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Propranolol: Drug information

Copyright 1978-2013 Lexicomp, Inc. All rights reserved. (For additional information see "Propranolol: Patient drug information" and see "Propranolol: Pediatric drug information" ) For abbreviations and symbols that may be used in Lexicomp (show table )

ALERT: U.S. Boxed Warning Brand Names: U.S.

The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov. Inderal LA; InnoPran XL

Brand Names: Canada

Apo-Propranolol; Dom-Propranolol; Inderal; Inderal LA; Novo-Pranol; Nu-Propranolol; PMS-Propranolol; Propranolol Hydrochloride Injection, USP; Teva-Propranolol

Pharmacologic Category Dosing: Adult

Antianginal Agent; Antiarrhythmic Agent, Class II; Beta-Blocker, Nonselective

Akathisia (unlabeled use): Oral: 30-120 mg/day in 2-3 divided doses Essential tremor: Oral: 40 mg twice daily initially; maintenance doses: Usually 120-320 mg/day Hypertension: Initial: Oral: 40 mg twice daily; increase dosage every 3-7 days; usual dose: 120-240 mg divided in 2-3 doses/day; maximum daily dose: 640 mg; usual dosage range (JNC 7): 40-160 mg/day in 2 divided doses Extended release formulations: Inderal LA: Initial: 80 mg once daily; usual maintenance: 120-160 mg once daily; maximum daily dose: 640 mg; usual dosage range (JNC 7): 60-180 mg/day once daily InnoPran XL: Initial: 80 mg once daily at bedtime; if initial response is inadequate, may be increased at 2-3 week intervals to a maximum dose of 120 mg Hypertrophic subaortic stenosis: Oral: 20-40 mg 3-4 times/day

Inderal LA: 80-160 mg once daily Migraine headache prophylaxis: Oral: Initial: 80 mg/day divided every 6-8 hours; increase by 20-40 mg/dose every 3-4 weeks to a maximum of 160-240 mg/day given in divided doses every 6-8 hours; if satisfactory response not achieved within 6 weeks of starting therapy, drug should be withdrawn gradually over several weeks Inderal LA: Initial: 80 mg once daily; effective dose range: 160-240 mg once daily Pheochromocytoma: Oral: 30-60 mg/day in divided doses Post-MI mortality reduction: Oral: 180-240 mg/day in 3-4 divided doses Stable angina: Oral: 80-320 mg/day in doses divided 2-4 times/day Inderal LA: Initial: 80 mg once daily; maximum dose: 320 mg once daily Tachyarrhythmias: Oral: 10-30 mg/dose every 6-8 hours I.V.: 1-3 mg/dose slow IVP; repeat every 2-5 minutes up to a total of 5 mg; titrate initial dose to desired response or 0.5-1 mg over 1 minute; may repeat, if necessary, up to a total maximum dose of 0.1 mg/kg (ACLS guidelines, 2010) Note: Once response achieved or maximum dose administered, additional doses should not be given for at least 4 hours. Thyroid storm (unlabeled use): Oral: 60-80 mg every 4 hours; may consider the use of an intravenous shorter-acting beta-blocker (ie, esmolol) (Bahn, 2011) I.V.: 0.5-1 mg administered over 10 minutes every 3 hours (Gardner, 2011) Thyrotoxicosis (unlabeled use): Oral: 10-40 mg/dose every 6-8 hours; may also consider administering extended or sustained release formulations (Bahn, 2011) Variceal hemorrhage prophylaxis (unlabeled use) (Garcia-Tsao, 2007): Oral: Primary prophylaxis: Initial: 20 mg twice daily; adjust to maximal tolerated dose. Note: Risk factors for hemorrhage include Child-Pugh class B/C or variceal red wale markings on endoscopy. Secondary prophylaxis: Initial: 20 mg twice daily; adjust to maximal tolerated dose

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

Hypertension (unlabeled use): Oral: Initial: 0.5-1 mg/kg/day in divided doses every 6-12 hours; increase gradually every 5-7 days; maximum: 16 mg/kg/24 hours Migraine headache prophylaxis (unlabeled use): Oral: Initial: 2-4 mg/kg/day or 35 kg: 10-20 mg 3 times/day >35 kg: 20-40 mg 3 times/day Tachyarrhythmias (unlabeled use): Oral: Initial: 0.5-1 mg/kg/day in divided doses every 6-8 hours; titrate dosage upward every 3-7 days; usual dose: 2-6 mg/kg/day; higher doses may be needed; do not exceed 16 mg/kg/day or 60 mg/day I.V.: 0.01-0.1 mg/kg/dose slow IVP over 10 minutes; maximum dose: 1 mg for infants; 3 mg for children Thyroid storm (unlabeled use): Oral: Children: 0.5 mg/kg/dose every 4-8 hours; titrate to effective dose (Eyal, 2008) Thyrotoxicosis (unlabeled use): Oral: Children: 10-40 mg every 6 hours; titrate to effective dose (Eyal, 2008) Adolescents: Refer to adult dosing. Hypercyanotic spells (TOF) (unlabeled use): Oral: Palliation: Initial: 1 mg/kg/day every 6 hours; if ineffective, may increase dose after 1 week by 1 mg/kg/day to a maximum of 5 mg/kg/day, if patient becomes refractory, may increase slowly to a maximum of 10-15 mg/kg/day. Allow 24 hours between dosing changes. I.V.: 0.01-0.2 mg/kg/dose infused over 10 minutes; maximum dose: 5 mg

Dosing: Geriatric
I.V.: Use caution; initiate at lower end of the dosing range. Oral: Hypertension: Consider lower initial doses and titrate to response (Aronow, 2011) Tachyarrhythmias: Initial: 10 mg twice daily; increase dosage every 3-7 days; usual dose range: 10-320 mg/day given in 1-2 divided doses. Refer to adult dosing for additional uses.

Dosing: Renal Impairment

Not dialyzable (0% to 5%); supplemental dose is not necessary. Peritoneal dialysis effects: Supplemental dose is not necessary.

Dosing: Hepatic Impairment

regular heart rate monitoring.

Marked slowing of heart rate may occur in chronic liver disease with conventional doses; low initial dose and

Dosage Forms: U.S.

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)] 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: Generic: 20 mg/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: U.S. Administration

Yes

I.V. dose is much smaller than oral dose. When administered acutely for cardiac treatment, monitor ECG and blood pressure. May administer by rapid infusion (I.V. 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. Do not crush long-acting oral forms.

Compatibility

Stable in D51/2NS, D5NS, D5W, LR, 1/2NS, NS.

Y-site administration: Compatible: Alteplase, fenoldopam, heparin, hydrocortisone sodium succinate, inamrinone, linezolid, meperidine, milrinone, morphine, nesiritide, potassium chloride, propofol, tacrolimus, tirofiban, vitamin B complex with C. Incompatible: Amphotericin B cholesteryl sulfate complex, pantoprazole. Compatibility in syringe: Compatible: Inamrinone, milrinone. Incompatible: Pantoprazole.

Use

Management of hypertension; angina pectoris; pheochromocytoma; essential tremor; supraventricular arrhythmias (such as atrial fibrillation and flutter, AV nodal re-entrant tachycardias), ventricular tachycardias (catecholamine-induced arrhythmias, digoxin toxicity); prevention of myocardial infarction; migraine headache prophylaxis; symptomatic treatment of hypertrophic subaortic stenosis (hypertrophic obstructive cardiomyopathy)

Use - Unlabeled

Tremor due to Parkinson's disease; aggressive behavior (not recommended for dementia-associated aggression), anxiety, schizophrenia; antipsychotic-induced akathisia; primary and secondary prophylaxis of variceal hemorrhage; acute panic; thyrotoxicosis; tetralogy of Fallot (TOF) hypercyanotic spells

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 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 I.V. dosing. Use caution when converting from one route of administration to another. International issues: Inderal [Canada and multiple international markets] and Inderal LA [U.S.] may be confused with Indiaral brand name for loperamide [France]

Adverse Reactions Significant

Frequency not defined.

Cardiovascular: Angina, arterial insufficiency, AV conduction disturbance increased, bradycardia, cardiogenic shock, CHF, hypotension, impaired myocardial contractility, mesenteric arterial thrombosis (rare), Raynaud's syndrome, syncope Central nervous system: Amnesia, catatonia, cognitive dysfunction, confusion, depression, dizziness, emotional lability, fatigue, hallucinations, hypersomnolence, insomnia, lethargy, lightheadedness, psychosis, vertigo, vivid dreams Dermatologic: Alopecia, contact dermatitis, cutaneous ulcers, eczematous eruptions, erythema multiforme, exfoliative dermatitis, hyperkeratosis, nail changes, oculomucocutaneous reactions, pruritus, psoriasiform eruptions, rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, ulcers, ulcerative lichenoid, urticaria

Endocrine & metabolic: Hyper-/hypoglycemia, hyperkalemia, hyperlipidemia Gastrointestinal: Anorexia, cramping, constipation, diarrhea, ischemic colitis, nausea, stomach discomfort, vomiting Genitourinary: Impotence, interstitial nephritis (rare), oliguria (rare), Peyronie's disease, proteinuria (rare) Hematologic: Agranulocytosis, nonthrombocytopenic purpura, thrombocytopenia, thrombocytopenic purpura Hepatic: Alkaline phosphatase increased, transaminases increased Neuromuscular & skeletal: Arthropathy, carpal tunnel syndrome (rare), myotonus, paresthesia, polyarthritis, weakness Ocular: Hyperemia of the conjunctiva, mydriasis, visual acuity decreased, visual disturbances, xerophthalmia Renal: BUN increased Respiratory: Bronchospasm, dyspnea, laryngospasm, pharyngitis, pulmonary edema, respiratory distress, wheezing Miscellaneous: Anaphylactic/anaphylactoid allergic reaction, cold extremities, lupus-like syndrome (rare)

Contraindications

Hypersensitivity to propranolol, beta-blockers, or any component of the formulation; uncompensated congestive heart failure (unless the failure is due to tachyarrhythmias being treated with propranolol), cardiogenic shock, severe sinus bradycardia or heart block greater than firstdegree (except in patients with a functioning artificial pacemaker), severe hyperactive airway disease (asthma or COPD)

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 (HF): Use with caution in patients with compensated HF and monitor for a worsening of the condition (efficacy of propranolol in HF has not been demonstrated). Hepatic impairment: Use with caution in patients with hepatic impairment; dosage adjustment required.

 Myasthenia gravis: Use with caution in patients with myasthenia gravis. Peripheral vascular disease (PVD) and Raynaud's disease: Can precipitate or aggravate symptoms of arterial insufficiency in patients with PVD and Raynaud's 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. Psychiatric disease: Use with caution in patients with a history of psychiatric illness; may cause or exacerbate CNS depression. 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. Concurrent drug therapy issues: Calcium channel blockers (nondihydropyridines): Use with caution in patients on concurrent verapamil or diltiazem; bradycardia or heart block can occur. Cardiac glycosides: Use with caution in patients receiving digoxin; bradycardia or heart block can occur. Inhaled anesthetic agents: Use with caution in patients receiving inhaled anesthetic agents known to depress myocardial contractility. Special populations: Elderly: Bradycardia may be observed more frequently in elderly patients (>65 years of age); dosage reductions may be necessary. Other warnings/precautions: Abrupt withdrawal: [U.S. Boxed Warning]: Beta-blocker therapy should not be withdrawn abruptly (particularly in patients with CAD), but gradually tapered to avoid acute tachycardia, hypertension, and/or ischemia. Severe exacerbation of angina, ventricular arrhythmias, and myocardial infarction (MI) have been reported following abrupt withdrawal of beta-blocker therapy. Temporary but prompt resumption of betablocker 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 Drug Interactions

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), CYP2D6 (weak), P-glycoprotein

(For additional information: Launch Lexi-Interact Drug Interactions Program)

Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Risk D: Consider therapy modification Abiraterone Acetate: May increase the serum concentration of CYP1A2 Substrates. Risk C: Monitor therapy Acetylcholinesterase Inhibitors: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. 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 Alpha-/Beta-Agonists (Direct-Acting): Beta-Blockers may enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Epinephrine used as a local anesthetic for dental procedures will not likely cause clinically relevant problems. Management: Cardioselective beta-blockers and lower doses of epinephrine may confer a more limited risk. Patients who may require acute subcutaneous epinephrine (e.g., bee sting kits) should probably avoid beta blockers. Exceptions: Dipivefrin. Risk D: Consider therapy modification 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 D: Consider therapy modification 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. Exceptions: Apraclonidine. Risk D: Consider therapy modification Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification Aminoquinolines (Antimalarial): May decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy 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 Anilidopiperidine Opioids: May enhance the bradycardic effect of Beta-Blockers. Anilidopiperidine Opioids may enhance the hypotensive effect of BetaBlockers. Risk C: Monitor therapy Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy Antipsychotic Agents (Phenothiazines): May enhance the hypotensive effect of Beta-Blockers. Antipsychotic Agents (Phenothiazines) may decrease the metabolism of Beta-Blockers. Beta-Blockers may decrease the metabolism of Antipsychotic Agents (Phenothiazines). Risk C: Monitor therapy

ARIPiprazole: CYP2D6 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Risk C: Monitor therapy Barbiturates: May decrease the serum concentration of Beta-Blockers. 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 Bosutinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bosutinib. Risk X: Avoid combination Brimonidine (Topical): May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy Bupivacaine: Beta-Blockers may increase the serum concentration of Bupivacaine. Risk C: Monitor therapy Calcium Channel Blockers (Dihydropyridine): May enhance the hypotensive effect of Beta-Blockers. Bradycardia and signs of heart failure have also been reported. Risk C: Monitor therapy Calcium Channel Blockers (Nondihydropyridine): May enhance the hypotensive effect of Beta-Blockers. Bradycardia and signs of heart failure have also been reported. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Beta-Blockers. Exceptions: Bepridil [Off Market]. Risk C: Monitor therapy Cardiac Glycosides: Beta-Blockers may enhance the bradycardic effect of Cardiac Glycosides. Risk C: Monitor therapy 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. Management: Administer these agents in combination with caution, and monitor for conduction disturbances. Avoid methacholine with any beta blocker due to the potential for additive bronchoconstriction. Risk C: Monitor therapy Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a pglycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. Risk D: Consider therapy modification CYP1A2 Inducers (Strong): May increase the metabolism of CYP1A2 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Risk D: Consider therapy modification CYP1A2 Inhibitors (Moderate): May decrease the metabolism of CYP1A2 Substrates. Risk C: Monitor therapy CYP1A2 Inhibitors (Strong): May decrease the metabolism of CYP1A2 Substrates. Risk D: Consider therapy modification CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Risk C: Monitor therapy CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Risk D: Consider therapy modification Cyproterone: May decrease the serum concentration of CYP1A2 Substrates. Risk C: Monitor therapy

Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Management: Dabigatran dose reductions may be needed. Specific recommendations vary considerably according to US vs Canadian labeling, specific P-gp inhibitor, renal function, and indication for dabigatran treatment. Refer to full monograph or dabigatran labeling. Risk D: Consider therapy modification Darunavir: May increase the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy Deferasirox: May increase the serum concentration of CYP1A2 Substrates. Risk C: Monitor therapy Diazoxide: May enhance the hypotensive effect of Antihypertensives. 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. 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. Risk D: Consider therapy modification Ergot Derivatives: Beta-Blockers may enhance the vasoconstricting effect of Ergot Derivatives. Risk D: Consider therapy modification Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Risk D: Consider therapy modification Fingolimod: Beta-Blockers may enhance the bradycardic effect of Fingolimod. Risk C: Monitor therapy Floctafenine: May enhance the adverse/toxic effect of Beta-Blockers. Risk X: Avoid combination FluvoxaMINE: May increase the serum concentration of Propranolol. Management: Use a lower initial propranolol dose and be cautious with propranolol dose titration. Risk D: Consider therapy modification Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive Agents. Risk C: Monitor therapy Insulin: Beta-Blockers may enhance the hypoglycemic effect of Insulin. Risk C: Monitor therapy Lacidipine: May enhance the hypotensive effect of Propranolol. Propranolol may decrease the serum concentration of Lacidipine. Lacidipine may increase the serum concentration of Propranolol. Risk C: Monitor therapy Lidocaine (Systemic): Beta-Blockers may increase the serum concentration of Lidocaine (Systemic). Risk C: Monitor therapy Lidocaine (Topical): Beta-Blockers may increase the serum concentration of Lidocaine (Topical). Risk C: Monitor therapy

MAO Inhibitors: May enhance the orthostatic hypotensive effect of Orthostatic Hypotension Producing 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 X: Avoid combination Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy Midodrine: Beta-Blockers may enhance the bradycardic effect of Midodrine. Risk C: Monitor therapy Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Beta-Blockers. Risk C: Monitor therapy PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: Avoid combination Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy P-glycoprotein/ABCB1 Substrates: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Pglycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy Pomalidomide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Pomalidomide. Risk X: Avoid combination Propafenone: May increase the serum concentration of Propranolol. Risk C: Monitor therapy Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy Prucalopride: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride. Risk C: Monitor therapy QuiNIDine: May decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy Regorafenib: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy Reserpine: May enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy Rifamycin Derivatives: May decrease the serum concentration of Beta-Blockers. Exceptions: Rifabutin. Risk C: Monitor therapy RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification Rivaroxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rivaroxaban. Risk C: Monitor therapy Rizatriptan: Propranolol may increase the serum concentration of Rizatriptan. Management: Rizatriptan adult dose should be reduced to 5 mg in patients who are also being treated with propranolol. Risk D: Consider therapy modification Selective Serotonin Reuptake Inhibitors: May increase the serum concentration of Beta-Blockers. Exceptions: Citalopram; Escitalopram; FluvoxaMINE.

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 Theophylline Derivatives: Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Theophylline Derivatives. Risk D: Consider therapy modification Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination Vemurafenib: May increase the serum concentration of CYP1A2 Substrates. Management: Consider alternatives to such combinations whenever possible, particularly if the CYP1A2 substrate has a relatively narrow therapeutic index. Risk D: Consider therapy modification VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Risk X: Avoid combination Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy Zileuton: May increase the serum concentration of Propranolol. Risk C: Monitor therapy ZOLMitriptan: Propranolol may increase the serum concentration of ZOLMitriptan. Risk C: Monitor therapy

Ethanol/Nutrition/Herb Interactions
Cigarette: Smoking may decrease plasma levels of propranolol by increasing metabolism. Management: Avoid smoking. 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. Herb/Nutraceutical: Dong quai has estrogenic activity. Some herbal medications may worsen hypertension (eg, licorice); others may enhance the antihypertensive effect of propranolol (eg, shepherd's purse). Management: Avoid dong quai if using for hypertension. Avoid bayberry, blue cohosh, cayenne, ephedra, ginger, ginseng (American), gotu kola, licorice, and yohimbe. Avoid black cohosh, california poppy, coleus, garlic, golden seal, hawthorn, mistletoe, periwinkle, quinine, and shepherd's purse.

Pregnancy Risk Factor Pregnancy Implications

C (show table)

Adverse events have been observed in some animal reproduction studies; therefore, the manufacturer classifies propranolol as pregnancy category C. Propranolol crosses the placenta and is measurable in the newborn serum following maternal use during pregnancy. In a cohort study, an increased risk of cardiovascular defects was observed following maternal use of beta-blockers during pregnancy. Intrauterine growth

restriction (IUGR), small placentas, as well as fetal/neonatal bradycardia, hypoglycemia, and/or respiratory depression have been observed following in utero exposure to beta-blockers as a class. Adequate facilities for monitoring infants at birth should be available. Untreated chronic maternal hypertension and pre-eclampsia are also associated with adverse events in the fetus, infant, and mother. The peak maternal serum concentrations of propranolol and the active metabolite 4-hydroxypropranolol do not change during pregnancy; peak serum concentrations of naphthoxylactic acid are lower in the third trimester when compared to postpartum. Propranolol is recommended for use in the management of thyrotoxicosis in pregnancy. Propranolol has been evaluated for the treatment of hypertension in pregnancy, but other agents may be more appropriate for use. Propranolol has also been used in the management of hypertrophic obstructive cardiomyopathy in pregnancy and has been studied for use as an adjunctive agent in the management of dysfunctional labor (dystocia).

Lactation

Enters breast milk/use caution

Breast-Feeding Considerations

Propranolol is excreted into breast milk with peak concentrations occurring ~2-3 hours after an oral dose. The inactive metabolites of propranolol have also been detected in breast milk. The manufacturer recommends that caution be exercised when administering propranolol to nursing women. Due to immature hepatic metabolism in newborns, breast-feeding infants should be monitored for adverse events.

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)

Pricing: U.S. (Medi-Span)

Capsule, 24-hour (Inderal LA Oral) 60 mg (100): $949.75 80 mg (100): $1109.33 120 mg (100): $1376.05 160 mg (100): $1801.60 Capsule, 24-hour (InnoPran XL Oral) 80 mg (30): $396.00 120 mg (30): $396.00 Capsule, 24-hour (Propranolol HCl ER Oral) 60 mg (100): $132.59 80 mg (100): $154.89 120 mg (100): $192.09 160 mg (100): $251.47

Solution (Propranolol HCl Intravenous) 1 mg/mL (1 mL): $9.85 Solution (Propranolol HCl Oral) 20 mg/5 mL (500 mL): $48.61 40 mg/5 mL (500 mL): $69.45 Tablets (Propranolol HCl Oral) 10 mg (100): $33.53 20 mg (100): $36.30 40 mg (100): $69.15 60 mg (100): $121.83 80 mg (100): $63.39 Disclaimer: The pricing data provided represent a median AWP and/or AAWP price for the brand and/or generic product, respectively. The pricing data should be used for benchmarking purposes only, and as such should not be used to set or adjudicate any prices for charging or reimbursement functions. Pricing data is updated monthly.

Monitoring Parameters
pressure with oral administration

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

Consult individual institutional policies and procedures.

Reference Range

Therapeutic: 50-100 ng/mL (SI: 190-390 nmol/L) at end of dose interval

International Brand Names

Anaprilan (RU); Angilol (IE); Apsolol (GB); Atensin (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM, ZW); Avlocardyl (FR); Bai Er Luo (CL); Bedranol (BB, BF, BJ, BM, BS, BZ, CI, ET, GH, GM, GN, GY, JM, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, SR, TN, TT, TZ, UG, ZM, ZW); Berkolol (HK); Beta-Timelets (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Betalol (TH); Betascan (TW); Cardiblok (ZA); Cardinol (NZ); Cardinol LA (NZ); Cardispare (ZA); Cardolol (TW); Ciplar (IN); Colliprol (MX); Corbeta (IN); Coriodal (CN); Deralin (AU, IL); Dideral (TR); Dociton (DE); Duranol (PH); Farmadral (ID); Frina (GR); Hipranol (MY); Indenol (KP); 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, HN, IE, IQ, IR, IT, JM, JO, KE, KP, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, MY, NE, NG, NL, NO, OM, PE, PH, PK, PT, PY, QA, SA, SC, SD, SE, SG, SL, SN, SR, SY, TN, TT, TW, TZ, UG, UY, VE, YE, ZM, ZW); Inderal LA (AE, BB, BF, BH, BJ, BM, BS, BZ, CI, CY, EG, ET, GB, GH, GM, GN, GY, IE, 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 (MX); Indesol (KP); Indicardin (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM, ZW); Inpanol (HK); Laining (TW); MIDDLEEAST (IL); Normpress (TH); Oposim (AR); Palon (TH); Pranidol (MX); Prestoral (ID); Prolol (IL); Propalong (AR); Propayerst

(AR); Propra (EE); Propra-Ratiopharm (PL); Propral (FI); Propranolol Eurogenerics (LU); Pu Le Xin (CL); Purbloka (ZA); Rebaten LA (BR); Rexigen (ZA); Sawatal (JP); Slow Deralin (IL); Sumial (ES); Tenomal (GR); Waucoton (GR)

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 betaadrenergic blockers (propranolol, nadolol) reduce portal pressure by producing splanchnic vasoconstriction (beta2 effect) thereby reducing portal blood flow.

Pharmacodynamics/Kinetics
Onset of action: Beta-blockade: Oral: 1-2 hours Duration: Immediate release: 6-12 hours; Extended-release formulations: ~24-27 hours Absorption: Oral: Rapid and complete Distribution: Vd: 4 L/kg in adults Protein binding: Newborns: 68%; Adults: ~90% (S-isomer primarily to alpha1-acid glycoprotein; R-isomer primarily to albumin) Metabolism: Hepatic via CYP2D6, and CYP1A2 to 4-hydroxypropranolol (active) and inactive compounds; extensive first-pass effect Bioavailability: ~25% reaches systemic circulation due to high first-pass metabolism; protein-rich foods increase bioavailability by ~50% Half-life elimination: Neonates and Infants: Possible increased half-life; Children: 3.9-6.4 hours; Adults: Immediate release formulation: 3-6 hours; Extended-release formulations: 8-10 hours Time to peak: Immediate release: 1-4 hours; Extended-release formulations: ~6-14 hours Excretion: Metabolites are excreted primarily in urine (96% to 99%); <1% excreted in urine as unchanged drug Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Adler LA, Peselow E, Rosenthal M, et al, A Controlled Comparison of the Effects of Propranolol, Benztropine, and Placebo on Akathisia: An Interim Analysis,
Psychopharmacol Bull, 1993, 29(2):283-6. [PubMed 8290678]

2. Anderson JL, Adams CD, Antman EM, et al, "2011 ACCF/AHA Focused Update Incorporated Into the ACC/AHA 2007 Guidelines for the Management of Patients With Unstable
Angina/Non-ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines," Circulation, 2011, 123(18):e426-579. [PubMed 21444888]

3. Annequin D, Tourniaire B, Massiou H, et al, Migraine and Headache in Childhood and Adolescence, Pediatr Clin North Am, 2000, 47(3):617-31. [PubMed 10835994] 4. Antman EM, Anbe DT, Armstrong PW, et al, ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction: A Report of the American College
of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute

Myocardial Infarction), Circulation, 2004, 110(9):e82-292. [PubMed 15339869]

5. Antman EM, Hand M, Armstrong PW, et al, 2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction. A
Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, J Am Coll Cardiol, 2008, 51(2):210-49. [PubMed 18191746]

6. Aronow WS, Fleg JL, Pepine CJ, et al, ACCF/AHA 2011 Expert Consensus Document on Hypertension in the Elderly: A Report of the American College of Cardiology
Foundation Task Force on Clinical Expert Consensus Documents, Circulation, 2011, 123(21):2434-506. [PubMed 21518977]

7. Bahn RS (Chair), Burch HB, Cooper DS, et al, Hyperthyroidism and Other Causes of Thyrotoxicosis: Management Guidelines of the American Thyroid Association and
American Association of Clinical Endocrinologists, Thyroid, 2011, 21(6):593-646. [PubMed 21510801]

8. Bartosh S and Aronson A, Childhood Hypertension. An Update on Etiology, Diagnosis and Treatment, Pediatr Clin North Am, 1999, 46(2):235-52. [PubMed 10218072] 9. Bille B, Ludvigsson J, and Sanner G. Prophylaxis of Migraine in Children, Headache, 1977, 17(2):61-3. [PubMed 324951] 10. Blomstrm-Lundqvist C, Scheinman MM, Aliot EM, et al, ACC/AHA/ESC Guidelines for the Management of Patients With Supraventricular Arrhythmias--Executive Summary. A
Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Supraventricular Arrhythmias), Circulation, 2003, 108(15):1871-909. [PubMed 14557344]

11. Brauchli YB, Jick SS, Curtin F, et al, Association Between Beta-Blockers, Other Antihypertensive Drugs and Psoriasis: Population-Based Case-Control Study, Br J Dermatol,
2008, 158(6):1299-307. [PubMed 18410416]

12. Chobanian AV, Bakris GL, Black HR, et al, The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure:
The JNC 7 Report, JAMA, 2003, 289(19):2560-71. [PubMed 12748199]

13. Cumming GR and Carr W, Hemodynamic Effects of Propranolol in Patients With Fallots Tetralogy, Am Heart J, 1967, 74(1):29-36. [PubMed 6027567] 14. Cumming GR, Propranolol in Tetralogy of Fallot, Circulation, 1970, 41(1):13-15. [PubMed 5420625] 15. Drugs for Pediatric Emergencies. Committee on Drugs, Committee on Drugs, 1996 to 1997, Liaison Representatives, and AAP Section Liaisons, Pediatrics, 1998,
101(1):E13. [PubMed 9734990]

16. Eades SK, Pharmacotherapy of Congenital Heart Defects, J Pediatr Pharm Prac, 2000, 5(1):15-34. 17. Eyal O and Rose SR, Thyroid Disease, in Rogers Textbook of Pediatric Intensive Care, 4th ed, David G Nichols, ed, Philadelphia, PA: Lippincott, Williams, & Wilkins, 2008. 18. Farine M and Arbus G, Management of Hypertensive Emergencies in Children, Pediatr Emerg Care, 1989, 5(1):51-5. [PubMed 2652097] 19. Field JM, Hazinski MF, Sayre MR, et al, Part 1: Executive Summary: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency
Cardiovascular Care, Circulation, 2010, 122 (18 Suppl 3):640-56. [PubMed 20956217]

20. Fihn SD, Gardin JM, Abrams J, et al, 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart
Disease: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons, Circulation, 2012, 126(25):3097-137. [PubMed 23166211]

21. Fleisher LA, Beckman JA, Brown KA, et al, 2009 ACCF/AHA Focused Update on Perioperative Beta Blockade Incorporated Into the ACC/AHA 2007 Guidelines on
Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery. A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, J Am Coll Cardiol, 2009, 54(22):e13-118. [PubMed 19926002]

22. Fuster V, Ryden LE, Cannom DS, et al, ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation-Executive Summary. A Report of the American
College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation). Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society, J Am Coll Cardiol, 2006, 48(4):854-906. [PubMed 16904574 ]

23. Garcia-Tsao G, Sanyal AJ, Grace ND, et al, Prevention and Management of Gastroesophageal Varices and Variceal Hemorrhage in Cirrhosis, Hepatology, 2007, 46(3):922-

38. [PubMed 17879356]

24. Gardner DG, Endocrine Emergencies, in Greenspans Basic & Clinical Endocrinology, 9th ed, Gardner DG and Shoback D eds, The McGraw-Hill Companies Inc, 2011. 25. Garson A Jr, Gillette PC, and McNamara DG, Propranolol: The Preferred Palliation for Tetralogy of Fallot, Am J Cardiol, 1981, 47(5):1098-104. [PubMed 6164284] 26. Geffner DL and Hershman JM, beta-Adrenergic Blockade for the Treatment of Hyperthyroidism, Am J Med, 1992, 93(1):61-8. [PubMed 1352658] 27. Hillis LD, Smith PK, Anderson JL, et al, 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery: A Report of the American College of Cardiology
Foundation/American Heart Association Task Force on Practice Guidelines, Circulation, 2011, 124(23):2610-42. [PubMed 22064600]

28. Hirsch AT, Haskal ZJ, Hertzer NR, et al, ACC/AHA 2005 Practice Guidelines for the Management of Patients With Peripheral Arterial Disease (Lower Extremity, Renal,
Mesenteric, and Abdominal Aortic). A Collaborative Report of the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease), Circulation , 2006, 113(11):e463-654. [PubMed 16549646]

29. Juul AB, Wetterslev J, Gluud C, et al, Effect of Perioperative Beta Blockade in Patients With Diabetes Undergoing Major Non-Cardiac Surgery: Randomized Placebo
Controlled, Blinded Multicentre Trial. DIPOM Trial Group, BMJ, 2006, 332(7556):1482. [PubMed 16793810]

30. Lang DM, Anaphylactoid and Anaphylactic Reactions. Hazards of Beta-Blockers, Drug Saf, 1995, 12(5):299-304. [PubMed 7669259] 31. Lindenauer PK, Pekow P, Wang K, et al, "Perioperative Beta-Blocker Therapy and Mortality After Major Noncardiac Surgery, N Engl J Med, 2005, 353(4):349-61. [PubMed
16049209]

32. Luedtke S, Kuhn R, and McCaffrey F, Pharmacologic Management of Supraventricular Tachycardias in Children. Part 2: Atrial flutter, Atrial Fibrillation, and Junctional and
Atrial Ectopic Tachycardia, Ann Pharmacother, 1997, 31(11):1347-59. [PubMed 9391691]

33. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents, The Fourth Report on the Diagnosis, Evaluation, and
Treatment of High Blood Pressure in Children and Adolescents, Pediatrics, 2004, 114(2 Suppl):555-76. [PubMed 15286277]

34. Neumar RW, Otto CW, Link MS, et al, Part 8: Adult Advanced Cardiovascular Life Support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation
and Emergency Cardiovascular Care, Circulation, 2010, 122(18 Suppl 3):729-67.

35. O'Gara PT, Kushner FG, Ascheim DD, et al, "2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction: A Report of the American College of
Cardiology Foundation/American Heart Association Task Force on Practice Guidelines," Circulation, 2013, 127(4):e362-425. [PubMed 3247304]

36. Pickoff AS, Zies L, Ferrer PL, et al, High-dose Propranolol Therapy in the Management of Supraventricular Tachycardia, J Pediatr, 1979, 94(1):144-6. [PubMed 758396] 37. POISE Study Group, Devereaux PJ, Yang H, et al, Effects of Extended-Release Metoprolol Succinate in Patients Undergoing Non-Cardiac Surgery (POISE Trial): A
Randomised Controlled Trial, Lancet, 2008, 371(9627):1839-47. [PubMed 18479744]

38. Rabins PV, Blacker D, Rovner BW, et al, American Psychiatric Association Practice Guideline for the Treatment of Patients With Alzheimer's Disease and Other Dementias.
Second Edition, Am J Psychiatry, 2007, 164(12 Suppl):5-56. Available at http://psychiatryonline.org/guidelines.aspx [PubMed 18340692]

39. Radack K and Deck C, Beta-Adrenergic Blocker Therapy Does Not Worsen Intermittent Claudication in Subjects With Peripheral Arterial Disease. A Meta-Analysis of
Randomized Controlled Trials, Arch Intern Med, 1991, 151(9):1769-76. [PubMed 1679624]

40. Redelmeier D, Scales D, and Kopp A, Beta Blockers for Elective Surgery in Elderly Patients: Population Based, Retrospective Cohort Study, BMJ, 2005, 331(7522):932.
[PubMed 16210252]

41. Schn MP and Boehncke WH, Psoriasis, N Eng J Med, 2005, 352(18):1899-1912. [PubMed 15872205] 42. Shah PM and Kidd L, Circulatory Effects of Propranolol in Children With Fallots Tetralogy, Am J Cardiol, 1967, 19(5):653-7. [PubMed 6024709] 43. Shanks RG, Hadden DR, Lowe DC, et al, Controlled Trial of Propranolol in Thyrotoxicosis, Lancet, 1969, 1(7603):993-4. [PubMed 4181181] 44. Skanes AC, Healey JS, Cairns JA, et al, Focused 2012 Update of the Canadian Cardiovascular Society Atrial Fibrillation Guidelines: Recommendations for Stroke Prevention
and Rate/Rhythm Control, Can J Cardiol, 2012, 28(2):125-36. [PubMed 22433576]

45. Smith SC Jr, Benjamin EJ, Bonow RO, et al, AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients With Coronary and Other Atherosclerotic Vascular
Disease: 2011 Update: A Guideline From the American Heart Association and American College of Cardiology Foundation, Circulation, 2011, 124(22):2458-73. [PubMed 22052934]

46. Smith CS and Howard NJ, Propranolol in Treatment of Neonatal Thyrotoxicosis, J Pediatr, 1973, 83:1046. [PubMed 4757519] 47. Strasburger JF, "Cardiac Arrhythmias in Childhood. Diagnostic Considerations and Treatment," Drugs, 1991, 42(6):974-83. [PubMed 1724643] 48. UK Prospective Diabetes Study Group, Efficacy of Atenolol and Captopril in Reducing Risk of Macrovascular and Microvascular Complications in Type 2 Diabetes: UKPDS
39, BMJ, 1998, 317(7160):713-20. [PubMed 9732338]

49. Wann SL, Curtis AB, January CT, et al, 2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Updating the 2006 Guideline): A Report
of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, Circulation, 2011, 123 (1):104-23. [PubMed 21173346]

50. Wensley DF, Karl T, Deanfield JE, et al, Assessment of Residual Right Ventricular Outflow Tract Obstruction Following Surgery Using the Response to Intravenous
Propranolol, Ann Thorac Surg, 1987, 44(6):633-6. [PubMed 3689047]

51. Yang H, Raymer K, Butler R, et al, The Effects of Perioperative Beta-Blockade: Results of the Metoprolol After Vascular Surgery (MaVS) Study, a Randomized Controlled
Trial, Am Hear J, 2006, 152(5):983-90. [PubMed 17070177]

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