ThisiscontentfromElsevier'sDrugInformation
Propranolol
Learn more about Elsevier's Drug Information today! Get the drug data and decision support you need, including TRUE Daily Updates™ including every day including weekends and holidays.
NOTE: Similar clinical efficacy (e.g., exercise tolerance, chest pain, blood pressure or heart rate control) are seen with equivalent daily doses of sustained-release propranolol (Inderal LA) compared to regular-release propranolol tablets (given in divided doses).
Initially, 10 to 20 mg PO 2 to 4 times per day, then increase at 3 to 7 day intervals up to 160 to 320 mg/day, given in 2 to 4 divided doses. In geriatric patients, begin with conservative initial doses and titrate carefully; the elderly have unpredictable responses to beta-blockers.
80 mg PO once daily, then increase at 3 to 7 day intervals up to 160 to 320 mg PO once daily. In geriatric patients, begin with conservative initial doses and titrate carefully; the elderly have unpredictable responses to beta-blockers.
0.5 to 1 mg IV, followed in 1 to 2 hours by a switch to oral therapy. Per clinical practice guidelines, the intravenous dose can be reserved for high-risk patients and eliminated from the regimen in intermediate- and low-risk patients.[23966] In geriatric patients, use conservative dose; the elderly have unpredictable responses to beta-blockers.
40 to 80 mg PO every 6 to 8 hours; begin 1 to 2 hours after initial IV therapy. Per clinical practice guidelines, the intravenous dose can be reserved for high-risk patients and eliminated from the regimen in intermediate- and low-risk patients.[23966] In geriatric patients, begin with conservative initial doses and titrate carefully; the elderly have unpredictable responses to beta-blockers.
1 mg IV every 2 minutes as needed for up to 3 doses.[56966] [66054] The FDA-approved dosage is 1 to 3 mg IV every 2 minutes for 2 doses with further doses given after 4 hours or more. Reserve use for atrial fibrillation or flutter that is unresponsive to standard therapy or when more prolonged control is required.[45870] Guidelines recommend IV beta-blockers to slow the ventricular response to atrial fibrillation in the acute setting in the absence of pre-excitation and to slow rapid ventricular response with acute coronary syndrome and no heart failure, hemodynamic instability, or bronchospasm.[56966] [65848]
0.01 mg/kg/dose IV every 6 to 8 hours as needed. May titrate dosage gradually as needed for clinical effect. Max: 0.15 mg/kg/dose or 3 mg/dose, whichever is less.[51735]
0.01 mg/kg/dose IV every 6 to 8 hours as needed. May titrate dosage gradually as needed for clinical effect. Max: 0.15 mg/kg/dose or 1 mg/dose, whichever is less.[51735] [53734]
0.01 mg/kg/dose IV every 6 to 8 hours as needed. May titrate dosage gradually as needed for clinical effect. Max: 0.15 mg/kg/dose or 1 mg/dose, whichever is less.[51735] [53734]
10 to 40 mg PO 3 or 4 times daily.[28271] [56966] Guidelines recommend the use of beta blockers to control the ventricular rate for patients with paroxysmal, persistent, or permanent atrial fibrillation.[56966]
0.5 to 1 mg/kg/day PO divided every 6 to 8 hours, initially. Increase the dose by 1 mg/kg/day every 3 to 5 days as needed for clinical effect. Usual dose: 2 to 4 mg/kg/day. Max: 16 mg/kg/day or 60 mg/day, whichever is less.[51735] [53675] [53676] In older adolescents, 10 to 30 mg/dose PO every 6 to 8 hours may be given.[53680]
0.5 to 1 mg/kg/day PO divided every 6 to 8 hours, initially. Increase the dose by 1 mg/kg/day every 3 to 5 days as needed for clinical effect. Usual dose: 2 to 4 mg/kg/day. Max: 16 mg/kg/day or 60 mg/day, whichever is less.[51735] [53675] [53676]
1 mg IV every 2 minutes as needed for up to 3 doses.[45870] [65743] The FDA-approved dosage is 1 to 3 mg IV every 2 minutes for 2 doses with further doses given after 4 hours or more.[45870]
0.01 mg/kg/dose IV every 6 to 8 hours as needed. May titrate dosage gradually as needed for clinical effect. Max: 0.15 mg/kg/dose or 3 mg/dose, whichever is less.[51735]
0.01 mg/kg/dose IV every 6 to 8 hours as needed. May titrate dosage gradually as needed for clinical effect. Max: 0.15 mg/kg/dose or 1 mg/dose, whichever is less.[51735] [53734]
0.01 mg/kg/dose IV every 6 to 8 hours as needed. May titrate dosage gradually as needed for clinical effect. Max: 0.15 mg/kg/dose or 1 mg/dose, whichever is less.[51735] [53734]
10 mg PO 3 to 4 times daily, initially. Adjust dose as needed based on response. Max: 160 mg/day.[65743]
0.5 to 1 mg/kg/day PO divided every 6 to 8 hours, initially. Increase the dose by 1 mg/kg/day every 3 to 5 days as needed for clinical effect. Usual dose: 2 to 4 mg/kg/day. Max: 16 mg/kg/day or 60 mg/day, whichever is less.[51735] [53675] [53676] In older adolescents, 10 to 30 mg/dose PO every 6 to 8 hours may be given.[53680]
0.5 to 1 mg/kg/day PO divided every 6 to 8 hours, initially. Increase the dose by 1 mg/kg/day every 3 to 5 days as needed for clinical effect. Usual dose: 2 to 4 mg/kg/day. Max: 16 mg/kg/day or 60 mg/day, whichever is less.[51735] [53675] [53676]
60 mg PO once daily, initially. Adjust dose as needed based on response. Max: 160 mg/day.[65743]
80 or 160 mg PO as a single dose at the onset of tachycardia episode, in combination with diltiazem.[65743] [70727] [70728]
180 to 240 mg/day PO, given in 3 to 4 divided doses starting in the first 24 hours post-MI.[28271] [50429]
40 mg PO twice daily, initially. May increase dose gradually if further control is needed. Usual dose: 120 to 240 mg/day in 2 to 3 divided doses. Max: 640 mg/day.[28271]
0.5 to 2 mg/kg/day PO in 2 to 4 divided doses, initially. May increase dose if further control is needed. Usual dose: 1 to 6 mg/kg/day. Max: 8 mg/kg/day or 640 mg/day.[32337] [42868] [53585] [53686] [53687] [53688]
0.25 mg/kg/dose PO every 6 to 8 hours, initially. May increase dose if further control is needed. Max: 3.5 mg/kg/dose; others recommend a maximum of 5 mg/kg/day.[53681] [53682]
0.25 mg/kg/dose PO every 6 to 8 hours, initially. May increase dose if further control is needed. Max: 3.5 mg/kg/dose; others recommend a maximum of 5 mg/kg/day.[53681] [53682]
80 mg PO once daily, initially. May increase dose gradually if further control is needed. Usual dose: 120 to 160 mg PO once daily. Max: 640 mg/day.[53617]
80 mg PO once daily, initially. May increase dose to 120 mg PO once daily if further control is needed. Max: 120 mg/day.[40143]
0.01 mg/kg/dose (Max: 0.15 mg/kg/dose) IV every 6 to 8 hours as needed.[53681] [53682]
20 to 40 mg PO 3 or 4 times daily. For geriatric patients, begin with low initial doses, followed by careful dosage titration; geriatric patients have unpredictable responses to beta-blockers.
80 to 160 mg PO once daily. For geriatric patients, begin with low initial doses, followed by careful dosage titration; geriatric patients have unpredictable responses to beta-blockers.
The usual dosage is 60 mg/day PO, given in divided doses for 3 days before surgery, in conjunction with an alpha-blocker. For the management of inoperable tumors, the usual dosage is 30 mg daily in divided doses as adjunctive therapy to alpha-adrenergic blockade. For geriatric patients, begin with low initial doses, followed by careful dosage titration; the elderly have unpredictable responses to beta-blockers.
80 mg/day PO in divided doses, initially. May increase the dose gradually as needed. Usual dose: 160 to 240 mg/day in divided doses. Discontinue if adequate results not achieved within 4 to 6 weeks.[28271] [53585] Guidelines classify propranolol as having established efficacy for migraine prophylaxis.[57981] [69288] [70645]
80 mg PO once daily, initially. May increase the dose gradually as needed. Usual dose: 160 to 240 mg/day. Discontinue if adequate results not achieved within 4 to 6 weeks.[53617] Guidelines classify propranolol as having established efficacy for migraine prophylaxis.[57981] [69288] [70645]
0.6 to 3 mg/kg/day PO in 2 to 3 divided doses. Max: 120 mg/day.[33312] [53692] [53693] [53694] [53695] [53696] Pediatric patients receiving propranolol are possibly more likely than those receiving placebo to have at least a 50% reduction in headache frequency.[64586]
0.6 to 3 mg/kg/day PO in 2 to 3 divided doses. Max: 60 mg/day.[33312] [53692] [53693] [53694] [53695] [53696] Pediatric patients receiving propranolol are possibly more likely than those receiving placebo to have at least a 50% reduction in headache frequency.[64586]
40 mg PO twice daily. Increase dose as needed to 120 to 320 mg/day PO given in 2 to 3 divided doses. In geriatric patients, begin with conservative initial doses and titrate carefully; geriatric patients have unpredictable responses to beta-blockers.[28271] Clinical practice guidelines consider propranolol effective for the treatment of essential tremor.[58395]
Limited experience; dosage often not reported in the literature; efficacy rate of 50%, along with side effect profile may lead to pursuit of other treatment options. 0.5 to 1 mg/kg/day PO, given in 3 divided doses has been recommended by some experts as an initial dose. Titrate dosage gradually once weekly. Alternatively, 30 mg PO once daily, then increased to 30 mg PO twice daily has been effective in improving hand tremor. Many patients respond to a total daily dosage of 60 to 80 mg/day PO. Max: 4 mg/kg/day PO. Dosage may also be taken as needed 30 minutes prior to activities disrupted by essential tremor. Pharmacotherapy should be reserved for patients whose tremor is functionally or socially limiting. Once an optimal dosage is determined, patients may transition to an extended-release formulation of propranolol, to be given once daily. Many patients require larger doses after 1 year of therapy, due to drug tolerance and disease progression.[53697] [53698]
Limited experience; dosage often not reported in the literature; efficacy rate of 50%, along with side effect profile may lead to pursuit of other treatment options. 0.5 to 1 mg/kg/day PO, given in 3 divided doses has been recommended by some experts as an initial dose using immediate release dose forms. Titrate dosage gradually once weekly as necessary; many patients respond to a total daily dosage of 60 to 80 mg/day PO. Max: 4 mg/kg/day PO. Dosage may also be taken as needed 30 minutes prior to activities disrupted by essential tremor. Pharmacotherapy should be reserved for patients whose tremor is functionally or socially limiting; most do not require therapy until adolescence. Once an optimal dosage is determined, patients may transition to an extended-release formulation of propranolol, to be given once daily. Many patients require larger doses after 1 year of therapy, due to drug tolerance and disease progression.[53697] [53698]
Limited data suggest 30 to 80 mg/day PO may be effective; the daily dose is divided into 3 or 4 doses for administration. A common starting dose is 10 mg PO 3 times daily. In a single-blind crossover comparison of propranolol and placebo in 10 patients with lithium-induced tremor, propranolol (30 to 80 mg/day PO) and placebo were administered during two 2-week periods, 1 week on propranolol and 1 on placebo in random order. In period 1, 8 patients reported a preference for propranolol over placebo and 5 patients in period 2 reported a preference for propranolol. Treatment with propranolol resulted in a reduction in the intensity of tremor from very troublesome or somewhat troublesome to noticeable but not troublesome or not present. No adverse reactions were reported with propranolol treatment.[43172] In a case report of 5 patients with lithium-induced tremor, treatment with propranolol 30 to 40 mg/day PO, in 3 or 4 divided doses, resulted in control of the tremor. Recurrence of the tremor was reported in 3 of the cases when propranolol therapy was discontinued.[43176] In geriatric patients, begin with conservative initial doses and titrate carefully; geriatric patients have unpredictable responses to beta-blockers.
10 to 80 mg PO, given 1 hour prior to the anxiety-producing event. For geriatric patients, begin with low initial doses, followed by careful dosage titration; geriatric patients have unpredictable responses to beta-blockers.
10 to 40 mg PO every 6 to 8 hours.[61515] [64934] [68190]
60 to 80 mg PO every 4 hours.[61515]
1 to 2 mg IV every 15 minutes up to 10 mg.[68189] [68190]
10 to 40 mg PO every 6 to 8 hours.[53789] [64934]
2 mg/kg/day PO divided every 6 to 12 hours (Max: 40 mg/dose); occasionally higher doses are required.[64934] Flat doses of 20 to 40 mg PO every 6 to 8 hours have been used to treat older children with thyroid storm.[53789] [53790]
1 to 2 mg/kg/day PO divided doses every 6 to 12 hours; occasionally higher doses are required.[53710] [53711] [53712] [53713] [53714] [53785] [53786] [53787] [64934]
1 to 2 mg/kg/day PO divided doses every 6 to 12 hours; occasionally higher doses are required.[53710] [53711] [53712] [53713] [53714] [53785] [53786] [53787] [64934]
1 to 3 mg IV as a single dose.[53789] [53790]
Initially, 40 mg PO twice daily, then increase at 3 to 7 day intervals up to 160 to 480 mg/day PO to attain desired blood pressure response. For geriatric patients, begin with low initial doses, followed by careful dosage titration; geriatric patients have unpredictable responses to beta-blockers.
20 to 40 mg PO twice daily, initially. Increase the dose every 2 to 3 days until resting heart rate of 55 to 60 beats per minute with systolic blood pressure of 90 mmHg or more. Max: 320 mg/day in persons without ascites; 160 mg/day in persons with ascites.[70539]
Most of the literature describing positive outcomes in the treatment of chronic aggression with propranolol involved patients with co-existing organic brain disease or schizophrenia recalcitrant to other aggression modalities. For patients without preexisting cardiovascular disorders, some authors have suggested a beginning dose of 20 mg PO 3 times per day, increasing the total dose by 40 to 60 mg/day every 3 days. Mean dosages range from 160 to 320 mg/day.[24581] For geriatric patients, begin with low initial doses, followed by careful dosage titration; geriatric patients have unpredictable responses to beta-blockers.
1 mg/kg/day PO divided every 6 hours, initially. After 1 week, may titrate dose by 1 mg/kg/day every 24 hours as necessary. Average dose: 2.3 mg/kg/day (range: 0.8 to 5 mg/kg/day). Usual Max: 5 mg/kg/day. If the patient becomes refractory after initial control, may increase dose gradually to a maximum of 10 to 15 mg/kg/day; monitor heart size, heart rate, and cardiac contractility closely. Alternatively, 4 mg/kg/day PO divided every 6 hours has been used as an initial dose.[53716] [53717]
0.15 to 0.25 mg/kg/dose (Max: 1 mg/dose) IV; may repeat once. Alternatively, 0.01 to 0.02 mg/kg/dose IV has been used, reserving higher doses for refractory spells.[32485] [44772]
To reduce the risk of hypoglycemia, administer propranolol immediately after or concurrently with a feeding. Avoid fasting; if inevitable, hold medication or support with a product such as Pedialyte or glucose-containing IV fluids.[53721] [56853] Vital signs and cardiorespiratory exam or ECG should be obtained at baseline.[53721] Obtain blood pressure and heart rate measurements at 1 and 2 hours after the initial dose and any significant dose increase (e.g., more than 0.5 mg/kg/day).[53721] [56853] Experts have recommended propranolol therapy continue until full involution of the lesion has occurred or the patient is at least 1 year of age; recurrences have been reported with early discontinuation. At the end of therapy, gradually taper propranolol over 2 to 4 weeks.[53640] [53722] [53723] [53724] [53725] [53726] [63864] If hemangiomas recur, treatment may reinitiated.[56853]
0.6 mg/kg/dose PO twice daily given at least 9 hours apart. After 1 week of treatment, increase dosage to 1.1 mg/kg/dose PO twice daily. After 2 weeks of treatment, increase dosage to 1.7 mg/kg/dose PO twice daily and maintain this dosage for 6 months. Readjust dosage periodically based on weight increases.[56853]
1 mg/kg/DAY PO initially, titrated to a target dose of 2 to 3 mg/kg/DAY, unless there are comorbidities (e.g., PHACE syndrome, progressive ulceration) or adverse reactions that require a lower dose. Administer in 2 to 3 divided doses; administer 3 times daily to minimize abrupt changes in blood pressure in high risk patients.[53721] [63864] [63885] Infantile hemangiomas often respond rapidly even to low doses of propranolol; dose escalation and optimal target dose should be based on individual patient response. Consensus guideline initiation protocols are based on corrected gestational age, social support status, and patient comorbidities affecting the cardiovascular or respiratory systems, and/or blood glucose maintenance. Inpatient initiation (neonates and infants younger than 8 weeks, inadequate social support, or comorbidities): 0.33 mg/kg/dose PO every 8 hours. If tolerated, increase dose to 0.66 mg/kg/dose PO every 8 hours and prepare for discharge. If the dose is not tolerated at any point in time, reduce the dosage and gradually increase to the target dose; it is recommended patients be discharged on a tolerated dose of at least 1 mg/kg/day. Outpatient initiation (infants older than 8 weeks and adequate social support): 0.33 mg/kg/dose PO given 3 times daily at least 6 hours apart. If tolerated for 3 to 7 days, increase dose to 0.5 mg/kg/dose PO given 3 times daily. If once again tolerated for 3 to 7 days, increase dose to 0.66 mg/kg/dose PO given 3 times daily. If the dose is not tolerated at any point in time, reduce the dosage and gradually increase to the target dose; consider a target dose of 1 mg/kg/day.[53721]
1 mg/kg/day PO, given in divided doses every 4 hours. Adjust dose as needed to achieve a target 20% reduction in heart rate from baseline to a maximum dose of 1.98 mg/kg/day. Median dose: 80 mg/day.[57432]
1 to 4 mg/kg/day PO, given in divided doses every 6 hours. Adjust dose as needed to decrease heart rate by 10% to 20% of the admission value or mean age-based population value. 4 mg/kg/day PO was the mean effective dose in an interim analysis of children (n = 90; mean age 7 +/- 5 years) with more than 30% total body surface area burns. Propranolol therapy began 96 hours postburn and continued for 1 year with few adverse effects. Propranolol therapy significantly reduced heart rate and resting energy expenditure, decreased truncal fat accumulation, prevented bone loss, and improved lean body mass accretion. Maximum dose not clearly defined; severely burned adult patients standardly receive 20 mg PO every 6 hours, with dosage titrated as needed.[53802] [53803] [53804]
Initially, 0.5 to 1 mg/kg/day PO, given in divided doses every 6 to 8 hours has been recommended for sympathetic inhibition. Titrate dosage gradually every 3 to 14 days to a target dose of 2 mg/kg/day PO (range: 1.5 to 3 mg/kg/day). Monitor heart rate and blood pressure.[53738] [53739] [53740]
10 to 40 mg PO every 6 hours.[65747] [68764]
60 to 160 mg PO every 12 hours.[65747] [68764]
1 to 3 mg IV every 5 minutes as needed up to a total of 5 mg.[65747]
160 mg/day PO for idiopathic hypertrophic subaortic stenosis (IHSS); 240 mg/day PO for migraine prophylaxis, myocardial infarction prophylaxis, or post-myocardial infarction; 320 mg/day PO for angina, paroxysmal supraventricular tachycardia (PSVT), or tremor; 640 mg/day PO for hypertension. NOTE: Assumes equivalent maximum daily dosage for immediate-release and extended-release products.
160 mg/day PO for idiopathic hypertrophic subaortic stenosis (IHSS); 240 mg/day PO for migraine prophylaxis, myocardial infarction prophylaxis, or post-myocardial infarction; 320 mg/day PO for angina, paroxysmal supraventricular tachycardia (PSVT), or tremor; 640 mg/day PO for hypertension. NOTE: Assumes equivalent maximum daily dosage for immediate-release and extended-release products.
Safety and efficacy have not been established; the dose required is dependent on route of administration, indication, and often clinical response. For tachyarrhythmias, doses up to 60 mg/day PO (or 120 mg/day PO in older adolescents) or 0.25 mg/kg/dose IV (Max: 3 mg/dose) have been used. For hypertension, doses up to 8 mg/kg/day PO (Max: 640 mg/day) have been used. For migraine prophylaxis, doses up to 120 mg/day PO have been used. For essential tremor, doses up to 4 mg/kg/day PO have been used.
Children weighing more than 35 kg: Safety and efficacy have not been established; the dose required is dependent on route of administration, indication, and often clinical response. For tachyarrhythmias, doses up to 60 mg/day PO or 0.25 mg/kg/dose IV (Max: 3 mg/dose) have been used. For hypertension, doses up to 8 mg/kg/day PO (Max: 640 mg/day) have been used. For migraine prophylaxis, doses up to 120 mg/day PO have been used. For essential tremor, doses up to 4 mg/kg/day PO have been used. For tetralogy spells, doses up to 15 mg/kg/day PO have been used (doses more than 5 mg/kg/day PO require close monitoring).
Children weighing 35 kg or less: Safety and efficacy have not been established; the dose required is dependent on route of administration, indication, and often clinical response. For tachyarrhythmias, doses up to 60 mg/day PO or 0.25 mg/kg/dose IV (Max: 3 mg/dose) have been used. For hypertension, doses up to 8 mg/kg/day PO (Max: 640 mg/day) have been used. For migraine prophylaxis, doses up to 60 mg/day PO have been used. For essential tremor, doses up to 4 mg/kg/day PO have been used. For tetralogy spells, doses up to 15 mg/kg/day PO have been used (doses more than 5 mg/kg/day PO require close monitoring).
3.4 mg/kg/day PO for infantile hemangiomas. Safety and efficacy for other indications have not been established; the dose required is dependent on route of administration, indication, and often clinical response. For tachyarrhythmias, doses up to 16 mg/kg/day PO (Max: 60 mg/day) or 0.15 mg/kg/dose IV (Max: 1 mg/dose) have been used. For hypertension, doses up to 3.5 mg/kg/dose PO have been used. For tetralogy spells, doses up to 15 mg/kg/day PO have been used (doses more than 5 mg/kg/day PO require close monitoring).
Safety and efficacy have not been established; the dose required is dependent on route of administration, indication, and often clinical response. For tachyarrhythmias, doses up to 16 mg/kg/day PO (Max: 60 mg/day) or 0.15 mg/kg/dose IV (Max: 1 mg/dose) have been used. For hypertension, doses up to 3.5 mg/kg/dose PO or 0.15 mg/kg/dose IV have been used.
Since propranolol is primarily metabolized by the liver, initiate therapy at a reduced dosage for the specified indication; carefully titrate the dosage to attain the desired clinical goals.
No dosage adjustment needed.
Intermittent hemodialysis
No dosage adjustments are needed; propranolol is not significantly dialyzable.[40143]
† Off-label indication
Propranolol is the prototype of the beta-adrenergic receptor antagonists. It is a competitive, nonselective beta-blocker without intrinsic sympathomimetic activity, similar to nadolol. Although propranolol has membrane-stabilizing effects on the action potential, these effects are clinically insignificant except in overdose situations. Propranolol is a racemic compound, with only its l-isomer having any adrenergic blocking activity. The 2007 AHA guidelines for the management of hypertension state beta-blockers should not be used as first-line therapy for the treatment of hypertension, as several comparative clinical trials have shown beta blockers to be inferior to ACE inhibitors, angiotensin-receptor blockers, or calcium channel blockers for preventing both stroke and coronary artery disease complications. These guidelines do, however, recommend the use of beta-blockers for the treatment of hypertension in patients with angina, prior myocardial infarction, or heart failure.[33826] Propranolol was first approved by the FDA in 1967; an extended-release formulation designed for bedtime-dosing was approved in March 2003. Hemangeol, an oral solution specifically approved for treatment of proliferating infantile hemangiomas, was approved by the FDA in March 2014.
For storage information, see the specific product information within the How Supplied section.
Immediate-release tablets: Administer with food.[28271]
Sustained-release capsules (e.g., Inderal LA): Administer once daily. Do not crush or chew; swallow whole. If patients are switched from immediate-release tablets to sustained-release capsules, assure desired therapeutic effects are maintained. Substitution should not be simply considered 1:1 as lower plasma concentrations are achieved with the long-acting product. Further titration may be necessary.[53617][53771]
Generic Oral Solution (4 mg/mL or 8 mg/mL):
Hemangeol Oral Solution (4.28 mg/mL; for infantile hemangioma):
IV bolus injection:
Continuous IV infusion:
Most adverse effects of propranolol are manifestations of its therapeutic effect. Sinus bradycardia and hypotension are rarely serious and can be reversed with IV atropine if necessary. AV block, secondary to depressed conduction at the AV node, may necessitate sympathomimetic and/or pressor therapy or use of a temporary pacemaker. Paresthesias of the hands and arterial insufficiency, usually of the Raynaud type, also have been reported.[28271] Peripheral coldness was reported in 7% to 8% of infants during infantile hemangioma clinical trials.[56853]
Heart failure has been reported with the use of propranolol.[28271] Congestive heart failure is more likely to occur in patients with preexisting left ventricular dysfunction and usually will respond to discontinuation of propranolol therapy. Elevations of blood urea nitrogen also have been reported in patients with severe heart failure who are taking propranolol.
Dizziness was reported in 4% to 7% and fatigue in 5% to 7% of patients with hypertension who received propranolol extended-release capsules in clinical trials.[40143] Additional adverse CNS effects reported with propranolol therapy include lethargy, weakness, catatonia, an acute reversible syndrome characterized by disorientation to time and place, visual impairment (reported as visual disturbances), hallucinations, short-term memory impairment, emotional lability, slightly clouded sensorium (e.g., confusion), vivid dreams (e.g., nightmares), decreased performance on neuropsychometrics, and depression manifested by insomnia. With immediate-release formulations, fatigue, lethargy, and vivid dreams appear to be dose-related.[28271] During clinical trials of propranolol oral solution for infantile hemangioma, unspecified sleep disorders (16% to 17.5%), nightmares, (2% to 6%), agitation (4.5% to 8.5%), irritability (1% to 5.5%), and drowsiness (0.9% to 5%) were among the most common adverse events.[56853] [69076]
Gastrointestinal adverse effects reported with propranolol use include nausea, vomiting, diarrhea, constipation, abdominal pain (cramping), epigastric distress, mesenteric arterial thrombosis, and ischemic colitis.[28271] During clinical trials of propranolol oral solution for infantile hemangioma, diarrhea (4.5% to 6%), anorexia (2.5% to 3.5%), abdominal pain (0.5% to 3.5%), and vomiting were commonly reported.[56853]
Patients with preexisting bronchospastic disease are at high risk for exacerbation of asthma, dyspnea, or bronchospasm when treated with propranolol. Bronchospasm has been reported coincident with propranolol therapy in pediatric patients.[28271] During infantile hemangioma clinical trials, aggravated respiratory tract infection such as bronchitis (8% to 13%) and bronchiolitis associated with cough and a febrile response were among the most frequently reported adverse events. In the event of a lower respiratory tract infection associated with dyspnea and wheezing, propranolol therapy should be interrupted if the clinical condition allows (e.g. migraine prophylaxis, treatment for hemangioma).[56853]
Beta-blockers may inhibit catecholamine-induced glycogenolysis, gluconeogenesis, and lipolysis, predisposing to hypoglycemia.[53721] [67279] Additionally, beta-blockers can also mask signs of hypoglycemia (e.g., tachycardia) and increase the risk for severe or prolonged hypoglycemia at any time during treatment especially in persons with diabetes mellitus, pediatric patients, and persons who are fasting (i.e., surgery, not eating regularly, or are vomiting).[40143] [53617] Hypoglycemia may present in the form of seizures, lethargy, or coma.[56853] Instruct caregivers and patients to seek immediate medical treatment if severe hypoglycemia occurs.[53617] [40143] To reduce the risk of hypoglycemia in pediatric patients, administer propranolol shortly before or after feeds and maintain a consistent feeding schedule. Carefully monitor vital signs and blood glucose concentration during drug initiation and dosage escalation. Advise caregivers with special instructions for dosage adjustment or discontinuation during intercurrent illness (if clinical condition allows) and alternative dietary recommendations.[53721] [56853] Beta-blockers may also inhibit insulin secretion through blockade of beta-2-receptors on pancreatic islet cells, which may cause hyperglycemia or reduce insulin secretion in response to hyperglycemia; adjust the dose of antidiabetic drugs as necessary.[26823] [30575] [67279] In addition to acute blood glucose effects, beta-blockers have been shown to increase the risk of developing diabetes mellitus in adult hypertensive patients.[26823] [67279] [67280]
Some beta-blockers have been shown to cause hypertriglyceridemia and decrease plasma HDL levels during therapy. The clinical implications of these effects, in light of other cardiovascular advantages of beta-blocker therapy, are not known.[24483] Hypertriglyceridemia is not reported as and adverse effect by the manufacturer of propranolol.[28271]
Propranolol therapy has been associated with isolated reports of exacerbation of myopathy and myotonia. Use caution in patients with pre-existing skeletal muscle disease.[40143]
In hypertensive patients, propranolol has been associated with hyperkalemia and elevated hepatic enzymes (e.g., serum transaminases and alkaline phosphatase).[28271]
Male impotence (erectile dysfunction) has been reported with various beta-blocker therapies, including propranolol. Peyronie disease (an abnormal curvature of the penis during erection with penile fibrosis) has also been reported with propranolol, but is considered to be very rare.[28271] [40143]
Rare but severe hematologic side effects, such as agranulocytosis, have been reported with propranolol therapy. Non-thrombocytopenic purpura and thrombotic thrombocytopenic purpura (TTP) also have been reported.[28271]
Hypersensitivity reactions, including anaphylactic/anaphylactoid reactions, pharyngitis and agranulocytosis, erythematous rash, urticaria, fever combined with aching and sore throat, laryngospasm, and respiratory distress have been reported with propranolol use. Dermatologic reactions with beta-blockers are usually mild and transient. Some of these reactions include pruritus, reversible alopecia, xerosis, xerophthalmia, psoriaform rash, psoriasis, dermatitis psoriasiform, and exfoliative dermatitis. In addition, more serious dermatologic reactions have been reported including Stevens-Johnson Syndrome, toxic epidermal necrolysis, and erythema multiforme.[28271] [53642] [56853]
Lupus-like symptoms and systemic lupus erythematosus have been reported with the use of propranolol.[28271]
Withdrawal symptoms, including headache, diaphoresis, palpitations, sinus tachycardia, tremor, and hypertension, have been associated with abrupt discontinuation of beta-blockers in hypertensive patients. Gradual tapering and/or prolonged administration of small doses of propranolol prior to complete cessation may prevent these symptoms.[54110] [54113]
Abrupt discontinuation of any chronically administered beta-adrenergic blocking agent, such as propranolol, can result in the exacerbation of angina and, in some cases, myocardial ischemia or myocardial infarction, ventricular arrhythmias, or severe hypertension, especially in patients with preexisting cardiac disease. If chronic, oral propranolol therapy is to be discontinued, gradually decrease the dosage over a minimum of 2 weeks. Downward titration of parenteral therapy may be advisable if the patient will discontinue propranolol treatment. Advise patients and caregivers against interruption or cessation of therapy without the advice of a physician. If exacerbation of angina occurs during discontinuation of therapy, it is advised to reinstitute propranolol therapy and take other measures appropriate for the management of unstable angina.[28271] [45870] [53585] [53617]
Beta-blockers, like propranolol, should be used with caution in patients with hyperthyroidism or thyrotoxicosis because beta-blockade can mask tachycardia, which is a useful monitoring parameter in thyroid disease. Abrupt withdrawal of beta-blockers in a patient with hyperthyroidism can precipitate thyroid storm. Note that beta-blockers (particularly atenolol, propranolol and esmolol) are generally useful for the acute symptomatic treatment of the thyrotoxic patient. Beta-blockers can reduce tachycardia, tremor, and anxiety in the hyperthyroid patient.[28271]
Propranolol is contraindicated in sinus bradycardia, sick sinus syndrome, and second or third-degree AV block, unless a permanent pacemaker is in place.[28271] [40143] [45870] Propranolol oral solution for infantile hemangioma is contraindicated in infants with bradycardia or hypotension defined as a heart rate less than 80 beats per minute or blood pressure less than 50/30 mmHg.[56853] Propranolol is also contraindicated in cardiogenic shock or acute heart failure. Sympathetic stimulation is necessary in supporting circulatory function in congestive heart failure, and beta blockade carries the potential hazard of further depressing myocardial contractility and precipitating more severe failure.[28271] [45870] [56853] Clinical guidelines state that evidence of cardiogenic shock or heart failure, sinus bradycardia, or heart block greater than first degree are potential exclusions for the use of propranolol for infantile hemangioma that require appropriate subspecialty evaluation and clearance.[63864]
Beta-blockade in patients with Wolff-Parkinson-White syndrome and tachycardia can result in severe bradycardia requiring treatment with a pacemaker. In one case, this occurred after an initial propranolol dose of 5 mg.[28271]
Because of potential effects of beta-blockade on blood pressure and pulse, beta-blockers, like propranolol, should be used with caution in patients with cerebrovascular insufficiency (cerebrovascular disease) or stroke. If signs or symptoms suggesting reduced cerebral blood flow develop after initiation of beta-blocker, alternative therapy should be considered.[53631] In young patients being treated for an infantile hemangioma, propranolol therapy may increase the risk of stroke in PHACE syndrome (Posterior fossa anomalies, Hemangioma, Arterial lesions, Cardiac abnormalities/aortic coarctation, and abnormalities of the Eye) patients with severe cerebrovascular anomalies. Prior to initiation of propranolol therapy, investigate patients with large facial hemangiomas for potential arteriopathy associated with PHACE syndrome.[56853]
Do not routinely withdraw chronic beta-blocker therapy before surgery; the impaired ability of the heart to respond to reflex adrenergic stimuli may increase the risk of surgical procedures and general anesthesia.[53617] Evaluate the risks versus benefits in individual patients by considering the type of surgery (e.g., cardiac vs. noncardiac), coexisting health conditions, and anesthetic strategy. Guidelines recommend continuance in patients already on beta-blocker therapy; however, initiation well before planned procedure and careful perioperative titration to achieve adequate heart rate control while avoiding significant bradycardia or hypotension is suggested.[56484] [70331]
Use propranolol with caution in patients with hepatic disease, because of possible decreased clearance of the drug; reduced doses may be indicated (see Dosage). Propranolol is extensively metabolized by the liver.[28271]
Propranolol oral solution for infantile hemangiomas is contraindicated in premature neonates, neonates, and infants with a corrected age younger than 5 weeks as well as any infant weighing less than 2 kg.[56853] Clinical guidelines recommend caution, but not exclusion, in infants younger than 5 weeks of age and/or postconceptual age younger than 48 weeks.[63864] Although other propranolol products are not FDA-approved for pediatric use, they are used clinically in patients as young as neonates. Bronchospasm and congestive heart failure have been reported coincident with propranolol use in children. Additionally, propranolol therapy can cause hypoglycemia, particularly in neonates, infants, and children.[28271] Neonates and infants are more sensitive to the negative inotropic and chronotropic effects of propranolol, and intravenous propranolol should be used with extreme caution in these populations.[53765] Monitor heart rate and blood pressure closely after treatment initiation or dose escalation with any dosage form; in patients being treated for infantile hemangiomas, heart rate and blood pressure should be closely monitored for 2 hours after initiation and any significant dose escalation.[53721] [56853] Discontinue treatment if severe (less than 80 bpm) or symptomatic bradycardia or hypotension (less than 50 mmHg systolic blood pressure) occurs.[56853] Propranolol-induced hypoglycemia may be more common during periods of fasting (e.g., irregular feeding schedules, preoperative intake abstinence, vomiting), after prolonged physical exertion, in patients with renal insufficiency, or when glucose demands are increased (e.g., cold, stress, infections).[28271] [53640] [56853] Neonates and infants younger than 3 months of age are at higher risk for drug-induced hypoglycemia; in patients receiving propranolol for hemangioma, doses should be held during periods of irregular feeding or vomiting.[53640] [56853] Hypoglycemic symptoms are often difficult to detect in infants and young children.[41518] Careful monitoring (vital signs, blood glucose concentrations) during initiation and slow dose escalation are recommended. Advise caregivers of appropriate measures to decrease the risk of hypoglycemia, focusing on the importance of frequent feedings (every 3 to 4 hours, with nutrition given shortly before or after administration). In addition, provide caregivers with special instructions for dosage adjustment or discontinuation during intercurrent illness (if clinical condition allows) and alternative dietary recommendations. Inform caregivers to discontinue propranolol and seek immediate medical attention if signs of hypoglycemia are present. Administration of dextrose-containing IV fluids may be necessary.[41518] [53640] [53721] [56853]
Beta-blockers may inhibit catecholamine-induced glycogenolysis, gluconeogenesis, and lipolysis, predisposing to hypoglycemia.[53721] [67279] Additionally, beta-blockers can also mask signs of hypoglycemia (e.g., tachycardia) and increase the risk for severe or prolonged hypoglycemia at any time during treatment, especially in persons with diabetes mellitus, neonates, infants, children, and persons who are fasting (i.e., surgery, not eating regularly, or are vomiting). Risk of hypoglycemia is also increased with renal insufficiency, after prolonged physical exertion, or when glucose demands are increased (e.g., cold, stress, infections).[28271] [40143] [53617] [53640] Neonates and infants younger than 3 months of age are at higher risk for drug-induced hypoglycemia; in patients receiving propranolol for hemangioma, doses should be held during periods of irregular feeding or vomiting.[53640] [56853] Instruct caregivers and patients to seek immediate medical treatment if severe hypoglycemia occurs.[28271] [40143] [53617] [53640] Beta-blockers may also inhibit insulin secretion through blockade of beta-2-receptors on pancreatic islet cells, which may cause hyperglycemia or reduce insulin secretion in response to hyperglycemia; adjust dose of antidiabetic drugs as necessary.[26823] [30575] [67279] In addition to acute blood glucose effects, beta-blockers have been shown to increase the risk of developing diabetes mellitus in adult hypertensive patients; evaluate this risk relative to the proven benefits of beta-blockers in reducing cardiovascular events.[26823] [67279] [67280]
Propranolol is contraindicated in patients with bronchial asthma or a history of bronchospasm. Propranolol should generally not be used in patients with pulmonary disease (e.g., chronic obstructive pulmonary disease (COPD), emphysema, bronchitis), or during acute bronchospasm because bronchodilation can be inhibited.[28271] When used for the treatment of hemangioma, the FDA-approved product label recommends interrupting propranolol therapy in the event of a lower respiratory tract infection associated with dyspnea and wheezing.[56853]
Propranolol is contraindicated in patients exhibiting hypersensitivity to the drug or any of its excipients. Hypersensitivity reactions, including anaphylactic/anaphylactoid reactions, have been associated with the administration of propranolol.[28271] Do not use propranolol in patients with known beta-blocker hypersensitivity. Cross-sensitivity between beta-blockers may occur.[32916] [44577] [44579] [44580] In addition, patients receiving beta-blockers who have a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated allergen challenge and unresponsive to usual doses of epinephrine used to treat anaphylaxis.[28271] [56853]
Avoid propranolol in patients with Raynaud's phenomenon or peripheral vascular disease because reduced cardiac output and the relative increase in alpha stimulation can exacerbate symptoms.[53654]
Beta-blockers, like propranolol, may potentiate muscle weakness in patients with myasthenia gravis. Use propranolol with caution in patients with other underlying skeletal muscle disease. Isolated cases of exacerbation of myopathy and myotonia have been reported.[40143]
The use of propranolol has been associated with depression.[28271] Beta-blockers with high lipophilicity, such as propranolol, are more likely to cause CNS adverse effects, including depression. Propranolol should be avoided in patients with major depression; alternative hydrophilic beta-blocking agents (e.g., acebutolol, atenolol, nadolol) may be considered as alternative therapy.
Beta-blockers, like propranolol, may be associated with dizziness or drowsiness in some patients.[28271] Patients should be cautioned to avoid driving or operating machinery until the drug response is known.
Use propranolol with caution in patients with renal impairment because decreased plasma clearance may occur. In patients with renal failure, down-regulation of hepatic microsomal enzymes may result in decreased drug metabolism.[28271] [45870]
Beta-blockers, like propranolol, may exacerbate conditions such as psoriasis.[28271]
Prolonged experience with propranolol in pregnancy, based on published interventional and observational studies, has not identified a drug-associated risk of major birth defects, miscarriage, or other adverse maternal outcomes. Propranolol crosses the placenta. Bradycardia, hypoglycemia, and respiratory depression have been observed with exposure to beta-blockers in utero near the time of obstetric delivery. Monitor neonates with in utero exposure to propranolol closely at birth and manage accordingly. There are inconsistent reports of intrauterine growth restriction associated with propranolol; hypertension also increases fetal risk for intrauterine growth restriction.[40143]
Propranolol is present in human milk at low concentrations but the related risk to the breast-feeding infant is unknown.[40143] Propranolol has generally been considered compatible with breast-feeding in clinical use. Other beta-blockers that previous AAP recommendations regarded as usually compatible with breast-feeding include labetalol, metoprolol, nadolol, sotalol, and timolol; these agents may represent preferable alternatives for some patients.[27500] There is no data on the effects of propranolol on milk production. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.[40143]
Clinical studies of propranolol (various dosage forms) have generally not included sufficient numbers of geriatric subjects aged 65 and over to determine whether they respond differently from younger adults. Most clinical experience has not determined differences between geriatric and younger adult patients given propranolol. Geriatric subjects have decreased clearance and a longer mean elimination half-life of propranolol. These findings suggest that dose adjustment of propranolol may be required for older adult patients. In general, dose selection should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of the decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Adjust doses to tolerance and desired clinical response.[28271] [53617] [45870] [40143]
Tobacco smoking can increase the clearance rate of propranolol, due to induction of hepatic microsomal enzymes by the hydrocarbons in tobacco.[28271] At this time, no specific dosage recommendations are recommended for smokers. Because the effect on hepatic microsomal enzymes is not related to the nicotine component of tobacco, sudden smoking cessation may result in a reduced clearance of propranolol (and potentially other beta-blockers), despite the initiation of nicotine replacement. Monitor patients carefully when changes in smoking status occur.
Propranolol oral solution for infantile hemangioma (Hemangeol) is contraindicated in patients with pheochromocytoma.[56853] In general, beta-blocker monotherapy should be used with caution in patients with a pheochromocytoma or vasospastic angina (Prinzmetal's angina) because of the risk of hypertension secondary to unopposed alpha-receptor stimulation. In patients with pheochromocytoma, an alpha-blocking agent should be used prior to the initiation of any beta-blocker.[28271] [40143] [45870]
Mechanism of Action: Like other beta-adrenergic antagonists, propranolol competes with adrenergic neurotransmitters (e.g., catecholamines) for binding at sympathetic receptor sites. Similar to atenolol and metoprolol, propranolol blocks sympathetic stimulation mediated by beta1-adrenergic receptors in the heart and vascular smooth muscle. Pharmacodynamic consequences of beta1-receptor blockade include a decrease in both resting and exercise heart rate and cardiac output, and a decrease in both systolic and diastolic blood pressure. Propranolol may reduce reflex orthostatic hypotension. The fall in cardiac output induced by beta1 effects is often countered by a moderate reflex increase in peripheral vascular resistance that can be magnified by beta2 blockade (unmasked alpha stimulation). As a result, nonselective beta-blocking agents can produce a more modest decrease in (diastolic) blood pressure compared with selective beta1-antagonists. In addition, propranolol also can competitively block beta2-adrenergic responses in the bronchial muscles, potentially inducing bronchospasm.
Actions that make propranolol useful in treating hypertension include a negative chronotropic effect that decreases heart rate at rest and after exercise; a negative inotropic effect that decreases cardiac output; reduction of sympathetic outflow from the CNS; and suppression of renin release from the kidneys. Thus, propranolol, like other beta-blockers, affects blood pressure via multiple mechanisms. In general, beta-blockers without intrinsic sympathomimetic activity (ISA) exert detrimental effects on LVH and the lipid profile, and cause sexual dysfunction.
Actions that make propranolol useful in treating hypertension also apply to managing chronic stable angina. The reduction in myocardial oxygen demand induced by propranolol results in decreases in the frequency of anginal attacks and requirements of nitrate, and increases exercise tolerance. Other postulated anti-anginal actions include an increase in oxygen delivery to tissues, due to propranolol-induced lowering of hemoglobin's affinity for oxygen, and a reduction of platelet aggregation, postulated to be related to interference with calcium ion flux.
Propranolol has been used to treat portal hypertension and to prevent bleeding of esophageal varices. Nonselective beta-blockers decrease portal venous pressure, decrease blood flow in the superior portosystemic collateral circulation, and decrease blood flow in the splanchnic region.[24084] Beta-blockade decreases cardiac output reducing hepatic arterial and portal venous perfusion. Activation of unopposed alpha-receptors lead to splanchnic vasoconstriction, thus decreasing portal perfusion.[24085]
Propranolol is used to treat hypertension and the subsequent decline of renal function in patients with scleroderma renal crisis (SRC). SRC is associated with elevated peripheral renin concentrations. Propranolol blocks beta-receptors located on the surface of the juxtaglomerular cells which decreases the release of renin. In turn, this affects the renin-angiotensin-aldosterone system reducing blood pressure.
Numerous mechanisms may contribute to the efficacy of propranolol in preventing migraine headaches.[23792] Beta-blockade can prevent arterial dilation, inhibit renin secretion, and can interfere with catecholamine-induced lipolysis. A decrease in lipolysis decreases arachidonic acid synthesis and, subsequent, prostaglandin production. Inhibition of platelet aggregation is due to this decrease in prostaglandins and blockade of catecholamine-induced platelet adhesion. Other actions include increased oxygen delivery to tissues and prevention of coagulation during epinephrine release.
Propranolol has two roles in the treatment of thyrotoxicosis; these actions are determined by the different isomers of propranolol. L-propranolol causes beta-blockade and can ameliorate the symptoms associated with thytotoxicosis such as tremor, palpitations, anxiety, and heat intolerance. D-propranolol blocks the conversion of T4 to T3, but the therapeutic effect of this action is minimal.[24123]
Propranolol has been used in the management of hereditary or familial essential tremor. Beta-blockade controls the involuntary, rhythmic and oscillatory movements of essential tremor. Tremor amplitude is reduced, but not the frequency of tremor. The mechanism of action is unclear, but the antitremor effect may be mediated by blockade of peripheral beta2 receptor mechanisms.
Propranolol can dampen the peripheral physiologic symptoms of anxiety. Beta-blockade can attenuate somatic symptoms of anxiety such as palpitations and tremor, but it is less effective in controlling psychologic components, such as intense fear. These effects are thought to be due to improvement in somatic symptoms secondary to beta-blockade, although the mechanism of action is unclear.
Revision Date: 12/07/2024, 01:50:00 AMPropranolol is administered orally or intravenously. Propranolol is highly lipophilic and is widely distributed throughout the body. It readily crosses the blood-brain barrier and the placenta, and is distributed into breast milk. Propranolol is about 90% bound to plasma proteins, the R(+)-enantiomer primarily binds albumin while the S(-)-enantiomer is primarily bound to alpha-1 acid glycoprotein. The volume of distribution is about 4 L/kg. In normal subjects receiving oral doses of racemic propranolol, S(-)-enantiomer concentrations exceeded those of the R(+)-enantiomer by 40% to 90% as a result of stereoselective hepatic metabolism.[53617]
Propranolol is extensively metabolized upon first pass through the liver, and the extent of metabolism is dependent on liver blood flow. The drug also binds to and saturates nonspecific hepatic binding sites before the drug reaches the systemic circulation. An equipotent, pharmacologically active metabolite, 4-hydroxypropranolol, is produced with the initiation of oral therapy, but it is eliminated faster than the parent drug. With chronic or IV therapy, this metabolite is produced to a lesser degree. Overall, at least 8 metabolites of propranolol have been identified. Important differences may exist among ethnic groups in the ability to metabolize propranolol, which can affect the overall efficacy of the drug in some instances. Excretion of propranolol occurs renally, primarily as metabolites, with only 1% to 4% of a dose excreted fecally as unchanged drug. Clearance of the pharmacologically active S(-)-propranolol is lower than R(+)-propranolol after intravenous and oral doses. The elimination half-life of propranolol ranges from 2 to 6 hours, with chronic administration yielding longer half-lives, possibly due to saturation of liver binding sites and/or systemic clearance.[53617]
Affected cytochrome P450 enzymes:
Cytochrome P450 enzymes involved in the metabolism of propranolol include 2D6, 1A2, and 2C19. Propranolol is also a substrate for the efflux transporter PGP. The aromatic hydroxylation of propranolol to form the active metabolite, 4-hydroxypropranolol, is mediated by CYP2D6. 4-hydroxypropranolol is a substrate and weak inhibitor of CYP2D6. In healthy subjects, no difference in clearance or half-life of propranolol was observed between extensive and poor CYP2D6 metabolizers. In extensive metabolizers, a significant increase in 4-hydroxypropranolol clearance and a significant decrease in the clearance of naphthyloxyactic acid, an inactive metabolite, was noted.[53617]
After oral administration of immediate-release propranolol, the dose is almost completely absorbed, however, due to high first pass metabolism, bioavailability is only about 25%. Peak concentrations of immediate release tablets and long acting capsules are achieved in 1 to 4 hours and about 6 hours, respectively. Food can increase the bioavailability of the immediate release formulation by approximately 50% but does not affect the time to peak concentration. The effect of food on the bioavailability of the sustained-release formulation has not been investigated.[53617]
The distribution half-life of intervenously administered propranolol is 5 to 10 minutes. Pharmacodynamic effects are seen immediately and maintained for 2 to 4 hours.[45870]
Propranolol undergoes extensive hepatic metabolism and half-life appears to be prolonged in patients with hepatic impairment. In one study, 7 patients with cirrhosis were compared to 9 healthy subjects, each were given 7 doses of 80 mg propranolol every 8 hours. The half-life of propranolol was prolonged in patients with cirrhosis (11 hours) compared to healthy subjects (4 hours). On average, patients with cirrhosis had 3 times the concentration of unbound propranolol as the healthy subjects. A similar study, conducted with the long acting formulation, yielded a similar result with unbound propranolol concentrations increasing 2.5-fold in cirrhosis patients. After a single IV dose, the half-life of propranolol in cirrhosis patients and healthy subjects was 7.2 hours and 2.9 hours, respectively.[53617] Another study examined propranolol pharmacokinetics after a single 40 mg IV dose was given to 6 healthy subjects and 20 subjects with chronic liver disease, including hepatic cirrhosis. Patients with chronic liver disease had decreased clearance, increased volume of distribution, decreased protein binding, and increased variation in half-life compared to healthy subjects.[45870]
A reduced propranolol half-life has been reported in patients with renal impairment. This reduction in half-life is seen in conjunction with delayed absorption rate and peak propranolol plasma levels 3 to 4 fold higher than healthy subjects. In a single dose study comparing 5 chronic renal failure patients, 6 dialysis patients, and 5 healthy subjects, peak propranolol concentrations in renal failure patients were 2 to 3 times higher than in dialysis patients or healthy subjects. The renal failure group also displayed reduced plasma propranolol clearance. However, propranolol is not appreciably removed by hemodialysis.[53617]
Children and Adolescents
The extent of propranolol protein binding in children and adolescents (age 6 to 15 years) is similar to that of adults.[53780] In a pharmacokinetic study of cyanotic infants and children (n = 5), ages 9 months to 6 years old, mean half-life for propranolol was 4.9 +/- 1 hours (range: 3.9 to 6.4 hours). Mean half-life for the active metabolite 4-hydroxy propranolol was 6.3 +/- 1.1 hours (range: 5.2 to 7.5 hours). Investigators found no correlation between half-life and age.[53781]
Infants
Pharmacokinetics of propranolol were evaluated in a multiple dose 12 week study of infants with hemangioma (n = 23; age range: 35 to 150 days). Propranolol was initiated at 1.2 mg/kg/day PO and titrated at weekly intervals to a target dose of 3.4 mg/kg/day PO, divided into twice daily dosing. Plasma propranolol concentrations were dose-proportional in the range studied. At target dose steady state, peak plasma concentrations were observed within 2 hours. Clearance (2.7 L/kg/hour in infants younger than 90 days and 3.3 L/kg/hour in infants older than 90 days) was similar to that in adults when adjusted for body weight. Median elimination half-life was 3.5 hours. The plasma concentration of 4-hydroxy propranolol was approximately 5% of total plasma exposure of propranolol.[56853] In pharmacokinetic study of cyanotic children (n = 5) including 1 infant (age: 9 months), mean half-life of propranolol was 4.9 +/- 1 hours (range: 3.9 to 6.4 hours). Mean half-life for the active metabolite 4-hydroxy propranolol was 6.3 +/- 1.1 hours (range: 5.2 to 7.5 hours). Investigators found no correlation between half-life and age.[53781]
Neonates
Protein binding of propranolol is approximately 70% in neonates.[53624] In a pharmacokinetic study of 36 neonates (mean gestational age 28 weeks; range: 23 to 42 weeks), patients were treated with high dose [HD] (n = 28; 0.5 mg/kg/dose PO every 6 hours) or low dose [LD] (n = 8; 0.25 mg/kg/dose PO every 6 hours) propranolol. All patients received propranolol administered by mouth or orogastric tube as a syrup shortly after a meal. As observed in children and adults, neonates displayed considerable interpatient variability in plasma propranolol concentrations in patients receiving the same dose; in neonates such variability may be a consequence of hepatic immaturity and a variable first pass effect. Drug plasma concentrations appeared to be directly related to the propranolol dose, suggesting good oral bioavailability. Mean peak plasma concentration (Cmax) was 71.7 +/- 29.8 ng/mL in the HD group and 33.9 +/- 19.1 ng/mL in the LD group; mean AUC was 364.7 +/- 150.2 ng/mL and 161.3 +/- 88.3 ng/mL in the HD and LD groups, respectively. Mean Tmax was 2.6 +/- 0.9 hours in the HD group and 2.3 +/- 0.8 hours in the LD group. Half-life was similar in both groups (HD = 14.9 +/- 4.3 hours; LD = 15.9 +/- 6.1 hours), but significantly prolonged compared to adults, most likely explained by hepatic immaturity in the neonate. Mean plasma clearance was 27.2 +/- 13.9 mL/kg/minute in the HD group and 31.3 mL/kg/minute in the LD group.[53797]
Propranolol clearance appears to be reduced and half-life prolonged in the older adult population. A single dose study of 32 patients of varying ages found an inverse correlation between age and clearance of propranolol metabolites (4 hydroxypropranolol and naphthoxylactic acid). A second study comparing 12 older adults (62 to 79 years old) and 12 young (25 to 33 years old) patients reported reduced clearance of the S(-) enantiomer in the older adult group. This study also reported prolonged half-life in the older adult (11 hours) compared to the young group (5 hours).[53617]
Intravenous propranolol was evaluated in 5 women and 6 men. After adjusting for weight, no significant differences were found in half-life, volume of distribution, protein binding or clearance.[45870] In women, neither estradiol nor testosterone have demonstrated any change to propranolol plasma binding or clearance. Conflicting evidence exists in regard to the role of testosterone in propranolol metabolism and clearance in men.[53617]
African-American patients appear to have increased propranolol clearance and Chinese patients may have increased unbound propranolol concentrations as compared to White patients. In a study of 12 White and 13 African-American men, clearance of both enantiomers was increased in the African-American group. Reported increase in clearance was 76% for the R(+) enantiomer and 53% for the S(-) enantiomer. In another study, unbound plasma propranolol was 18% to 45% higher in Chinese subjects than White subjects.[53617]
In one study, obese subjects had higher AUC and lower total clearance of IV propranolol than non-obese subjects. No significant difference between the groups was noted for plasma protein binding.[45870]
Thyroid Dysfunction
No significant pharmacokinetic changes have been noted between hyperthyroid, hypothyroid and euthyroid subjects.[45870]
Prolonged experience with propranolol in pregnancy, based on published interventional and observational studies, has not identified a drug-associated risk of major birth defects, miscarriage, or other adverse maternal outcomes. Propranolol crosses the placenta. Bradycardia, hypoglycemia, and respiratory depression have been observed with exposure to beta-blockers in utero near the time of obstetric delivery. Monitor neonates with in utero exposure to propranolol closely at birth and manage accordingly. There are inconsistent reports of intrauterine growth restriction associated with propranolol; hypertension also increases fetal risk for intrauterine growth restriction.[40143]
Propranolol is present in human milk at low concentrations but the related risk to the breast-feeding infant is unknown.[40143] Propranolol has generally been considered compatible with breast-feeding in clinical use. Other beta-blockers that previous AAP recommendations regarded as usually compatible with breast-feeding include labetalol, metoprolol, nadolol, sotalol, and timolol; these agents may represent preferable alternatives for some patients.[27500] There is no data on the effects of propranolol on milk production. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.[40143]
Cookies are used by this site. To decline or learn more, visit our cookie notice.
Copyright © 2024 Elsevier, its licensors, and contributors. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
