VA Class:CV100
Propranolol hydrochloride is a nonselective β-adrenergic blocking agent (β-blocker).
Propranolol is used for the management of hypertension,201, 314, 323, 1200 angina,201, 314, 315, 1101 supraventricular and ventricular arrhythmias,201, 700, 701 acute myocardial infarction (MI),201, 248, 260, 315 and essential tremor.201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229 Propranolol also is used for prophylaxis of migraine headache, 201, 314, 315, 326 management of hypertrophic subaortic stenosis,201, 314, 315 and as an adjunct in the management of pheochromocytoma.201, 315 The drug also has been used in the management of thyrotoxicosis†.
The choice of a β-adrenergic blocking agent (β-blocker) depends on numerous factors, including pharmacologic properties (e.g., relative β-selectivity, intrinsic sympathomimetic activity, membrane-stabilizing activity, lipophilicity), pharmacokinetics, intended use, and adverse effect profile, as well as the patient's coexisting disease states or conditions, response, and tolerance.330, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350 While specific pharmacologic properties and other factors may appropriately influence the choice of a β-blocker in individual patients,1235 evidence of clinically important differences among the agents in terms of overall efficacy and/or safety is limited. 339, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350 Patients who do not respond to or cannot tolerate one β-blocker may be successfully treated with a different agent.341, 342, 343, 344, 347, 349, 350
In the management of hypertension or chronic stable angina pectoris in patients with chronic obstructive pulmonary disease (COPD) or type 1 diabetes mellitus, many clinicians prefer to use low dosages of a β1-selective adrenergic blocking agent (e.g., atenolol, metoprolol), rather than a nonselective agent (e.g., nadolol, pindolol, propranolol, timolol). However, selectivity of these agents is relative and dose dependent. Some clinicians also will recommend using a β1-selective agent or an agent with intrinsic sympathomimetic activity (e.g., pindolol), rather than a nonselective agent, for the management of hypertension or angina pectoris in patients with peripheral vascular disease, but there is no evidence that the choice of β-blocker substantially affects efficacy. Nonselective β-blockers are preferred for the management of hypertension or angina pectoris in patients with coexisting essential tremor or vascular (e.g., migraine) headache. For further information on management and classification of migraine headache, see Vascular Headaches: General Principles in Migraine Therapy, under Uses in Sumatriptan 28:32.28.
Propranolol is used alone or in combination with other classes of antihypertensive agents in the management of hypertension.1200
Current evidence-based practice guidelines for the management of hypertension in adults generally recommend the use of drugs from 4 classes of antihypertensive agents (angiotensin-converting enzyme [ACE] inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, and thiazide diuretics).501, 502, 503, 504, 1200 Most guidelines no longer recommend β-blockers as first-line therapy for hypertension because of the lack of established superiority over other recommended drug classes and evidence from at least one study demonstrating that β-blockers may be less effective than angiotensin II receptor antagonists in preventing cardiovascular death, MI, or stroke.353, 501, 503, 504, 515, 1200 However, therapy with a β-blocker may still be considered in hypertensive patients who have a compelling indication (e.g., prior MI, ischemic heart disease, heart failure) for their use or as add-on therapy in those who do not respond adequately to the preferred drug classes.501, 502, 503, 504, 523, 524, 527, 800, 1200 (See Considerations for Drug Therapy in Patients with Underlying Cardiovascular and Other Risk Factors under Uses: Hypertension, in Atenolol 24:24 and in Metoprolol 24:24.) Ultimately, choice of antihypertensive therapy should be individualized, considering the clinical characteristics of the patient (e.g., age, ethnicity/race, comorbid conditions, cardiovascular risk factors) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, costs).501, 502, 503, 504, 515, 1200, 1201
A 2017 multidisciplinary hypertension guideline of the American College of Cardiology (ACC), American Heart Association (AHA), and a number of other professional organizations generally recommends a target blood pressure goal (i.e., blood pressure to achieve with drug therapy and/or nonpharmacologic intervention) of less than 130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk.1200 In addition, a systolic blood pressure goal of less than 130 mm Hg generally is recommended for noninstitutionalized ambulatory patients 65 years of age or older with an average systolic blood pressure of at least 130 mm Hg.1200 These blood pressure goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of systolic blood pressure.1200, 1202, 1210 Previous hypertension guidelines, such as those from an expert panel of the Eighth Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8), generally have recommended initiation of antihypertensive treatment in patients with a systolic blood pressure of at least 140 mm Hg or diastolic blood pressure of at least 90 mm Hg, targeted a blood pressure goal of less than 140/90 mm Hg regardless of cardiovascular risk, and used higher systolic blood pressure thresholds and targets in geriatric patients501, 504, 536 compared with those recommended by the 2017 ACC/AHA hypertension guideline.1200 The blood pressure thresholds used to define hypertension, the optimum blood pressure threshold at which to initiate antihypertensive drug therapy, and the ideal target blood pressure values remain controversial.501, 503, 504, 505, 506, 507, 508, 515, 523, 526, 530, 1200, 1201, 1207, 1209, 1222, 1223, 1229
Most patients with hypertension, especially black patients, will require at least 2 antihypertensive drugs to achieve adequate blood pressure control.1200 In general, black hypertensive patients tend to respond better to monotherapy with thiazide diuretics or calcium-channel blocking agents than to monotherapy with β-blockers.330, 336, 337, 501, 504, 1200 Although β-blockers have lowered blood pressure in all races studied, monotherapy with these agents has produced a smaller reduction in blood pressure in black hypertensive patients; however, this population difference in response does not appear to occur during combined therapy with a β-blocker and a thiazide diuretic.500 (See Race under Hypertension: Other Special Considerations for Antihypertensive Drug Therapy, in Uses in Atenolol 24:24 and in Metoprolol 24:24.)
Propranolol is not indicated for the treatment of hypertensive emergencies.
In contrast to many other antihypertensive agents, propranolol lowers blood pressure equally well in the upright or supine position. The drug appears to be safe and effective for the treatment of hypertension in patients with renal damage. Although it apparently is more effective in patients with normal or elevated plasma renin concentrations than in those with low plasma renin concentrations, propranolol does lower blood pressure in patients with low-renin hypertension.
For additional information on the role of β-blockers in the management of hypertension, see Uses: Hypertension, in Atenolol 24:24 and in Metoprolol 24:24. For information on overall principles and expert recommendations for treatment of hypertension, see Uses: Hypertension in Adults and also see Uses: Hypertension in Pediatric Patients, in the Thiazides General Statement 40:28.20.
Propranolol is used for the long-term management of chronic stable angina pectoris.602β-Blockers are recommended as the anti-ischemic drugs of choice in most patients with chronic stable angina; despite differences in cardioselectivity, intrinsic sympathomimetic activity, and other clinical factors, all β-blockers appear to be equally effective for this indication.1101 In a double-blind study in patients with stable angina, propranolol reduced the frequency of anginal attacks and increased exercise tolerance compared with placebo.602
Combination therapy with a β-blocker and a nitrate appears to be more effective than either drug alone because β-blockers attenuate the increased sympathetic tone and reflex tachycardia associated with nitrate therapy while nitrate therapy (e.g., nitroglycerin) counteracts the potential increase in left-ventricular wall tension associated with a decrease in heart rate.1101 Combined therapy with a β-blocker and a dihydropyridine calcium-channel blocker also may be useful because the tendency to develop tachycardia with the calcium-channel blocker is counteracted by the β-blocker.1101 However, caution should be exercised in the concomitant use of β-blockers and the nondihydropyridine calcium-channel blockers verapamil or diltiazem because of the potential for excessive fatigue, bradycardia, or atrioventricular (AV) block.1101 (See Drug Interactions: Diuretics and Cardiovascular Drugs.)
β-Blockers, including propranolol, are used to slow ventricular rate in patients with supraventricular tachycardia (SVT).338, 401, 700, 701 The American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) guideline for the management of adult patients with supraventricular tachycardia recommends the use of β-blockers in the treatment of various SVTs (e.g., atrial flutter, junctional tachycardia, focal atrial tachycardia, atrioventricular nodal reentrant tachycardia [AVNRT]); in general, an IV β-blocker is recommended for acute treatment, while an oral β-blocker is recommended for ongoing management of these arrhythmias.700, 701 Vagal maneuvers and/or IV adenosine generally are considered first-line interventions for the acute treatment of SVT and should be attempted prior to other therapies when clinically indicated; if such measures are ineffective or not feasible, an IV β-blocker may be considered in hemodynamically stable patients.700 Although evidence of efficacy is limited, experts state that the overall safety of β-blockers warrants their use in patients with SVT.700 Patients should be closely monitored for hypotension and bradycardia during administration of these drugs.700
IV β-blockers may be used for the acute treatment of patients with hemodynamically stable focal atrial tachycardia (i.e., regular SVT arising from a localized atrial site), and an oral β-blocker may be used for ongoing management.700 Multifocal atrial tachycardia, characterized by a rapid, irregular rhythm with at least 3 distinct P-wave morphologies, is commonly associated with an underlying condition (e.g., pulmonary, coronary, or valvular heart disease) and is generally not responsive to antiarrhythmic drug therapy.700
Propranolol is used to slow ventricular rate in patients with atrial fibrillation or atrial flutter when ventricular rate cannot be controlled with standard measures.201, 338, 701 For acute treatment of atrial fibrillation or flutter, an IV β-blocker (e.g., esmolol, propranolol, metoprolol) may be used for ventricular rate control in patients without preexcitation; an oral β-blocker may be used for ongoing rate control in such patients.700, 701 Choice of a specific β-blocker should be individualized based on the patient's clinical condition.701
IV β-blockers may be used for the acute treatment of hemodynamically stable patients with paroxysmal supraventricular tachycardia (PSVT), including AVNRT, that is uncontrolled or unconverted by vagal maneuvers and adenosine; an oral β-blocker may be used for the ongoing management of such patients who are not candidates for, or prefer not to undergo, catheter ablation.700 Propranolol may be useful in the prophylactic management of refractory PSVT, especially when caused by catecholamines or cardiac glycosides or associated with Wolff-Parkinson-White syndrome.
β-Blockers are considered one of several drug therapy options for the treatment of junctional tachycardia (i.e., nonreentrant SVT originating from the AV junction), a rapid, occasionally irregular, narrow-complex tachycardia.700 While evidence is limited, there is some data indicating that β-blockers (specifically propranolol) are modestly effective in terminating and/or reducing the incidence of junctional tachycardia.700
Although propranolol generally is less effective in the management of ventricular arrhythmias than supraventricular arrhythmias and is usually not the first drug of choice for ventricular arrhythmias, it may be considered when cardioversion or other drugs are not effective.338 Propranolol also may be used in the treatment of persistent premature ventricular complexes that impair the well-being of the patient and do not respond to conventional therapy.338
β-Blockers may be useful in the management of certain forms of polymorphic ventricular tachycardia (e.g., associated with acute ischemia).401
β-Blockers also have been used in patients with cardiac arrest precipitated by ventricular fibrillation† or pulseless ventricular tachycardia†.400 However, AHA states that routine administration of β-blockers after cardiac arrest is potentially harmful (e.g., may worsen hemodynamic instability, exacerbate heart failure, or cause bradyarrhythmias) and is therefore not recommended.400
Tachyarrhythmias Associated with Cardiac Glycoside Intoxication
When AV block is not present, propranolol may be useful in the management of supraventricular or ventricular tachyarrhythmias associated with cardiac glycoside toxicity; however, because of the risk of adverse cardiovascular effects, the drug has a limited role in the management of these arrhythmias and other drugs are usually preferred. Propranolol can compromise conduction through the SA and AV nodes (possibly resulting in sinus bradycardia or asystole) and decrease myocardial automaticity; in addition, β-adrenergic blockade may result in deterioration of hemodynamic status in patients whose myocardial contractility depends on increased sympathetic nervous system activity. Oral propranolol may be useful in some patients for the management of cardiac glycoside-induced tachyarrhythmias that persist following discontinuance of the glycoside and correction of electrolyte abnormalities. IV propranolol should be used only if arrhythmias caused by cardiac glycoside intoxication are life-threatening and other therapy is ineffective. Use of digoxin immune Fab, if available, may be preferable and should be considered for the management of life-threatening cardiac glycoside-induced tachyarrhythmias that are unresponsive to conventional therapy.
Resistant Tachyarrhythmias Associated with Catecholamine Excess During Anesthesia
Propranolol may be used with extreme caution and constant ECG and central venous pressure monitoring in the management of resistant tachyarrhythmias associated with catecholamine excess during anesthesia; however, more effective and less hazardous therapy such as lessening the depth of anesthesia or improving ventilation is preferred. (See Cautions: Precautions and Contraindications.)
Hypertrophic Subaortic Stenosis
Propranolol may be of benefit in the management of exertional or other stress-induced angina, vertigo, syncope, and palpitation in some patients with hypertrophic subaortic stenosis; however, clinical improvement may be only temporary.
An α-adrenergic blocking agent (e.g., phenoxybenzamine or phentolamine) alone is usually sufficient for management of the signs and symptoms of pheochromocytoma. Propranolol, however, may be used as an adjunct to α-adrenergic blocking agents to control symptoms resulting from excessive β-receptor stimulation in patients with inoperable or metastatic pheochromocytoma, or to control tachycardia prior to or during surgery in patients with pheochromocytoma. To prevent severe hypertension caused by unopposed α-adrenergic stimulation, treatment with an α-adrenergic blocking agent must always be instituted prior to the use of propranolol and continued during propranolol therapy in patients with pheochromocytoma.
Propranolol, which will not alter thyroid function tests, may be used orally as short-term (2-4 weeks) adjunctive therapy in the treatment of tachycardia and supraventricular arrhythmias in patients with thyrotoxicosis when these symptoms are distressful or hazardous, or when immediate therapy is necessary. Propranolol has been used IV and orally to treat symptomatic hypercalcemia secondary to thyrotoxicosis†, but this use requires further study. Propranolol has also been used for the management of thyrotoxicosis in neonates†. Safety of long-term administration of the drug in patients with thyrotoxicosis has not been established. The drug does not affect the underlying disease, which must be treated with an antithyroid agent.
Propranolol may be used for the prophylaxis of common migraine headache. When used prophylactically, the drug can prevent common migraine or reduce the number of attacks in some patients. The US Headache Consortium states that there is good evidence from multiple well-designed clinical trials that propranolol has medium to high efficacy for the prophylaxis of migraine headache.326 Propranolol is not recommended for the treatment of a migraine attack that has already started nor for the prevention or treatment of cluster headaches. For further information on management and classification of migraine headache, see Vascular Headaches: General Principles in Migraine Therapy, under Uses in Sumatriptan 28:32.28.
Propranolol is used to reduce the risk of cardiovascular mortality in patients who have survived the acute phase of MI and are clinically stable. In these patients, long-term (up to 39 months) administration of propranolol (begun within 5-21 days following MI) reduced overall mortality, cardiovascular mortality, arteriosclerotic heart disease (ASHD) mortality, and sudden death mortality within the ASHD category. Evidence of efficacy was obtained from a double-blind, placebo-controlled, multicenter study (Beta-Blocker Heart Attack Trial; BHAT).602 The effect of propranolol on reinfarction remains to be fully evaluated. For information on the use of β-blockers during the acute phase of MI, see Uses in Metoprolol 24:24.
The benefits of long-term β-blocker therapy for secondary prevention of MI have been well established in numerous clinical studies.527, 804, 806, 1101 Patients with MI complicated by heart failure, left ventricular dysfunction, or ventricular arrhythmias appear to derive the most benefit from long-term β-blocker therapy.527 Several large, randomized studies have demonstrated that prolonged oral therapy with a β-blocker can reduce the long-term rates of reinfarction and mortality (e.g., sudden or nonsudden cardiac death) following acute MI.245, 248, 249, 250, 252, 253, 254, 255, 256, 261 It is estimated that such therapy could result in a relative reduction in mortality of about 25% annually for years 1-3 after infarction, with high-risk patients exhibiting the greatest potential benefit;245, 248, 249, 250, 252, 253, 254, 255, 256, 257, 258, 261 the benefit of continued therapy may persist for at least several years beyond this period, although less substantially.248, 252, 260, 261 Therefore, propranolol, like other β-blockers, can be used for secondary prevention following acute MI to reduce the risk of reinfarction and mortality.245, 248, 249, 261, 527, 602 The American Heart Association/American College of Cardiology Foundation (AHA/ACCF) secondary prevention guideline recommends β-blocker therapy in all patients with left ventricular systolic dysfunction (ejection fraction of 40% or less) and prior MI; use of a β-blocker with proven mortality benefit (e.g., bisoprolol, carvedilol, or metoprolol succinate) is recommended.525 (See Uses: Heart Failure, in Carvedilol 24:24.) Although the benefits of long-term β-blockade in post-MI patients with normal left ventricular function are less well established, the guideline recommends continued β-blocker therapy for at least 3 years in such patients.525
Propranolol is used for the management of essential (familial, hereditary) tremor.201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229 The tremor is a postural and action tremor manifested as involuntary, rhythmic, oscillatory movements, principally of the upper limbs and, less frequently, the head;201, 202, 206, 207, 213, 214, 215, 217, 219, 226 other areas, including the voice, legs, jaw, eyelids, and mouth, also may be involved.202, 206, 207, 214, 217, 219 Essential tremor occurs during active movement and when the limb is held in a fixed posture or position against gravity;201, 202, 207, 214, 215, 229 the tremor usually is absent at rest,201, 202, 214, 229 although, when it is of large amplitude, tremor occasionally may be evident at rest, particularly in geriatric patients.202
Propranolol decreases the amplitude but not the frequency of essential tremor;201, 202, 203, 204, 205, 207, 208, 212, 214, 218, 219, 220, 224, 225, 227, 234 complete suppression of the tremor rarely is achieved with treatment.205, 206, 207, 214, 215, 220, 225, 226 Response to propranolol therapy is variable,202, 205, 209, 210, 216, 219, 222, 224, 225, 226, 227, 229 but the drug appears to be most effective in the management of high-amplitude, low-frequency tremor.202, 210, 211, 222, 224, 225, 227 Clinical benefit often is most evident for tremor affecting the upper extremities,202, 206, 214, 215, 217 although benefit also has been observed for head and other tremors;206, 207, 214, 215, 219 voice tremor may be less responsive to therapy with the drug.207, 217 Propranolol hydrochloride doses of 120-320 mg generally produce tremor amplitude reductions averaging about 4-50%;203, 204, 205, 208, 209, 211, 212, 214, 216, 217, 219, 221, 223, 224, 225, 227, 228, 234 however, reductions averaging 25-75% have been reported.204, 206, 214, 216, 218, 223, 224 Therapy with the drug may improve functional ability (e.g., handwriting, eating, drinking, dressing)204, 207, 214, 215, 218, 226 and provide some subjective improvement (e.g., reduced anxiety and embarrassment),207, 213, 214, 218, 220, 226 but patients should be advised that complete relief rarely is achieved so that their expectations about potential therapeutic benefit are realistic.207, 226 Although propranolol often is used for chronic suppressive therapy in essential tremor, single oral doses may be useful in some patients to prevent or minimize tremor that is considered bothersome during specific, planned activity or to manage an exacerbation of tremor during periods of stress (e.g., business meetings, examinations).202, 208, 210, 211, 215, 222, 227, 229
Propranolol has been used in the management of cyanotic spells of Fallot's tetralogy†, acute exacerbations of schizophrenic disorder† and anxiety states†, recurrent GI bleeding in patients with cirrhosis†, and many other conditions. In addition to essential tremor (see Uses: Essential Tremor), propranolol also has been used in the management of other action tremors†, including those associated with lithium therapy (see Cautions: Nervous System and Neuromuscular Effects, in Lithium Salts 28:28), anxiety, and thyrotoxicosis.
Propranolol hydrochloride is usually administered orally. When administered orally in divided doses, the drug should be given before meals and at bedtime. When propranolol hydrochloride extended-release capsules are administered, the entire daily dose is given once daily. When propranolol hydrochloride oral concentrate solution is used, the dose should be diluted (e.g., with water, juice, carbonated beverages) or mixed with semisolid foods (e.g., applesauce, puddings) just prior to administration.
For the treatment of cardiac arrhythmias, propranolol has been given IV.338, 700, 701 Oral therapy should replace IV therapy as soon as possible.
Since there is no consistent interpatient correlation between the dosage of propranolol hydrochloride and therapeutic response, especially after oral administration, dosage must be carefully individualized according to the response of the patient. If patients are switched from the conventional tablets to the extended-release capsules, care should be taken to ensure that the desired therapeutic effect is maintained. The extended-release capsules should not be considered a simple substitute for the conventional tablets on a mg-for-mg basis, since the capsules produce lower blood concentrations. If patients are switched to the extended-release capsules, the need for dosage retitration should be considered, especially to maintain effectiveness at the end of the dosing interval.
The manufacturers of propranolol hydrochloride injection state that a reduction in the dosage of propranolol hydrochloride may be necessary in geriatric patients.338
For the management of hypertension in adults, the initial oral dosage of propranolol hydrochloride, administered either alone or in combination with a diuretic, is 40 mg twice daily as conventional tablets or oral solution or 80 mg once daily as extended-release capsules.201, 314, 600, 601, 602 The usual effective oral dosage is 120-240 mg daily as conventional tablets or oral solution or 120-160 mg once daily as extended-release capsules; some manufacturers state that some patients may require dosages up to 640 mg daily.201, 314 However, the manufacturer of Innopran XL® states that dosage of the extended-release capsules may be increased, if needed, up to 120 mg once daily, since dosages exceeding 120 mg once daily did not provide additional hypotensive effects.600 Some experts state the usual dosage range is 80-160 mg daily given in 2 divided doses as conventional tablets or oral solution or 80-160 mg once daily as extended-release capsules.1200 It usually is preferable to add another antihypertensive agent to the regimen than to continue increasing propranolol hydrochloride dosage since the patient may not tolerate such continued increases.354 The full hypotensive effect of the drug usually is evident within 2-3 weeks, but the timing is variable.600 While twice-daily dosing using the conventional tablets or oral solution is usually effective, some patients may require larger doses or 3 divided doses daily to maintain effective blood pressure control throughout the day.201
Propranolol/Hydrochlorothiazide Fixed-combination Therapy
When combination therapy is required, the manufacturers recommend that commercially available preparations containing propranolol hydrochloride in fixed combination with a thiazide diuretic should not be used initially. Dosage should first be adjusted by administering each drug separately. If it is determined that the optimum maintenance dosage corresponds to the ratio in the commercial combination preparation, the fixed combination may be used. Therapy with propranolol hydrochloride in fixed combination with hydrochlorothiazide is administered twice daily for a total daily dosage of up to 160 mg of propranolol hydrochloride and 50 mg of hydrochlorothiazide; use of this combination formulation is not appropriate for propranolol hydrochloride dosages exceeding 160 mg daily since it would provide an excessive dosage of the thiazide component.323 When necessary, another antihypertensive agent may be added gradually using half of the usual initial dosage to avoid an excessive decrease in blood pressure.323
Blood Pressure Monitoring and Treatment Goals
Blood pressure should be monitored regularly (i.e., monthly) during therapy and dosage of the antihypertensive drug adjusted until blood pressure is controlled.1200 If an adequate blood pressure response is not achieved, the dosage may be increased or another antihypertensive agent with demonstrated benefit and preferably with a complementary mechanism of action (e.g., angiotensin-converting enzyme [ACE] inhibitor, angiotensin II receptor antagonist, calcium-channel blocker, thiazide diuretic) may be added; if target blood pressure is still not achieved with the use of 2 antihypertensive agents, a third drug may be added.1200, 1216 (See Uses: Hypertension.) In patients who develop unacceptable adverse effects with propranolol, the drug should be discontinued and another antihypertensive agent from a different pharmacologic class should be initiated.1200, 1216
The goal of hypertension management and prevention is to achieve and maintain optimal control of blood pressure.1200 However, the optimum blood pressure threshold for initiating antihypertensive drug therapy and specific treatment goals remain controversial.505, 506, 507, 508, 515, 523, 530, 1201, 1207, 1209, 1222 While previous hypertension guidelines have based target blood pressure goals on age and comorbidities,501, 504, 536 the 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guideline incorporates underlying cardiovascular risk into decision making regarding treatment and generally recommends the same target blood pressure (i.e., less than 130/80 mm Hg) for all adults.1200 Many patients will require at least 2 drugs from different pharmacologic classes to achieve this blood pressure goal; the potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs also should be considered when deciding a patient's blood pressure treatment goal.1200, 1220
For the management of angina pectoris, the initial oral dosage of propranolol hydrochloride as extended-release capsules is 80 mg daily; dosage is gradually increased as needed to control symptoms, usually at 3- to 7-day intervals.314 Although optimum response usually occurs at a dosage of 160 mg daily, there is a wide variation in individual requirements.314
When using conventional tablets or oral solutions, the usual dosage of propranolol hydrochloride is 80-320 mg daily (given in 2-4 divided doses).201, 315 The value and safety of dosages greater than 320 mg daily have not been established, but some clinicians have stated that dosage may be increased further if there is only a partial response to usual dosage.
During long-term therapy, the patient should be periodically reevaluated to determine the need for dosage alteration or continued therapy. When propranolol hydrochloride is to be discontinued, dosage should be reduced slowly over a period of at least a few weeks (about 2). (See Cautions: Precautions and Contraindications.)
The usual adult oral dosage of propranolol hydrochloride for the treatment of arrhythmias is 10-30 mg 3 or 4 times daily as conventional tablets or oral solution. For arrhythmias in adults which are life-threatening or occur during anesthesia, the manufacturer states that 1-3 mg may be administered IV under careful monitoring (e.g., ECG, central venous pressure).201 If necessary, a second IV dose may be administered after 2 minutes.201 Additional IV doses may be administered at intervals of no less than 4 hours until the desired response is obtained.201
For the acute treatment of supraventricular tachycardia (SVT) (e.g., atrial flutter, junctional tachycardia, paroxysmal supraventricular tachycardia [PSVT], atrial tachycardia) in adults, some experts recommend an initial IV propranolol hydrochloride dose of 1 mg administered over 1 minute; additional doses may be given every 2 minutes up to a total of 3 doses.700 The usual oral maintenance dosage for ongoing treatment of SVT is 40-160 mg daily in divided doses or single doses (with long-acting preparations).700 To slow ventricular response in adults with acute atrial fibrillation, experts recommend an initial IV propranolol hydrochloride dose of 1 mg administered over 1 minute; additional doses may be given at 2-minute intervals up to a total of 3 doses.701 The usual oral maintenance dosage for ongoing treatment of atrial fibrillation is 40-160 mg daily in divided doses.701
Hypertrophic Subaortic Stenosis
Hypertrophic subaortic stenosis in adults is usually treated with 20-40 mg of propranolol hydrochloride orally 3 or 4 times daily as conventional tablets or oral solution or 80-160 mg once daily as extended-release capsules.201, 314, 315
In adults with pheochromocytoma, 60 mg of oral propranolol hydrochloride may be administered daily in divided doses as conventional tablets or oral solution in conjunction with an α-adrenergic blocking agent for 3 days prior to surgery.201, 315 As an adjunct to prolonged treatment of inoperable pheochromocytoma, 30 mg of propranolol hydrochloride daily in divided doses with an α-adrenergic blocker is usually sufficient.201, 315
For prophylaxis of migraine in adults, the initial oral dosage of propranolol hydrochloride is 80 mg daily, given in divided doses as the conventional tablets or oral solution or once daily as the extended-release capsules.201, 314, 315 Dosage may be increased gradually to achieve optimum migraine prophylaxis. The usual effective dosage is 80-240 mg daily.201, 314, 315, 326 If an adequate response is not obtained within 4-6 weeks after reaching the maximum dose, propranolol therapy should be discontinued; it may be advisable to withdraw the drug gradually over several weeks.201, 314, 315
When used for secondary prevention after the acute phase of myocardial infarction (MI), the recommended oral dosage of propranolol hydrochloride is 180-240 mg daily (in divided doses) as conventional tablets or oral solution.201, 315 In the study demonstrating mortality benefit with propranolol, the drug was initiated 5-21 days following infarction.602 Although the drug was given in 3 or 4 divided doses daily in clinical studies, there are considerable clinical, pharmacologic, and pharmacokinetic data suggesting that a twice-daily dosing regimen would also be adequate.201 Safety and efficacy of propranolol hydrochloride dosages exceeding 240 mg daily for the prevention of cardiac mortality have not been established; however, higher dosages may be required for the treatment of coexisting conditions such as angina or hypertension.201, 315 Although the optimal duration of β-blocker therapy following MI remains to be clearly established, experts generally recommend that such therapy be continued long-term in post-MI patients with left ventricular systolic dysfunction, and for at least 3 years in those with normal left ventricular function.525, 802, 804, 1101
The initial oral dosage of propranolol hydrochloride for the management of essential tremor in adults is 40 mg twice daily as conventional tablets.201, 229 Response to the drug is variable and dosage must be individualized; optimum suppression of tremor usually is achieved with a dosage of 120-320 mg daily (administered in 3 divided doses when conventional tablets are used).201, 202, 203, 204, 205, 207, 208, 211, 213, 214, 215, 216, 219, 220, 221, 228, 229 In adjusting propranolol hydrochloride dosage, it should be remembered that complete suppression of essential tremor rarely is achieved.205, 206, 207, 214, 215, 220, 225, 226 Some evidence suggests that dosages exceeding 320 mg daily do not provide substantial added benefit but are associated with an increased risk of adverse effects.205, 209, 221 Although currently not recommended by the manufacturer, usual dosages administered once daily each morning as extended-release capsules appear to be at least as effective as equivalent dosages administered in divided doses daily as conventional tablets.216 Some patients may benefit from intermittent rather than maintenance therapy; single 80- to 120-mg doses as conventional tablets have been administered 1-3 hours before planned activity or anticipated stress associated with tremor.202, 208, 211, 227
For the management of hypertension in children†, some experts have recommended an initial oral propranolol hydrochloride dosage of 1-2 mg/kg daily given in 2 or 3 divided doses as an immediate-release formulation.335 Dosage may be increased as necessary to a maximum dosage of 4 mg/kg (up to 640 mg) daily given in 2 or 3 divided doses.335 The extended-release formulation may be administered once daily.335
Although parenteral propranolol hydrochloride currently is not recommended by the manufacturer for use in children†, an initial IV dose of 10-20 mcg/kg infused over 10 minutes has been recommended by some clinicians for the treatment of cardiac arrhythmias in children. Some clinicians state that pediatric oral dosages exceeding 4 mg/kg daily may be necessary for the management of supraventricular tachyarrhythmias.231, 232 Oral propranolol hydrochloride therapy has been initiated at 1.5-2 mg/kg daily and titrated upward as necessary to control the arrhythmia, up to a maximum dosage of 16 mg/kg daily given in 4 divided doses.231, 232
For the treatment of tachyarrhythmias in neonates with thyrotoxicosis†, an oral propranolol hydrochloride dosage of 2 mg/kg daily given in 2-4 divided doses has been used, although higher dosages occasionally may be needed.
The manufacturers of propranolol hydrochloride injection state that a reduction in the dosage of propranolol hydrochloride may be necessary in patients with hepatic impairment.338
The most common, serious adverse effects of propranolol hydrochloride are related to its β-adrenergic blocking activity. Adverse reactions are more frequent and may be more severe after IV administration than after oral administration. In one large study of hospitalized patients receiving propranolol, reactions were most common in azotemic patients and in those older than 60 years of age. The incidence of adverse reactions to oral propranolol was unrelated to the dose, and adverse reactions usually occurred soon after the initiation of therapy. The investigators concluded that many severe adverse reactions result from the inability of severely ill patients to withstand a decrease in normal β-adrenergic stimulation.
The most common adverse cardiovascular effect of propranolol is bradycardia, especially in patients with digitalis intoxication. Bradycardia is occasionally severe and may be accompanied by hypotension, syncope, shock, or angina pectoris. Severe bradycardia should be treated with IM or IV administration of atropine sulfate. (See Drug Interactions: Sympathomimetic Agents.) In patients with Wolff-Parkinson-White syndrome, propranolol has produced severe bradycardia requiring a demand pacemaker.
In patients with heart failure, sympathetic stimulation is vital for the support of circulatory function. In patients with inadequate cardiac function, heart failure may be precipitated as a result of removal of β-adrenergic stimulation when propranolol therapy is initiated. A decrease in exercise tolerance may be experienced by patients with left ventricular dysfunction. In patients without a prior history of heart failure, prolonged depression of the myocardium by propranolol has resulted in heart failure in rare instances. (See Cautions: Precautions and Contraindications.) Intensification of AV block, AV dissociation, AV conduction delays, complete heart block, or cardiac arrest may occur, especially in patients with preexisting partial heart block caused by a cardiac glycoside or other factors. Ventricular fibrillation has been reported in a patient with hypertrophic subaortic stenosis.
After sudden cessation of propranolol therapy in some patients treated for angina, increased frequency, duration, and severity of angina episodes have occurred, often within 24 hours. These episodes are unstable and are not relieved by nitroglycerin. Acute and sometimes fatal myocardial infarction and sudden death have also occurred after abrupt withdrawal of propranolol therapy in some patients treated for angina. In hypertensive patients, sudden cessation of propranolol has produced a syndrome similar to florid thyrotoxicosis, characterized by tenseness, anxiety, tachycardia, and excessive perspiration; these symptoms occurred within one week of cessation of the drug and were relieved by reinstituting propranolol therapy.
During surgery, some patients who have been receiving propranolol may experience severe, protracted hypotension and, occasionally, difficulty in restarting and maintaining heart beat. These adverse cardiovascular effects of propranolol may be reversed during surgery by IV administration of β-adrenergic agonists such as isoproterenol or norepinephrine.
Severe hypertension has been reported in a few patients with schizophrenic disorder who received only propranolol orally in rapidly increasing doses; the hypertension responded to treatment with IV phentolamine followed by oral phenoxybenzamine.
Fluid retention, pulmonary edema, and peripheral arterial insufficiency, usually of the Raynaud's type, may occur in patients receiving propranolol. When the drug is used alone, dietary sodium restriction may be necessary. Intermittent claudication has occurred in patients with previously asymptomatic peripheral arterial disease who received propranolol, although one study which used the drug for the treatment of intermittent claudication did not note any deterioration of occlusive peripheral arterial disease.
A number of adverse CNS effects, which are usually reversible after withdrawal of the drug, have been reported with propranolol. Adverse CNS effects usually occur after long-term treatment with high dosages of propranolol hydrochloride and range from lightheadedness, giddiness, ataxia, dizziness, irritability, sleepiness, hearing loss, and visual disturbances to vivid dreams, hallucinations, and confusion. Insomnia, lassitude, weakness, fatigue, and mental depression progressing to catatonia have been reported. Dosages exceeding 160 mg daily, when administered in divided doses exceeding 80 mg each, may be associated with an increased incidence of fatigue, lethargy, and vivid dreams.201 Organic brain syndrome, characterized by disorientation to time and place, short-term memory loss, emotional lability, slightly clouded sensorium, and decreased performance on neuropsychometric tests, has been reported rarely. Paresthesia of the hands, peripheral neuropathy, and precipitation of myotonia have been reported. Impotence has been reported rarely. Ptosis has been reported in at least 2 patients. A few patients receiving propranolol for hypertrophic obstructive cardiomyopathy have developed migraine in some cases associated with sensory disturbances and teichopsia.
Adverse GI effects such as nausea, vomiting, diarrhea, epigastric distress, abdominal cramping, constipation, and flatulence may occur in patients receiving propranolol and occasionally necessitate reduction of dosage or withdrawal of the drug. Mesenteric arterial thrombosis and ischemic colitis have also occurred.
Dermatologic and Sensitivity Reactions
Rarely, rashes have been reported during propranolol usage. Rashes are most commonly erythematous (maculopapular or acneiform), dry, scaly, pruritic, psoriasiform lesions which occur on the trunk, extremities, and scalp. Hyperkeratosis of the scalp, palms, and soles of the feet have been reported during treatment with propranolol; nail changes such as thickening, pitting, and discoloration have occurred. At least one case of exfoliative dermatitis has been reported. Dermatologic reactions disappear after the drug is withdrawn. Other allergic manifestations reported during propranolol therapy include fever accompanied by aching and sore throat, rhinitis, dry mouth, laryngospasm, respiratory distress, and pharyngitis. A lupus-like syndrome characterized by fever, pruritus, severe myalgia, and positive lupus erythematosus cell tests has been reported. Reversible alopecia, which recurred following readministration of the drug, also has been reported.
Adverse hematologic effects of propranolol include transient eosinophilia (a pharmacologic effect of β-adrenergic blockade) and idiosyncratic reactions including thrombocytopenic and nonthrombocytopenic purpura and, rarely, agranulocytosis.
Results of a large prospective cohort study of adults 45-64 years of age indicate that use of β-adrenergic blocking agents (β-blockers) in hypertensive patients is associated with increased risk (about 28%) of developing type 2 diabetes mellitus compared with hypertensive patients who were not receiving hypotensive therapy.306, 307 In this study, the number of new cases of diabetes per 1000 person-years was 33.6 or 26.3 in patients receiving a β-blocker or no drug therapy, respectively.306 The association between the risk of developing diabetes mellitus and use of β-blockers reportedly was not confounded by weight gain, hyperinsulinemia, or differences in heart rate.306, 307 It is not known if the risk of developing diabetes is affected by β-receptor selectivity.306 Further studies are needed to determine whether concomitant use of ACE inhibitors (which may improve insulin sensitivity) would abrogate β-blocker-induced adverse effects related to glucose intolerance.307 Therefore, until results of such studies are available, the proven benefits of β-blockers in reducing cardiovascular events in hypertensive patients must be weighed carefully against the possible risks of developing diabetes mellitus.306
Hypoglycemia,305, 314 which may result in loss of consciousness, also may occur in nondiabetic patients receiving β-blockers.314 Patients most at risk for the development of β-blocker-induced hypoglycemia are those undergoing dialysis, prolonged fasting, or severe exercise regimens.305, 314
β-Blockers may mask signs and symptoms of hypoglycemia (e.g., palpitation, tachycardia, tremor) and potentiate insulin-induced hypoglycemia.305 Acute increases in blood pressure have occurred after insulin-induced hypoglycemia in patients receiving propranolol.201, 314, 323 Although it has been suggested that nonselective β-blockers are more likely to induce hypoglycemia than selective β-blockers, such an adverse effect also has been reported with selective β-blockers (e.g., atenolol).305 In addition, selective β-blockers are less likely to mask symptoms of hypoglycemia or delay recovery from insulin-induced hypoglycemia than nonselective β-blockers because of their vascular sparing effects; however, selective β-blockers can decrease insulin sensitivity by approximately 15-30%, which may result in increased insulin requirements.305
Propranolol may cause elevated BUN in patients with severe heart disease, elevated serum creatinine, aminotransferase, alkaline phosphatase, or lactic dehydrogenase concentrations. In hypertensive patients, propranolol may cause small increases in serum potassium concentration. Peyronie's disease has been reported rarely. Generalized hyperemia of the conjunctivae with decreased tear production and a prickling sensation of the eyes, eye dryness, eye pain, discoloration of the tongue, and bad taste have been reported rarely.
Precautions and Contraindications
Propranolol shares the toxic potentials of β-blockers, and the usual precautions of these agents should be observed. When propranolol is used as a fixed-combination preparation that includes hydrochlorothiazide, the cautions, precautions, and contraindications associated with thiazide diuretics must be considered in addition to those associated with propranolol.
In patients with heart failure, sympathetic stimulation is vital for the support of circulatory function. Propranolol should be used with caution in patients with inadequate cardiac function, since heart failure may be precipitated by blockade of β-adrenergic stimulation when propranolol therapy is administered. In addition, in patients with latent cardiac insufficiency, prolonged β-adrenergic blockade may lead to cardiac failure. Although β-blockers should be avoided in patients with overt heart failure, propranolol may be administered cautiously, if necessary, to patients with well-compensated heart failure (e.g., those controlled with cardiac glycosides and/or diuretics). Patients receiving propranolol therapy should be instructed to consult their physician at the first sign or symptom of impending cardiac failure and should be adequately treated (e.g., with a cardiac glycoside and/or diuretic) and observed closely; if cardiac failure continues, propranolol should be discontinued, gradually if possible.
Abrupt withdrawal of propranolol may exacerbate angina symptoms or precipitate myocardial infarction in patients with coronary artery disease. Abrupt withdrawal of the drug in patients treated for hypertension has also been associated with adverse effects. (See Cautions: Cardiovascular Effects.) Therefore, patients receiving propranolol (especially those with ischemic heart disease) should be warned not to interrupt or discontinue therapy without consulting their clinician. When discontinuance of propranolol therapy is planned, particularly in patients with ischemic heart disease, dosage of the drug should be gradually reduced over a period of at least a few (about 2) weeks. When propranolol therapy is discontinued, patients should be carefully monitored and their activity restricted. If exacerbation of angina occurs after propranolol therapy is interrupted, treatment with the drug should generally be reinstituted and appropriate measures taken for the management of unstable angina pectoris. Because coronary artery disease is common and may be unrecognized, the manufacturers caution that it may be prudent not to discontinue propranolol therapy abruptly, even in patients receiving the drug for conditions other than angina.
The necessity of withdrawing β-adrenergic blocking therapy prior to major surgery is controversial. Severe, protracted hypotension and difficulty in restarting or maintaining a heart beat have occurred during surgery in some patients who have received β-blockers. As with other β-blockers, the effects of propranolol can be reversed by administration of β-agonists (e.g., dobutamine, isoproterenol). If propranolol therapy is discontinued prior to major surgery, oral therapy with the drug may be restarted as soon after surgery as possible; patients who are unable to take oral drugs after surgery may be treated with IV propranolol if necessary.
Caution should be used when administering propranolol to patients with sinus node dysfunction, since the drug can cause marked depression of SA node automaticity. Propranolol should be used with extreme caution for the management of arrhythmias occurring during anesthesia with myocardial depressant anesthetics, since excessive myocardial depression, bradycardia, and hypotension may occur.338, 338
Signs of hyperthyroidism may be masked by propranolol, and patients with thyrotoxicosis who receive the drug should be monitored closely. In addition, the drug may alter thyroid function test results, increasing thyroxine (T4) and reverse triiodothyronine (rT3) and decreasing triiodothyronine (T3) determinations.
It is recommended that propranolol be used with caution in patients with diabetes mellitus (especially those with labile diabetes or those prone to hypoglycemia) since the drug also may block the signs and symptoms of hypoglycemia (e.g., tachycardia and blood pressure changes but not sweating). However, many clinicians state that patients with diabetes mellitus may be particularly likely to experience a reduction in morbidity and mortality with the use of β-blockers.304 In addition, the drug occasionally causes hypoglycemia, even in nondiabetic patients, presumably by interfering with catecholamine-induced glycogenolysis. Propranolol may also inhibit the insulin-releasing mechanism of the pancreas and has been implicated in hyperglycemic reactions. Propranolol-induced alterations in glucose tolerance appear to occur only rarely. (See Cautions: Endocrine Effects.) Some sources state that hypertensive patients who are prone to hypoglycemia should not receive propranolol because the drug may cause a sharp rise in blood pressure.
Since β-blockers may inhibit bronchodilation produced by endogenous catecholamines, the drugs generally should not be used in patients with bronchospastic disease. Propranolol should be used with caution in patients with a history of nonallergic bronchospasm (e.g., chronic bronchitis, emphysema). β-adrenergic blockade may lead to an increase in airway resistance and bronchospasm, particularly in patients with a history of asthma. Bronchospasm may be treated with IV administration of aminophylline; isoproterenol may also be administered. (See Drug Interactions: Sympathomimetic Agents.) IV administration of atropine has been suggested if the patient fails to respond to the above or if bradycardia is present.
Since treatment with β-blockers (e.g., propranolol) may reduce intraocular pressure,338 patients should be advised that such therapy may interfere with glaucoma screening tests.338 Withdrawal of propranolol may lead to an increase in intraocular pressure.338
Propranolol should be used with caution in patients with renal or hepatic impairment. Laboratory parameters should be monitored in patients receiving prolonged therapy with the drug.
Patients with a history of severe anaphylactic reactions to a variety of allergens may be more reactive to repeated, accidental, diagnostic, or therapeutic challenge with such allergens while receiving a β-blocker.201, 314 These patients may be unresponsive to usual doses of epinephrine or may develop a paradoxical response to epinephrine when it is used to treat anaphylactic reactions.201, 314
Propranolol is contraindicated in patients with Raynaud's syndrome, bronchial asthma, sinus bradycardia and heart block greater than first degree, and overt and decompensated heart failure (unless the failure is secondary to a tachyarrhythmia treatable with propranolol).201, 314, 323 The drug is not indicated in the management of hypertensive emergencies.201, 314 Although the manufacturers state that propranolol is contraindicated in patients with cardiogenic shock, results of some studies indicate that the drug may have a beneficial effect in patients with myocardial infarction with or without cardiogenic shock. (See Uses: Acute Myocardial Infarction.) Because propranolol has produced a myasthenic condition characterized by ptosis, weakness of limbs, and double vision in 2 patients, the drug may be contraindicated in patients with myasthenia gravis. In addition, since propranolol appears to impair metabolism of thioridazine which may result in increased plasma concentrations of thioridazine that may be associated with prolongation of the QT interval, the manufacturer of thioridazine states that concomitant use of thioridazine and propranolol is contraindicated.310 (See Drug Interactions: Phenothiazines and Other Psychotherapeutic Agents.)
Although safety and efficacy of propranolol have not been as extensively or systematically studied in children as in adults, current information from the medical literature allows fair estimates, and specific dosing information has been reasonably studied.201 Cardiovascular diseases that are common to adults and children generally are as responsive to propranolol therapy in children as in adults, and adverse reactions also are similar.201 For information on overall principles and expert recommendations for treatment of hypertension in pediatric patients, see Uses: Hypertension in Pediatric Patients, in the Thiazides General Statement 40:28.20. One manufacturer states that the possibility that oral bioavailability of propranolol hydrochloride may be increased in children with Down's syndrome should be considered.201 Safety and efficacy of propranolol hydrochloride extended-release capsules, oral solution, and injection have not been established in children.
Clinical studies of propranolol tablets, injections, and extended-release capsules did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger patients. If propranolol is used in geriatric patients, dosage of the drug should be selected with caution, usually initiating therapy at the low end of the dosage range since decreased hepatic, renal, or cardiac function and concomitant disease or other drug therapy are more common in this age group than in younger patients.
Decreased propranolol clearance and a prolonged elimination half-life have been reported in geriatric patients receiving propranolol hydrochloride injection, and the manufacturers recommend that dosage reduction be considered in these patients.338
In long-term studies in animals, no evidence of propranolol-related tumorigenic effects was observed.
Pregnancy, Fertility, and Lactation
There are no adequate and well-controlled studies to date using propranolol in pregnant women.338 Safe use of propranolol during pregnancy has not been established. Low birthweight infants with respiratory distress and hypoglycemia have been born to women who received propranolol throughout pregnancy. Bradycardia, hypoglycemia, and respiratory depression also have been reported in neonates whose mothers received propranolol at parturition;338 adequate facilities for monitoring such infants at birth should be available.338 The manufacturers state that the drug should be used during pregnancy only when the possible benefits outweigh the potential risks to the fetus.338
Embryotoxicity (reduced litter size, increased resorption rates) and neonatal toxicity (deaths) have been reported in reproductive studies in rats receiving propranolol hydrochloride 150 mg/kg daily by gavage or in the diet throughout pregnancy and lactation; however, such effects were not observed in rats receiving 80 mg/kg daily (equivalent to the maximum recommended human dosage on a mg/m2 basis).338 No evidence of embryotoxicity or neonatal toxicity was observed in rabbits receiving oral doses of propranolol hydrochloride of up to 150 mg/kg daily (about 5 times the maximum recommended oral human daily dose) throughout pregnancy and lactation.338
Reproduction studies in animals using propranolol have not revealed evidence of impaired fertility.
Since propranolol is distributed into milk, the drug should be used with caution in nursing women.338
Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes
Because metabolism of propranolol is mediated by cytochrome P-450 (CYP) isoenzymes 2D6, 1A2, and 2C19, drugs that induce or inhibit these isoenzymes may alter the metabolism of propranolol, which may result in clinically important drug interactions.338 Inhibitors or substrates of the isoenzymes 2D6 (e.g., amiodarone, cimetidine, delavirdine, fluoxetine, paroxetine, quinidine, ritonavir), 1A2 (e.g., cimetidine, ciprofloxacin, fluvoxamine, imipramine, isoniazid, ritonavir, rizatriptan, theophylline, zileuton, zolmitriptan), or 2C19 (e.g., cimetidine, fluconazole, fluoxetine, fluvoxamine, teniposide, tolbutamide) could decrease the metabolism and increase plasma concentrations of propranolol.338 Drugs that induce cytochrome P-450 activity (e.g., alcohol, rifampin) may increase the metabolism of propranolol and decrease its plasma concentrations; in current smokers, plasma propranolol concentrations also may be decreased because cigarette smoking may induce hepatic metabolism of the drug, increasing propranolol clearance up to 100%.338
Phenothiazines and Other Psychotherapeutic Agents
Phenothiazines and propranolol may have additive hypotensive activity, especially when phenothiazines are administered in large doses. Chlorpromazine has been shown to reduce the clearance of propranolol and increase plasma propranolol concentrations.338 Increased plasma concentrations of chlorpromazine also have been reported in patients receiving the drug concomitantly with propranolol.338 Hypotension and cardiac arrest have occurred during concomitant therapy with propranolol and haloperidol.
In addition, since propranolol may inhibit metabolism of thioridazine, concomitant use of propranolol hydrochloride (100-800 mg daily) and thioridazine, reportedly resulted in increased plasma concentrations of thioridazine and its metabolites by about 50-400 and 80-300%, respectively.310 Because such increased concentrations of thioridazine may enhance thioridazine-induced prolongation of the QTc interval, and increase the risk of serious, potentially fatal cardiac arrhythmias (e.g., torsades de pointes), the manufacturer of thioridazine states that concomitant use of thioridazine and propranolol is contraindicated.310
Complete heart block has been reported in a patient receiving fluoxetine concomitantly with propranolol.272, 273 The mechanism of this interaction is not known; however, it has been postulated that fluoxetine may inhibit metabolism of lipophilic β-adrenergic blocking agents (β-blockers) (e.g., propranolol, metoprolol), increase their bioavailability, and increase their β-adrenergic blocking effects.272, 273 Therefore, some clinicians recommend that fluoxetine be administered with caution in patients receiving β-blockers and in those with impaired cardiac conduction.272
The hypotensive effects of monoamine oxidase (MAO) inhibitors or tricyclic antidepressants may be exacerbated in patients receiving β-blockers.338
Decreased metabolism and increased plasma concentrations of diazepam and its metabolites have been reported in patients receiving the drug concomitantly with propranolol;338 propranolol does not appear to alter pharmacokinetics of other benzodiazepines (e.g., alprazolam, lorazepam, oxazepam, triazolam).338 Diazepam does not alter pharmacokinetics of propranolol.338
The β-adrenergic stimulating effects of sympathomimetic agents are antagonized by propranolol. This interaction is especially pronounced with isoproterenol, and very large doses of isoproterenol may be needed to overcome the β-adrenergic blocking effects of propranolol. The effects of propranolol also can be reversed by administration of dobutamine.338 In addition, propranolol may reduce sensitivity to dobutamine stress echocardiography in patients undergoing evaluation for myocardial ischemia.338 Patients receiving long-term propranolol therapy may experience uncontrolled hypertension upon administration of epinephrine as a result of unopposed α-receptor stimulation.338 In patients receiving propranolol, epinephrine should be administered with caution since a decrease in pulse rate with first- and second-degree heart block may occur.
Antimuscarinic Agents and Drugs with Anticholinergic Effects
Antimuscarinic agents, such as atropine, may counteract the bradycardia caused by propranolol by reestablishing the balance between sympathetic and parasympathetic actions on the heart. Tricyclic antidepressants (e.g., amitriptyline) also have anticholinergic activity and may similarly antagonize the cardiac β-adrenergic blocking effects of propranolol, although not as intensely as do the antimuscarinics.
When propranolol and a catecholamine-depleting drug (e.g., reserpine) are administered concomitantly, the effects of the drugs may be additive.338 Excessive reduction of resting sympathetic nervous system activity, which may lead to hypotension, severe bradycardia, vertigo, syncope, or orthostatic hypotension, has been reported in patients receiving both drugs concurrently.338 Concomitant use of reserpine and propranolol also may potentiate depression.338
Increased concentrations of zolmitriptan and rizatriptan have been reported in patients receiving concomitant propranolol therapy.338
Diuretics and Cardiovascular Drugs
When propranolol is administered with diuretics or other antihypertensive drugs, the hypotensive effect of propranolol may be increased. This effect is usually used to therapeutic advantage, but careful adjustment of dosage is necessary when these drugs are used concomitantly. In addition to its potentially additive hypotensive effect, reserpine theoretically may add to the β-adrenergic blocking activity of propranolol through its catecholamine-depleting activity. (See Drug Interactions: Catecholamine-depleting Drugs.)
The antihypertensive effects of clonidine may be antagonized by β-blockers, including propranolol.338 Because β-blockers (e.g., propranolol) may exacerbate rebound hypertension that may occur following discontinuance of clonidine therapy, β-blockers should be discontinued several days before gradual withdrawal of clonidine when clonidine therapy is to be discontinued in patients receiving a β-blocker and clonidine concurrently.351
Angiotensin-converting Enzyme Inhibitors
Concomitant therapy with angiotensin-converting enzyme (ACE) inhibitors and β-blockers (e.g., propranolol) may result in hypotension, particularly in patients with acute myocardial infarction.338 Increased bronchial hyperreactivity has been reported in patients receiving ACE inhibitors concomitantly with propranolol.338
Beta-Adrenergic Blocking Agents
Prolonged hypotension associated with administration of a first prazosin dose has been reported in patients receiving β-blockers.338 In addition, postural hypotension has been reported in patients receiving β-blockers concomitantly with terazosin or doxazosin.338
When propranolol is administered with antiarrhythmic drugs such as lidocaine, phenytoin, procainamide, quinidine, or verapamil (see Drug Interactions: β-Adrenergic Blocking Agents, in Verapamil 24:28.92), cardiac effects may be additive or antagonistic and toxic effects may be additive.
Concomitant use of β-blockers (e.g., propranolol) and certain other cardiovascular drugs (e.g., cardiac glycosides, lidocaine, nondihydropyridine calcium-channel blocking agents) can have additive negative effects on SA or AV nodal conduction.338 Slowing or complete suppression of SA node activity with development of slow ventricular rates (e.g., 30-40 bpm), often misdiagnosed as complete AV block, has been reported in patients receiving the nondihydropyridine calcium-channel blocking agent mibefradil (no longer commercially available in the US), principally in geriatric patients and in association with concomitant β-adrenergic blocker therapy. Concomitant therapy with an IV β-blocker and IV verapamil has resulted rarely in serious adverse reactions, especially in patients with severe cardiomyopathy, heart failure, or recent myocardial infarction. Severe bradycardia, heart failure, and cardiovascular collapse have been reported in patients receiving verapamil concomitantly with β-blockers.
Caution should be used in patients receiving propranolol concomitantly with a calcium-channel blocking agent with negative inotropic and/or chronotropic effects, since both drugs may depress myocardial contractility and AV conduction.338 Severe bradycardia, asystole, heart failure, and cardiovascular collapse have been reported in patients receiving propranolol concomitantly with disopyramide or verapamil.338 In addition, bradycardia, hypotension, high-degree heart block, and heart failure have been reported in patients with cardiac disease receiving concomitant therapy with propranolol and diltiazem.338 Concomitant use of propranolol with amiodarone also may result in additive negative chronotropic effects, while additive negative inotropic and β-adrenergic blocking effects may occur when propafenone and propranolol are used concomitantly.338 In patients currently receiving a cardiac glycoside, concomitant propranolol therapy may reduce the positive inotropic effect of the glycoside. (See Cautions: Precautions and Contraindications.)
Increased propafenone exposure has been reported in patients receiving the drug concomitantly with propranolol.338 Verapamil does not appear to affect pharmacokinetics of propranolol and propranolol does not affect pharmacokinetics of verapamil or norverapamil.338 Increased propranolol concentrations have been reported in patients receiving concomitant therapy with nisoldipine or nicardipine with propranolol; 338 increased concentrations of nifedipine may occur in patients receiving the drug concomitantly with propranolol.338
Administration of quinidine has been reported to cause decreased propranolol metabolism, resulting in increased propranolol plasma concentrations and increased β-blocking effects (and possible postural hypotension).338 Reduced lidocaine metabolism and clearance resulting in lidocaine toxicity have been reported in patients receiving the drug concomitantly with propranolol.338
Decreased propranolol plasma concentrations have been reported in patients receiving the drug concomitantly with cholestyramine or colestipol.338 Decreased plasma concentrations of lovastatin and pravastatin have been reported in patients receiving the drugs concomitantly with propranolol; however, the pharmacodynamics of the antilipemics were not altered.338
Increases in warfarin bioavailability and prothrombin time have been reported in patients receiving warfarin concomitantly with propranolol.338 Prothrombin time should be monitored in patients receiving warfarin concomitantly with propranolol.338
High doses of propranolol may potentiate the effects of neuromuscular blocking agents such as tubocurarine chloride, possibly because of propranolol's interference with ionic permeability of the postjunctional membrane. Propranolol should be administered with caution to patients who are receiving neuromuscular blocking agents or who are recovering from their effects.
β-Blockers may impair glucose tolerance; increase the frequency or severity of hypoglycemia; block hypoglycemia-induced tachycardia but not hypoglycemic sweating, which may actually be increased; delay the rate of recovery of blood glucose concentration following drug-induced hypoglycemia; alter the hemodynamic response to hypoglycemia, possibly resulting in an exaggerated hypertensive response; and possibly impair peripheral circulation. Nonselective β-blockers (e.g., propranolol, nadolol) without intrinsic sympathomimetic activity are more likely to affect glucose metabolism than more selective β-blockers (e.g., metoprolol, atenolol) or those with intrinsic sympathomimetic activity (e.g., acebutolol, pindolol). Signs of hypoglycemia (e.g., tachycardia, blood pressure changes, tremor, feelings of anxiety) mediated by catecholamines may be masked by either nonselective or selective β-blockers. When an oral antidiabetic agent or insulin and a β-blocker are used concomitantly, the patient should be advised about and monitored closely for altered antidiabetic response.
One case of severe peripheral vasoconstriction with pain and cyanosis has been reported in a patient who received propranolol orally and high doses of ergotamine in a rectal suppository concurrently for the treatment of migraine; however, several patients have received these drugs concomitantly without adverse effects. Caution should be used during simultaneous administration of propranolol and high doses of ergot alkaloids because of the possibility of additive peripheral vasoconstriction.
Cimetidine can substantially reduce the clearance of propranolol (apparently by inhibiting the hepatic metabolism of propranolol), which results in increased propranolol concentrations.338 If propranolol and cimetidine are administered concomitantly, the patient should be monitored for signs and symptoms of increased β-adrenergic blocking activity.
Concomitant oral administration of an aluminum hydroxide antacid with propranolol may reduce the GI absorption of propranolol.201, 235, 236, 237 In a study in healthy adults, oral administration of 30 mL of an aluminum hydroxide (1.2 g) suspension with a single, 80-mg dose of propranolol hydrochloride reduced the peak plasma propranolol concentration and bioavailability of the drug by about 60%.235, 237 The mechanism of this potential interaction has not been elucidated, but propranolol adsorption to or complexation with aluminum hydroxide does not appear to be involved.237, 239 In another study in healthy adults, however, concomitant oral administration of 30 mL of an aluminum hydroxide suspension with a single, 40-mg dose of propranolol hydrochloride did not substantially affect bioavailability of propranolol.237, 238 The need to avoid concomitant use or stagger dosing of an aluminum hydroxide antacid and propranolol has not been fully elucidated,237, 238 but increasing propranolol dosage may be considered if an interaction is suspected.235, 237
Propranolol may antagonize the hypotensive and positive inotropic effects of levodopa. This interaction is not well documented; however, the possibility of its occurrence should be kept in mind.
Nonsteroidal Anti-inflammatory Agents
The possibility that nonsteroidal anti-inflammatory agents (NSAIAs; e.g., indomethacin) may reduce the hypotensive effect of β-blockers such as propranolol should be considered. (See Drug Interactions, in Indomethacin 28:08.04.92.)
Propranolol decreases the clearance of theophylline338 in a dose-dependent manner by inhibiting hepatic microsomal metabolism (principally demethylation). In addition, propranolol can antagonize theophylline-induced bronchodilation.
Limited information is available on the acute toxicity of propranolol hydrochloride. In adults who intentionally ingested the drug, estimates of the ingested doses have ranged from 0.8-6 g. The principal manifestations of overdosage were bradycardia and severe hypotension (which may result in peripheral cyanosis); loss of consciousness and seizures have also occurred. In most cases of acute propranolol overdosage, the patient recovered; however, in a few cases, toxicity was severe enough to result in death. Two small children who ingested a total of 150 mg of propranolol hydrochloride became drowsy, perspired, and experienced periods of SA node block; they were treated with IV and oral dextrose. Severe paradoxical rise in blood pressure has been reported in 8 patients with schizophrenic disorder who received propranolol hydrochloride in rapidly increasing doses (600 mg in the first 24 hours); these patients responded to IV phentolamine.
Treatment of propranolol hydrochloride overdosage generally involves symptomatic and supportive care. Following acute ingestion of the drug, the stomach should be emptied immediately by inducing emesis or by gastric lavage. If the patient is comatose, having seizures, or lacks the gag reflex, gastric lavage may be performed if an endotracheal tube with cuff inflated is in place to prevent aspiration of gastric contents. For symptomatic bradycardia, IV atropine may be given; if bradycardia persists, IV isoproterenol hydrochloride may be administered cautiously (large doses may be required), and in refractory cases, use of a transvenous cardiac pacemaker should be considered. A vasopressor (e.g., norepinephrine, dopamine) may be given for severe hypotension. For heart failure, a cardiac glycoside and diuretic may be used. Because of the possibility of uncontrolled hypertension secondary to unopposed α-receptor stimulation in patients receiving long-term propranolol therapy, epinephrine is not indicated for the treatment of propranolol overdosage.338 Glucagon also may be useful for the management of myocardial depression and hypotension. Phosphodiesterase inhibitors also may be useful in the management of propranolol overdosage.338 A β2-adrenergic agonist and/or a theophylline derivative may be used for bronchospasm. IV diazepam may be useful for controlling seizures. Hemodialysis is probably not useful for enhancing elimination of propranolol in acute overdosage.
Propranolol hydrochloride is a nonselective β-adrenergic blocking agent (β-blocker). Propranolol inhibits response to adrenergic stimuli by competitively blocking β-adrenergic receptors within the myocardium and within bronchial and vascular smooth muscle. Only the l -isomer of propranolol has substantial β-adrenergic blocking activity. Propranolol has no intrinsic sympathomimetic activity.
Through its myocardial β-adrenergic blocking action, propranolol decreases heart rate and prevents exercise-induced increases in heart rate, decreases myocardial contractility, decreases cardiac output, increases systolic ejection time, and increases cardiac volume. The drug also decreases conduction velocity through the sinoatrial (SA) and atrioventricular (AV) nodes and decreases myocardial automaticity via β-adrenergic blockade. At blood concentrations greater than those required for β-adrenergic blockade, propranolol has a membrane-stabilizing effect on the heart which is similar to that of quinidine. The clinical importance of this effect is not clear, but it appears to be less important than its β-adrenergic blocking activity.
β-Adrenergic blockade may also increase peripheral resistance initially, but peripheral resistance tends to decrease after chronic administration of the drug as a result of unopposed α-adrenergic vasoconstriction. The cardiac effects of β-adrenergic blockade cause an increase in sodium reabsorption because of alterations in renal hemodynamics; renal blood flow and glomerular filtration rate generally decrease during chronic therapy. Plasma volume may increase if dietary sodium is not restricted. Hepatic blood flow is decreased.
The precise mechanism of propranolol's hypotensive effect has not been determined. It has been postulated that β-blockers reduce blood pressure by blocking peripheral (especially cardiac) adrenergic receptors (decreasing cardiac output), by decreasing sympathetic outflow from the CNS, and/or by suppressing renin release. In patients with high concentrations of circulating renin, low doses of the drug are associated with a fall in both blood pressure and in plasma renin concentrations, probably because of acute peripheral β-adrenergic blockade. With higher doses of propranolol, the hypotensive effect is probably unrelated to plasma renin activity and may be caused by a delayed centrally mediated reduction of adrenergic outflow. However, there appears to be some overlap between these mechanisms, and both mechanisms seem to be operative with usual therapeutic doses. Propranolol decreases blood pressure in both the supine and standing positions.
Several effects of propranolol may contribute to its usefulness in the management of angina pectoris. The drug usually causes decreased myocardial oxygen consumption and, secondarily, a decrease in coronary blood flow. The drug may reduce the oxygen requirements of the heart because of its β-adrenergic blockade. Propranolol also appears to cause redistribution of 2,3-diphosphoglyceric acid in erythrocytes which results in a decrease in the affinity of hemoglobin for oxygen, enhancing oxygen delivery to the tissues. This action is unrelated to β-adrenergic blockade. Propranolol may also affect platelet aggregation through a nonspecific platelet membrane effect unrelated to β-adrenergic blockade and possibly because of interference with calcium flux. In one study of patients with angina, the drug restored previously elevated platelet aggregability to normal. Abrupt withdrawal of the drug in patients with angina may cause rebound platelet hyperaggregability.
When used prophylactically, propranolol can prevent common migraine or reduce the number of attacks in some patients. β-Adrenergic receptors have been shown to be present in the pial vessels of the brain;602 however, the exact mechanism of the antimigraine effect of propranolol is not known.602, 603 Some evidence suggests that propranolol may prevent migraines through diminishing central catecholaminergic hyperactivity, possibly by inhibiting norepinephrine release, reducing neuronal activity and excitability, exerting membrane-stabilizing effects, and inhibiting nitric oxide production.603
Through its β-adrenergic blocking action in other body systems, propranolol increases airway resistance (especially in asthmatic patients), inhibits glycogenolysis in the skeletal and cardiac muscles, blocks the release of free fatty acids and insulin by adrenergic stimulation, and increases the number of circulating eosinophils. Propranolol increases uterine activity, more in the nonpregnant than in the pregnant uterus.
Propranolol is almost completely absorbed from the GI tract; however, plasma concentrations attained are quite variable among individuals. There is no difference in the rate of absorption of the 2 isomers of propranolol. Propranolol appears in the plasma within 30 minutes, and peak plasma concentrations are reached about 60-90 minutes after oral administration of the conventional tablets. The time when peak plasma concentrations are reached may be delayed, but concentrations are not necessarily lowered, when the drug is administered with food. One manufacturer states that oral bioavailability of the drug may be increased in children with Down's syndrome; higher than expected plasma propranolol concentrations have been observed in such children.201 Bioavailability of a single 40-mg oral dose of propranolol hydrochloride as a conventional tablet or oral solution reportedly is equivalent in adults. Propranolol is slowly absorbed following administration of the drug as extended-release capsules, and peak blood concentrations are reached about 6 hours after administration. When measured at steady-state over a 24-hour period, the area under the plasma concentration-time curve (AUC) for the extended-release capsules is about 60-65% of the AUC for a comparable divided daily dose of the conventional tablets. The lower AUC is probably caused by the slower rate of absorption of the drug from the extended-release capsules with resultant greater hepatic metabolism. After administration of a single dose of propranolol hydrochloride as the extended-release capsules, blood concentrations of propranolol are fairly constant for about 12 hours and then decline exponentially during the following 12 hours.
Plasma propranolol concentrations attained after IV administration of the drug are relatively consistent among individuals. After administration of a 0.5-mg IV bolus of propranolol hydrochloride, peak plasma propranolol concentrations of 40 ng/mL are produced in 1 minute and the drug is undetectable in the plasma in 5 minutes. Following IV administration of propranolol, the onset of action is almost immediate. Animal studies indicate that propranolol is rapidly absorbed after IM administration.
After absorption from the GI tract, propranolol is bound by the liver through nonspecific tissue binding. There are large individual differences in hepatic extraction, probably because of differences in hepatic blood flow. Following oral administration, the drug does not reach the general circulation until hepatic binding sites are saturated. Once saturation occurs, hepatic binding no longer affects the passage of the drug into the blood. The amount of drug that reaches the circulation after oral administration also depends on the amount of drug metabolized on the first pass through the liver. Propranolol decreases its own rate of metabolism by decreasing hepatic blood flow. Studies indicate that hepatic extraction and possibly metabolism of propranolol are reduced following oral administration of the drug in patients with chronic renal disease, resulting in higher peak plasma concentrations of the drug after the first dose than are attained in patients with normal renal function.
There is considerable interpatient variation in the relationship of plasma propranolol concentrations and therapeutic effect, but therapeutic plasma concentrations of propranolol are usually 50-100 ng/mL. Concentrations of 100 ng/mL generally represent a high degree of β-adrenergic blockade. There are several possible metabolic explanations for the discrepancies between plasma concentrations and therapeutic effect. (See Pharmacokinetics: Elimination.) Individual differences in sympathetic tone may also contribute to interpatient differences in response.
Propranolol is widely distributed into body tissues including lungs, liver, kidneys, and heart. Propranolol readily crosses the blood-brain barrier and the placenta. The drug is distributed into milk.
The apparent volume of distribution of propranolol at steady-state varies widely in proportion to the fraction of unbound drug in whole blood. Propranolol is more than 90% bound to plasma proteins over a wide range of blood concentrations. Both free and protein-bound propranolol are metabolized. Increased plasma protein binding of the drug increases its metabolism and decreases its volume of distribution, resulting in a shorter terminal half-life.
Elimination of propranolol appears to follow first-order kinetics and seems to be independent of plasma concentration or the dose administered, at least with oral doses of 160-320 mg/day. The reported elimination half-life varies considerably among different studies. After IV administration of 10 mg of propranolol hydrochloride at a rate of 1.03 mg/minute in one study, plasma concentrations declined in a biphasic manner; the half-life during the initial phase (t½α) was 10 minutes and that during the terminal phase (t½β) was 2.3 hours. Results from one study indicate that the half-life of the l -isomer is about 50% longer than that of the d -isomer. When usual therapeutic doses of propranolol hydrochloride are administered chronically, the half-life of propranolol ranges from 3.4-6 hours. Single-dose studies generally have shown a shorter half-life of 2-3 hours. This difference in half-life between chronic and single-dose studies may be the result of initial removal of the drug into a large extravascular space (especially hepatic binding sites) and also a saturation of systemic clearance (including drug metabolizing enzymes and excretion). The half-life of propranolol may decrease with decreasing renal function; however, there is insufficient evidence to indicate that any alteration in maintenance dosage is necessary in patients with impaired renal function.
During initial oral therapy (but not during IV or chronic oral therapy), an active metabolite, 4-hydroxypropranolol, is formed. 4-Hydroxypropranolol has about the same β-adrenergic blocking potency as does propranolol and may be present in plasma in amounts about equal to propranolol. This metabolite is eliminated more rapidly than propranolol and is virtually absent from the plasma 6 hours after oral administration of the drug. Results of one study indicate that after IV administration or chronic oral administration of propranolol, 4-hydroxypropranolol is not formed to a substantial extent, and β-adrenergic blocking activity is more closely reflected by propranolol concentrations. Individual variations in ability to hydroxylate propranolol to the active metabolite may also exist. In addition, some other metabolites of propranolol may possess antiarrhythmic activity without β-adrenergic blocking activity.
Propranolol is almost completely metabolized in the liver and at least 8 metabolites have been identified in urine. Only 1-4% of an oral or IV dose of the drug appears in feces as unchanged drug and metabolites. In patients with severely impaired renal function, a compensatory increase in fecal excretion of propranolol occurs. Reduced propranolol plasma clearance and increased peak plasma concentrations have been reported in patients with chronic renal failure compared with healthy individuals and patients receiving dialysis.338 Chronic renal failure may be associated with reduced drug metabolism secondary to downregulation of hepatic cytochrome P-450 (CYP) enzyme system activity.338 Propranolol is apparently not substantially removed by hemodialysis.
Decreased propranolol clearance and prolonged elimination half-life have been reported in geriatric patients compared with younger patients.338 In addition, reduced clearance, increased volume of distribution, decreased protein binding, and considerable variation in elimination half-life of propranolol have been reported in patients with chronic liver disease compared with individuals with normal liver function.338 Increased propranolol exposure and decreased clearance also have been reported in obese individuals compared with nonobese individuals.338
Propranolol hydrochloride is a nonselective β-adrenergic blocking agent (β-blocker). Propranolol hydrochloride occurs as a white or off-white, crystalline powder with a bitter taste and is soluble in water and in alcohol. The commercially available drug is a racemic mixture of the 2 optical isomers. Solutions of propranolol hydrochloride fluoresce at pH 4-5. The injection is adjusted to pH 2.8-3.5 with citric acid.
Propranolol hydrochloride preparations should be protected from light and stored at room temperature (20-25°C).201, 314 The manufacturer recommends that propranolol hydrochloride extended-release capsules be stored in tight, light-resistant containers and be protected from moisture, freezing, and excessive heat. Propranolol hydrochloride injection also should be protected from freezing and excessive heat.338 USP recommends that propranolol hydrochloride preparations be stored in well-closed containers. Solutions of the drug have maximum stability at pH 3 and decompose rapidly at alkaline pH. Decomposition in aqueous solution is accompanied by a lowered pH and discoloration. Propranolol hydrochloride injection is reportedly compatible with 0.9% sodium chloride injection; however, specialized references should be consulted for specific compatibility information.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Capsules, extended-release | 60 mg | Inderal® LA | |
80 mg | Inderal® LA | Ani Pharms | ||
Innopran® XL | Ani Pharms | |||
120 mg | Inderal® LA | Ani Pharms | ||
Innopran® XL | Ani Pharms | |||
160 mg | Inderal® LA | Ani Pharms | ||
Solution | 20 mg/5 mL* | |||
40 mg/5 mL* | Propranolol Hydrochloride Solution | |||
Tablets | 10 mg* | |||
20 mg* | Propranolol Hydrochloride Tablets | |||
40 mg* | Propranolol Hydrochloride Tablets | |||
60 mg* | Propranolol Hydrochloride Tablets | |||
80 mg* | Propranolol Hydrochloride Tablets | |||
Parenteral | Injection | 1 mg/mL* |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets | 40 mg Propranolol Hydrochloride and Hydrochlorothiazide 25 mg* | ||
80 mg Propranolol Hydrochloride and Hydrochlorothiazide 25 mg* | Propranolol Hydrochloride and hydroCHLOROthiazide Tablets |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
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