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.
Mechanism of Action
US Drug Names
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. 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. 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.  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. 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. 
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.
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. 
10 to 40 mg PO 3 or 4 times daily.  Guidelines recommend the use of beta blockers to control the ventricular rate for patients with paroxysmal, persistent, or permanent atrial fibrillation.
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.   In older adolescents, 10 to 30 mg/dose PO every 6 to 8 hours may be given.
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.  
1 mg IV every 2 minutes as needed for up to 3 doses.  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.
10 mg PO 3 to 4 times daily, initially. Adjust dose as needed based on response. Max: 160 mg/day.
60 mg PO once daily, initially. Adjust dose as needed based on response. Max: 160 mg/day.
NOTE: For ST-elevation myocardial infarction, oral beta-blocker therapy should be initiated in the first 24 hours for patients who do not have signs of cardiac failure, evidence of low output, increased risk for cardiogenic shock, or other contraindications for beta-blocker therapy.
0.1 mg/kg IV, administered in 3 equal divided doses at 2 to 3 minute intervals.
180 to 320 mg/day PO, given in 3 to 4 divided doses.
180 to 240 mg/day PO, given in 3 to 4 divided doses starting in the first 24 hours post-MI. 
Initially, 40 mg PO twice daily, then increase at 3 to 7 day intervals up to 160 to 480 mg/day, given in 2 to 3 divided doses. Max: 640 mg/day. In geriatric patients, begin with conservative initial doses and titrate carefully; the elderly have unpredictable responses to beta-blockers.
Initially, 0.5 to 2 mg/kg/day PO in 2 to 4 divided doses. Titrate gradually every 3 to 7 days as needed for clinical effect; heart rate may be dose-limiting. Usual effective dosage is 1 to 6 mg/kg/day. Max: 8 mg/kg/day or 640 mg/day, whichever is less..     
Initially, 0.25 mg/kg/dose PO every 6 to 8 hours. Titrate gradually as needed for clinical effect; heart rate may be dose-limiting. Max: 3.5 mg/kg/dose; others recommend a max of 5 mg/kg/day. 
Initially, 80 mg PO once daily. Increase dosage at 3 to 7 day intervals up to 120 to 160 mg PO once daily. Max: 640 mg/day. In geriatric patients, begin with conservative initial doses and titrate carefully; the elderly have unpredictable responses to beta-blockers.
Initially, 80 mg PO once daily at bedtime (approximately 10 PM). If needed, increase dosage to 120 mg PO once daily at bedtime. Max: 120 mg/day. In geriatric patients, begin with conservative initial doses and titrate carefully; the elderly have unpredictable responses to beta-blockers.
Limited data suggest a continuous infusion of propranolol may be effective in post-surgical patients who cannot tolerate oral therapy. An infusion rate of 2 to 3 mg/hour achieved therapeutic propranolol serum levels within 3 hours. Continuous infusions were administered for up to 9 days. 
0.01 mg/kg/dose slow IV push over 10 minutes, repeated every 6 to 8 hours as needed. Titrate gradually as needed for clinical effect; heart rate may be dose-limiting. Max: 0.15 mg/kg/dose. 
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.  Guidelines classify propranolol as having established efficacy for migraine prophylaxis. 
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. Guidelines classify propranolol as having established efficacy for migraine prophylaxis. 
0.6 to 3 mg/kg/day PO in 2 to 3 divided doses. Max: 120 mg/day.      Pediatric patients receiving propranolol are possibly more likely than those receiving placebo to have at least a 50% reduction in headache frequency.
0.6 to 3 mg/kg/day PO in 2 to 3 divided doses. Max: 60 mg/day.      Pediatric patients receiving propranolol are possibly more likely than those receiving placebo to have at least a 50% reduction in headache frequency.
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. Clinical practice guidelines consider propranolol effective for the treatment of essential tremor.
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. 
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. 
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. 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. 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.  
60 to 80 mg PO every 4 hours.
1 to 2 mg IV every 15 minutes up to 10 mg. 
10 to 40 mg PO every 6 to 8 hours. 
2 mg/kg/day PO divided every 6 to 12 hours (Max: 40 mg/dose); occasionally higher doses are required. Flat doses of 20 to 40 mg PO every 6 to 8 hours have been used to treat older children with thyroid storm. 
1 to 2 mg/kg/day PO divided doses every 6 to 12 hours; occasionally higher doses are required.        
1 to 3 mg IV as a single dose. 
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. A non-selective beta-blocker, including propranolol, or endoscopic variceal ligation (EVL) is recommended to prevent first variceal hemorrhage (primary prophylaxis) in persons with medium/large esophageal varices or high-risk small esophageal varices, and the combination of propranolol plus EVL is recommended in the prevention of rebleeding (secondary prophylaxis).
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. 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. 
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. 
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.  Vital signs and cardiorespiratory exam or ECG should be obtained at baseline. 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).  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.       If hemangiomas recur, treatment may reinitiated.
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.
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.   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.
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.
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.  
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.  
10 to 40 mg PO every 6 hours. 
60 to 160 mg PO every 12 hours. 
1 to 3 mg IV every 5 minutes as needed up to a total of 5 mg.
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.
No dosage adjustments are needed; propranolol is not significantly dialyzable.
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. 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.
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.
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. Peripheral coldness was reported in 7% to 8% of infants during infantile hemangioma clinical trials.
Heart failure has been reported with the use of propranolol. 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. 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. 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. 
Gastrointestinal adverse effects reported with propranolol use include nausea, vomiting, diarrhea, constipation, abdominal pain (cramping), epigastric distress, mesenteric arterial thrombosis, and ischemic colitis. 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.
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. 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).
Beta-blockers, such as propranolol, have been shown to increase the risk of developing diabetes mellitus in hypertensive patients; however this risk should be evaluated relative to the proven benefits of beta-blockers in reducing cardiovascular events. Propranolol can prolong or enhance hypoglycemia by interfering with glycogenolysis; this effect may be less pronounced with beta-1-selective beta-blockers than with nonselective agents. Propranolol can also mask signs of hypoglycemia, especially tachycardia, palpitations, sweating, and tremors; in contrast, the hypertensive response to hypoglycemia is not suppressed with beta-blockade. Hypoglycemia may present in the form of seizures, lethargy, or coma. When given to infants or children, diabetic or not, propranolol has been associated with hypoglycemia especially during periods of fasting (e.g., irregular feeding schedules, preoperative intake abstinence, vomiting).  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.  Beta-blockers can occasionally cause hyperglycemia. This is thought to be due to blockade of beta-2-receptors on pancreatic islet cells, which would inhibit insulin secretion.
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. Hypertriglyceridemia is not reported as and adverse effect by the manufacturer of propranolol.
Propranolol therapy has been associated with isolated reports of exacerbation of myopathy and myotonia. Use caution in patients with pre-existing skeletal muscle disease.
In hypertensive patients, propranolol has been associated with hyperkalemia and elevated hepatic enzymes (e.g., serum transaminases and alkaline phosphatase).
Male impotence (erectile dysfunction) has been reported with various beta-blocker therapies, including propranolol. Peyronie's 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. 
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.
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.  
Lupus-like symptoms and systemic lupus erythematosus have been reported with the use of propranolol.
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. 
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.   
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.
Because beta-blockers, including propranolol, depress conduction through the AV node, they are contraindicated in patients with severe bradycardia or advanced AV block, unless a functioning pacemaker is present. Propranolol is also contraindicated in patients with sick sinus syndrome unless a functioning pacemaker is present. In addition, beta-blockers should be used with caution in combination with other drugs that depress conduction through the AV node. Reduction in heart rate and cardiac output may cause or worsen bradycardia and hypotension. Propranolol oral solution for infantile hemangioma (Hemangeol) is specifically contraindicated in babies with significant bradycardia (less than 80 beats per minute) or hypotension (blood pressure less than 50/30 mmHg). In general, beta-blockers should not be used in patients with acute pulmonary edema and are contraindicated in patients with cardiogenic shock or decompensated acute heart failure, particularly in those with severely compromised left ventricular dysfunction, because the negative inotropic effect of these drugs can further depress cardiac output. In stable patients with heart failure, however, beta-blockers (e.g., bisoprolol, carvedilol, metoprolol) given in low doses have been documented to be beneficial. Many beta-blockers are used in the treatment of hypertrophic cardiomyopathy. Propranolol oral solution for infantile hemangioma (Hemangeol) is strictly contraindicated in patients with pheochromocytoma. 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. In the treatment of myocardial infarction, beta-blockers are contraindicated in patients with hypotension (SBP less than 100 mmHg). 
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.
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. 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.
Beta-blockers, such as propranolol, have been shown to increase the risk of developing diabetes mellitus in hypertensive patients; however, this risk should be evaluated relative to the proven benefits of beta-blockers in reducing cardiovascular events. Use propranolol with caution in patients with poorly controlled diabetes mellitus, particularly brittle diabetes. Beta-blockers can prolong or enhance hypoglycemia by interfering with glycogenolysis; this effect may be less pronounced with beta-1-selective beta-blockers than with nonselective agents. Beta-blockers can also mask signs of hypoglycemia, especially tachycardia, palpitations, diaphoresis, and tremors; in contrast, the hypertensive response to hypoglycemia is not suppressed with beta-blockade. Beta-blockers can occasionally cause hyperglycemia. This is thought to be due to blockade of beta-2-receptors on pancreatic islet cells, which would inhibit insulin secretion. Thus, monitor blood glucose concentrations closely if a beta-blocker is used in a patient with diabetes mellitus. Hypoglycemia has been reported in patients taking propranolol after prolonged physical exertion. Patients with renal insufficiency may be more likely to have hypoglycemic reactions to propranolol. Pediatric patients receiving propranolol, particularly those younger than 3 months, are also at higher risk for drug-induced hypoglycemia.
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.
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. 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.
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. Do not use propranolol in patients with known beta-blocker hypersensitivity. Cross-sensitivity between beta-blockers may occur.    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. 
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.
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.
The use of propranolol has been associated with depression. 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. 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. 
Beta-blockers, like propranolol, may exacerbate conditions such as psoriasis.
The necessity or desirability of withdrawing beta-blockers, such as propranolol, prior to major surgery is controversial; the risks versus benefits should be evaluated in individual patients. Patients receiving beta-blockers before or during surgery involving the use of general anesthetics with negative inotropic effects (e.g., ether, cyclopropane, or trichloroethylene) should be monitored closely for signs of heart failure. Severe, protracted hypotension and difficulty in restarting the heart have been reported after surgery in patients receiving beta-blockers. It should also be noted that because beta-blocker therapy reduces the ability of the heart to respond to beta-adrenergically mediated sympathetic reflex stimuli, the risks of general anesthesia and surgical procedures may be augmented. Although, gradual withdrawal of beta-blockers is sometimes recommended prior to general anesthesia to limit the potential for hypotension and heart failure, the manufacturer does not recommend withdrawal of chronically-administered propranolol prior to major surgery. The risk of precipitating adverse cardiac events (e.g., myocardial infarction, tachycardia) following preoperative withdrawal of beta-blockers may outweigh the risks of ongoing beta-blocker therapy, particularly in patients with co-existing cardiovascular disease. Consideration should be given to the type of surgery (e.g., cardiac vs. noncardiac), anesthetic strategy, and co-existing health conditions. The anesthetic technique may be modified to reduce the risk of concurrent beta-blocker therapy. If needed, the negative inotropic effects of beta-blockers may be cautiously reversed by sufficient doses of adrenergic agonists such as isoproterenol, dopamine, dobutamine, or norepinephrine. Vagal dominance, if it occurs, may be corrected with atropine (1—2 mg IV).
Propranolol oral solution for infantile hemangiomas (Hemangeol) 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. Clinical guidelines recommend caution, but not exclusion, in infants younger than 5 weeks of age and/or postconceptual age younger than 48 weeks. 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. 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).   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.  Hypoglycemic symptoms are often difficult to detect in infants and young children. 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.   
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.
Propranolol is present in human milk at low concentrations but the related risk to the breast-feeding infant is unknown. 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. 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.
Clinical studies of propranolol (various dose forms) have generally not included sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. 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.    The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities. According to the OBRA guidelines, antihypertensive regimens should be individualized to achieve the desired outcome while minimizing adverse effects. Antihypertensives may cause dizziness, postural hypotension, fatigue, and there is an increased risk for falls. Additionally, beta-blockers are associated with depression, bronchospasm, cardiac decompensation that may require dose adjustments in those with acute heart failure, and they may mask some symptoms of hypoglycemia (e.g., tachycardia). Beta-blockers metabolized in the liver may have an increased effect or accumulate in those with hepatic impairment. There are many drug interactions that can potentiate the effects of antihypertensives. Beta-blockers may cause or exacerbate bradycardia, particularly in patients receiving other medications that affect cardiac conduction. When discontinuing, a gradual taper may be required to avoid adverse consequences caused by abrupt discontinuation. The OBRA guidelines also caution that antiarrhythmic agents can have serious adverse effects (e.g., impairment of mental function, appetite, behavior, heart function, or falls) in older individuals.
Tobacco smoking can increase the clearance rate of propranolol, due to induction of hepatic microsomal enzymes by the hydrocarbons in tobacco. 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.
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. 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.
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. 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.
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.
Propranolol 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 40-90% as a result of stereoselective hepatic metabolism.
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 eight 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—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—6 hours, with chronic administration yielding longer half-lives, possibly due to saturation of liver binding sites and/or systemic clearance.
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.
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 1-4 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.
The distribution half-life of intervenously administered propranolol is 5 to 10 minutes. Pharmacodynamic effects are seen immediately and maintained for 2—4 hours.
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. 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.
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—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—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.
Pharmacokinetics of propranolol oral solution were evaluated in a multiple dose 12 week study of infants with hemangioma (n = 23; age range: 35—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 < 90 days old and 3.3 L/kg/hour in infants > 90 days old) 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.
Propranolol clearance appears to be reduced and half-life prolonged in the geriatric 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 elderly (62—79 years old) and 12 young (25—33 years old) patients reported reduced clearance of the S(-) enantiomer in the elderly group. This study also reported prolonged half-life in the elderly (11 hours) compared to the young group (5 hours).
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. 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.
African-Americans appear to have increased propranolol clearance and Chinese may have increased unbound propranolol concentrations as compared to Caucasians. In a study of 12 Caucasian 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 18-45% higher in Chinese subjects than Caucasians.
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.
No significant pharmacokinetic changes have been noted between hyperthyroid, hypothyroid and euthyroid subjects.
Cookies are used by this site. To decline or learn more, visit our cookie notice.