Propranolol Hydrochloride

INNOPRAN XL® is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes, including beta-blockers.

Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program's Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).

Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly.

Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.

Some antihypertensive drugs have smaller blood pressure effects (as montherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy.

You should not use this medication if you are allergic to propranolol, if you have asthma, a slow heart rate, or a serious heart condition such as "sick sinus syndrome" or "AV block" (unless you have a pacemaker).

If you need surgery, tell the surgeon ahead of time that you are using propranolol. You may need to stop using the medicine for a short time.

Do not skip doses or stop using propranolol without first talking to your doctor. You may need to use less and less before you stop the medication completely.

Avoid drinking alcohol. It may increase your blood levels of propranolol.

Propranolol is only part of a complete program of treatment for hypertension that may also include diet, exercise, and weight control. Follow your diet, medication, and exercise routines very closely if you are being treated for hypertension.

If you are being treated for high blood pressure, keep using this medication even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adverse reactions occurring at a rate of ≥ 3%, excluding those reported more commonly in placebo, encountered in the INNOPRAN XL placebo-controlled hypertension trials and plausibly related to treatment are shown in Table 1.

Table 1: Treatment Emergent Adverse Reactions Reported In ≥ 3% of Subjects

Body System	INNOPRAN XL
	Placebo (N=88)	80 mg (N=89)	120 mg (N=85)
Fatigue	3 (3%)	4 (5%)	6 (7%)
Dizziness (except vertigo)	2 (2%)	6 (7%)	3 (4%)
Constipation	0	3 (3%)	1 (1%)

Postmarketing Experience

In addition to adverse reactions reported from clinical trials, the following reactions have been identified during post-marketing use of INNOPRAN XL. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The following adverse reactions were observed and have been reported with use of formulations of sustained-or immediate-release propranolol.

Allergic: Hypersensitivity reactions, including anaphylactic/anaphylactoid reactions; pharyngitis and agranulocytosis; erythematous rash, fever combined with aching and sore throat, laryngospasm, and respiratory distress.

Autoimmune: Systemic lupus erythematosus (SLE).

Cardiovascular: exacerbation of peripheral arterial disease, arterial insufficiency, usually of the Raynaud type.

Central Nervous System: Light-headedness, mental depression, insomnia, lassitude, weakness, fatigue visual disturbances, hallucinations, vivid dreams, short-term memory loss, emotional lability, slightly clouded sensorium, paresthesia of hands

Gastrointestinal: Nausea, vomiting, epigastric distress, abdominal cramping, diarrhea, mesenteric arterial thrombosis, ischemic colitis.

Genitourinary: Male impotence; Peyronie's disease.

Hematologic: Agranulocytosis, nonthrombocytopenic purpura, thrombocytopenic purpura.

Musculoskeletal: Myopathy, myotonia

Skin and mucous membranes: Stevens-Johnson syndrome, toxic epidermal necrolysis, dry eyes, exfoliative dermatitis, erythema multiforme, urticaria, alopecia, SLE-like reactions, and psoriasisiform rashes.

Read the entire FDA prescribing information for InnoPran XL (Propranolol Hydrochloride)

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Hypertension

Management of hypertension, alone or in combination with other antihypertensive agents.201 314 323 500 b c Not indicated for the treatment of hypertensive emergencies.b c

β-Blockers generally not preferred for initial management of hypertension, but may be considered in 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 (ACE inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, or thiazide diuretics).353 501 502 503 504 515 523 524 527 800

Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to β-blockers.330 336 337 500 501 504 However, diminished response to β-blockers is largely eliminated when administered concomitantly with a thiazide diuretic.500

Angina

Management of chronic stable angina pectoris.b c

A component of the standard therapeutic measures in the management of unstable angina/non-ST-segment elevation MI†.a

Supraventricular Arrhythmias

Treatment of supraventricular tachycardia (SVT) (e.g., atrial flutter, junctional tachycardia, focal atrial tachycardia, paroxysmal supraventricular tachycardia [PSVT]).201 338 401 700 701

Vagal maneuvers and/or IV adenosine are considered first-line interventions for acute treatment of SVT when clinically indicated; if such measures are ineffective or not feasible, may consider an IV β-blocker.700 Oral β-blockers may be used for ongoing management.700 Although evidence of efficacy is limited, experts state that overall safety of β-blockers warrants use.700

Used to slow ventricular rate in patients with atrial fibrillation or flutter when ventricular rate cannot be controlled by standard measures.201 338 701

Ventricular Arrhythmias

Generally less effective in the management of ventricular arrhythmias than supraventricular arrhythmias, but may be considered when cardioversion or other drugs not effective.338

May be used in the treatment of persistent premature ventricular complexes.338

β-Blockers have been used in patients with cardiac arrest precipitated by ventricular fibrillation† or pulseless VT†; however, routine administration after cardiac arrest is potentially harmful and not recommended.400

β-Blockers may be useful in the management of certain forms of polymorphic VT† (e.g., associated with acute ischemia).401

Tachyarrhythmias Associated with Cardiac Glycoside Intoxication or Catecholamine Excess

Management of supraventricular or ventricular tachyarrhythmias associated with cardiac glycoside toxicity when AV block is not present.b

Management of resistant tachyarrhythmias associated with catecholamine excess during anesthesia; use with extreme caution and constant ECG and central venous pressure monitoring.a b More effective and less hazardous therapy, such as lessening the depth of anesthesia or improving ventilation, is preferred.a

Hypertrophic Subaortic Stenosis

Management of exertional or other stress-induced angina, vertigo, syncope, and palpitation in patients with hypertrophic subaortic stenosis; clinical improvement may be temporary.b

Pheochromocytoma

Management of symptoms resulting from excessive β-receptor stimulation in patients with inoperable or metastatic pheochromocytoma, as an adjunct to α-adrenergic blocking agents.b Initiate therapy with an α-adrenergic blocking agent prior to treatment of pheochromocytoma.b (See Pheochromocytoma under Cautions.)

Management of tachycardia prior to or during surgery in patients with pheochromocytoma, as an adjunct to α-adrenergic blocking agents.a b Initiate therapy with an α-adrenergic blocking agent prior to treatment of pheochromocytoma.b (See Pheochromocytoma under Cautions.)

Thyrotoxicosis

Short-term (2–4 weeks) adjunctive therapy of tachycardia and supraventricular arrhythmias in patients with thyrotoxicosis when these symptoms are distressful or hazardous, or when immediate therapy is necessary.a

Vascular Headache

Prophylaxis of common migraine headache; not recommended for the treatment of a migraine attack that has already started.b

Acute MI

Secondary prevention following acute MI to reduce the risk of reinfarction† and mortality.245 246 248 249 261 292 a b

Essential Tremor

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

Not indicated for tremor associated with Parkinsonism.b

General

BP Monitoring and Treatment Goals

• Carefully monitor BP during initial titration or subsequent upward adjustment in dosage.500 501

• When available, use evidence-based dosing information (i.e., dosages shown in randomized controlled trials to reduce complications of hypertension) to determine target dosages; target dosages usually can be achieved within 2–4 weeks but may take up to several months.501

• Goal is to achieve and maintain optimal control of BP; individualize specific target BP based on consideration of multiple factors, including patient age and comorbidities, and currently available evidence from clinical studies.500 501

Acute MI

• In patients with acute MI, administer therapy in 2, 3, or 4 divided doses daily.201 Continue therapy for at least 1–3 years unless contraindicated;246 248 260 some experts recommend that therapy be continued indefinitely unless contraindicated.292

Angina

• Periodically reevaluate chronic therapy for angina to determine the need for dosage adjustment or continued therapy.a

• In patients with unstable angina/non-ST-segment elevation MI, ACC and the AHA suggest initiation with IV loading dose of a β-blocker (in patients who tolerate IV therapy), followed by oral therapy.321

• If long-term therapy is to be discontinued, reduce dosage gradually over a period of about 2 weeks.a (See Abrupt Withdrawal of Therapy under Cautions.)

Vascular Headache

• If an adequate response for prophylaxis of migraine is not obtained within 4–6 weeks after reaching the maximum dose, discontinue therapy gradually over several weeks.201 314 315

Administration

Administer orally or IV.338 700 701 b

Individualize dosage according to patient response.a

Oral Administration

Administer conventional tablets in divided doses before meals and at bedtime.a

Administer extended-release capsules once daily.a c

Extended-release capsules produce lower blood concentrations than conventional tablets; do not substitute on a mg-for-mg basis.c Consider dosage retitration when switching from conventional tablets to extended-release capsules, especially to maintain effectiveness at the end of the dosing interval.c

Dilute oral concentrate solution with water, juice, or carbonated beverages or mix with semisolid foods (e.g., applesauce, puddings) just prior to administration.a

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Monitor ECG and central venous pressure carefully during IV administration.201

Replace IV therapy with oral therapy as soon as possible.b

Rate of Administration

Administer by slow IV injection at a rate not >1 mg/minute.b

Dosage

Available as propranolol hydrochloride; dosage expressed in terms of the salt.600 601 602 b

Pediatric Patients

Usual Dosage Oral

Conventional tablets: 2–4 mg/kg daily in 2 equally divided doses.b Weight-adjusted initial dosage is approximate; adjust dosage according to response, up to 16 mg/kg daily.201 231 b

Do not calculate dosage based on body surface area; may result in excessive plasma concentrations.a

If propranolol is to be discontinued, decrease dosage gradually over 7–14 days.b

Hypertension Oral

Conventional tablets: Initially, 1 mg/kg daily in 2 equally divided doses.201 240 243 Adjust according to response and tolerance.a 240 241

Usual maintenance dosage is 2–4 mg/kg daily in 2 equally divided doses, up to 16 mg/kg daily.201

Alternatively, some experts recommend a usual initial dosage of 1–2 mg/kg daily given in 2 or 3 divided doses.335 Increase dosage as necessary up to a maximum dosage of 4 mg/kg (up to 640 mg) daily given in 2 or 3 divided doses.335

Cardiac Arrhythmias Oral

Initially, 1.5–2 mg/kg daily; titrate upward as necessary to 16 mg/kg daily in 4 divided doses to control the arrhythmia.231 232

Dosages >4 mg/kg daily may be necessary for the management of supraventricular tachyarrhythmias.231 232

IV

10–20 mcg/kg infused over 10 minutes has been recommended.a

Thyrotoxicosis Treatment of Tachyarrhythmias in Neonates with Thyrotoxicosis Oral

2 mg/kg daily in 2–4 divided doses has been used.a Higher dosages occasionally may be needed.a

Adults

Hypertension Propranolol Therapy Oral

Conventional tablets or oral solution: Initially, 40 mg twice daily, either alone or in combination with a diuretic.201 602 Manufacturers state usual effective dosage is 120–240 mg daily;201 some experts recommend 40–160 mg daily given in 2 divided doses.500 If satisfactory BP response is not maintained throughout the day, larger doses or administration in 3 divided doses daily may be required.201

Extended-release capsules: Initially, 80 mg once daily, either alone or in combination with a diuretic.314 600 601 Manufacturers state usual effective dosage is 120–160 mg once daily;314 some experts recommend 60–180 mg once daily.500 However, manufacturer of Innopran XL states that dosages >120 mg once daily did not provide additional hypotensive effects.600

Full hypotensive effect usually evident within 2–3 weeks, but timing is variable.600

If intolerable adverse effects occur, consider dosage reduction; if adverse effects worsen or fail to resolve, may need to discontinue and switch to another antihypertensive drug class.501

Propranolol/Hydrochlorothiazide Fixed-combination Therapy Oral

Administer in 2 divided doses daily (up to 160 mg of propranolol hydrochloride and 50 mg of hydrochlorothiazide total daily dosage).c

Combination preparation is inappropriate with propranolol hydrochloride dosages >160 mg daily due to excessive dosage of the thiazide component.323 May gradually add another antihypertensive agent when necessary using half of the usual initial dosage to avoid an excessive decrease in BP.323

Initial use of fixed-combination preparations is not recommended; adjust by administering each drug separately, then use the fixed combination if the optimum maintenance dosage corresponds to the drug dosages in the combination preparation.a

Angina Chronic Stable Angina Oral

Conventional tablets or oral solution: Usual dosage is 80–320 mg daily in 2–4 divided doses.201 315 More than 320 mg daily has been recommended when there is only a partial response to usual dosage.a

Extended-release capsules: Initially, 80 mg daily.314 Gradually increase dosage at 3- to 7-day intervals as needed to control symptoms.314 Optimum response usually occurs at 160 mg daily, but there is wide variation in response.314

Unstable Angina/Non-ST-Segment Elevation MI IV

Initial dose of 0.5–1 mg, followed in 1–2 hours by oral therapy.321

Oral

Conventional tablets or oral solution: Initially, 40–80 mg every 6–8 hours; thereafter, maintain on 20–80 mg twice daily.321 Titrate to target heart rate of 50–60 bpm in the absence of dose-limiting adverse effects.321

Cardiac Arrhythmias Oral

Conventional tablets or oral solution: usually 10–30 mg 3 or 4 times daily.b

Life-threatening Arrhythmias or Those Occurring during Anesthesia IV

1–3 mg by slow IV injection.201 If necessary, repeat dose after 2 minutes.201 May administer additional doses at intervals of ≥4 hours until desired response is obtained.201

SVT (e.g., Atrial Flutter, Junctional Tachycardia, PSVT, Atrial Tachycardia) IV

Some experts recommend initial dose of 1 mg over 1 minute; may repeat at 2-minute intervals up to 3 doses.700

Oral

Usual maintenance dosage: 40–160 mg daily in single (with long-acting preparations) or divided doses.700

Atrial Fibrillation IV

Experts recommend initial dose of 1 mg over 1 minute; may repeat at 2-minute intervals up to 3 doses.701

Oral

Usual maintenance dosage: 40–160 mg daily in divided doses.701

Hypertrophic Subaortic Stenosis Oral

Conventional tablets or oral solution: 20–40 mg 3 or 4 times daily.201 314 315

Extended-release capsules: 80–160 mg once daily.201 314 315

Pheochromocytoma Prior to Surgery Oral

Conventional tablets or oral solution: 60 mg daily in divided doses (in conjunction with an α-adrenergic blocking agent) for 3 days prior to surgery.201 315 (See Pheochromocytoma under Cautions.)

Adjunctive Treatment for Inoperable Pheochromocytoma. Oral

30 mg daily in divided doses (in conjunction with an α-adrenergic blocker).201 315 (See Pheochromocytoma under Cautions.)

Vascular Headache Prevention of Common Migraine Oral

Conventional tablets or oral solution: initially, 80 mg daily in divided doses.201 314 315

Extended-release capsules: 80 mg once daily.201 314 315

Gradually increase dosage to achieve optimum response; usual effective dosage is 80–240 mg daily.201 314 315 326

Discontinue if response is inadequate after 4–6 weeks; gradual withdrawal over several weeks may be advisable.201 314 315

Acute MI Mortality Reduction after Acute MI Oral

Conventional tablets or oral solution: 180–240 mg daily in divided doses, beginning 5–21 days after infarction.201 315 Higher dosage may be necessary for patients with coexisting conditions (e.g., angina, hypertension).201 315

Administered in 3–4 divided doses daily in clinical studies, but twice-daily dosing also may be adequate.201

Optimum benefit may be achieved when oral therapy with β-blocker is continued for at least 1–3 years after infarction (when not contraindicated);246 248 260 some experts recommend continuing therapy indefinitely unless contraindicated.292

Essential Tremor Routine Therapy Oral

Conventional tablets: Initially, 40 mg twice daily.201 229

Response is variable and dosage must be individualized; optimal suppression of tremor usually occurs with 120–320 mg daily in 3 divided doses.201 202 203 204 205 207 208 211 213 214 215 216 219 220 221 228 229

Complete suppression of tremor rarely is achieved;205 206 207 214 215 220 225 226 dosages exceeding 320 mg daily may not provide substantial added benefit but are associated with an increased risk of adverse effects.205 209 221

Extended-release capsules: Usual dosages administered once daily each morning appear to be at least as effective as equivalent dosages of conventional tablets administered in divided doses daily.216

Intermittent Therapy Oral

Conventional tablets: 80–120 mg as a single dose 1–3 hours before planned activity or anticipated stress associated with tremor.202 208 211 227

Prescribing Limits

Pediatric Patients

Hypertension Oral

Maximum 16 mg/kg daily;201 231 232 240 241 however, some experts recommend a maximum dosage of 4 mg/kg (up to 640 mg) daily.335

Adults

Angina Oral

320 mg daily; some clinicians recommend higher dosage if there is only a partial response to usual dosage.a

Acute MI Oral

240 mg daily.201 315

Essential Tremor Oral

320 mg daily; higher dosages do not provide substantial added benefit and are associated with an increased risk of adverse effects.205 209 221

Special Populations

Hepatic Impairment

Use with caution.b

Renal Impairment

Dosage adjustments not required.a Use with caution.b

Geriatric Patients

Use caution in dosage selection; initiate therapy at low end of dosage range.b

Contraindications

• Sinus bradycardia.b

• Heart block greater than first degree.b

• Cardiogenic shock.b

• CHF (unless secondary to a tachyarrhythmia treatable with propranolol).b (See Heart Failure under Cautions.)

• Raynaud’s syndrome.a

• Malignant hypertension.a

• Bronchial asthma.a (See Bronchospastic Disease under Cautions.)

• Concomitant thioridazine therapy.310 (See Specific Drugs under Interactions.)

Warnings/Precautions

Warnings

Heart Failure

Possible precipitation of heart failure.b

Avoid use in patients with overt heart failure;b may use cautiously in patients with inadequate myocardial function and, if necessary, in patients with well-compensated heart failure (e.g., those controlled with heart glycosides and/or diuretics).b a Adequate treatment (e.g., with a cardiac glycoside and/or diuretic) and close observation recommended if signs or symptoms of impending heart failure occur; if heart failure continues, discontinue therapy, gradually if possible.b

Possible decreased exercise tolerance in patients with left ventricular dysfunction.a

Abrupt Withdrawal of Therapy

Abrupt withdrawal of propranolol is not recommended as it may exacerbate angina symptoms or precipitate MI in patients with CAD.a b Gradually decrease dosage over about 2 weeks and monitor patients carefully.b a If exacerbation of angina occurs or acute coronary insufficiency develops, reinstitute therapy promptly, at least temporarily, and initiate appropriate measures for the management of unstable angina.b

Bronchospastic Disease

Possible inhibition of bronchodilation produced by endogenous catecholamines.b Possible increased airway resistance and bronchospasm, particularly in patients with a history of asthma.a

Use with caution in patients with a history of nonallergic bronchospasm (e.g., chronic bronchitis, emphysema).b Use not recommended in patients with bronchial asthma.b (See Contraindications under Cautions.)

Major Surgery

Possible increased risks associated with general anesthesia (e.g., severe hypotension, difficulty restarting or maintaining heart beat) due to decreased ability of the heart to respond to reflex β-adrenergic stimuli.b a Use with extreme caution for management of arrhythmias occurring during anesthesia with myocardial depressant anesthetics.a (See Specific Drugs under Interactions.)

Diabetes and Hypoglycemia

Possible decreased signs and symptoms of hypoglycemia (e.g., tachycardia, palpitation, BP changes, tremor).305 b Possible hypoglycemia, especially in those undergoing dialysis, prolonged fasting, or severe exercise regimens.305 314

Use with caution in patients with diabetes mellitus.a

Thyrotoxicosis

Signs of hyperthyroidism may be masked.b Possible thyroid storm if therapy is abruptly withdrawn; carefully monitor patients having or suspected of developing thyrotoxicosis.b a Possible altered thyroid function test results.b a

Bradycardia

Possible bradycardia, occasionally severe and accompanied by hypotension, syncope, shock, or angina.b a Severe bradycardia requiring a demand pacemaker has occurred in patients with Wolff-Parkinson-White syndrome.b Treat severe bradycardia with IM or IV atropine sulfate.a If response is inadequate, consider cautious administration of IV isoproterenol.a

Possible depressed SA node automaticity; use with caution in patients with sinus node dysfunction.a

AV Block

Possible intensification of AV block, AV dissociation, AV conduction delays, complete heart block, or cardiac arrest, especially in patients with preexisting heart block caused by digitalis or other factors.a

Pheochromocytoma

To prevent severe hypertension, institute α-adrenergic blocking agent therapy prior to the use of propranolol and continue during propranolol therapy.b

General Precautions

History of Anaphylactic Reactions

Possible increased reactivity to a variety of allergens; patients may be unresponsive to usual doses of epinephrine used to treat anaphylactic reactions.201 314

Ocular Effects

Possible dry eyes, generalized hyperemia of the conjunctivae, decreased tear production, and eye pain.a

Myasthenia Gravis

Myasthenic condition (e.g., ptosis, weakness of limbs, and double vision) reported rarely with propranolol; use may be contraindicated in patients with myasthenia gravis.a

Other Precautions

Shares the toxic potentials of β-blockers; observe usual precautions of these agents.a

When used in fixed combination with hydrochlorothiazide, consider the cautions, precautions, and contraindications associated with thiazide diuretics.a

Specific Populations

Pregnancy

Category C.b c d

Lactation

Distributed into milk.b c d Use with caution.b c d

Pediatric Use

Efficacy and adverse effect profiles in children generally similar to such profiles in adults.201 Bioavailability may be increased in children with Down’s syndrome.201 Safety and efficacy of extended-release capsules, oral solution, and injection not established in children.a

Geriatric Use

Insufficient evidence in patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients.a Select dosage with caution, usually initiating therapy at the low end of the dosage range because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.a

Hepatic Impairment

Use with caution;b assess hepatic function prior to and periodically during prolonged therapy.a

Renal Impairment

Use with caution;b assess renal function prior to and periodically during prolonged therapy.a

Common Adverse Effects

Bradycardia, nausea, vomiting, diarrhea, epigastric distress, abdominal cramping, constipation, flatulence.b a

Specific Drugs

Drug	Interaction	Comments
Antipsychotic agents (e.g., phenothiazines)	Possible additive hypotensive effect, especially with large doses of phenothiazinesa
Chlorpromazine	Possible decreased propranolol clearancea
Thioridazine	Possible decreased thioridazine metabolism.310 Possible increased risk of serious, potentially fatal cardiac arrhythmias (e.g., torsades de pointes)310	Concomitant use contraindicated310
Haloperidol	Possible hypotension and cardiac arresta
Fluoxetine	Possible decreased propranolol metabolism;272 273 complete heart block reported272 273	Caution recommended with concomitant use and in those with impaired cardiac conduction272
Sympathomimetic agents	Possible antagonism of β-adrenergic stimulating effects;a very large doses of isoproterenol may be needed to overcome β-adrenergic blocking effectsa	Administer epinephrine with caution; decreased pulse rate with first- and second-degree heart block may occura
Drugs with anticholinergic effects	Possible antagonism of cardiac β-adrenergic blocking effectsa
Diuretics	Possible increased hypotensive effecta	Careful dosage adjustments recommendeda
Reserpine	Possible additive effectsa
Antiarrhythmic drugs (lidocaine, phenytoin, procainamide, quinidine, verapamil)	Possible additive or antagonistic cardiac effects and additive toxic effectsa
Verapamil	Serious adverse reactions reported rarely with concomitant IV verapamil, especially in patients with severe cardiomyopathy, CHF, or recent MIa
Other cardiovascular drugs (e.g., cardiac glycosides, nondihydropyridine calcium-channel blocking agents)	Possible additive negative effects on SA or AV nodal conductiona
Neuromuscular blocking agents	Possible increased effects of neuromuscular blocking agentsa	Administer with caution to patients receiving or recovering from the effects of neuromuscular blocking agentsa
Antidiabetic agents	Possible altered antidiabetic responsea	Close monitoring recommendeda
Ergot alkaloids	Possible additive peripheral vasoconstrictiona	Use concomitantly with cautiona
Cimetidine	Possible decreased propranolol clearancea	Monitor for signs and symptoms of increased β-adrenergic blocking activitya
Antacids	Possible decreased propranolol absorption201 235 236 237	Need to avoid concomitant use or stagger dosing of an aluminum hydroxide antacid has not been fully elucidated;237 238 consider increasing propranolol dosage if interaction suspected235 237
Levodopa	Possible decreased hypotensive and positive inotropic effects of levodopaa
NSAIAs	Possible decreased hypotensive effects of propranolola
Theophylline	Possible decreased theophylline clearance.a Possible decreased theophylline-induced bronchodilationa
Myocardial depressant general anesthetics	Possible increased risk of myocardial depression, bradycardia, hypotensiona

Absorption

Bioavailability

Oral absorption almost complete.a

Bioavailabilities of conventional tablet and oral solution reportedly equivalent in adults.a

Oral bioavailability may be increased in children with Down’s syndrome.a

Onset

Conventional oral tablets: peak effect in 1–1.5 hours.b

Plasma Concentrations

100–150 ng/mL with considerable interpatient variation; 100 ng/mL generally represents high degree of β-blockade.a

Distribution

Extent

Widely distributed into body tissues, including lungs, liver, kidneys, and heart.a Portion of orally administered dose immediately bound by liver.b

Crosses blood-brain barrier.a

Crosses placenta and is distributed into milk.a

Plasma Protein Binding

>90% over a wide range of blood concentrations.a

Elimination

Metabolism

Almost completely metabolized in the liver.a

Elimination Route

Excreted principally in urine; at least 8 metabolites have been identified.a

1–4% of an oral or IV dose of the drug appears in feces as unchanged drug and metabolites.a

Half-life

IV: 10 minutes (initial phase), 2.3 hours (terminal phase).b

Conventional oral tablets: about 4 hours.b

3.4–6 hours with chronic administration of usual therapeutic doses; 2–3 hours after single dose.a

Extended-release capsules: apparent half-life about 10 hours.c

Special Populations

In patients with severely impaired renal function, a compensatory increase in fecal excretion of propranolol occurs.a Propranolol apparently not substantially removed by hemodialysis.a