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Propranolol: Drug information

Propranolol: Drug information
(For additional information see "Propranolol: Patient drug information" and see "Propranolol: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Hemangeol;
  • Inderal LA;
  • Inderal XL;
  • InnoPran XL
Brand Names: Canada
  • APO-Propranolol;
  • Hemangiol;
  • Inderal LA;
  • PMS-Propranolol;
  • TEVA-Propranolol
Pharmacologic Category
  • Antianginal Agent;
  • Antiarrhythmic Agent, Class II;
  • Antihypertensive;
  • Beta-Blocker, Nonselective
Dosing: Adult

Note: Dosing recommendations are expressed as the total daily dose unless stated otherwise. The total daily oral dose is given in 1 to 4 divided doses per day, depending on the type of preparation. Available preparations include: oral immediate release (usually dosed 2 to 4 times daily), extended release (usually dosed once daily), and IV injection. If tolerability is a concern, immediate release may be preferred initially; after establishing appropriate maintenance dose, may convert to once-daily extended release using same total daily dose.

Akathisia, antipsychotic-induced

Akathisia, antipsychotic-induced (off-label use):

Immediate release: Oral: Initial: 10 mg twice daily; if needed, adjust dose based on response and tolerability (eg, at intervals of ≥1 week) up to 120 mg/day (Adler 1986; APA [Keepers 2020]; Kramer 1989; Stroup 2021).

Angina, chronic stable

Angina, chronic stable (alternative agent):

Note: For vasospastic angina, beta-blockers are not recommended; other agents (eg, calcium channel blockers, 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]), while other experts recommend targeting 60 to 70 beats per minute (Kannam 2021). Some experts prefer a cardioselective beta-blocker (Kannam 2021).

Oral: Initial: 80 mg/day (may choose an IR or ER formulation); increase dose as tolerated to desired effect; usual dosage range: 80 to 320 mg/day.

Atrial fibrillation/flutter

Atrial fibrillation/flutter:

Acute ventricular rate control (alternative agent):

IV: 1 mg over 1 minute; repeat as needed every 2 minutes up to a maximum of 3 doses (AHA/ACC/HRS [January 2014]; Ganz 2020).

Maintenance of ventricular rate control:

Immediate release: Oral: Usual dosage range: 30 to 160 mg/day in 3 to 4 divided doses (AHA/ACC/HRS [January 2014]).

Essential tremor

Essential tremor:

Note: May be used as monotherapy or in combination with primidone (AAN [Zesiewicz 2005]).

Oral: Initial: 60 to 80 mg/day (may choose an IR or ER formulation); increase dose as needed based on response and tolerability; usual dosage range: 60 to 320 mg/day (AAN [Zesiewicz 2005]; AAN [Zesiewicz 2011]; Deuschl 2011).

Hypertension

Hypertension (alternative agent):

Note: Not recommended in the absence of specific comorbidities (eg, ischemic heart disease, essential tremor, migraine) (ACC/AHA [Whelton 2018]).

Oral: Initial: 80 mg/day (may choose an IR or ER formulation); titrate at ≥1-week intervals as needed based on patient response; usual dosage range: 80 to 160 mg/day (ACC/AHA [Whelton 2018]). Some experts favor using an ER formulation unless there is concern for tolerability, in which case the IR formulation may be appropriate (Mann 2020).

Migraine headache, prophylaxis

Migraine headache, prophylaxis:

Oral: Initial: 40 to 80 mg/day (may choose an IR or ER formulation); increase dose gradually based on response and tolerability to usual effective dosage range of 40 to 160 mg/day (Linde 2004; Pringsheim 2010; Smith 2019). Some patients may benefit from titration to a maximum of 240 mg/day (manufacturer's labeling). The maximum tolerated dose should be maintained for ≥3 months before deeming treatment failure. Some experts recommend beginning the IR formulation at 20 mg twice daily with up-titration as needed (Smith 2019).

Myocardial infarction, early treatment and secondary prevention

Myocardial infarction, early treatment and secondary prevention (alternative agent):

Note: An oral beta-blocker is recommended within the first 24 hours for most patients (ACCF/AHA [O'Gara 2013]). Some experts prefer a cardioselective beta-blocker. Patients who did not receive a beta-blocker within 24 hours of myocardial infarction should be reevaluated for secondary prevention at a later date. The optimal duration of therapy is unknown; some experts treat for a minimum of 3 years and continue longer for patients with high-risk features at initial presentation (Rosenson 2019).

Immediate release: Oral: Initial: 60 to 120 mg/day in 2 to 3 divided doses; titrate dose based on heart rate and blood pressure as tolerated up to 240 mg/day (BHAT 1982; Hansteen 1982).

Performance anxiety disorder

Performance anxiety disorder (off-label use):

Immediate release: Oral: 10 or 20 mg administered 30 to 60 minutes prior to anxiety-provoking situation; if initial dose is not sufficiently effective, may increase by 10 to 20 mg prior to next anxiety-provoking situation up to a maximum of 60 mg (Hartley 1983; Stein 2019).

Pheochromocytoma

Pheochromocytoma (adjunctive agent):

Note: An alpha-1 blocker must be started several days before propranolol (ES [Lenders 2014]).

Immediate release: Oral: Initial: 10 mg every 6 hours (Young 2019) or 20 mg 3 times daily (ES [Lenders 2014]); begin 3 to 4 days after initiation of an alpha-1 blocker and adjust to goal heart rate up to 120 mg/day in divided doses (ES [Lenders 2014]).

Postural tachycardia syndrome

Postural tachycardia syndrome (off-label use):

Immediate release: Oral: Initial: 10 mg twice daily; may titrate based on response and tolerability to a maximum of 20 mg twice daily (Arnold 2013; Moon 2018; Raj 2009).

Supraventricular tachycardia

Supraventricular tachycardia (eg, atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia, focal atrial tachycardia):

Acute treatment (alternative agent) (off-label dose):

IV: Initial: 1 mg over 1 minute; repeat as needed every 2 minutes up to 3 doses.

Note: Initiate cautiously in patients with heart failure. Avoid in patients with decompensated heart failure; electrical cardioversion preferred (ACC/AHA/HRS [Page 2016]).

Maintenance therapy (off-label use):

Immediate release: Oral: Initial: 30 to 60 mg/day in 2 or 3 divided doses titrated to effect; maximum recommended dose: 160 mg/day (ACC/AHA/HRS [Page 2016]).

Thyroid storm

Thyroid storm (off-label use):

Immediate release: Oral: Initial: 60 to 80 mg every 4 to 6 hours adjusted for heart rate and blood pressure (ATA [Ross 2016]; Ross 2021).

IV: 0.5 to 1 mg administered over 10 minutes while under continuous cardiac monitoring; a repeat dose of 1 to 3 mg over 10 to 15 minutes may be given every few hours as needed until oral therapy can be initiated and takes effect (Braverman 2013; Ross 2021).

Thyrotoxicosis

Thyrotoxicosis (alternative agent) (off-label use):

Note: For control of cardiovascular effects until euthyroidism established.

Oral: Initial: 30 to 160 mg/day (may choose an IR or ER formulation) adjusted for heart rate and blood pressure (ATA [Ross 2016]).

Tremor, lithium-induced, moderate to severe

Tremor, lithium-induced, moderate to severe (off-label use):

Immediate release: Oral: Initial: 10 mg 3 to 4 times daily; if needed, titrate dose based on response and tolerability up to 80 mg/day (Gelenberg 1995; Kirk 1973; Lapierre 1976).

Variceal hemorrhage prophylaxis

Variceal hemorrhage prophylaxis (off-label use):

Immediate release: Oral: Initial: 10 to 20 mg twice daily; titrate according to resting heart rate (target 55 to 60 beats per minute), while maintaining blood pressure (eg, systolic blood pressure ≥90 mm Hg) (AASLD [Garcia-Tsao 2017]; Bañares 2002; Sanyal 2019a; Sanyal 2019b).

Maximal daily dose:

No ascites: 320 mg/day (AASLD [Garcia-Tsao 2017]).

Ascites: 160 mg/day (AASLD [Garcia-Tsao 2017]).

Ventricular arrhythmias

Ventricular arrhythmias:

Ventricular tachycardia, hemodynamically stable:

Acute ventricular tachycardia (incessant ventricular tachycardia or electrical storm) (adjunctive agent):

Note: Beta-blockers are generally administered in addition to an IV antiarrhythmic drug (eg, amiodarone), and some experts prefer propranolol over other beta-blockers in this setting (Chatzidou 2018; Passman 2020). A beta-blocker may also be used to reduce shocks in patients with an implantable cardioverter defibrillator (AHA/ACC/HRS [Al-Khatib 2018]).

IV: 1 to 3 mg every 5 minutes up to a total of 5 mg in combination with an IV antiarrhythmic (AHA/ACC/HRS [Al-Khatib 2018]).

Immediate release: Oral: 40 mg every 6 hours in combination with an IV antiarrhythmic (Chatzidou 2018); additional IV doses may be given for breakthrough ventricular arrhythmias (Passman 2020).

Prevention of ventricular tachycardia:

Immediate release: Oral: Initial: 10 to 40 mg every 6 hours; adjust dose as needed based on response and tolerability (AHA/ACC/HRS [Al-Khatib 2018]; Chatzidou 2018; Nademanee 2000).

Nonsustained ventricular tachycardia or ventricular premature beats, symptomatic:

Immediate release: Oral: Initial: 10 to 40 mg every 6 hours; adjust dose as needed based on patient response and tolerability (AHA/ACC/HRS [Al-Khatib 2018]). Some experts recommend initiating 10 mg every 8 to 12 hours; then titrate based on response and tolerability to the lowest effective dose that alleviates symptoms; maximum dose: 320 mg/day (Manolis 2019).

Extended release: Oral: Initial: 80 mg once daily; then titrate based on response and tolerability to the lowest effective dose that alleviates symptoms; maximum dose: 320 mg/day (Manolis 2019).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling. However, renal impairment increases systemic exposure to propranolol. Use with caution.

Not dialyzable (0% to 5%); supplemental dose is not necessary.

Peritoneal dialysis effects: Supplemental dose is not necessary.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling. However, hepatic impairment increases systemic exposure to propranolol. Use with caution.

Dosing: Pediatric

(For additional information see "Propranolol: Pediatric drug information")

Note: Dosage should be individualized based on patient response.

Essential tremor: Limited data available: Children and Adolescents: Oral: Immediate-release formulations: Initial: 0.5 to 1 mg/kg/day in 3 divided doses; maximum daily dose: 4 mg/kg/day (Ferrara 2009).

Hemangioma, infantile; proliferating:

In-person evaluation:

Hemangeol: Infants ≥5 weeks and ≥2 kg: Note: Therapy should be initiated at age 5 weeks to 5 months: Oral: Initial dose: 0.6 mg/kg/dose twice daily for 1 week, then increase dose to 1.1 mg/kg/dose twice daily for 1 week, and then increase to a maintenance dose of 1.7 mg/kg/dose twice daily for 6 months; doses should be separated by at least 9 hours; readjust dose for patient growth. May repeat course if hemangiomas recur.

Immediate-release formulations: Limited data available: Infants and Children <5 years: Oral: Initial: 1 mg/kg/day in 2 or 3 divided doses, increase by 1 mg/kg/day at weekly intervals to maintenance dose; usual daily maintenance dose: 1 to 3 mg/kg/day in 2 or 3 divided doses; optimal duration not defined, duration ranged from 3 to 12 months; discontinuation of therapy may be gradually tapered over 1 to 3 weeks to prevent rebound sinus tachycardia (Darrow 2015; Hogeling 2011; Léauté-Labrèze 2015).

Telemedicine evaluation: Hemangeol, immediate-release formulations: Limited data available: Infants >5 weeks: Oral: Initial: 0.5 mg/kg/day in 2 divided doses; may increase by 0.5 mg/kg/day every 3 to 4 days as tolerated to a target dose of 2 to 3 mg/kg/day in 2 divided doses (Frieden 2020).

Hypertension: Note: Beta-blockers are not recommended as initial antihypertensive agents in children (AAP [Flynn 2017). Children and Adolescents ≤17 years: Immediate-release formulations: Oral: Initial: 1 to 2 mg/kg/day divided in 2 to 3 doses/day; titrate dose to effect; maximum daily dose: 4 mg/kg/day up to 640 mg/day; sustained-release formulation may be dosed once daily (NHBPEP 2004; NHLBI 2012). Others have suggested a higher maximum daily dose of 16 mg/kg/day up to 640 mg/day (Flynn 2006; Kavey 2010).

Migraine headache; prophylaxis: Limited data available; efficacy results variable; optimal dose not established: Oral: Immediate-release formulations:

Weight-directed dosing: Children ≥3 years and Adolescents: Reported range: 0.5 to 3 mg/kg/day in 2 to 3 divided doses; some trials initiated therapy at the low end of the range and titrated upward to response; doses as low as 0.5 to 1 mg/kg/day may be effective; doses up to 4 mg/kg/day have been used; maximum daily dose: 120 mg/day (AAN [Lewis 2004]; Ashrafi 2005; Bonfert 2013; Eidlitz-Markus 2012; El-Chammas 2013; Lanteri-Minet 2014).

Fixed dose: Children ≥7 years and Adolescents: Initial: 10 mg daily; increase at weekly intervals in 10 mg increments; usual dose range: 10 to 20 mg 3 times daily (Kliegman 2016); doses as high as 120 mg daily have been used (AAN [Lewis 2004]).

Tachyarrhythmias: Limited data available: Infants, Children, and Adolescents:

Oral: Immediate-release formulations: Initial: 0.5 to 1 mg/kg/day in divided doses every 6 to 8 hours; titrate dosage upward every 3 to 5 days; usual daily dose: 2 to 4 mg/kg/day; higher doses may be needed; maximum daily dose: 16 mg/kg/day or 60 mg/day (Kliegman 2016; Park 2014).

IV: 0.01 to 0.15 mg/kg/dose slow IV over 10 minutes; may repeat every 6 to 8 hours as needed; maximum dose is age-dependent: Infants: 1 mg/dose; children and adolescents: 3 mg/dose (Kliegman 2016; Park 2014).

Tetralogy spells:

Oral: Immediate-release formulations: Palliative therapy: Infants and Children: 0.5 to 1 mg/kg/dose every 6 hours (Kliegman 2016). Others have used the following: Initial: 0.25 mg/kg/dose every 6 hours (1 mg/kg/day); if ineffective within first week of therapy, may increase by 1 mg/kg/day every 24 hours to maximum of 5 mg/kg/day; if patient becomes refractory may increase slowly to a maximum of 10 to 15 mg/kg/day but must carefully monitor heart rate, heart size, and cardiac contractility; average dose: 2.3 mg/kg/day; range: 0.8 to 5 mg/kg/day (Garson 1981).

IV: Infants and Children: 0.15 to 0.25 mg/kg/dose infused over 10 minutes; maximum initial dose: 1 mg; may repeat dose once (AAP [Hegenbarth 2008]); alternatively, initiate lower doses of 0.015 to 0.02 mg/kg/dose and titrate to effect, up to 0.1 to 0.2 mg/kg/dose (Anderson 2009).

Thyrotoxicosis: Limited data available:

Infants and Children: Oral: Immediate-release formulations: 0.5 to 2 mg/kg/day divided every 8 hours; maximum dose: 40 mg/dose (Kliegman 2016).

Adolescents: Oral: Immediate-release formulations: 10 to 40 mg every 6 to 8 hours (ATA [Ross 2016]).

Thyroid storm: Limited data available:

Infants and Children: Oral: Immediate-release formulations: 1 to 4 mg/kg/day in divided doses, titrate based on blood pressure and heart rate (Cameron 2012; Fuhrman 2011); usual frequency in adolescents and adults is every 4 to 6 hours (ATA [Ross 2016]; Kleigman 2016).

Adolescents:

Oral: Immediate-release formulations: 20 to 40 mg every 4 to 6 hours (Kliegman 2016); titrate based on blood pressure and heart rate; doses as high as 60 to 80 mg every 4 hours have been recommended (ATA [Ross 2016]).

IV: 0.5 to 1 mg slow IV push over 10 minutes (Braverman 2013; Kliegman 2016). Dosing interval in adolescents is not defined; in adults, doses may be repeated every several hours with continuous cardiac monitoring; when transitioning to oral therapy, IV therapy may need to be continued until the effects of oral therapy are achieved (Braverman 2013).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Not dialyzable (0% to 5%). There are no dosage adjustments provided in the manufacturer's labeling; however, renal impairment increases systemic exposure to propranolol. Use with caution.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; however, hepatic impairment increases systemic exposure to propranolol. Use with caution.

Dosing: Older Adult

IV: Use caution; initiate at lower end of the dosing range.

Oral:

Hypertension: Consider lower initial doses and titrate to response (Aronow 2011).

Cardiac arrhythmias, maintenance or prevention: Immediate release: Oral: Initial: 10 mg twice daily; increase dosage every 3 to 7 days; usual dose range: 10 to 320 mg/day given in divided doses.

Refer to adult dosing for additional uses.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule Extended Release 24 Hour, Oral, as hydrochloride:

Inderal LA: 60 mg, 80 mg, 120 mg, 160 mg [contains brilliant blue fcf (fd&c blue #1)]

Inderal XL: 80 mg, 120 mg

InnoPran XL: 80 mg, 120 mg

Generic: 60 mg, 80 mg, 120 mg, 160 mg

Solution, Intravenous, as hydrochloride:

Generic: 1 mg/mL (1 mL)

Solution, Oral, as hydrochloride:

Hemangeol: 4.28 mg/mL (120 mL) [alcohol free, paraben free, sugar free; contains saccharin sodium]

Generic: 20 mg/5 mL (5 mL, 500 mL); 40 mg/5 mL (500 mL)

Tablet, Oral, as hydrochloride:

Generic: 10 mg, 20 mg, 40 mg, 60 mg, 80 mg

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule Extended Release 24 Hour, Oral, as hydrochloride:

Inderal LA: 60 mg, 80 mg, 120 mg, 160 mg [contains brilliant blue fcf (fd&c blue #1)]

Solution, Intravenous, as hydrochloride:

Generic: 1 mg/mL (1 mL)

Solution, Oral, as hydrochloride:

Generic: 4.28 mg/mL (120 mL)

Tablet, Oral:

Generic: 120 mg

Tablet, Oral, as hydrochloride:

Generic: 10 mg, 20 mg, 40 mg, 80 mg

Prescribing and Access Restrictions

Prescriptions for Hemangeol may be obtained via the Hemangeol Patient Access program. Visit http://www.hemangeol.com/hcp/hemangeol-direct/ or call 855-618-4950 for ordering information.

Administration: Adult

IV: IV dose is much smaller than oral dose. When administered acutely for cardiac treatment, monitor ECG and blood pressure. May administer by rapid infusion (IV push) at a rate of 1 mg/minute or by slow infusion over ~30 minutes. Necessary monitoring for surgical patients who are unable to take oral beta-blockers (prolonged ileus) has not been defined. Some institutions require monitoring of baseline and postinfusion heart rate and blood pressure when a patient's response to beta-blockade has not been characterized (ie, the patient's initial dose or following a change in dose). Consult individual institutional policies and procedures.

Oral: Tablets (immediate release) should be taken on an empty stomach; capsules (extended release) may be taken with or without food, but should always be taken consistently (with food or on an empty stomach). Do not crush long-acting oral forms.

Bariatric surgery: Capsule, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. ER capsules should be swallowed whole. Do not crush or chew. IR tablet, oral solution, and injectable formulations are available. If safety and efficacy can be effectively monitored, no change in formulation or administration is required after bariatric surgery; however, selection of IR formulations or alternative therapy should be strongly considered for cardiovascular and other high-risk labeled and off-label indications for propranolol.

Administration: Pediatric

Oral:

Immediate-release tablets: Take on an empty stomach

Extended-release capsules: Administer consistently either with food or on an empty stomach; do not chew or crush sustained or extended release capsules, swallow whole

Oral solution: Mix concentrated oral solution with water, fruit juice, liquid, or semisolid food before administration.

Hemangeol oral solution: Infants: Administer during or after a feeding to minimize the risk for hypoglycemia; skip the dose if the patient is not eating or is vomiting. Administer doses at least 9 hours apart. Do not shake bottle before use. Administer Hemangeol directly into the child's mouth using the supplied oral dosing syringe; if needed, dose may be diluted with a small quantity of milk or fruit juice and administered in a baby's bottle.

Parenteral: Note: IV dose is much smaller than oral dose. When administered acutely for cardiac treatment, monitor ECG and blood pressure; consult individual institutional policies and procedures.

Neonates, Infants, Children, and Adolescents: Administer undiluted by slow IV injection/infusion over 10 minutes (AAP [Hegenbarth 2008])

Use: Labeled Indications

Angina, chronic stable: To decrease angina frequency and increase exercise tolerance in patients with angina pectoris.

Cardiac arrhythmias: Control of supraventricular arrhythmias (eg, atrial fibrillation and flutter, atrioventricular nodal reentrant tachycardia) and ventricular tachycardias (eg, catecholamine-induced arrhythmias, digoxin toxicity).

Essential tremor: Management of familial or hereditary essential tremor.

Hypertension: Management of hypertension. Note: Beta-blockers are not recommended as first-line therapy (ACC/AHA [Whelton 2018]).

Hypertrophic cardiomyopathy with left ventricular outflow tract obstruction: Symptomatic treatment of hypertrophic cardiomyopathy with left ventricular outflow tract obstruction..

Migraine headache prophylaxis: Prophylaxis of common migraine headache.

Myocardial infarction, early treatment and secondary prevention: To reduce cardiovascular mortality in patients who have survived the acute phase of myocardial infarction and are clinically stable.

Pheochromocytoma: As an adjunct to alpha-adrenergic blockade to control blood pressure and reduce symptoms of catecholamine-secreting tumors.

Proliferating infantile hemangioma (Hemangeol): Treatment of proliferating infantile hemangioma requiring systemic therapy.

Use: Off-Label: Adult

Akathisia, antipsychotic-induced; Performance anxiety disorder; Postural tachycardia syndrome; Thyroid storm; Thyrotoxicosis; Tremor, lithium-induced, moderate to severe; Variceal hemorrhage prophylaxis

Medication Safety Issues
Sound-alike/look-alike issues:

Propranolol may be confused with prasugrel, Pravachol, Propulsid.

Inderal may be confused with Adderall, Enduron, Imdur, Imuran, Inderide, Isordil, Toradol.

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication (IV formulation) among its list of drugs which have a heightened risk of causing significant patient harm when used in error.

Administration issues:

Significant differences exist between oral and IV dosing. Use caution when converting from one route of administration to another.

International issues:

Deralin [Australia, Israel] may be confused with Deptran brand name for doxepin [Australia].

Inderal [Canada and multiple international markets], Inderal LA [US], and Inderal XL [US] may be confused with Indiaral brand name for loperamide [France] or Indamol brand name for indapamide [Italy].

Adverse Reactions (Significant): Considerations
Bradyarrhythmias

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, propranolol) due to their partial agonist effects (Ref). In most cases (up to 72%), AV block will resolve with dose reduction or 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 conduction 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)

Bronchospasm

Nonselective beta-blockers (eg, propranolol) have a higher risk of bronchospasm compared to cardioselective beta-blockers (Ref) and may lead to drug discontinuation in patients with chronic obstructive pulmonary disease (COPD) or asthma (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 (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: Varied; reports after one dose (Ref). In another study with carvedilol-induced bronchospasm, the onset appeared to be slightly longer (Ref).

Risk factors:

• Reactive airway disease (asthma) (study with carvedilol-induced bronchospasm) (Ref)

• Nonselective beta-blockers (Ref)

• Patients with asthma who possess 1 or 2 copies of arginine-16 beta-2 receptor polymorphism (Ref)

• Acute use (Ref)

CNS effects

Beta-blockers may cause reversible CNS effects such as fatigue, insomnia, vivid dreams, memory impairment, and sexual disorder (Ref). Depression has been 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 propranolol, which is highly 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)

Potentiation/masking of hypoglycemia

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 non-selective or selective beta blockers are more likely to cause hypoglycemia; data are conflicting (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; blood glucose recovery was significantly reduced after 1 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)

• Patients who are hospitalized and not requiring basal insulin (Ref)

Withdrawal

Beta-blocker therapy should not be withdrawn abruptly, but gradually tapered to avoid acute tachycardia, hypertension, and/or ischemia (Ref). Beta-blocker withdrawal (propranolol withdrawal syndrome), characterized by the development of severe exacerbation of angina pectoris, ventricular arrhythmias, and acute myocardial infarction (MI) has been reported following abrupt withdrawal of beta-blocker therapy (Ref). One study did not find changes in infarct size and left ventricular function when beta-blocker was abruptly withdrawn in patients with MI (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. 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)

• Propranolol doses >120 mg per day (Ref)

• Past medical history of hypertension (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Nervous system: Sleep disorder (infants: 16% to 18%)

Respiratory: Bronchiolitis (infants), bronchitis (infants: 8% to 13%)

1% to 10%:

Cardiovascular: Cold extremity (infants: 7% to 8%)

Gastrointestinal: Abdominal pain (infants: 4%), constipation (1% to 3%), decreased appetite (infants: 3% to 4%), diarrhea (infants: 5% to 6%)

Nervous system: Agitation (infants: 5% to 9%), dizziness (4% to 7%), drowsiness (infants: 5%), fatigue (5% to 7%), irritability (infants: 6%), nightmares (infants: 6%)

<1%:

Cardiovascular: Second degree atrioventricular block (including infants and patients with an underlying conduction disorder) (Zeltser 2004)

Dermatologic: Alopecia (Hilder 1979), urticaria (Léauté-Labrèze 2016)

Postmarketing:

Cardiovascular: Acute myocardial infarction (with drug withdrawal) (Fonarow 2008; Psaty 1990), arterial insufficiency, arterial mesenteric thrombosis (Köksal 2005), bradycardia (Clark 1989, Frishman 1988, Léauté-Labrèze 2016), cardiac failure (Conway 1968, Frishman 1988, Léauté-Labrèze 2016), complete atrioventricular block (Zeltser 2004), exacerbation of angina pectoris (with drug withdrawal) (Fonarow 2008, Psaty 1990), first degree atrioventricular block (López-Sendón 2004), hypertension (with drug withdrawal) (Lederballe Pederson 1979, Rangno 1982, Shand 1978), hypotension (Ashikaga 2000, de Graaf 2011, Frishman 1988), peripheral arterial disease (exacerbation), Raynaud's disease (Frishman 1988, Marshall 1976), tachycardia (with drug withdrawal) (Lederballe Pederson 1979, Rangno 1982, Shand 1978)

Dermatologic: Dermal ulcer, dermatitis (Léauté-Labrèze 2016), erythema multiforme, exfoliative dermatitis, psoriasiform eruption (Kim 2010), Stevens-Johnson syndrome (Mukul 1989), toxic epidermal necrolysis

Endocrine & metabolic: Hypoglycemia (higher risk in infants) (Holland 2010, Leaute-Labrexe 2016), increased serum potassium (Al-Rwebah 2020, Mandić 2014)

Gastrointestinal: Abdominal cramps, epigastric discomfort (Frishman 1988), ischemic colitis, nausea (Frishman 1988), sore throat, vomiting

Genitourinary: Peyronie's disease (Sommer 2002), sexual disorder (Ko 2002)

Hematologic & oncologic: Agranulocytosis (Frishman 1988), immune thrombocytopenia, nonthrombocytopenic purpura (Frishman 1988), purpuric rash

Hepatic: Increased serum alkaline phosphatase (Léauté-Labrèze 2016; Wilkinson 1971), increased serum transaminases (Léauté-Labrèze 2016, Wilkinson 1971)

Hypersensitivity: Anaphylaxis (Jacobs 1981), nonimmune anaphylaxis (Greenberger 1987)

Nervous system: Depression (Ko 2002), emotional lability, generalized ache or pain, hallucination (Frishman 1988), insomnia (Frishman 1988), lassitude, memory impairment, tingling of extremities (hands), vivid dream (Frishman 1988), withdrawal syndrome (Shand 1978)

Neuromuscular & skeletal: Asthenia (Léauté-Labrèze 2016), laryngospasm, lupus-like syndrome (Hughes 1982), myopathy, myotonia

Ophthalmic: Oculomucocutaneous syndrome (involving the skin) (Frishman 1988), visual disturbance (Frishman 1988), xerophthalmia

Respiratory: Bronchospasm (Kotlyar 2002), dyspnea (Léauté-Labrèze 2016), pharyngitis, respiratory distress (Léauté-Labrèze 2016)

Miscellaneous: Fever (Frishman 1988)

Contraindications

Hypersensitivity to propranolol, beta-blockers, or any component of the formulation; uncompensated heart failure (unless the failure is due to tachyarrhythmias being treated with propranolol); cardiogenic shock; severe sinus bradycardia; sick sinus syndrome; or heart block greater than first-degree (except in patients with a functioning artificial pacemaker); bronchial asthma.

Hemangeol (additional contraindications): Premature infants with corrected age <5 weeks; infants weighing <2 kg; heart rate <80 bpm; BP <50/30 mm Hg; pheochromocytoma; history of bronchospasm.

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.

Canadian labeling: Additional contraindications (not in US labeling): Bronchospasm; right ventricular failure secondary to pulmonary hypertension; allergic rhinitis during pollen season; patients prone to hypoglycemia; hypotension (BP parameters not specified in labeling); metabolic acidosis; vasospastic angina (also referred to as Prinzmetal angina or variant angina); severe peripheral arterial circulatory disturbance; untreated pheochromocytoma; hereditary problems of galactose intolerance, glucose-galactose malabsorption, or Lapp lactase deficiency (lactose-containing products only).

Hemangiol (additional contraindications): Infants weighing <2.5 kg; breastfed infants if mother is treated with medicines contraindicated with propranolol; heart rate <100 bpm or BP <65/45 mm Hg (<3 months of age), heart rate <90 bpm or BP <70/50 mm Hg (3 to <6 months of age), heart rate <80 bpm or BP <80/55 mm Hg (6 to 12 months of age).

Warnings/Precautions

Concerns related to adverse events:

• Anaphylactic reactions: Use caution with history of severe anaphylaxis to allergens; patients taking beta-blockers may become more sensitive to repeated challenges. Treatment of anaphylaxis (eg, epinephrine) in patients taking beta-blockers may be ineffective or promote undesirable effects.

Disease-related concerns:

• Bronchospastic disease: In general, patients with bronchospastic disease should not receive beta-blockers; if used at all, should be used cautiously with close monitoring.

• Conduction abnormality: Consider pre-existing conditions such as sick sinus syndrome before initiating.

• Diabetes: Use with caution in patients with diabetes mellitus; may potentiate hypoglycemia and/or mask signs and symptoms.

• Heart failure: Use with caution in patients with compensated heart failure and monitor for a worsening of the condition (efficacy of propranolol in heart failure has not been demonstrated).

• 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 and Raynaud disease: Can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease 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; may have increased side effects.

• Thyroid disease: May mask signs of hyperthyroidism (eg, tachycardia). If thyrotoxicosis is suspected, carefully manage and monitor; abrupt withdrawal may exacerbate symptoms of hyperthyroidism or precipitate thyroid storm. Alterations in thyroid function tests may be observed.

• Vasospastic angina: Beta-blockers without alpha-1 adrenergic receptor blocking activity should be avoided in patients with vasospastic angina since unopposed alpha-1 adrenergic receptors mediate coronary vasoconstriction and can worsen anginal symptoms (Mayer 1998).

Special populations:

• Infants and children: Considerations when treating infantile hemangioma:

- Cardiovascular concerns: Bradycardia and/or hypotension may occur or be worsened; monitor heart rate and blood pressure after propranolol initiation or increase in dose; discontinue treatment if severe (<80 bpm) or symptomatic bradycardia or hypotension (systolic blood pressure <50 mm Hg) occurs. Infants with large facial infantile hemangioma should be investigated for potential arteriopathy associated with PHACE syndrome prior to propranolol therapy; decreases in blood pressure caused by propranolol may increase risk of stroke in PHACE syndrome patients with cerebrovascular anomalies.

- Hypoglycemia: May potentiate hypoglycemia and/or mask signs and symptoms. Administer during or after a feeding to minimize the risk for hypoglycemia. Withhold the dose in infants or children who are not feeding regularly or who are vomiting; discontinue therapy and seek immediate treatment if hypoglycemia occurs.

- Respiratory concerns: May cause bronchospasm. Interrupt therapy in infants or children with lower respiratory tract infection associated with dyspnea or wheezing.

• Elderly: Bradycardia may be observed more frequently in elderly patients (>65 years of age); dosage reductions may be necessary.

• Smokers: Cigarette smoking may decrease plasma levels of propranolol by increasing metabolism. Patients should be advised to avoid smoking.

Other warnings/precautions:

• Abrupt withdrawal: Beta-blocker therapy should not be withdrawn abruptly (particularly in patients with coronary artery disease), but gradually tapered to avoid acute tachycardia, hypertension, and/or ischemia. Severe exacerbation of angina, ventricular arrhythmias, and myocardial infarction have been reported following abrupt withdrawal of beta-blocker therapy. Temporary but prompt resumption of beta-blocker therapy may be indicated with worsening of angina or acute coronary insufficiency.

• Major surgery: Chronic beta-blocker therapy should not be routinely withdrawn prior to major surgery.

Metabolism/Transport Effects

Substrate of CYP1A2 (major), CYP2C19 (minor), CYP2D6 (major), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP1A2 (weak)

Drug Interactions

Acetylcholinesterase Inhibitors: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy

Ajmaline: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Alcohol (Ethyl): May decrease the serum concentration of Propranolol. Alcohol (Ethyl) may increase the serum concentration of Propranolol. 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

Artemether and Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). 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 (Nonselective) may diminish the bronchodilatory effect of Beta2-Agonists. Risk X: Avoid combination

Bile Acid Sequestrants: May decrease the serum concentration of Propranolol. 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

Broccoli: May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). 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

Cannabis: May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). 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

CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy

CYP1A2 Inducers (Moderate): May decrease the serum concentration of Propranolol. Risk C: Monitor therapy

CYP1A2 Inhibitors (Moderate): May increase the serum concentration of Propranolol. Risk C: Monitor therapy

CYP1A2 Inhibitors (Strong): May increase the serum concentration of Propranolol. Management: Use a lower initial propranolol dose and be more cautious during propranolol dose titration when combined with strong CYP1A2 inhibitors. Risk D: Consider therapy modification

CYP2D6 Inhibitors (Moderate): May increase the serum concentration of Propranolol. Risk C: Monitor therapy

CYP2D6 Inhibitors (Strong): May increase the serum concentration of Propranolol. 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

Doxofylline: Propranolol may increase the serum concentration of Doxofylline. 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 (Nonselective) may enhance the hypertensive effect of EPINEPHrine (Nasal). Risk C: Monitor therapy

EPINEPHrine (Oral Inhalation): Beta-Blockers (Nonselective) may enhance the hypertensive effect of EPINEPHrine (Oral Inhalation). Risk C: Monitor therapy

Epinephrine (Racemic): Beta-Blockers (Nonselective) may enhance the hypertensive effect of Epinephrine (Racemic). Risk C: Monitor therapy

EPINEPHrine (Systemic): Beta-Blockers (Nonselective) may enhance the hypertensive 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

Lacidipine: May enhance the hypotensive effect of Propranolol. Lacidipine may increase the serum concentration of Propranolol. Propranolol may decrease the serum concentration of Lacidipine. Risk C: Monitor therapy

Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Risk C: Monitor therapy

Lasmiditan: May enhance the bradycardic effect of Propranolol. Lasmiditan may diminish the therapeutic effect of Propranolol. Specifically, blood pressure may increase during coadministration. 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

Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). 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: Propranolol may increase the serum concentration of Propafenone. Propafenone may increase the serum concentration of Propranolol. 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

QuiNIDine: May increase the serum concentration of Propranolol. Risk C: Monitor therapy

Reserpine: May enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy

RifAMPin: May decrease the serum concentration of Propranolol. Risk C: Monitor therapy

Rifapentine: May decrease the serum concentration of Propranolol. Risk C: Monitor therapy

Rivastigmine: May enhance the bradycardic effect of Beta-Blockers. Risk X: Avoid combination

Rizatriptan: Propranolol may increase the serum concentration of Rizatriptan. Management: For adults, limit rizatriptan dose to 5 mg (maximum of 3 doses per 24 hours). For pediatric patients, if weight is 40 kg or more, limit rizatriptan to a single 5 mg dose per 24 hours; do not combine if weight is less than 40 kg. Risk D: Consider therapy modification

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 (Nonselective) may diminish the bronchodilatory effect of Theophylline Derivatives. Risk C: Monitor therapy

Theophylline Derivatives: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy

Thioridazine: Propranolol may increase the serum concentration of Thioridazine. Thioridazine may increase the serum concentration of Propranolol. Risk X: Avoid combination

TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use is necessary, initiate tizanidine at an adult dose of 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Risk D: Consider therapy modification

Tobacco (Smoked): May decrease the serum concentration of Propranolol. 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

Zileuton: May increase the serum concentration of Propranolol. Risk C: Monitor therapy

Food Interactions

Ethanol: Ethanol may increase or decrease plasma levels of propranolol. Reports are variable and have shown both enhanced as well as inhibited hepatic metabolism (of propranolol). Management: Caution advised with consumption of ethanol and monitor for heart rate and/or blood pressure changes.

Food: Propranolol serum levels may be increased if taken with food. Protein-rich foods may increase bioavailability; a change in diet from high carbohydrate/low protein to low carbohydrate/high protein may result in increased oral clearance. Management: Tablets (immediate release) should be taken on an empty stomach. Capsules (extended release) may be taken with or without food, but be consistent with regard to food.

Reproductive Considerations

In general, preventive treatment for migraine in patients trying to become pregnant should be avoided; treatment should be individualized considering the available safety data and needs of the patient should pregnancy occur (AHS [Ailani 2021]).

Erectile dysfunction and male impotence are noted in product labeling following use of propranolol. As a class, outcomes from available studies evaluating beta-blockers and sexual dysfunction are inconsistent, and the negative effects on erectile function and libido are considered controversial. A clear relationship between use of beta-blockers and erectile dysfunction has not been established. Hypertension itself is associated with erectile dysfunction. Patients on a beta-blocker presenting with sexual dysfunction should be evaluated for underlying disease (Farmakis 2021; Levine 2012; Semet 2017; Terentes-Printzios 2022; Viigimaa 2020).

Pregnancy Considerations

Propranolol crosses the placenta.

Exposure to beta-blockers during the third trimester of pregnancy may increase the risk for bradycardia, hypoglycemia, hypotension, and respiratory depression in the neonate. Newborns should be monitored and managed accordingly. 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).

The pharmacokinetics of propranolol are not significantly changed by pregnancy (Livingstone 1983; O'Hare 1984; Rubin 1987; Smith 1983).

When treatment of chronic hypertension in pregnancy is indicated, agents other than propranolol are preferred (ACOG 203 2019; ESC [Regitz-Zagrosek 2018]); however, use of propranolol may be considered (Magee 2014). Patients with preexisting hypertension may continue their medication during pregnancy unless contraindications exist (ESC [Regitz-Zagrosek 2018]).

Propranolol may be used for the treatment of maternal ventricular arrhythmias, atrial fibrillation/atrial flutter, or supraventricular tachycardia during pregnancy; consult current guidelines for specific recommendations (ACC/AHA/HRS [Page 2016]; ESC [Regitz-Zagrosek 2018]).

Propranolol is recommended for use in controlling hypermetabolic symptoms of thyrotoxicosis in pregnancy (ATA [Alexander 2017]).

In general, preventive treatment for migraine in pregnant patients should be avoided; treatment during pregnancy should be individualized considering the available safety data, the potential for adverse maternal and fetal events, and the needs of the patient (AHS [Ailani 2021]). Based on available data, propranolol may be used if prophylaxis of migraine is needed in pregnant patients; it should be discontinued 2 to 3 days prior to delivery to decrease the risk of adverse events to the fetus/neonate and potential reductions in uterine contraction (Pringsheim 2012).

Breastfeeding Considerations

Propranolol and its inactive metabolites are present in breast milk (Smith 1983).

Information related to the presence of propranolol in breast milk is available from 3 lactating patients 1-week postpartum receiving propranolol for hypertension. Breast milk was sampled ~3, 4, 6, and 8 hours after the maternal dose. The first 2 patients received propranolol 1.2 mg/kg/day and the third received propranolol 2.6 mg/kg/day. The highest propranolol milk concentration was 74.9 ng/mL observed in the first patient ~3 hours after the dose. The lowest propranolol milk concentration was 13.5 ng/mL in the second patient, observed ~8 hours after the dose. The overall half-life of propranolol in breast milk was 6.5 ± 3.4 hours. In comparison, the overall half-life in the maternal plasma was 2.6 ± 1.2 hours (Smith 1983). Peak milk concentrations are reported to occur between 2 to 3 hours after an oral dose (Bauer 1979).

Bradycardia was reported in an infant exposed to propranolol via breast milk (Soussan 2014).

In general, preventive treatment for migraine in lactating patients should be avoided; treatment should be individualized considering the available safety data and needs of the patient (AHS [Ailani 2021]). Based on available data, propranolol may be used if prophylaxis of migraine is needed in lactating patients (Pringsheim 2012).

When used for hypertension, propranolol is compatible for use in patients who are breastfeeding (ESC [Cífková 2020]).

In general, propranolol may be compatible with breastfeeding when used at usual doses. Breastfeeding infants should be monitored for bradycardia, cyanosis, and hypoglycemia (WHO 2002).

Dietary Considerations

Tablets (immediate release) should be taken on an empty stomach; capsules (extended release) may be taken with or without food, but should always be taken consistently (with food or on an empty stomach). Hemangeol should be administered during or right after a feeding to reduce the risk of hypoglycemia; skip dose if child is not eating or is vomiting.

Monitoring Parameters

Acute cardiac treatment: Monitor ECG, heart rate, and blood pressure with IV administration; heart rate and blood pressure with oral administration.

Consult individual institutional policies and procedures.

Hypertension: Blood pressure, heart rate, serum glucose regularly (in patients with diabetes).

The 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults (ACC/AHA [Whelton 2018]):

Confirmed hypertension and known CVD or 10-year ASCVD risk ≥10%: Target blood pressure <130/80 mm Hg is recommended.

Confirmed hypertension without markers of increased ASCVD risk: Target blood pressure <130/80 mm Hg may be reasonable.

Proliferating infantile hemangioma (Hemangeol): Monitor heart rate and blood pressure for 2 hours after initiation or dose increases.

Mechanism of Action

Nonselective beta-adrenergic blocker (class II antiarrhythmic); competitively blocks response to beta1- and beta2-adrenergic stimulation which results in decreases in heart rate, myocardial contractility, blood pressure, and myocardial oxygen demand. Nonselective beta-adrenergic blockers (propranolol, nadolol) reduce portal pressure by producing splanchnic vasoconstriction (beta2 effect) thereby reducing portal blood flow.

Pharmacokinetics

Onset of action: Beta-blockade: Oral: 1 to 2 hours; IV: ≤5 minutes; Peak effect: Hypertension: A few days to several weeks.

Duration: Immediate release: 6 to 12 hours; Extended-release formulations: ~24 to 27 hours.

Absorption: Oral: Rapid and complete.

Distribution: Vd: 4 L/kg (adults); crosses the blood-brain barrier.

Protein binding: Newborns: 68%; Adults: ~90% (S-isomer primarily to alpha-1 acid glycoprotein; R-isomer primarily to albumin).

Metabolism: Extensive first-pass effect, hepatically metabolized to active and inactive compounds; the 3 main metabolic pathways include: Aromatic hydroxylation (primarily 4-hydroxylation), N-dealkylation followed by further side-chain oxidation and direct glucuronidation; the 4 primary metabolites include: Propranolol glucuronide, naphthyloxylactic acid, and sulfate and glucuronic acid conjugates of 4-hydroxy propranolol; Note: Aromatic hydroxylation is catalyzed primarily by isoenzyme CYP2D6; side chain oxidation is mainly via CYP1A2, but also CYP2D6; 4-hydroxypropranolol possesses beta-adrenergic receptor blocking activity and is a weak inhibitor of CYP2D6.

Bioavailability: ~25% reaches systemic circulation due to high first-pass metabolism; oral bioavailability may be increased in Down syndrome children; protein-rich foods increase bioavailability by ~50%.

Half-life elimination: Neonates: Possible increased half-life; Infants (35 to 150 days of age): Median 3.5 hours; Children: 3.9 to 6.4 hours; Adults: Immediate release formulation: 3 to 6 hours; Extended-release formulations: 8 to 10 hours.

Time to peak: Immediate release: Adults: 1 to 4 hours; Infants: ≤2 hours (Hemangeol); Extended release capsule (Inderal XL, InnoPran XL): 12 to 14 hours; Long acting capsule (Inderal LA): 6 hours.

Excretion: Metabolites are excreted primarily in urine (96% to 99%); <1% excreted in urine as unchanged drug.

Pricing: US

Capsule ER 24 Hour Therapy Pack (Inderal LA Oral)

60 mg (per each): $77.01

80 mg (per each): $89.95

120 mg (per each): $101.41

160 mg (per each): $103.41

Capsule ER 24 Hour Therapy Pack (Inderal XL Oral)

80 mg (per each): $88.82

120 mg (per each): $88.82

Capsule ER 24 Hour Therapy Pack (InnoPran XL Oral)

80 mg (per each): $88.82

120 mg (per each): $88.82

Capsule ER 24 Hour Therapy Pack (Propranolol HCl ER Oral)

60 mg (per each): $2.04 - $2.06

80 mg (per each): $2.38 - $2.41

120 mg (per each): $2.98 - $2.99

160 mg (per each): $3.88 - $3.90

Solution (Hemangeol Oral)

4.28 mg/mL (per mL): $5.79

Solution (Propranolol HCl Intravenous)

1 mg/mL (per mL): $9.60 - $12.08

Solution (Propranolol HCl Oral)

20 mg/5 mL (per mL): $0.84

40 mg/5 mL (per mL): $0.19

Tablets (Propranolol HCl Oral)

10 mg (per each): $0.19 - $0.41

20 mg (per each): $0.24 - $1.34

40 mg (per each): $0.31 - $0.72

60 mg (per each): $0.86 - $1.74

80 mg (per each): $0.46 - $0.97

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Adlock (BD);
  • Anaprilan (RU);
  • Anaprilins (LV);
  • Arteflo (LK);
  • Atensin (BF, BJ, CI, ET, GH, GM, GN, JO, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM, ZW);
  • Avlocardyl (FR, VN);
  • Bai Er Luo (CN);
  • Bedranol (AE, BB, BF, BJ, BM, BS, BZ, CH, CI, ET, GH, GM, GN, GY, JM, KE, LB, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, SR, TN, TT, TZ, UG, ZM, ZW);
  • Beta-Prograne (IE);
  • Beta-Timelets (AE, CY, IL, IQ, IR, JO, KW, LB, LY, OM, SA, SY, YE);
  • Betabex (BD);
  • Betalol (TH);
  • Betapress (HK, TH);
  • Betascan (TW);
  • Cardiblok (ZA);
  • Cardilol (AE);
  • Cardinol (NZ);
  • Cardinol LA (NZ);
  • Cardispare (ZA);
  • Cardolol (TW);
  • Ciplar (IN);
  • Colliprol (MX);
  • Corbeta (IN, SG);
  • Coriodal (CL);
  • Deralin (AU, HK, IL);
  • Dideral (TR);
  • Dociton (DE);
  • Duranol (PH);
  • Emforal (MT, TR);
  • Farmadral (ID);
  • Frina (GR);
  • Frixopel (PY);
  • Half Beta-Prograne (IE);
  • Hamangiol (FI, FR);
  • Hemangiol (AU, BE, CH, CZ, DE, DK, ES, HR, IE, JP, KR, NL, NO, RO);
  • Hipranol (MY);
  • Impanol (SG);
  • Indenol (KR);
  • Inderal (AE, AR, AT, AU, BB, BE, BF, BG, BH, BJ, BM, BR, BS, BZ, CH, CI, CO, CY, DK, EC, EG, ET, GH, GM, GN, GR, GY, IE, IQ, IR, IT, JM, JO, JP, KE, KR, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, MY, NE, NG, OM, PE, PH, PK, PT, PY, QA, SA, SC, SD, SE, SG, SI, SL, SN, SR, SY, TN, TT, TW, TZ, UG, UY, VE, VN, YE, ZM, ZW);
  • Inderal LA (AE, BB, BF, BJ, BM, BS, BZ, CI, CY, ET, GH, GM, GN, GY, IQ, IR, JM, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, PE, PT, QA, SA, SC, SD, SL, SN, SR, SY, TN, TT, TZ, UG, YE, ZM, ZW);
  • Inderalici (CR, DO, GT, HN, MX, NI, PA, SV);
  • Indesol (KR);
  • Indever (BD);
  • Indicardin (BF, BH, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM, ZW);
  • Indirin (PH);
  • Inpanol (HK);
  • Kamodyl (FR);
  • Laining (TW);
  • MIDDLEEAST (IL);
  • Normpress (TH);
  • Oposim (AR);
  • Palon (TH);
  • Pranidol (MX);
  • Pranolol (NO);
  • Pranosol (LK);
  • Presin (PY);
  • Presoral (BD);
  • Prestoral (ID);
  • Prolol (EG, IL);
  • Pronol (BD);
  • Propal (DK);
  • Propalem (MX);
  • Propalong (AR);
  • Propayerst (AR);
  • Propra (EE);
  • Propra-Ratiopharm (PL);
  • Propral (FI);
  • Propranolol Eurogenerics (LU);
  • Protolif (EC);
  • Pu Le Xin (CN);
  • Purbloka (ZA);
  • Rebaten LA (BR);
  • Rexigen (ZA, ZW);
  • Slow Deralin (IL);
  • Sumial (ES);
  • Synolol (SG);
  • Syprol (MT);
  • Tenomal (GR);
  • Tepra (KR);
  • Waucoton (GR)


For country abbreviations used in Lexicomp (show table)

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