|
This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or
standards of non-Merck sources.
ALERT: U.S. Boxed Warning
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.
Pronunciation
(proe PRAN oh lole)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
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
Pregnancy Risk Factor
C
Pregnancy Considerations
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 (AAP rates “compatible”; AAP 2001 update pending)
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.
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 first-degree (except in patients with a functioning artificial pacemaker), severe hyperactive airway disease (asthma or COPD)
Warnings/Precautions
Boxed warnings:
• Abrupt withdrawal: See “Other warnings/precautions” below
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 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.
Adverse Reactions
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)
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), CYP2D6 (weak), P-glycoprotein
Drug Interactions
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
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: Beta-Blockers may enhance the rebound hypertensive effect of Alpha2-Agonists. This effect can occur when the alpha2-agonist is abruptly withdrawn. Exceptions: Apraclonidine; Brimonidine. 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 Beta-Blockers. 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. Beta-Blockers may decrease the metabolism of Antipsychotic Agents (Phenothiazines). Antipsychotic Agents (Phenothiazines) may decrease the metabolism of Beta-Blockers. 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 product labeling 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
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 p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. Risk D: Consider therapy modification
Conivaptan: May increase the serum concentration of CYP3A4 Substrates (Low risk). Risk C: Monitor therapy
CYP1A2 Inducers (Strong): May increase the metabolism of CYP1A2 Substrates. Risk C: Monitor therapy
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
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. Lacidipine may increase the serum concentration of Propranolol. Propranolol may decrease the serum concentration of Lacidipine. Risk C: Monitor therapy
Lidocaine: Beta-Blockers may increase the serum concentration of Lidocaine. Risk C: Monitor therapy
Lidocaine (Systemic): Beta-Blockers may decrease the metabolism of Lidocaine (Systemic). Risk C: Monitor therapy
Lidocaine (Topical): Beta-Blockers may decrease the metabolism 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
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. P-glycoprotein 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
Propafenone: May increase the serum concentration of Beta-Blockers. Propafenone possesses some independent beta blocking activity. Risk C: Monitor therapy
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
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
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Risk X: Avoid combination
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
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. 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.
Storage
Injection: Store at 20°C to 25°C (68°F to 77°F); protect from freezing or excessive heat. Once diluted, propranolol is stable for 24 hours at room temperature in D5W or NS. Protect from light. Solution has a maximum stability at pH of 3 and decomposes rapidly in alkaline pH.
Capsule, tablet: Store at 20°C to 25°C (68°F to 77°F); protect from freezing or excessive heat. Protect from light and moisture.
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.
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.
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
Dosage
Akathisia (unlabeled use): Oral: Adults: 30-120 mg/day in 2-3 divided doses
Essential tremor: Oral: Adults: 40 mg twice daily initially; maintenance doses: Usually 120-320 mg/day
Hypertension:
Oral:
Children (unlabeled use): 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
Adults: Initial: 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
Elderly: Consider lower initial doses and titrate to response (Aronow, 2011)
Hypertrophic subaortic stenosis: Oral: Adults: 20-40 mg 3-4 times/day
Inderal® LA: 80-160 mg once daily
Migraine headache prophylaxis: Oral:
Children (unlabeled use): Initial: 2-4 mg/kg/day or
≤35 kg: 10-20 mg 3 times/day
>35 kg: 20-40 mg 3 times/day
Adults: 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
Post-MI mortality reduction: Oral: Adults: Initial: 40 mg 3 times/day; usual dosage range: 180-240 mg/day in 3-4 divided doses
Pheochromocytoma: Oral: Adults: 30-60 mg/day in divided doses
Stable angina: Oral: Adults: 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:
Children (unlabeled use): 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
Adults: 10-30 mg/dose every 6-8 hours
Elderly: Initial: 10 mg twice daily; increase dosage every 3-7 days; usual dosage range: 10-320 mg given in 2 divided doses
I.V.:
Children (unlabeled use): 0.01-0.1 mg/kg/dose slow IVP over 10 minutes; maximum dose: 1 mg for infants; 3 mg for children
Adults: 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.
Elderly: Use caution; initiate at lower end of the dosing range.
Hypercyanotic spells (TOF) (unlabeled use): Children:
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
Thyroid storm (unlabeled use):
Children: 0.5 mg/kg/dose every 4-8 hours; titrate to effective dose (Eyal, 2008)
Adults:
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:
Children: 10-40 mg every 6 hours; titrate to effective dose (Eyal, 2008)
Adolescents and Adults: 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: Adults:
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 adjustment in renal impairment:
Not dialyzable (0% to 5%); supplemental dose is not necessary.
Peritoneal dialysis effects: Supplemental dose is not necessary.
Dosing adjustment in hepatic disease: Marked slowing of heart rate may occur in chronic liver disease with conventional doses; low initial dose and regular heart rate monitoring
Administration: Oral
Do not crush long-acting forms.
Administration: I.V.
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.
Administration: I.V. Detail
pH: 2.8-3.5
Monitoring Parameters
Acute cardiac treatment: Monitor ECG, heart rate, and blood pressure with I.V. administration; heart rate and blood pressure with oral administration
Reference Range
Therapeutic: 50-100 ng/mL (SI: 190-390 nmol/L) at end of dose interval
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)
Patient Education
If administered by infusion, report immediately any pain, redness, or swelling at infusion site; palpitations or chest pain; dizziness; or difficulty breathing. Oral: If you have diabetes, monitor blood sugars carefully; beta-blockers may mask hypoglycemic symptoms. Do not crush or chew long-acting forms; swallow whole. Report to your prescriber symptoms of orthostatic hypotension, dizziness, drowsiness, or blurred vision. May cause nausea, vomiting, clay-colored stool, or stomach discomfort. Report chest pain or palpitations; persistent dizziness or lethargy; any CNS symptoms (amnesia, change in cognition, confusion, depression, hallucinations, insomnia, vivid dreams); discolored skin or rash; difficulty breathing or wheezing; or weakness, pain, or loss of sensation in extremities.
Geriatric Considerations
Since bioavailability increased in about twofold in elderly patients, geriatrics may require lower maintenance doses. Also, as serum and tissue concentrations increase beta1 selectivity diminishes. Beta-adrenergic blockade may result in less hemodynamic response than seen in younger adults due to alterations in the beta-adrenergic autonomic system. Studies indicate that despite decreased sensitivity to the chronotropic effects of beta-blockade with age, there appears to be an increased myocardial sensitivity to the negative inotropic effect during stress (ie, exercise). Controlled trials have shown the overall response rate for propranolol to be only 20% to 50% in elderly populations. Therefore, all beta-adrenergic blocking drugs may result in a decreased response as compared to younger adults. Due to propranolol's CNS penetration and nonselective action, it may not be the beta-blocker of choice for use in elderly.
Anesthesia and Critical Care Concerns/Other Considerations
Evidence-Based Information:
Surgery: The ACCF/AHA 2009 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery recommend beta-blockers be continued in patients undergoing surgery who are receiving beta-blockers to treat ACCF/AHA Class I guideline indications such as angina, symptomatic arrhythmias, or hypertension (Class I recommendation).
The majority of published trials suggest a benefit of perioperative beta-blocker use during noncardiac surgery especially in high-risk patients; however, more recent clinical trials have not shown a benefit to perioperative beta-blockade for noncardiac surgery especially when higher fixed-dose regimens are employed (Juul, 2006; POISE study group, 2008; Yang, 2006). Therefore, the guidelines suggest that perioperative beta-blocker therapy titrated to goal heart rate and blood pressure may be beneficial to patients undergoing intermediate risk (eg, carotid endarterectomy, prostate surgery) or vascular surgeries who have coronary artery disease identified or are at high cardiac risk (Class IIa recommendation). High cardiac risk is defined as having >1 of the following clinical risk factors: History of ischemic heart disease, compensated or prior heart failure, cerebrovascular disease, diabetes mellitus, or renal insufficiency (serum creatinine: >2 mg/dL). The use of beta-blockers is uncertain in patients undergoing intermediate risk or vascular surgery with ≤1 clinical risk factor (Class IIb recommendation). Based on available evidence, beta-blockers should be started days to weeks before elective surgery in selected patients when possible and titrated to adequate heart rate control (eg, between 60-80 beats per minute) while avoiding clinically significant bradycardia and hypotension. Routine administration of high fixed-dose beta-blockade without dose titration is not useful and may be harmful to beta-blocker naïve patients undergoing noncardiac surgery.
Cardiovascular Considerations
Atrial Fibrillation: Beta-blocker therapy provides effective rate control in patients with atrial fibrillation.
Chronic Stable Angina: Beta-blockers are effective in the treatment of angina as monotherapy or when combined with nitrates and/or calcium channel blockers. In patients with severe intractable angina requiring negative cardiac chronotropic medications, pacemaker placement has been carried out to maintain heart rate in the setting of large doses of beta-blockers and/or calcium channel blockers. Beta-blockers are ineffective in the treatment of pure vasospastic (Prinzmetal) angina.
Coronary Artery Bypass Graft (CABG) Surgery: In patients undergoing CABG, the use of beta-blockers has consistently demonstrated a reduction in the incidence of postoperative atrial fibrillation (POAF). The 2011 ACCF/AHA CABG guidelines recommend the administration of beta-blockers (not specified) for at least 24 hours prior to CABG in all patients unless a contraindication exists. Beta-blockade should be reinstituted as soon as possible after the surgery and prescribed to all CABG patients who do not have contraindications at the time of hospital discharge. Patients who are at high risk of developing POAF who have contraindications to beta-blockade may receive preoperative amiodarone instead. The use of preoperative beta-blockers has also demonstrated a reduction of in-hospital mortality (especially in patients with and LVEF>30%). Beta-blockers also reduce perioperative myocardial ischemia therefore strengthening the need for perioperative administration. In patients who cannot tolerate oral beta-blockade, the use of I.V. beta-blockers (eg, esmolol, metoprolol) is reasonable (Hillis, 2011).
Hypertension: Beta-blocker therapy in the treatment of hypertension has been associated with improved cardiovascular outcomes. According to the 2003 JNC-VII guidelines for the treatment of hypertension, most patients with hypertension will require treatment with at least 2 antihypertensives. First-line therapy for hypertension is a diuretic (eg, hydrochlorothiazide or chlorthalidone). When a diuretic cannot be used or when a compelling indication exists that requires the use of other drugs, other types of antihypertensives may be used (eg, ACEIs, ARBs, beta-blockers, CCBs). Beta-blockers are among the multiple choices of agents that have shown benefit in a number of different patient subtypes. Compelling indications for a beta-blocker include patients with heart failure, postmyocardial infarction, high coronary disease risk, or diabetes. In type 2 diabetic patients, a UK Prospective Diabetes Study Group (UKPDS) trial showed that beta-blocker therapy (atenolol) was as effective as an ACE inhibitor in reducing cardiovascular events and that the benefits of therapy were related more to the degree of antihypertensive efficacy rather than the class of drug used.
Treatment should be targeted to a goal blood pressure of <140/90 mm Hg. If diabetes or renal disease coexists, the blood pressure goal should be <130/80 mm Hg.
ST-Segment Elevation Myocardial Infarction (STEMI): Beta-blockers, without intrinsic sympathomimetic activity (ISA), have been shown to decrease morbidity and mortality when initiated in the acute treatment of STEMI and continued long-term. Oral beta-blockade should be initiated promptly in patients without contraindications (eg, signs of heart failure, evidence of a low output state, risk of cardiogenic shock, or other beta-blocker contraindications) (Class I recommendation). Use of intravenous beta-blockade may be considered and given promptly if the patient is experiencing concomitant hypertension or a tachyarrhythmia (Class IIa recommendation).
Unstable Angina/Non-ST-Segment Elevation MI (UA/NSTEMI): In the treatment of UA/NSTEMI, oral beta-blockade should be initiated within the first 24 hours in patients without contraindications (eg, signs of heart failure, evidence of a low output state, risk of cardiogenic shock, or other beta-blocker contraindications) (Class I recommendation). Use of intravenous beta-blockade should only be considered if the patient is experiencing concomitant hypertension upon presentation (Class IIa recommendation).
Withdrawal: Beta-blocker therapy should not be withdrawn abruptly, but gradually tapered to avoid acute tachycardia and hypertension.
Dental Health: Effects on Dental Treatment
Propranolol is a nonselective beta-blocker and may enhance the pressor response to epinephrine, resulting in hypertension and bradycardia. Many nonsteroidal anti-inflammatory drugs, such as ibuprofen and indomethacin, can reduce the hypotensive effect of beta-blockers after 3 or more weeks of therapy with the NSAID. Short-term NSAID use (ie, 3 days) requires no special precautions in patients taking beta-blockers.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
Use with caution; epinephrine has interacted with nonselective beta-blockers to result in initial hypertensive episode followed by bradycardia
Mental Health: Effects on Mental Status
Fatigue and malaise are common and often mistaken for depression; may also cause dizziness, confusion, insomnia, or hallucinations
Mental Health: Effects on Psychiatric Treatment
Low-dose propranolol is considered by many to be the drug of choice for akathisia. Concurrent use with psychotropic drugs may produce additive hypotensive effects; monitor blood pressure. Cutaneous reactions, including Stevens-Johnson syndrome, have been reported with use of propranolol; use caution with lamotrigine or valproic combination as combined usage with propranolol has been associated with these reactions.
Nursing: Physical Assessment/Monitoring
Assess potential for adverse interactions with cardiac medications, antihypertensives, antimalarials, antipsychotics, or antidiabetic agents. I.V. infusion usually requires hemodynamic monitoring; consult institution protocols. When discontinuing, drug must be tapered gradually over 2 weeks to avoid acute tachycardia, hypertension, and/or ischemia. Caution patients with diabetes to monitor blood glucose levels closely; beta-blockers can mask hypoglycemic symptoms.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, extended release, oral, as hydrochloride: 60 mg, 80 mg, 120 mg, 160 mg
InnoPran XL®: 80 mg, 120 mg
Capsule, sustained release, oral, as hydrochloride:
Inderal® LA: 60 mg, 80 mg, 120 mg, 160 mg
Injection, solution, as hydrochloride: 1 mg/mL (1 mL)
Injection, solution, as hydrochloride [preservative free]: 1 mg/mL (1 mL)
Solution, oral, as hydrochloride: 4 mg/mL (500 mL); 8 mg/mL (500 mL)
Tablet, oral, as hydrochloride: 10 mg, 20 mg, 40 mg, 60 mg, 80 mg
Pricing: U.S. (www.drugstore.com)
Capsule, 24-hour (Inderal LA)
60 mg (30): $155.99
120 mg (30): $182.00
160 mg (30): $260.00
Capsule, 24-hour (InnoPran XL)
80 mg (30): $71.74
120 mg (30): $71.99
Capsule, 24-hour (Propranolol HCl CR)
60 mg (100): $124.99
80 mg (100): $145.98
120 mg (30): $55.99
160 mg (100): $179.98
Tablets (Propranolol HCl)
10 mg (100): $13.99
20 mg (100): $13.99
40 mg (30): $12.99
60 mg (60): $55.99
80 mg (90): $15.99
References
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.
American Academy of Pediatrics Committee on Drugs, "Transfer of Drugs and Other Chemicals Into Human Milk," Pediatrics, 2001, 108(3):776-89.
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.
Annequin D, Tourniaire B, Massiou H, et al, “Migraine and Headache in Childhood and Adolescence,” Pediatr Clin North Am, 2000, 47(3):617-31.
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.
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.
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.
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.
Bartosh S and Aronson A, “Childhood Hypertension. An Update on Etiology, Diagnosis and Treatment,” Pediatr Clin North Am, 1999, 46(2):235-52.
Bille B, Ludvigsson J, and Sanner G. “Prophylaxis of Migraine in Children,” Headache, 1977, 17(2):61-3.
Blomström-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.
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.
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.
Cumming GR and Carr W, “Hemodynamic Effects of Propranolol in Patients With Fallot's Tetralogy,” Am Heart J, 1967, 74(1):29-36.
Cumming GR, “Propranolol in Tetralogy of Fallot,” Circulation, 1970, 41(1):13-15.
“Drugs for Pediatric Emergencies. Committee on Drugs, Committee on Drugs, 1996 to 1997, Liaison Representatives, and AAP Section Liaisons,” Pediatrics, 1998, 101(1):E13.
Eades SK, “Pharmacotherapy of Congenital Heart Defects,” J Pediatr Pharm Prac, 2000, 5(1):15-34.
Eyal O and Rose SR, “Thyroid Disease,” in Roger's Textbook of Pediatric Intensive Care, 4th ed, David G Nichols, ed, Philadelphia, PA: Lippincott, Williams, & Wilkins, 2008.
Farine M and Arbus G, “Management of Hypertensive Emergencies in Children,” Pediatr Emerg Care, 1989, 5(1):51-5.
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.
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.
Fraker TD, Fihn SD, Gibbons RJ, et al, “2007 Chronic Angina Focused Update of the ACC/AHA 2002 Guidelines for the Management of Patients With Chronic Stable Angina: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Writing Group to Develop the Focused Update of the 2002 Guidelines for the Management of Patients With Chronic Stable Angina,” Circulation, 2007, 116(23):2762-72.
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.
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.
Gardner DG, “Endocrine Emergencies,” in Greenspan's Basic & Clinical Endocrinology, 9th ed, Gardner DG and Shoback D eds, The McGraw-Hill Companies Inc, 2011.
Garson A Jr, Gillette PC, and McNamara DG, “Propranolol: The Preferred Palliation for Tetralogy of Fallot,” Am J Cardiol, 1981, 47(5):1098-104.
Geffner DL and Hershman JM, “beta-Adrenergic Blockade for the Treatment of Hyperthyroidism,” Am J Med, 1992, 93(1):61-8.
Gibbons RJ, Abrams J, Chatterjee K, et al, “ACC/AHA 2002 Guideline Update for the Management of Patients With Chronic Stable Angina - Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina),” J Am Coll Cardiol, 2003, 41(1):159-68.
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.
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.
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.
Lang DM, “Anaphylactoid and Anaphylactic Reactions. Hazards of Beta-Blockers,” Drug Saf, 1995, 12(5):299-304.
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.
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.
Mokhlesi B, Leikin JB, Murray P, et al, “Adult Toxicology in Critical Care: Part II: Specific Poisonings,” Chest, 2003, 123(3):897-922.
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.
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.
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.
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.
Rabins PV, Blacker D, Rovner BW, et al, “Practice Guideline for the Treatment of Patients With Alzheimer's Disease and Other Dementias,” October, 2007. Available at http://www.psych.org/psych_pract/treatg/pg/prac_guide.cfm
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.
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.
Schön MP and Boehncke WH, “Psoriasis,” N Eng J Med, 2005, 352(18):1899-1912.
Shah PM and Kidd L, “Circulatory Effects of Propranolol in Children With Fallot's Tetralogy,” Am J Cardiol, 1967, 19(5):653-7.
Shanks RG, Hadden DR, Lowe DC, et al, “Controlled Trial of Propranolol in Thyrotoxicosis,” Lancet, 1969, 1(7603):993-4.
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.
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.
Smith CS and Howard NJ, “Propranolol in Treatment of Neonatal Thyrotoxicosis,” J Pediatr, 1973, 83:1046.
Strasburger JF, "Cardiac Arrhythmias in Childhood. Diagnostic Considerations and Treatment," Drugs, 1991, 42(6):974-83.
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.
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.
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.
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.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
Content last modified March 2012
| 
