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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.
Medication Safety Issues
Sound-alike/look-alike issues:
Propranolol may be confused with Pravachol®, Propulsid®
Inderal® may be confused with Adderall®, Enduron®, Enduronyl®, Imdur®, Imuran®, Inderide®, Isordil®, Toradol®
Inderal® 40 may be confused with Enduronyl® Forte
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.
Significant differences exist between oral and I.V. dosing. Use caution when converting from one route of administration to another.
International issues:
Inderal® may be confused with Indiaral® which is a brand name for loperamide in France
Pronunciation
(proe PRAN oh lole)
U.S. Brand Names
Index Terms
Generic Available
Yes
Canadian Brand Names
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/Investigational
Tremor due to Parkinson's disease; ethanol withdrawal; 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 (manufacturer); D (2nd and 3rd trimesters - expert analysis)
Pregnancy Considerations
Embryotoxicity has been observed in some animal studies. Propranolol crosses the placenta. Beta-blockers have been associated with bradycardia, hypotension, and IUGR. IUGR is probably related to maternal hypertension. Available evidence suggests beta-blockers are generally safe during pregnancy (JNC 7). Neonatal hypoglycemia, respiratory depression and congenital abnormalities have been reported following maternal use of beta-blockers.
Lactation
Enters breast milk/use caution (AAP rates “compatible”)
Breast-Feeding Considerations
Propranolol is excreted in breast milk and breast-feeding is considered compatible by the AAP. It is recommended that the infant be monitored for signs or symptoms of beta-blockade (hypotension, bradycardia, etc) with long-term use.
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 (2nd or 3rd degree), 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): Use with caution in patients with PVD (including Raynaud's).
• 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.
• Thyrotoxicosis: Beta-blockade may mask signs of hyperthyroidism (eg, tachycardia). Abrupt discontinuation of beta-blockade may exacerbate symptoms of hyperthyroidism and may also induce thyroid storm. Alterations in thyroid-function tests may be observed.
Concurrent drug therapy issues:
• Anesthetic agents: Use with caution in patients receiving anesthetic agents which decrease myocardial function (eg, ether, cyclopropane and trichloroethylene); avoid concurrent I.V. use of both agents.
• Calcium channel blockers (nondihydropyridines): Use with caution in patients on concurrent verapamil or diltiazem; bradycardia or heart block can occur.
Special populations:
• Pediatrics: Safety and efficacy have not been established in children.
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.
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), 2C19 (minor), 2D6 (major), 3A4 (minor); Inhibits CYP1A2 (weak), 2D6 (weak)
Drug Interactions
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 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
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 D: Consider therapy modification
Bile Acid Sequestrants: May decrease the serum concentration of Propranolol. 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. Risk C: Monitor therapy
Cardiac Glycosides: Beta-Blockers may enhance the bradycardic effect of Cardiac Glycosides. Risk C: Monitor therapy
Colchicine: P-Glycoprotein 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
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
Dabigatran Etexilate: P-Glycoprotein Inhibitors may increase the serum concentration of Dabigatran Etexilate. Risk X: Avoid combination
Darunavir: May increase the serum concentration of CYP2D6 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
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
Lidocaine: Beta-Blockers may decrease the metabolism 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 effect of Orthostasis Producing Agents. 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 Substrates: P-Glycoprotein Inhibitors may increase the serum concentration of P-Glycoprotein 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
Propoxyphene: May decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. 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 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 enhance the bradycardic effect of Beta-Blockers. Exceptions: 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 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
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). Caution advised with consumption of alcohol 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.
Cigarette: Smoking may decrease plasma levels of propranolol by increasing metabolism.
Herb/Nutraceutical: Avoid dong quai if using for hypertension (has estrogenic activity). Avoid bayberry, blue cohosh, cayenne, ephedra, ginger, ginseng (american), gotu kola, licorice, yohimbe (may worsen hypertension). Avoid black cohosh, california poppy, coleus, garlic, golden seal, hawthorn, mistletoe, periwinkle, quinine, shepherd's purse (have antihypertensive activity, may cause hypotension).
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, gatifloxacin, heparin, hydrocortisone sodium succinate, inamrinone, linezolid, meperidine, milrinone, morphine, potassium chloride, propofol, tacrolimus, vitamin B complex with C. Incompatible: Amphotericin B cholesteryl sulfate complex, lansoprazole.
Compatibility in syringe: Compatible: Inamrinone, milrinone. Incompatible: HCO3.
Compatibility when admixed: Compatible: Dobutamine, verapamil. Incompatible: HCO3.
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
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
0.1 mg/kg divided into 3 equal doses given at 2-3 minute intervals. May repeat total dose in 2 minutes if necessary (ACLS guidelines, 2005)
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
Thyrotoxicosis (unlabeled use):
Oral:
Children: 2 mg/kg/day, divided every 6-8 hours, titrate to effective dose
Adolescents and Adults: Oral: 10-40 mg/dose every 6 hours
I.V.: Adults: 1-3 mg/dose slow IVP as a single dose
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
Do not take any new medication during therapy without consulting prescriber. If administered by infusion; report immediately any pain, redness, or swelling at infusion site; any palpitations or chest pain, dizziness, difficulty breathing, or other adverse reactions. Oral: Take exactly as directed; do not increase, decrease, or discontinue without consulting prescriber. If you have diabetes, monitor blood sugars carefully; beta-blockers may mask hypoglycemic symptoms. Tablets may be crushed and taken with liquids. Do not crush or chew long-acting forms; swallow whole. You may experience orthostatic hypotension, dizziness, drowsiness, or blurred vision. Use caution when driving, climbing stairs, changing position (rising from sitting or lying to standing), or engaging in tasks requiring alertness until response to drug is know. May cause nausea vomiting, or stomach discomfort (small, frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help). Report chest pain or palpitations; persistent dizziness or lethargy; any CNS symptoms (amnesia, change in cognition, confusion, depression, hallucinations, insomnia, vivid dreams; rash; difficulty breathing or wheezing; weakness, pain, or loss of sensation in extremities or other adverse symptoms. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.
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
Clinical Pearls/Comments:
Surgery: Based on available evidence, beta-blockers should be started days to weeks before elective surgery in selected patients when possible and titrated to a heart rate <65 beats per minute. Additional data suggest that long acting beta-blockers may be superior to short acting ones (Redelmeier, 2005). The ACC/AHA 2007 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 angina, symptomatic arrhythmias, hypertension, or other ACC/AHA Class I guideline indications (Class I recommendation). The guidelines also recommend that beta-blockers be given to patients undergoing vascular surgery who have myocardial ischemia demonstrated during preoperative testing (Class I recommendation).
The guidelines also state that beta-blockers are probably recommended in patients undergoing intermediate risk (eg, carotid endarterectomy, prostate surgery) or vascular surgery in whom preoperative assessment identifies coronary heart disease or 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. The use of beta-blockers is uncertain in patients undergoing intermediate risk or vascular surgery with ?1 clinical risk factor (Class IIb 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 (Juul, 2006; Yang, 2006).
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.
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 other pharmacological agents or herbal products patient may be taking (eg, cardiac medications, antihypertensives, antimalarials, antipsychotics, or antidiabetic agents). I.V. infusion usually requires hemodynamic monitoring (consult institution protocols). Assess therapeutic effect (according to purpose for use) and adverse reactions when starting or adjusting dosage and on a regular basis. 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. Teach patient proper use (when self-administered), possible side effects/appropriate interventions, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, extended release, as hydrochloride: 60 mg, 80 mg, 120 mg, 160 mg
InnoPran XL®: 80 mg, 120 mg
Capsule, sustained release, as hydrochloride:
Inderal® LA: 60 mg, 80 mg, 120 mg, 160 mg
Injection, solution, as hydrochloride: 1 mg/mL (1 mL)
Inderal®: 1 mg/mL (1 mL) [DSC]
Solution, oral, as hydrochloride: 4 mg/mL (500 mL); 8 mg/mL (500 mL)
Tablet, 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): $131.37
80 mg (30): $132.48
120 mg (30): $157.40
160 mg (30): $194.99
Capsule, 24-hour (InnoPran XL)
80 mg (30): $71.75
120 mg (30): $73.85
Capsule, 24-hour (Propranolol HCl CR)
60 mg (100): $99.99
80 mg (100): $115.99
120 mg (100): $139.98
160 mg (100): $182.98
Solution (Propranolol HCl)
20 mg/5 mL (240): $25.99
Tablets (Propranolol HCl)
10 mg (100): $12.99
20 mg (100): $13.99
40 mg (30): $12.99
60 mg (60): $55.99
80 mg (90): $15.99
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Last full review/revision January 2010
Content last modified January 2010
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