>10%:

Central nervous system: Drowsiness, insomnia

Endocrine & metabolic: Decreased sexual ability

1% to 10%:

Cardiovascular: Bradycardia, palpitation, edema, CHF, reduced peripheral circulation

Central nervous system: Mental depression

Gastrointestinal: Diarrhea or constipation, nausea, vomiting, stomach discomfort

Ocular: Mild ocular stinging and discomfort, tearing, photophobia, decreased corneal sensitivity, keratitis

Respiratory: Bronchospasm

Miscellaneous: Cold extremities

<1% (Limited to important or life-threatening): Angioedema, arrhythmia, bronchospasm, chest pain, confusion (especially in the elderly), depression, dyspnea, exfoliative dermatitis, hallucinations, headache, itching, leukopenia, nervousness, orthostatic hypotension, Peyronie's disease, psoriasiform eruption, syncope, thrombocytopenia, vasculitis

Alpha-blockers (prazosin, terazosin): Concurrent use of beta-blockers may increase risk of orthostasis.

AV conduction-slowing agents (digoxin): Effects may be additive with beta-blockers.

Clonidine: Hypertensive crisis after or during withdrawal of either agent.

CYP3A4 inducers: CYP3A4 inducers may decrease the levels/effects of bisoprolol. Example inducers include aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins.

CYP3A4 inhibitors: May increase the levels/effects of bisoprolol. Example inhibitors include azole antifungals, ciprofloxacin, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, and verapamil.

Glucagon: Bisoprolol may blunt the hyperglycemic action of glucagon.

Insulin: Bisoprolol may mask tachycardia from hypoglycemia.

NSAIDs (ibuprofen, indomethacin, naproxen, piroxicam) may reduce the antihypertensive effects of beta-blockers.

Salicylates may reduce the antihypertensive effects of beta-blockers.

Sulfonylureas: Beta-blockers may alter response to hypoglycemic agents.

Onset of action: 1-2 hours

Absorption: Rapid and almost complete

Distribution: Widely; highest concentrations in heart, liver, lungs, and saliva; crosses blood-brain barrier; enters breast milk

Protein binding: 26% to 33%

Metabolism: Extensively hepatic; significant first-pass effect

Half-life elimination: 9-12 hours

Time to peak: 1.7-3 hours

Excretion: Urine (3% to 10% as unchanged drug); feces (<2%)

Adults: 2.5-5 mg once daily, may be increased to 10 mg, and then up to 20 mg once daily, if necessary

Hypertension (JNC 7): 2.5-10 mg once daily

Elderly: Initial dose: 2.5 mg/day; may be increased by 2.5-5 mg/day; maximum recommended dose: 20 mg/day

Dosing adjustment in renal/hepatic impairment: Clcr<40 mL/minute: Initial: 2.5 mg/day; increase cautiously.

Hemodialysis: Not dialyzable

Surgery: Atenolol has also been shown to improve cardiovascular outcomes when used in the perioperative period in patients with underlying cardiovascular disease who are undergoing noncardiac surgery. Bisoprolol in high-risk patients undergoing vascular surgery reduced the perioperative incidence of death from cardiac causes and nonfatal myocardial infarction.

Withdrawal: Beta-blocker therapy should not be withdrawn abruptly, but gradually tapered to avoid acute tachycardia and hypertension.

Hypertension: Beta-blocker therapy in the treatment of hypertension has been associated with improved cardiovascular outcomes. This class of drug is beneficial for elderly patients with hypertension. A recent UKPDS study showed that beta-blocker therapy (atenolol) was as effective as an ACE inhibitor in reducing cardiovascular events and that the benefits of therapy were related more to the degree of antihypertensive efficacy rather than the class of drug used.

Myocardial infarction: Beta-blockers, in general without intrinsic sympathomimetic activity (ISA), have been shown to decrease morbidity and mortality when initiated in the acute treatment of myocardial infarction and continued long-term. In this setting, therapy should be avoided in patients with hypotension, cardiogenic shock, or heart block.

Surgery: Atenolol has also been shown to improve cardiovascular outcomes when used in the perioperative period in patients with underlying cardiovascular disease who are undergoing noncardiac surgery. Bisoprolol in high-risk patients undergoing vascular surgery reduced the perioperative incidence of death from cardiac causes and nonfatal myocardial infarction.

Atrial fibrillation: Beta-blocker therapy provides effective rate control in patients with atrial fibrillation.

Angina: Beta-blockers are effective in the treatment of angina as monotherapy or when combined with nitrates and/or calcium channel blockers. In patients with severe intractable angina requiring negative cardiac chronotropic medications, pacemaker placement has been carried out to maintain heart rate in the setting of large doses of beta-blockers and/or calcium channel blockers. Beta-blockers are ineffective in the treatment of pure vasospastic (Prinzmetal) angina.

Unstable angina/non-ST-segment elevation MI: In the treatment of unstable angina/non-ST-segment elevation MI, a beta-blocker, with the first dose administered intravenously if there is ongoing chest pain, followed by oral administration, is recommended (in the absence of contraindications).

Withdrawal: Beta-blocker therapy should not be withdrawn abruptly, but gradually tapered to avoid acute tachycardia and hypertension.

Heart failure: There is emerging evidence that beta-blocker therapy, without intrinsic sympathomimetic activity (ISA), should be initiated in select patients with stable congestive heart failure (NYHA Class II-III). To date, carvedilol, sustained release metoprolol, and bisoprolol have demonstrated a beneficial effect on morbidity and mortality. It is important that beta-blocker therapy be instituted initially at very low doses with gradual and very careful titration. In the CIBIS-II trial, bisoprolol (beta-1 selective beta-blocker) improved morbidity and mortality in patients with moderate heart failure (NYHA Class III-IV).

Antman EM, Anbe SC, Alpert JS, et al, "ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction - Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction),"Circulation, 2004, 110:588-636. Available at: http://www.circulationaha.org/cgi/content/full/110/5/588. Last accessed August 26, 2004.

Braunwald E, Antman EM, Beasley JW, et al, "ACC/AHA 2002 Guideline Update for the Management of Patients With Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction - Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina),"J Am Coll Cardiol, 2002, 40(7):1366-74. Available at: http://www.acc.org/clinical/guidelines/unstable/incorporated/index.htm. Accessed May 20, 2003.

Chobanian AV, Bakris GL, Black HR, et al, "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report,"JAMA, 2003, 289(19):2560-71.

"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,"Am J Cardiol, 1999, 83(2A):1A-38A.

Gibbons RJ, Abrams J, Chatterjee K, et al, "ACC/AHA 2002 Guideline Update for the Management of Patients With Chronic Stable Angina - Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina),"J Am Coll Cardiol, 2003, 41(1):159-68.

Mokhlesi B, Leikin JB, Murray P, et al, "Adult Toxicology in Critical Care: Part II: Specific Poisonings,"Chest, 2003, 123(3):897-922.

Poldermans D, Boersma E, Bax JJ, et al, "The Effect of Bisoprolol on Perioperative Mortality and Myocardial Infarction in High-Risk Patients Undergoing Vascular Surgery,"N Engl J Med, 1999, 341(24):1789-94.