability

Storage

Oral

Tablets

Tight containers at 20–25°C.¹

Tablets (Bisoprolol Fumarate and Hydrochlorothiazide)

Tight containers at 20–25°C.²

ActionsActions

• 
  

  Inhibits response to adrenergic stimuli by competitively blocking β₁-adrenergic receptors within the myocardium.¹ Blocks β₂-adrenergic receptors within the bronchial and vascular smooth muscle only at high doses.^{1 2 3 4 7}

  
  


• 
  

  Decreases resting and exercise-stimulated heart rate and cardiac output, decreases isoproterenol-induced tachycardia, prolongs sinus node recovery time, refractory period of the AV node, and AV nodal conduction (with rapid atrial stimulation).^{1 2}

  
  


• 
  

  No intrinsic sympathomimetic activity or membrane-stabilizing effect on the heart.^{1 2}

  
  


• 
  

  Reduces blood pressure by decreasing cardiac output, decreasing sympathetic outflow from the CNS, and or suppressing renin release.^{1 2}

  
  

Advice to Patients

• 
  

  Importance of taking medication exactly as prescribed.¹

  
  


• 
  

  Importance of not interrupting or discontinuing therapy without consulting clinician.^{1 2}

  
  


• 
  

  Importance of informing clinician at the first sign or symptom of congestive cardiac failure, excessive bradycardia, or if any difficulty in breathing occurs.^{1 2}

  
  


• 
  

  Importance of informing anesthesiologist or dentist that they are receiving bisoprolol therapy prior to undergoing major surgery.^{1 2}

  
  


• 
  

  Importance of informing patients with diabetes that the drug may mask signs and symptoms of hypoglycemia, including increased heart rate.^{1 2}

  
  


• 
  

  Importance of avoiding some activities (e.g., operating machinery or driving a motor vehicle or those requiring mental alertness).^{1 2}

  
  


• 
  

  Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs.^{1 2}

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{1 2}

  
  


• 
  

  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.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Bisoprolol Fumarate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	5 mg*	Bisoprolol Fumarate Tablets
			Zebeta (scored)	Barr
		10 mg*	Bisoprolol Fumarate Tablets
			Zebeta	Barr

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Bisoprolol Fumarate and Hydrochlorothiazide

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	2.5 mg with Hydrochlorothiazide 6.25 mg*	Ziac	Barr
		5 mg with Hydrochlorothiazide 6.25 mg*	Ziac	Barr
		10 mg with Hydrochlorothiazide 6.25 mg*	Ziac	Barr

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Bisoprolol Fumarate 10MG Tablets (SANDOZ): 30/$37.99 or 90/$95.97

Bisoprolol Fumarate 5MG Tablets (MYLAN): 30/$35.99 or 90/$92.98

Bisoprolol-Hydrochlorothiazide 10-6.25MG Tablets (SANDOZ): 30/$22.99 or 90/$59.97

Bisoprolol-Hydrochlorothiazide 2.5-6.25MG Tablets (SANDOZ): 90/$59.99 or 180/$105.97

Bisoprolol-Hydrochlorothiazide 5-6.25MG Tablets (SANDOZ): 90/$19.96 or 180/$39.93

Zebeta 10MG Tablets (TEVA PHARMACEUTICALS USA): 30/$104.99 or 90/$309.98

Zebeta 5MG Tablets (TEVA PHARMACEUTICALS USA): 30/$104.99 or 90/$309.98

Ziac 10-6.25MG Tablets (TEVA PHARMACEUTICALS USA): 30/$105.18 or 90/$288.6

Ziac 2.5-6.25MG Tablets (TEVA PHARMACEUTICALS USA): 30/$105.16 or 90/$293.46

Ziac 5-6.25MG Tablets (TEVA PHARMACEUTICALS USA): 30/$105.13 or 90/$288.58

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions April 2007. 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

1. Lederle Pharmaceutical. Zebeta (bisoprolol fumarate) tablets prescribing information. Pearl River, NY; 2001 Dec.

2. Lederle Pharmaceutical. Ziac (bisoprolol fumarate and hydrochlorothiazide) tablets prescribing information. Pearl River, NY; 2001 Apr 3.

3. Lederle Laboratories. Product information summary on Ziac and Zebeta. Pearl River, NY; 1993 May.

4. Lancaster SG, Sorkin EM. Bisoprolol: a preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in hypertension and angina pectoris. Drugs. 1988; 36:256-85. [IDIS 246149] [PubMed 2903820]

5. Boeijinga JK, Van Zwienen JCW, Schmitz PIM et al. A dose-finding study with bisoprolol in the treatment of mild tomoderate essential hypertension. Curr Ther Res. 1990; 48: 1036-43.

6. Steinwandt SM, Abadi AH, Rutledge DR. Focus on bisoprolol: a once-daily beta blocker providing 24-hour blood pressure control with balanced renal and hepatic elimination. Hosp Formul. 1993; 28:453-64.

7. Prichard BNC. Bisoprolol: a new beta-adrenoceptor blocking drug. Eur Heart J. 1987; 8(Suppl M):121-9.

8. Kirch W, Rose I, Demers HG et al. Pharmacokinetics of bisoprolol during repeated oral administration to healthy volunteers and patients with kidney or liver disease. Clin Pharmacokinet. 1987; 13:110-7. [IDIS 233463] [PubMed 2887325]

9. Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The 1984 Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1984; 144: 1045-57.

10. Anon. Drugs for hypertension. Med Lett Drugs Ther. 1984; 26:107-12. [PubMed 6150424]

11. Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The 1988 Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1988; 148: 1023-38.

12. Haeusler G, Shliep HJ, Schelling P et al. High β₁-in selectivity and favourable pharmacokinetics as the outstanding properties of bisoprolol. J Cardiovasc Pharmacol. 1986; 8(Suppl 11):S2-15. [PubMed 2439793]

13. Cuthbert MF, Owusu-Ankomah K. Effect of M&B 17803A, a new β-adrenoceptor blocking agent, on the cardiovascular responses to tilting and to isoprenaline in man. Br J Pharmacol. 1971; 43:639-48. [PubMed 4400530]

14. Conolly ME, Kersting F, Dollery CT. The clinical pharmacology of beta-adrenoceptor-blocking drugs. Prog Cardiovasc Dis. 1976; 19:203-4. [PubMed 10600]

15. Weiner N. Drugs that inhibit adrenergic nerves and block adrenergic receptors. In: Gilman AG, Goodman LS, Rall TW et al, eds. Goodman and Gilman’s the pharmacologic basis of therapeutics. 7th ed. New York: Macmillan Publishing Company; 1985:181-214.

16. Mimnaugh MW, Gearien JE. Adrenergic drugs. In: Foye WE, ed. Principles of medicinal chemistry. 2nd ed. Philadelphia: Lea and Febiger; 1981:377-93.

17. Machin PJ, Jurst DN, Bradshaw RW et al. β-Selective adrenoceptor antagonists.Part 2: 4-ether-linked phenoxypropanolamines. J Med Chem. 1983; 26:1570-6. [IDIS 177952] [PubMed 6138435]

18. Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The fifth report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V). Arch Intern Med. 1993; 153:154-83. [IDIS 309043] [PubMed 8422206]

19. Anon. Drugs for hypertension. Med Lett Drugs Ther. 1993; 35:55-60. [PubMed 8099706]

20. Lederle Laboratories, Pearl River, NY: Personal communication.

21. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). Bethesda, MD: National Institutes of Health; 1997 Nov. (NIH publication No. 98-4080.)

22. 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 heart failure (MERIT-HF). Am J Cardiol. 1999; 83:9-38A.

23. Packer M, Colucci WS, Sackner-Bernstein JD et al, for the PRECISE Study Group. Double-blind, placebo-controlled study of the effects of carvedilol in patients with moderate to severe heart failure: the PRECISE trial. Circulation. 1996; 94:2793-9.

24. Fisher ML, Gottlieb SS, Plotnick GD et al. Beneficial effects of metoprolol in heart failure associated with coronary artery disease: a randomized trial. J Am Coll Cardiol. 1994; 23:943-50. [IDIS 326479] [PubMed 8106700]

25. Bristow MR, Gilbert EM, Abraham WT et al, for the MOCHA Investigators. Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. Circulation. 1996; 94:2807-16.

26. Metra M, Nardi M, Raffaele G et al. Effects of short- and long-term carvedilol administration on rest and exercise hemodynamic variables, exercise capacity and clinical conditions in paatients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol. 1994; 24:1678-87. [IDIS 339059] [PubMed 7963115]

27. Olsen SL, Gilbert EM, renlund DG et al. Carvedilol improves left ventricular function and symptoms in chronic heart failre: a double-blind randomized study. J Am Coll Cardiol. 1995; 25:1225-31. [IDIS 347002] [PubMed 7722114]

28. Krum H, Sackner-Bernstein JD, Goldsmith RL et al. Double-blind placebo controlled study of the long-term efficacy of carvedilol in patients with severe chronic heart failure. Circulation. 1995; 92:1499-506. [IDIS 353924] [PubMed 7664433]

29. Waagstein F, Bristow MR, Swedberg K et al. Beneficial effects of metoprolol in idiopathic dilated cardiomyopathy. Lancet. 1993; 342:1441-6. [IDIS 322759] [PubMed 7902479]

30. CIBIS Investigators and Committees. A randomized trial of β-blockade in heart failure: the cardiac insufficiency bisoprolol study (CIBIS). Circulation. 1990; 90:1765-73.

31. Colucci WS, Packer M, Bristow MR et al, for the US Carvedilol Heart Failure Study Group. Carvedilol inhibits clinical progression in patients with mild symptoms of heart failure. Circulation. 1996; 94:2800-6.

32. MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet. 1999; 353:2001-7. [PubMed 10376614]

33. Bristow MR, Gilbert EM, Abraham WT et al. Effect of carvedilol on LV function and mortality in diabetic versus non-diabetic patients with ischemic or nonischemic dilated cardimyopathy. Circulation. 1996; 94(Suppl I):I664.

34. Lechat P, Packer M, Chalon S et al. Clinical effects of β-adrenergic blockade in chronic heart failure: a meta-analysis of double-blind, placebo-controlled, randomized trials. Circulation. 1998; 98:1184-91. [IDIS 414954] [PubMed 9743509]

35. Van Campen LC, Visser FC, Visser CA. Ejection fraction improvement by beta-blocker treatment in patients with heart failure: an analysis of studies published in the literature. J Cardiovasc Pharmacol. 1998; 32(Suppl 1):S31-5. [IDIS 413510] [PubMed 9731693]

36. SmithKline Beecham Pharmaceuticals. Coreg (carvedilol) tablets prescribing information. Philadelphia, PA; 1998 May.

37. Rousseau MF, Chapelle F, Van Eyll C et al. Medium-term effects of beta-blockade on left ventricular mechanics: a double-blind, placebo-controlled comparison of nebivolol and atenolol in patients with ischemic left ventricular dysfunction. J Card Fail. 1996; 2:15-23. [PubMed 8798100]

38. Mattioli AV, Modena MG, Fantini G et al. Atenolol in dilated cardiomyopathy: a clinical instrumental study. Cardiovasc Drugs Ther. 1990; 4:505-7. [PubMed 2285633]

39. Califf RM, O’Connor CM. β-Blocker therapy for heart failure. The evidence is in, now the work begins. JAMA. 2000; 283:1335-6. [IDIS 441609] [PubMed 10714735]

40. Hunt SA, Baker DW, Chin MH et al. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure). 2001. Available at: . Accessed July 25, 2002.

41. Hjalmarson A, Goldstein S, Fagerberg B et al. Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF). JAMA. 2000; 283:1295-1302. [IDIS 441604] [PubMed 10714728]

42. Appel LJ. The verdict from ALLHAT—thiazide diuretics are the preferred initial therapy for hypertension. JAMA. 2002; 288:3039-42. [IDIS 490723] [PubMed 12479770]

43. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002; 288:2981-97. [IDIS 490721] [PubMed 12479763]

44. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII) Express. Bethesda, MD: May 14 2003. From NIH website. (). (Also published in JAMA. 2003; 289.

45. Douglas JG, Bakris GL, Epstein M et al. Management of high blood pressure in African Americans: Consensus statement of the Hypertension in African Americans Working Group of the International Society on Hypertension in Blacks. Arch Intern Med. 2003; 163:525-41.

46. Guidelines Committee. 2003 European Society of Hypertension–European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertension. 2003; 21:1011-53.

47. The Guidelines Subcommitee of the WHO/ISH Mild Hypertension Liaison Committee. 1999 guidelines for the management of hypertension. J Hypertension. 1999; 17:392-403.

48. Izzo JL, Levy D, Black HR. Importance of systolic blood pressure in older Americans. Hypertension. 2000; 35:1021-4. [PubMed 10818056]

49. Frohlich ED. Recognition of systolic hypertension for hypertension. Hypertension. 2000; 35:1019-20. [PubMed 10818055]

50. Bakris GL, Williams M, Dworkin L et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. Am J Kidney Dis. 2000; 36:646-61. [IDIS 452007] [PubMed 10977801]

51. American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care. 2003; 26(Suppl 1):S80-2.

52. National High Blood Pressure Education Program Working Group on Hypertension Control in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004; 114(Suppl 2):555-76. [PubMed 15286277]

53. Wright JT, Dunn JK, Cutler JA et al. Outcomes in hypertensive black and nonblack patients treated with chlorthalidone, amlodipine, and lisinopril. JAMA. 2005; 293:1595-607. [IDIS 531054] [PubMed 15811979]

54. Neaton JD, Kuller LH. Diuretics are color blind. JAMA. 2005; 293:1663-6. [IDIS 531056] [PubMed 15811986]

55. American College of Cardiology and American Heart Association. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society. Summary Article. Circulation. 2005; 112:1825-52.

56. Thadani U. Beta blockers in hypertension. Am J Cardiol. 1983; 52:10-5D.

57. Shand DG. State-of-the-art: comparative pharmacology of the β-adrenoceptor blocking drugs. Drugs. 1983; 25(Suppl 2):92-9.

58. Breckenridge A. Which beta blocker? Br Med J. 1983; 286:1085-8.

59. Anon. Choice of a beta-blocker. Med Lett Drugs Ther. 1986; 28:20-2. [PubMed 2869400]

60. Wallin JD, Shah SV. β-Adrenergic blocking agents in the treatment of hypertension: choices based on pharmacological properties and patient characteristics. Arch Intern Med. 1987; 147:654-9. [IDIS 227948] [PubMed 2881524]

61. McDevitt DG. β-Adrenoceptor blocking drugs and partial agonist activity: is it clinically relevant? Drugs. 1983; 25:331-8.

62. McDevitt DG. Clinical significance of cardioselectivity: state-of-the-art. Drugs. 1983; 25(Suppl 2):219-26.

63. Frishman WH. β-Adrenoceptor antagonists: new drugs and new indications. N Engl J Med. 1981; 305:500-6. [IDIS 136600] [PubMed 6114433]

64. Thadani U, Davidson C, Chir B et al. Comparison of the immediate effects of five β-adrenoceptor-blocking drugs with different ancillary properties in angina pectoris. N Engl J Med. 1979; 300:750-5. [PubMed 581782]

65. Lewis RV, McDevitt DG. Adverse reactions and interactions with β-adrenoceptor blocking drugs. Med Toxicol. 1986; 1:343-61. [IDIS 239050] [PubMed 2878346]

66. Frishman WH. Clinical differences between beta-adrenergic blocking agents: implications for therapeutic substitution. Am Heart J. 1987; 113:1190-8. [IDIS 229873] [PubMed 2883867]

a. AHFS Drug Information 2005. McEvoy GK, ed. Bisoprolol. American Society of Health System Pharmacists; 2005:1763--5.

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