Angina (off-label use):
Note: For vasospastic angina, beta-blockers are not recommended; calcium channel blockers and nitrates are preferred. For nonvasospastic angina, guidelines recommend titrating dose to a resting heart rate of 55 to 60 beats per minute (ACCF/AHA [Fihn 2012]).
Oral: Initial: 5 to 10 mg once daily; may increase dose after ≥1 week to achieve the desired effect to a maximum dose of 20 mg once daily (de Muinck 1992; Maisch 1989; von Arnim 1995).
Atrial fibrillation/flutter, maintenance of ventricular rate control (off-label use):
Oral: Initial: 2.5 mg once daily; increase dose gradually as tolerated to achieve ventricular rate control; usual dosage range: 2.5 to 10 mg once daily (AHA/ACC/HRS [January 2014]).
Heart failure with reduced ejection fraction (off-label use):
Note: Initiate only in stable, euvolemic patients. In hospitalized patients, volume status should be optimized and IV diuretics, IV vasodilators, and IV inotropic agents successfully discontinued prior to initiation of therapy. Use caution when initiating in patients with NYHA class IV symptoms or recent heart failure exacerbation (particularly if inotropes were required during hospital course) (ACCF/AHA [Yancy 2013]; Meyer 2021).
Oral: Initial: 1.25 mg once daily; up-titrate gradually (eg, doubling the dose at 2-week, or longer, intervals) to a target dose of 10 mg once daily while monitoring for signs and symptoms of heart failure (ACC [Maddox 2021]; ACC/AHA [Yancy 2017]; ACCF/AHA [Yancy 2013]; CIBIS-II Investigators and Committees 1999). Note: A dose of 1.25 mg requires splitting a round 5 mg tablet into quarters in the United States and Canada, which may be cumbersome and may result in inaccurate dosing. Smaller tablet strengths are available in other countries.
Hypertension (alternative agent):
Note: Not recommended in the absence of specific comorbidities (eg, ischemic heart disease, heart failure with reduced ejection fraction, arrhythmia) (ACC/AHA [Whelton 2018]).
Oral: Initial: 2.5 to 5 mg once daily; titrate at weekly (or longer) intervals as needed based on patient response; usual dosage range: 2.5 to 10 mg once daily; maximum dose: 20 mg/day (ACC/AHA [Whelton 2018]).
Ventricular arrhythmias (off- label use):
Oral: Initial: 2.5 mg once daily; titrate dose as needed based on response and tolerability up to a maximum dose of 10 mg once daily (AHA/ACC/HRS [Al-Khatib 2017]).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: Bisoprolol has renal and hepatic clearance; total clearance in patients with severe kidney dysfunction (eg, CrCl <20 mL/minute/1.73 m2) is decreased ~50% compared to those with normal kidney function (Grevel 1989; Kirch 1987; Payton 1987).
Altered kidney function:
CrCl ≥20 mL/minute/1.73 m2: No dosage adjustment necessary (Kirch 1987; Payton 1987).
CrCl <20 mL/minute/1.73 m2: Start with low initial doses (eg, 1.25 to 2.5 mg daily, depending on indication); consider a reduced maximum dose of 10 mg daily (Kirch 1987; Payton 1987; expert opinion).
Hemodialysis, intermittent (thrice weekly): Moderately dialyzable (25% to 35%) (Kanegae 1999): Initial: 1.25 to 2.5 mg daily, depending on indication; consider a reduced maximum dose of 10 mg daily (Payton 1987; expert opinion). When scheduled dose falls on a hemodialysis day, administer dose after hemodialysis (expert opinion).
Peritoneal dialysis: Slightly dialyzable (Payton 1987): Initial 1.25 to 2.5 mg daily, depending on indication; consider a reduced maximum dose of 10 mg daily (Payton 1987; expert opinion).
CRRT: Initial 1.25 to 2.5 mg daily, depending on indication; consider a reduced maximum dose of 10 mg daily (expert opinion).
PIRRT (eg, sustained, low-efficiency diafiltration): Initial 1.25 to 2.5 mg daily, depending on indication; consider a reduced maximum dose of 10 mg daily (expert opinion).
Hepatitis or cirrhosis: Initial: 2.5 mg once daily; increase cautiously.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as fumarate:
Generic: 5 mg, 10 mg
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as fumarate:
Generic: 5 mg, 10 mg
Oral: May be administered without regard to meals. The smallest tablet size available in the United States and Canada is 5 mg. A dose of 1.25 mg for heart failure with reduced ejection fraction would require splitting a round tablet into quarters.
Hypertension: Management of hypertension. Note: Beta-blockers are not recommended as first-line therapy (ACC/AHA [Whelton 2018]).
Angina; Atrial fibrillation/flutter, maintenance of ventricular rate control; Heart failure with reduced ejection fraction; Ventricular arrhythmias
Zebeta may be confused with DiaBeta, Zetia
Beta-blockers may cause first degree atrioventricular (AV) block, second degree atrioventricular block, or complete atrioventricular block (Ref). At maintenance dosing, second- or third-degree AV block are less likely (Ref). Beta-blocking agents with intrinsic sympathomimetic activity (eg, pindolol) may cause fewer AV conduction abnormalities than those without intrinsic sympathomimetic activity (eg, bisoprolol) due to their partial agonist effects (Ref). In most cases (up to 72%), AV block will resolve upon discontinuation; however, there are reported cases of recurrent AV block and nearly 50% of patients with more severe AV block may require a permanent pacemaker (Ref).
Mechanism: Dose-related; related to the pharmacologic action. Blockade of cardiac beta-1 adrenergic receptors results in slowed conduction and prolongation in the refractory period of the AV node. Slowing of AV conduction can lead to AV block (Ref).
Onset: Varied; reports range from 1 day to 1 month of treatment (Ref).
Risk factors:
• Impaired AV node and sinus node dysfunction (Ref)
• Acute myocardial infarction (MI) especially inferior and posterior MI or heart failure (Ref)
• Concurrent use of other agents that impair AV nodal conduction (eg, nondihydropyridine calcium channel blockers, digoxin, ivabradine, antiarrhythmic agents) (Ref)
• Older patients (Ref)
Selective beta-blockers (eg, bisoprolol) have a lower risk of bronchospasm compared to noncardioselective beta-blockers (Ref). Specifically, patients with moderate to severe asthma or COPD have a higher risk of symptoms or exacerbation leading to hospitalization even with selective beta-blocker use (Ref). Concurrent use of inhaled bronchodilators and/or corticosteroids are protective against beta-blocker-induced bronchospasm in patients with COPD or asthma (Ref). Bronchospasm is reversible upon discontinuation or use of bronchodilators (Ref).
Mechanism: Dose-related; related to pharmacologic action. Beta-blocking agents can lead to airway smooth muscle constriction by antagonism of beta-2 receptors (Ref).
Onset: Rapid; reports suggest the single doses or acute use are more likely to cause changes in FEV1 compared to chronic use (Ref)
Risk factors:
• Nonselective beta-blockers (Ref)
• Reactive airway disease (asthma) (study with carvedilol-induced bronchospasm) (Ref)
• Acute use (Ref)
Beta-blockers may cause reversible CNS effects such as fatigue, insomnia, vivid dreams, memory impairment, and sexual disorder (Ref). Depression has also been rarely reported as a potential adverse reaction with older data; however, more recent data have not shown a difference versus placebo (Ref). Sexual disorders may occur; however, those patients who require beta-blocker therapy have risk factors for erectile dysfunction (eg, coronary artery disease, heart failure) (Ref). In addition, there may be a psychosomatic component (Ref). Lipophilic beta-blockers (such as bisoprolol, which is moderately lipophilic) penetrate the blood-brain barrier to a greater degree than hydrophilic beta-blockers, possibly leading to a greater incidence of CNS effects (Ref). CNS effects generally resolve with dose reduction or discontinuation (Ref).
Mechanism: Dose-related; exact mechanism is not fully understood. Proposed mechanisms include presence of beta receptors in the brain, affinity and in some instances, inhibition of beta-blocking agents towards serotonin (5-HT) receptors in the brain (affecting mood and sleep), and beta-blocker-induced decreases in central sympathetic output (Ref). Beta-1 blockade may also impact sleep by blocking sympathetic signaling to the pineal gland, resulting in suppression of nighttime levels of melatonin (Ref). Beta-blockers may cause erectile dysfunction through decreased sympathetic nervous system output and subsequent decreases in luteinizing hormone secretion and testosterone stimulation (Ref).
Onset: Intermediate; CNS effects often occur within the first few weeks of treatment (Ref).
Risk factors:
• Higher starting doses (Ref)
• Older patients (Ref)
• Depression may be more likely to occur in patients with preexisting neuropsychiatric disorders (Ref)
Beta-blockers may worsen, prolong, or cause hypoglycemia (Ref). In addition, beta-blockers may mask symptoms of hypoglycemia (tremor, irritability, palpitations), making diaphoresis the only symptom unaffected by beta-blockers (Ref). It is unclear if nonselective or selective beta-blockers are more likely to cause hypoglycemia; data are conflicting. One study suggests bisoprolol has no effect on blood glucose (Ref).
Mechanism: Dose-related; related to the pharmacologic action. Beta-blockers inhibit hepatic gluconeogenesis and glycogenolysis (Ref). Beta-blockers also reduce activation of the sympathetic nervous system; therefore, masking hypoglycemic symptoms that are catecholamine-mediated (Ref).
Onset: Varied. Data are limited for bisoprolol; suggested that bisoprolol does not affect blood glucose (Ref). Onset is extrapolated from other beta-blocking agents. Blood glucose recovery was significantly reduced after one dose (Ref). In another study, episodes of severe hypoglycemia were reported over the course of 4 years (Ref).
Risk factors:
• Insulin-dependent diabetes (Ref)
• Type 2 diabetes mellitus (Ref)
• Hospitalized patients not requiring basal insulin (Ref)
Beta-blocker therapy should not be withdrawn abruptly, but gradually tapered to avoid acute tachycardia, hypertension, and/or ischemia (Ref). Some studies have found an increase in propensity-adjusted mortality and coronary heart disease; however, one study did not find changes in infarct size and left ventricular function when beta-blocker was abruptly withdrawn in patients with myocardial infarction (Ref).
Mechanism: Dose-dependent; related to the pharmacologic action. Beta blockade causes upregulation of beta-receptors, enhanced receptor sensitivity, and decreased sympathetic nervous system response (Ref). Abrupt withdrawal leads to a transient sympathetic hyper-response (Ref). Another proposed mechanism involves increased platelet aggregability to epinephrine and thrombin (Ref).
Onset: Rapid/varied and transient; increases in heart rate and blood pressure appear 24 hours after abrupt withdrawal, peak after 48 hours, and subside after 7 days (Ref). Anginal symptoms reported to begin 12 to 24 hours after discontinuation (Ref). Development of adverse reactions also reported to occur 1 to 21 days after withdrawal (Ref).
Risk factors:
• Abrupt withdrawal in chronic users (Ref)
• Past medical history of coronary artery disease (including chronic stable angina) (Ref)
• Past medical history of hypertension (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%:
Cardiovascular: Chest pain (1%)
Gastrointestinal: Diarrhea (3%), vomiting (1%)
Nervous system: Fatigue (7%) (table 1) , hypoesthesia (1%)
Drug (Bisoprolol) |
Placebo |
Dose |
Number of Patients (Bisoprolol) |
Number of Patients (Placebo) |
---|---|---|---|---|
7% |
2% |
5 mg to 20 mg |
273 |
132 |
Respiratory: Dyspnea (1%), upper respiratory tract infection (5%)
<1%:
Cardiovascular: Bradycardia
Neuromuscular & skeletal: Asthenia
Frequency not defined:
Cardiovascular: Cardiac arrhythmia, cardiac failure, claudication, cold extremity, edema, flushing, hypersensitivity angiitis, hypotension, orthostatic hypotension, palpitations
Dermatologic: Alopecia, diaphoresis, eczema, pruritus, skin irritation, skin rash
Endocrine & metabolic: Decreased libido, gout, increased serum glucose, increased serum phosphate, increased serum potassium, increased serum triglycerides, increased uric acid, weight gain
Gastrointestinal: Abdominal pain, constipation, dysgeusia, dyspepsia, epigastric pain, gastritis, nausea, peptic ulcer, stomach pain, xerostomia
Genitourinary: Cystitis, sexual disorder
Hematologic & oncologic: Decreased white blood cell count, positive ANA titer, purpuric rash, thrombocytopenia
Hepatic: Increased serum alanine aminotransferase, increased serum aspartate aminotransferase
Nervous system: Anxiety, depression, dizziness, drowsiness, headache, hyperesthesia, lack of concentration, malaise, memory impairment, paresthesia, restlessness, sensation of eye pressure, twitching, vertigo, vivid dream
Neuromuscular & skeletal: Back pain, muscle cramps, myalgia, neck pain, tremor
Ophthalmic: Abnormal lacrimation, eye pain, visual disturbance
Otic: Otalgia, tinnitus
Renal: Increased blood urea nitrogen, increased serum creatinine, polyuria, renal colic
Respiratory: Asthma, bronchitis, bronchospasm, cough, dyspnea on exertion, pharyngitis, rhinitis, sinusitis
Postmarketing:
Cardiovascular: Complete atrioventricular block (Zeltser 2004), first degree atrioventricular block (Zeltser 2004), second degree atrioventricular block (Zeltser 2004), syncope
Dermatologic: Dermatitis, exacerbation of psoriasis (Waqar 2009), exfoliative dermatitis
Genitourinary: Peyronie's disease
Hypersensitivity: Angioedema
Nervous system: Insomnia (Chang 2013), sleep disturbance, unsteadiness
Neuromuscular & skeletal: Arthralgia
Otic: Auditory impairment
Cardiogenic shock; overt cardiac failure; marked sinus bradycardia or heart block greater than first-degree (except in patients with a functioning artificial pacemaker).
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to bisoprolol or any component of the formulation; overt cardiac failure requiring IV inotropic therapy; sick sinus syndrome or sinoatrial block; hypotension (systolic BP <100 mm Hg); severe bronchial asthma or chronic obstructive pulmonary disease; peripheral arterial occlusive disease (late stages); Raynaud syndrome; pheochromocytoma (untreated); metabolic acidosis.
Documentation of allergenic cross-reactivity for beta-blockers is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Disease-related concerns:
• Anaphylaxis reactions: Beta-blockers are unlikely to cause anaphylaxis; however, in susceptible patients, beta-blockers have been associated with an increase in the severity of anaphylaxis. Anaphylaxis in the presence of a beta-blocker may be severe, protracted, and resistant to conventional treatment (Lang 2008; Toogood 1987). This is due to beta-2-adrenergic blockade and the resulting diminution of endogenous catecholamine effect.
• Heart failure (HF): Stabilize patients on heart failure regimen prior to initiation or titration of beta-blocker. Beta-blocker therapy should be initiated at very low doses with gradual and very careful titration. Adjustment of other medications (ACE inhibitors and/or diuretics) may be required
• Hepatic impairment: Use with caution in patients with hepatic impairment; dosage adjustment may be required.
• Myasthenia gravis: Use with caution in patients with myasthenia gravis.
• Peripheral vascular disease (PVD) and Raynaud disease: Can precipitate or aggravate symptoms of arterial insufficiency in patients with PVD and Raynaud disease. Use with caution and monitor for progression of arterial obstruction.
• Pheochromocytoma (untreated): Adequate alpha-blockade is required prior to use of any beta-blocker.
• Psoriasis: Beta-blocker use has been associated with induction or exacerbation of psoriasis, but cause and effect have not been firmly established.
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment may be required.
• Thyroid disease: May mask signs of hyperthyroidism (eg, tachycardia). If hyperthyroidism is suspected, carefully manage and monitor; abrupt withdrawal may precipitate thyroid storm.
• Vasospastic angina: Beta-blockers without alpha1-adrenergic receptor blocking activity should be avoided in patients with vasospastic angina since unopposed alpha1-adrenergic receptors mediate coronary vasoconstriction and can worsen anginal symptoms (Mayer 1998).
Special populations:
• Elderly: Dosage reductions may be necessary.
Other warnings/precautions:
• Abrupt withdrawal: Beta-blocker therapy should not be withdrawn abruptly (particularly in patients with CAD), but gradually tapered to avoid acute tachycardia, hypertension, and/or ischemia.
• Major surgery: Chronic beta-blocker therapy should not be routinely withdrawn prior to major surgery.
Substrate of CYP2D6 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Acetylcholinesterase Inhibitors: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Alpha1-Blockers: Beta-Blockers may enhance the orthostatic hypotensive effect of Alpha1-Blockers. The risk associated with ophthalmic products is probably less than systemic products. Risk C: Monitor therapy
Alpha2-Agonists: May enhance the AV-blocking effect of Beta-Blockers. Sinus node dysfunction may also be enhanced. Beta-Blockers may enhance the rebound hypertensive effect of Alpha2-Agonists. This effect can occur when the Alpha2-Agonist is abruptly withdrawn. Management: Closely monitor heart rate during treatment with a beta blocker and clonidine. Withdraw beta blockers several days before clonidine withdrawal when possible, and monitor blood pressure closely. Recommendations for other alpha2-agonists are unavailable. Risk D: Consider therapy modification
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
Amiodarone: May enhance the bradycardic effect of Beta-Blockers. Possibly to the point of cardiac arrest. Amiodarone may increase the serum concentration of Beta-Blockers. Risk C: Monitor therapy
Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Antipsychotic Agents (Phenothiazines): May enhance the hypotensive effect of Beta-Blockers. Beta-Blockers may decrease the metabolism of Antipsychotic Agents (Phenothiazines). Antipsychotic Agents (Phenothiazines) may decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Beta2-Agonists: Beta-Blockers (Beta1 Selective) may diminish the bronchodilatory effect of Beta2-Agonists. Of particular concern with nonselective beta-blockers or higher doses of the beta1 selective beta-blockers. Risk C: Monitor therapy
Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Risk C: Monitor therapy
Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Bupivacaine: Beta-Blockers may increase the serum concentration of Bupivacaine. Risk C: Monitor therapy
Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Risk D: Consider therapy modification
Cholinergic Agonists: Beta-Blockers may enhance the adverse/toxic effect of Cholinergic Agonists. Of particular concern are the potential for cardiac conduction abnormalities and bronchoconstriction. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Bisoprolol. Risk C: Monitor therapy
Dabigatran Etexilate: Bisoprolol may increase the serum concentration of Dabigatran Etexilate. Risk C: Monitor therapy
Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Dipyridamole: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy
Disopyramide: May enhance the bradycardic effect of Beta-Blockers. Beta-Blockers may enhance the negative inotropic effect of Disopyramide. Risk C: Monitor therapy
DOBUTamine: Beta-Blockers may diminish the therapeutic effect of DOBUTamine. Risk C: Monitor therapy
Dronedarone: May enhance the bradycardic effect of Beta-Blockers. Dronedarone may increase the serum concentration of Beta-Blockers. This likely applies only to those agents that are metabolized by CYP2D6. Management: Use lower initial beta-blocker doses; adequate tolerance of the combination, based on ECG findings, should be confirmed prior to any increase in beta-blocker dose. Increase monitoring for clinical response and adverse effects. Risk D: Consider therapy modification
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
EPHEDrine (Systemic): Beta-Blockers may diminish the therapeutic effect of EPHEDrine (Systemic). Risk C: Monitor therapy
EPINEPHrine (Nasal): Beta-Blockers (Beta1 Selective) may diminish the therapeutic effect of EPINEPHrine (Nasal). Risk C: Monitor therapy
EPINEPHrine (Oral Inhalation): Beta-Blockers (Beta1 Selective) may diminish the therapeutic effect of EPINEPHrine (Oral Inhalation). Risk C: Monitor therapy
Epinephrine (Racemic): Beta-Blockers (Beta1 Selective) may diminish the therapeutic effect of Epinephrine (Racemic). Risk C: Monitor therapy
EPINEPHrine (Systemic): Beta-Blockers (Beta1 Selective) may diminish the therapeutic effect of EPINEPHrine (Systemic). Risk C: Monitor therapy
Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): Beta-Blockers may enhance the vasoconstricting effect of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor therapy
Etofylline: Beta-Blockers may diminish the therapeutic effect of Etofylline. Risk X: Avoid combination
Fexinidazole: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole. Risk X: Avoid combination
Fingolimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Fingolimod. Management: Consult with the prescriber of any bradycardia-causing agent to see if the agent could be switched to an agent that does not cause bradycardia prior to initiating fingolimod. If combined, perform continuous ECG monitoring after the first fingolimod dose. Risk D: Consider therapy modification
Grass Pollen Allergen Extract (5 Grass Extract): Beta-Blockers may enhance the adverse/toxic effect of Grass Pollen Allergen Extract (5 Grass Extract). More specifically, Beta-Blockers may inhibit the ability to effectively treat severe allergic reactions to Grass Pollen Allergen Extract (5 Grass Extract) with epinephrine. Some other effects of epinephrine may be unaffected or even enhanced (e.g., vasoconstriction) during treatment with Beta-Blockers. Management: Consider alternatives to either grass pollen allergen extract (5 grass extract) or beta-blockers in patients with indications for both agents. Canadian product labeling specifically lists this combination as contraindicated. Risk D: Consider therapy modification
Herbal Products with Blood Pressure Increasing Effects: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Insulins: Beta-Blockers may enhance the hypoglycemic effect of Insulins. Risk C: Monitor therapy
Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Risk C: Monitor therapy
Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Risk C: Monitor therapy
Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy
Lidocaine (Systemic): Beta-Blockers may increase the serum concentration of Lidocaine (Systemic). Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Mepivacaine: Beta-Blockers may increase the serum concentration of Mepivacaine. Risk C: Monitor therapy
Methacholine: Beta-Blockers may enhance the adverse/toxic effect of Methacholine. Risk C: Monitor therapy
Methoxyflurane: May enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
NIFEdipine: May enhance the hypotensive effect of Beta-Blockers. NIFEdipine may enhance the negative inotropic effect of Beta-Blockers. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Beta-Blockers. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (Topical): May diminish the therapeutic effect of Beta-Blockers. Risk C: Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification
Ozanimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Ponesimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Ponesimod. Management: Avoid coadministration of ponesimod with drugs that may cause bradycardia when possible. If combined, monitor heart rate closely and consider obtaining a cardiology consult. Do not initiate ponesimod in patients on beta-blockers if HR is less than 55 bpm. Risk D: Consider therapy modification
Propafenone: May increase the serum concentration of Beta-Blockers. Propafenone possesses some independent beta blocking activity. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Reserpine: May enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy
Rivastigmine: May enhance the bradycardic effect of Beta-Blockers. Risk X: Avoid combination
Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. If combined, consider obtaining a cardiology consult regarding patient monitoring. Risk D: Consider therapy modification
Succinylcholine: Beta-Blockers may enhance the neuromuscular-blocking effect of Succinylcholine. Risk C: Monitor therapy
Sulfonylureas: Beta-Blockers may enhance the hypoglycemic effect of Sulfonylureas. Cardioselective beta-blockers (eg, acebutolol, atenolol, metoprolol, and penbutolol) may be safer than nonselective beta-blockers. All beta-blockers appear to mask tachycardia as an initial symptom of hypoglycemia. Ophthalmic beta-blockers are probably associated with lower risk than systemic agents. Risk C: Monitor therapy
Tasimelteon: Beta-Blockers may diminish the therapeutic effect of Tasimelteon. Management: Consider avoiding nighttime administration of beta-blockers during tasimelteon therapy due to the potential for reduced tasimelteon efficacy. Risk D: Consider therapy modification
Terlipressin: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Theophylline Derivatives: Beta-Blockers (Beta1 Selective) may diminish the bronchodilatory effect of Theophylline Derivatives. Management: Monitor for reduced theophylline efficacy during concomitant use with any beta-blocker. Beta-1 selective agents are less likely to antagonize theophylline than nonselective agents, but selectivity may be lost at higher doses. Risk C: Monitor therapy
Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
White Birch Allergen Extract: Beta-Blockers may enhance the adverse/toxic effect of White Birch Allergen Extract. Specifically, beta-blockers may reduce the effectiveness of beta-agonists that may be required to treat systemic reactions to white birch allergen extract. Risk X: Avoid combination
Exposure to beta-blockers during pregnancy may increase the risk for adverse events in the neonate. If maternal use of a beta-blocker is needed, fetal growth should be monitored during pregnancy and the newborn should be monitored for 48 hours after delivery for bradycardia, hypoglycemia, and respiratory depression (ESC [Regitz-Zagrosek 2018]).
Chronic maternal hypertension is also associated with adverse events in the fetus/infant. Chronic maternal hypertension may increase the risk of birth defects, low birth weight, premature delivery, stillbirth, and neonatal death. Actual fetal/neonatal risks may be related to duration and severity of maternal hypertension. Untreated chronic hypertension may also increase the risks of adverse maternal outcomes, including gestational diabetes, preeclampsia, delivery complications, stroke, and myocardial infarction (ACOG 203 2019).
When treatment of chronic hypertension in pregnancy is indicated, agents other than bisoprolol are preferred (ACOG 203 2019; ESC [Regitz-Zagrosek 2018]; Magee 2014). Females with preexisting hypertension may continue their medication during pregnancy unless contraindications exist (ESC [Regitz-Zagrosek 2018]).
It is not known if bisoprolol is present in breast milk.
The manufacturer recommends that caution be exercised when administering bisoprolol to breastfeeding women. Use of a beta-blocker other than bisoprolol may be preferred in a lactating female (Anderson 2017; Ito 2000).
BP, heart rate, ECG; serum glucose (in diabetic patients); signs and symptoms of bronchospasm (in patients with preexisting bronchospastic disease).
Hypertension: The 2017 guideline for the prevention, detection, evaluation, and management of high BP in adults (ACC/AHA [Whelton 2018]):
Confirmed hypertension and known cardiovascular disease or 10-year atherosclerotic cardiovascular disease risk ≥10%: Target BP <130/80 mm Hg is recommended.
Confirmed hypertension without markers of increased atherosclerotic cardiovascular disease risk: Target BP <130/80 mm Hg may be reasonable.
Selective inhibitor of beta1-adrenergic receptors; competitively blocks beta1-receptors, with little or no effect on beta2-receptors at doses ≤20 mg
Onset of action: 1 to 2 hours
Absorption: Rapid and almost complete
Distribution: Widely; highest concentrations in heart, liver, lungs, and saliva; crosses blood-brain barrier
Protein binding: ~30%
Metabolism: Extensively hepatic; significant first-pass effect (~20%)
Bioavailability: ~80%
Half-life elimination: Normal renal function: 9 to 12 hours; CrCl <40 mL/minute: 27 to 36 hours; Hepatic cirrhosis: 8 to 22 hours
Time to peak: 2 to 4 hours
Excretion: Urine (50% as unchanged drug, remainder as inactive metabolites); feces (<2%)
Tablets (Bisoprolol Fumarate Oral)
5 mg (per each): $1.40 - $2.25
10 mg (per each): $1.40 - $2.25
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