Propranolol Hydrochloride

Pronunciation

Class: beta-Adrenergic Blocking Agents
VA Class: CV100
CAS Number: 318-98-9
Brands: Inderal, Inderal LA, Inderide, Innopran XL

Introduction

Nonselective β-adrenergic blocking agent.b c

Uses for Propranolol Hydrochloride

Hypertension

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

Angina

Management of chronic stable angina pectoris.b c

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

Supraventricular Tachyarrhythmias

β-Adrenergic blocking agents, including propranolol, are one of several preferred antiarrhythmic agents for the treatment of stable, narrow-complex supraventricular tachycardias (e.g., paroxysmal supraventricular tachycardia [reentry supraventricular tachycardia], ectopic or multifocal atrial tachycardia, junctional tachycardia) if the rhythm is not controlled by vagal maneuvers or adenosine in patients with preserved left ventricular function and for rate control in atrial fibrillation or flutter in patients with preserved left ventricular function.352

Paroxysmal atrial tachycardias, especially those caused by catecholamines or cardiac glycosides, or those associated with the Wolff-Parkinson-White syndrome.a

Treatment of persistent atrial extrasystoles and noncompensatory sinus tachycardia that impair the well-being of the patient and do not respond to conventional therapy.a

Slideshow: Living with Your Migraines: Tips for Treatment and Prevention

May be especially useful in conjunction with a cardiac glycoside to slow ventricular rates in the treatment of atrial flutter and fibrillation in patients whose arrhythmia is not controlled by adequate doses of a cardiac glycoside alone.a

Ventricular Arrhythmias

Treatment of tachyarrhythmias during cardiovascular surgery, including decreasing ventricular fibrillation time during cardiopulmonary bypass surgery.a

Treatment of persistent ventricular premature contractions that impair the well-being of the patient and do not respond to conventional therapy.a

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

AMI

Secondary prevention following AMI to reduce the risk of reinfarction and mortality.a b 352

Management of ventricular arrhythmias complicating AMI.352

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

Propranolol Hydrochloride Dosage and Administration

General

Hypertension

  • In patients with hypertension, monitor BP during initial titration or subsequent upward dosage adjustment;289 large or abrupt reductions in BP should generally be avoided.289 Full hypotensive effect may require weeks of therapy, especially when low initial doses are used.a

  • Adjust antihypertensive dosage at 1–2 month intervals (more aggressively in high-risk patients) if response is inadequate.289 Larger doses or 3 divided doses daily may be required to maintain effective response throughout the day.201

  • Propranolol hydrochloride/hydrochlorothiazide fixed combination is not recommended for initial combination therapy;a d adjust initial and subsequent dosages by administering each drug separately.a

AMI

  • In patients with AMI, 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 or non-ST-segment elevation/non-Q-wave MI, the 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.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

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
Monotherapy
Oral

Conventional tablets or oral solution: initially, 40 mg twice daily.201 Usual effective dosage is 120–240 mg daily.201

Extended-release capsules: initially, 80 mg once daily.314 Usual effective dosage is 120–160 mg once daily.314

Increase dosage gradually at 3- to 7-day intervals until optimum affect is achieved;a some patients may require doses of 640 mg daily.201 314

Fixed Combination Therapy
Oral

Propranolol in fixed combination with hydrochlorothiazide: administer in 2 divided doses daily (up to 160 mg of propranolol and 50 mg of hydrochlorothiazide total daily dosage).c

Combination preparation is inappropriate with propranolol 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 Administer separately for subsequent dosage adjustment.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 or Non-ST-Segment Elevation/Non-Q-Wave 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 patients with unstable angina 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

Supraventricular Tachyarrhythmias
IV

Initial dosage: 0.1 mg/kg (divided in 3 equal doses) by slow IV injection (≤1 mg/minute) at 2- to 3-minute intervals has been recommended.352 May repeat total dose in 2 minutes if needed.352

Rate Control in Atrial Fibrillation and Flutter
IV

Initial dosage: 0.1 mg/kg (divided in 3 equal doses) by slow IV injection (≤1 mg/minute) at 2- to 3-minute intervals has been recommended.352 May repeat total dose in 2 minutes if needed.352

Slowing of Ventricular Response during Acute Atrial Fibrillation
IV

Loading dose: 0.15 mg.319

Oral

Maintenance dosage for persistent atrial fibrillation: 80–240 mg daily in divided doses.319

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

AMI
Mortality Reduction after AMI
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-adrenergic blocking agent 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.317 a

AMI
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

Cautions for Propranolol Hydrochloride

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 Cardiac 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.)

  • Pre-excited atrial fibrillation or flutter.313

Warnings/Precautions

Warnings

Cardiac Failure

Possible precipitation of CHF.b Avoid use in patients with overt CHF;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 cardiac 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 cardiac failure occur; if cardiac 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).200 305 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 352 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,352 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-adrenergic blocking agents; 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.317 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

Interactions for Propranolol Hydrochloride

Specific Drugs

Drug

Interaction

Comments

Antipsychotic agents (e.g., phenothiazines)

Potential pharmacodynamic interaction (additive hypotensive effect), especially with large doses of phenothiazinesa

Chlorpromazine

Potential pharmacokinetic interaction (decreased propranolol clearance)a

Thioridazine

Potential pharmacokinetic interaction (decreased thioridazine metabolism).310 Possible increased risk of serious, potentially fatal cardiac arrhythmias (e.g., torsades de pointes)310

Concomitant use contraindicated310

Haloperidol

Potential pharmacodynamic interactions (hypotension and cardiac arrest)a

Fluoxetine

Potential pharmacokinetic interaction (decreased propranolol metabolism);272 273 complete heart block reported272 273

Caution recommended with concomitant use and in those with impaired cardiac conduction272

Sympathomimetics

Potential pharmacodynamic interaction (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

Potential pharmacodynamic interaction (antagonism of cardiac β-adrenergic blocking effects)a

Diuretics

Potential pharmacodynamic interaction (increased hypotensive effect)a

Careful dosage adjustments recommendeda

Reserpine

Potential pharmacodynamic interaction (additive effects)a

Antiarrhythmic drugs (lidocaine, phenytoin, procainamide, quinidine, verapamil)

Potential pharmacodynamic interaction (additive or antagonistic cardiac effects and additive toxic effects)a

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)

Potential pharmacodynamic interaction (additive negative effects on SA or AV nodal conduction)a

Neuromuscular blocking agents

Potential pharmacodynamic interaction (increased effects of neuromuscular blocking agents)a

Administer with caution to patients receiving or recovering from the effects of neuromuscular blocking agentsa

Antidiabetic agents

Potential pharmacologic interaction (altered antidiabetic response)a

Close monitoring recommendeda

Ergot alkaloids

Potential pharmacokinetic interaction (additive peripheral vasoconstriction)a

Use concomitantly with cautiona

Cimetidine

Potential pharmacokinetic interaction (decreased propranolol clearance)a

Monitor for signs and symptoms of increased β-adrenergic blocking activitya

Antacids

Potential pharmacokinetic interaction (decreased propranolol absorption)201 235 236 237

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

Potential pharmacodynamic interaction (decreased hypotensive and positive inotropic effects of levodopa)a

Nonsteroidal anti-inflammatory agents

Potential pharmacodynamic interaction (decreased hypotensive effects of propranolol)a

Theophylline

Potential pharmacokinetic interaction (decreased theophylline clearance).a Potential pharmacologic interaction (decreased theophylline-induced bronchodilation)a

Myocardial depressant general anesthetics

Potential pharmacodynamic interaction (increased risk of myocardial depression, bradycardia, hypotension)a

Propranolol Hydrochloride Pharmacokinetics

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

Stability

Storage

Oral

Capsules

Tight, light-resistant containers at 20–25°C; protect from moisture, freezing or excessive heat.c

Tablets

10, 60, and 80 mg: Tight containers at 20–25°C.b

20 and 40 mg: Tight, light-resistant containers at 20–25°C.b

Tablets (Propranolol Hydrochloride and Hydrochlorothiazide)

Tight containers at about 25°C; protect from moisture, freezing or excessive heat.d

Solution and Solution Concentrate

Tight, light-resistant containers at 20–25°C.a

Maximum stability at pH 3, rapidly decomposes at alkaline pH.a

Decomposition in aqueous solution is accompanied by lowered pH and discoloration.a

Parenteral

Injection

20–25°C; Protect from freezing or excessive heat.b

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution CompatibilityHID

Compatible

Dextrose 5% in sodium chloride 0.45 or 0.9%

Dextrose 5% in water

Ringer’s injection, lactated

Sodium chloride 0.45 or 0.9%

Drug Compatibility
Admixture CompatibilityHID

Compatible

Dobutamine HCl

Verapamil HCl

Y-Site CompatibilityHID

Compatible

Alteplase

Fenoldopam mesylate

Heparin sodium

Hydrocortisone sodium succinate

Linezolid

Meperidine HCl

Milrinone lactate

Morphine sulfate

Nesiritide

Potassium chloride

Propofol

Tacrolimus

Tirofiban HCl

Incompatible

Amphotericin B cholesteryl sulfate complex

Actions

  • Inhibits response to adrenergic stimuli by competitively blocking β-adrenergic receptors within the myocardium and within bronchial and vascular smooth muscle; no intrinsic sympathomimetic activity.a

  • Decreases resting and exercise-stimulated heart rate, myocardial contractility, and cardiac output; increases systolic ejection time and cardiac volume; decreases conduction velocity through the sinoatrial (SA) and atrioventricular (AV) nodes; and decreases myocardial automaticity.a

  • Initially increases peripheral resistance; however, peripheral resistance decreases with chronic administration.a

  • Decreases renal blood flow, glomerular filtration rate, and hepatic blood flow.a

  • Membrane-stabilizing effect on the heart occurs at high dosages.a

  • Reduces BP by decreasing cardiac output, decreasing sympathetic outflow from the CNS, and/or by suppressing renin release.a

  • Reduces the frequency of anginal attacks and increases exercise tolerance by decreasing myocardial oxygen consumption and coronary blood flow.a May reduce myocardial oxygen requirements.a

  • Antimigraine effect results from inhibition of vasodilation, the presence of β-adrenergic receptors in pial vessels of the brain, and inhibition of arteriolar spasms over the cortex.a

  • Increases airway resistance (especially in asthmatic patients), inhibits glycogenolysis in the skeletal and cardiac muscles, blocks the release of free fatty acids and insulin, increases the number of circulating eosinophils, and increases uterine activity.a

Advice to Patients

  • Importance of taking medication exactly as prescribed.a

  • Importance of not interrupting or discontinuing therapy without consulting clinician; importance of temporarily limiting physical activity when discontinuing therapy.a

  • Importance of immediately informing clinician at the first sign or symptom of impending cardiac failure or if any difficulty in breathing occurs.a

  • Importance of patient informing anesthesiologist or dentist about propranolol therapy before undergoing major surgery.a

  • Importance of informing patients that propranolol may interfere with glaucoma screening test.b

  • Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs.a

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.a

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Propranolol Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules, extended-release

60 mg

Inderal LA

Wyeth

80 mg

Inderal LA

Wyeth

Innopran XL

Reliant

120 mg

Inderal LA

Wyeth

Innopran XL

Reliant

160 mg

Inderal LA

Wyeth

Solution

20 mg/5 mL*

Propranolol Hydrochloride Solution

40 mg/5 mL*

Propranolol Hydrochloride Solution

Solution, concentrate

80 mg/mL*

Propranolol Hydrochloride Intensol (with calibrated dropper)

Tablets

10 mg*

Inderal (scored)

Wyeth

Propranolol Hydrochloride Tablets

20 mg*

Inderal (scored)

Wyeth

Propranolol Hydrochloride Tablets

40 mg*

Inderal (scored)

Wyeth

Propranolol Hydrochloride Tablets

60 mg*

Inderal (scored)

Wyeth

Propranolol Hydrochloride Tablets

80 mg*

Inderal (scored)

Wyeth

Propranolol Hydrochloride Tablets

Parenteral

Injection

1 mg/mL*

Inderal

Wyeth

Propranolol Hydrochloride Injection

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Propranolol Hydrochloride and Hydrochlorothiazide

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

40 mg Propranolol Hydrochloride and Hydrochlorothiazide 25 mg*

Inderide (scored)

Wyeth

Propranolol Hydrochloride and Hydrochlorothiazide Tablets

80 mg Propranolol Hydrochloride and Hydrochlorothiazide 25 mg*

Inderide (scored)

Wyeth

Propranolol Hydrochloride and Hydrochlorothiazide Tablets

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Inderal LA 120MG 24-hr Capsules (AKRIMAX PHARMACEUTICALS): 30/$185.99 or 90/$536.96

Inderal LA 160MG 24-hr Capsules (AKRIMAX PHARMACEUTICALS): 30/$264.99 or 90/$755.97

Inderal LA 60MG 24-hr Capsules (AKRIMAX PHARMACEUTICALS): 30/$155.99 or 90/$449.97

InnoPran XL 120MG 24-hr Capsules (GLAXO SMITH KLINE): 30/$71.99 or 90/$200.97

InnoPran XL 80MG 24-hr Capsules (GLAXO SMITH KLINE): 30/$71.74 or 90/$202.51

Propranolol HCl 10MG Tablets (HERITAGE PHARMACEUTICALS): 100/$13.99 or 200/$17.98

Propranolol HCl 20MG/5ML Solution (ROXANE): 240/$25.99 or 480/$45.97

Propranolol HCl 20MG Tablets (HERITAGE PHARMACEUTICALS): 100/$13.99 or 200/$21.98

Propranolol HCl 40MG Tablets (HERITAGE PHARMACEUTICALS): 30/$12.99 or 90/$14.99

Propranolol HCl 60MG Tablets (HERITAGE PHARMACEUTICALS): 60/$58.99 or 180/$156.97

Propranolol HCl 80MG Tablets (HERITAGE PHARMACEUTICALS): 90/$15.99 or 270/$35.96

Propranolol HCl CR 120MG 24-hr Capsules (UPSHER-SMITH): 30/$55.99 or 60/$105.96

Propranolol HCl CR 160MG 24-hr Capsules (UPSHER-SMITH): 100/$179.98 or 300/$509.98

Propranolol HCl CR 60MG 24-hr Capsules (UPSHER-SMITH): 100/$124.99 or 300/$355.96

Propranolol HCl CR 80MG 24-hr Capsules (UPSHER-SMITH): 100/$145.98 or 300/$390.00

Propranolol-HCTZ 40-25MG Tablets (MYLAN): 30/$30.79 or 60/$50.57

Propranolol-HCTZ 80-25MG Tablets (MYLAN): 60/$67.99 or 180/$197.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions September 4, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

200. Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The 1984 report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1984; 144:1045-57. [IDIS 184763] [PubMed 6143542]

201. Ayerst Laboratories Inc. Inderal (propranolol hydrochloride) tablets prescribing information. Philadelphia, PA; 2002 Jan.

202. Findley LJ. The pharmacological management of essential tremor. Clin Neuropharmacol. 1986; 9:S61-75. [PubMed 2885088]

203. Larsen AT, Teravainen H. β1 versus nonselective blockade in therapy of essential tremor. Adv Neurol. 1983; 37:247-51. [PubMed 6344590]

204. Calzetti S, Findley LJ, Perucca E et al. Controlled study of metoprolol and propranolol during prolonged administration in patients with essential tremor. J Neurol Neurosurg Psychiatry. 1982; 45:893-7. [PubMed 6815306]

205. Koller WC. Dose-response relationship of propranolol in the treatment of essential tremor. Arch Neurol. 1986; 43:42-3. [PubMed 3942513]

206. Young RR. Propranolol in essential tremor. Neurology. 1985; 35:445-6. [IDIS 196852] [PubMed 3974911]

207. Koller W, Biary N, Cone S. Disability in essential tremor: effect of treatment. Neurology. 1986; 36:1001-4. [IDIS 218288] [PubMed 2940473]

208. Koller WC, Royse VL. Time course of a single oral dose of propranolol in essential tremor. Neurology. 1985; 35:1494-8. [IDIS 206086] [PubMed 4033931]

209. Koller WC. Treatment of essential tremor—further comment. Ann Neurol. 1985; 18:369. [IDIS 206723] [PubMed 3931542]

210. Koller WC, Royse VL. Time course of a single oral dose of propranolol in essential tremor. Neurology. 1986; 36:876. [IDIS 216671] [PubMed 3703304]

211. Findley LJ, Cleeves L. Tremor. BMJ. 1984; 288:1536-7. [IDIS 186365] [PubMed 6426631]

212. Findley LJ, Cleeves L. Beta adrenoreceptor antagonists in essential tremor. Lancet. 1984; 1:856-7.

213. Murray TJ. Long-term therapy of essential tremor with propranolol. Can Med Assoc J. 1976; 115:892-4. [PubMed 791468]

214. Winkler GF, Young RR. Efficacy of chronic propranolol therapy in action tremors of the familial senile or essential varieties. N Engl J Med. 1974; 290:984-8. [PubMed 4594525]

215. Tolosa ES, Loewenson RB. Essential tremor: treatment with propranolol. Neurology. 1975; 25:1041-4. [PubMed 1237822]

216. Koller WC. Long-acting propranolol in essential tremor. Neurology. 1985; 35:108-10. [IDIS 194949] [PubMed 3965982]

217. Koller W, Graner D, Mlcoch A. Essential voice tremor: treatment with propranolol. Neurology. 1985; 35:106-8. [IDIS 194948] [PubMed 3880874]

218. Baruzzi A, Procaccianti G, Martinelli P et al. Phenobarbital and propranolol in essential tremor: a double-blind controlled clinical trial. Neurology. 1983; 33:296-300. [IDIS 166559] [PubMed 6338416]

219. Koller WC. Propranolol therapy for essential tremor of the head. Neurology. 1984; 34:1077-9. [IDIS 188048] [PubMed 6379505]

220. Teravainen H, Fogelholm R, Larsen A. Effect of propranolol on essential tremor. Neurology. 1976; 26:27-30. [PubMed 1107883]

221. Koller WC. Dose-response relationship of propranolol in essential tremor. Neurology. 1985; 35(Suppl 1):160.

222. Cleeves L, Findley LJ. Time course of a single oral dose of propranolol in essential tremor. Neurology. 1986; 36:876. [IDIS 216671] [PubMed 3703304]

223. Calzetti S, Findley LJ, Perucca E et al. Metoprolol in essential tremor. Lancet. 1981; 2:1227. [IDIS 140990] [PubMed 6118649]

224. Calzetti S, Findley LJ, Perucca S et al. The response of essential tremor to propranolol: evaluation of clinical variables governing its efficacy on prolonged administration. J Neurol Neurosurg Psychiatry. 1983; 46:393-8. [PubMed 6101174]

225. Findley LJ, Calzetti S, Gresty MA et al. Amplitude of benign essential tremor and response to propranolol. Lancet. 1981; 2:479-80. [IDIS 136446] [PubMed 6115243]

226. Koller WC. Propranolol in essential tremor. Neurology. 1985; 35:446. [PubMed 3974912]

227. Calzetti S, Findley LJ, Gresty MA et al. Effect of a single oral dose of propranolol on essential tremor: a double-blind controlled study. Ann Neurol. 1983; 13:165-71. [IDIS 165922] [PubMed 6338809]

228. Huttunen J, Teravainen H, Larsen TA. Beta adrenoreceptor antagonists in essential tremor. Lancet. 1984; 1:57.

229. Wilson JF, Marshall RW, Richens A. Essential tremor: treatment with beta-adrenoceptor blocking drugs. In: Findley LJ, Capildea R. Movement disorders: tremor. London: Macmillan; 1984:245-60.

230. National Heart, Lung, and Blood Institute Task Force on Blood Pressure Control in Children. Report of the Second Task Force on Blood Pressure Control in Children—1987. Pediatrics. 1987; 79:1-25. [IDIS 224856] [PubMed 3797155]

231. Gillette PC. Advances in the diagnosis and treatment of tachydysrhythmias in children. Am Heart J. 1981; 102:111-20. [IDIS 134545] [PubMed 7246397]

232. Pickoff AS, Zies L, Ferrer PL et al. High-dose propranolol therapy in the management of supraventricular tachycardia. J Pediatr. 1979; 94:144-6. [IDIS 107683] [PubMed 758396]

233. Cohen SN, Kauffman RE, Strebel L. Appendix: Drugs. In: Behrman RE, Vaughan VC, eds. Nelson textbook of pediatrics. 13th ed. Philadelphia: W. B. Saunders Company; 1987: 1520-34.

234. Cleeves L, Findley LJ. Beta-adrenoreceptor mechanisms in essential tremor: a comparative single dose study of the effect of non-selective and a beta-2 selective adrenoreceptor antagonist. J Neurol Neurosurg Psychiatry. 1984; 47:976-82. [PubMed 6148382]

235. Dobbs JH, Skoutakis VA, Acchiardo SR et al. Effects of aluminum hydroxide on the absorption of propranolol. Curr Ther Res. 1977; 21:887-92.

236. Remon JP, Belpaire F, Van Severen R et al. Interaction of antacids with antiarrhythmics. V. Effect of aluminum hydroxide and magnesium oxide on the bioavailability of quinidine, procainamide and propranolol in dogs. Arzneimittelforschung. 1983; 33:117-20. [PubMed 6681962]

237. Mangini RJ, ed. Drug interactions facts. St. Louis: JB Lippincott Co; 1986(Apr):105.

238. Hong CY, Hu SC, Lin SJ et al. Lack of influence of aluminum hydroxide on the bioavailability and beta-adrenoceptor blocking activity of propranolol. Int J Pharmacol Ther Toxicol. 1985; 23:244-6.

239. McElnay JC, Temple DJ. The use of buccal partitioning as a model to examine the effects of aluminum hydroxide gel on the absorption of propranolol. Br J Clin Pharmacol. 1982; 13:399-403. [IDIS 148018] [PubMed 7059441]

240. Potter DE, Schambelan M, Salvatierra O et al. Treatment of high-renin hypertension with propranolol in children after renal transplantation. J Pediatr. 1977; 90:307-11. [PubMed 318685]

241. Ozsoylu S, Kocak N, Yuce A. Propranolol therapy for portal hypertension in children. J Pediatr. 1985; 106:317-21. [IDIS 196196] [PubMed 3968624]

242. Pennisi AJ, Takahashi M, Bernstein BH et al. Minoxidil therapy in children with severe hypertension. J Pediatr. 1977; 90:813-9. [PubMed 323442]

243. Park MK. Pediatric cardiology for practitioners. Chicago, IL: Year Book Medical Publishers; 1984:284.

244. 1988 Joint National Committee. The 1988 report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1988; 148:1023-38. [IDIS 242588] [PubMed 3365073]

245. Yusuf S, Wittes J, Friedman L. Overview of results of randomized clinical trials in heart disease: I. Treatments following myocardial infarction. JAMA. 1988; 260:2088-93. [IDIS 246179] [PubMed 2901501]

246. American College of Cardiology and American Heart Association. ACC/AHA guidelines for the early management of patients with acute myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Subcommittee to Develop Guidelines for the Early Management of Patients with Acute Myocardial Infarction). Circulation. 1990; 82:664-707. [IDIS 269868] [PubMed 2197021]

247. Roque F, Amuchastegui LM, Lopez Morillos MA et al. The TIARA Study Group. Beneficial effects of timolol on infarct size and late ventricular tachycardia in patients with acute myocardial infarction. Circulation. 1987; 76:610-7. [IDIS 252227] [PubMed 3304706]

248. Goldman L, Sia STB, Cook EF et al. Costs and effectiveness of routine therapy with long-term beta-adrenergic antagonists after acute myocardial infarction. N Engl J Med. 1988; 319:152-7. [IDIS 243813] [PubMed 2898733]

249. Yusuf S, Peto R, Lewis J et al. Beta blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis. 1985; 27:335-71. [PubMed 2858114]

250. Yusuf S, Sleight P, Held P et al. Routine medical management of acute myocardial infarction: lessons from overviews of recent randomized controlled trials. Circulation. 1990; 82(Suppl 11):11-117-34.

251. Held P, Yusuf S. Early intravenous beta-blockade in acute myocardial infarction. Cardiology. 1989; 76:132-43. [PubMed 2568179]

252. Pedersen TR for the Norwegian Multicenter Study Group. Six-year follow-up of the Norwegian multicenter study on timolol after acute myocardial infarction. N Engl J Med. 1985; 313:1055-8. [IDIS 206156] [PubMed 2864634]

253. Pedersen TR for the Norwegian Multicenter Study Group. The Norwegian multicenter study of timolol after myocardial infarction. Circulation. 1983; 67(Suppl I):I-49-53.

254. The Beta-Blocker Pooling Project Research Group. The Beta-Blocker Pooling Project (BBPP): subgroup findings from randomized trials in post infarction patients. Eur Heart J. 1988; 9:8-16.

255. β-Blocker Heart Attack Trial Research Group. A randomized trial of propranolol in patients with acute myocardial infarction: I. Mortality results. JAMA. 1982; 247:1707-14. [PubMed 7038157]

256. The Norwegian Multicenter Study Group. Timolol-induced reduction in mortality and reinfarction in patients surviving acute myocardial infarction. N Engl J Med. 1981; 304:801-7. [IDIS 128981] [PubMed 7010157]

257. Gheorghiade M, Schultz L, Tilley B et al. Effects of propranolol in non-Q-wave acute myocardial infarction in the beta blocker heart attack trial. Am J Cardiol. 1990; 66:129-33. [IDIS 269724] [PubMed 2196771]

258. Yusuf S, Wittes J, Probstfield J. Evaluating effects of treatment in subgroups of patients within a clinical trial: the case of non-Q-wave myocardial infarction and beta blockers. Am J Cardiol. 1990; 66:220-22. [IDIS 269732] [PubMed 1973589]

259. Griggs TR, Wagner GS, Gettes LS. Beta-adrenergic blocking agents after myocardial infarction: an undocumented need in patients at lowest risk. J Am Coll Cardiol. 1983; 1:1530-3. [PubMed 6133891]

260. Pedersen TR for the Norwegian Multicenter Study Group. Six-year follow-up of the Norwegian multicenter study on timolol after myocardial infarction. N Engl J Med. 1986; 314:1052.

261. Frishman WH, Furberg CD, Friedewald WT. β-Adrenergic blockade for survivors of acute myocardial infarction. N Engl J Med. 1984; 310:830-7. [IDIS 182809] [PubMed 6142420]

262. Roberts R, Rogers WJ, Mueller H et al. Immediate versus deferred β-blockade following thrombolytic therapy in patients with acute myocardial infarction: results of the Thrombolysis in Myocardial Infarction (TIMI) II-B study. Circulation. 1991; 83:422-37. [IDIS 278007] [PubMed 1671346]

263. Reviewers’ comments (personal observations).

264. Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The fifth report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V). Arch Intern Med. 1993; 153:154-83. [IDIS 309043] [PubMed 8422206]

265. Weber MA, Laragh JH. Hypertension: steps forward and steps backward: the Joint National Committee fifth report. Arch Intern Med. 1993; 153:149-52. [PubMed 8422205]

266. Collins R, Peto R, MacMahon S et al. Blood pressure, stroke, and coronary heart disease. Part 2, short-term reductions in blood pressure: an overview of randomized drug trials in their epidemiological context. Lancet. 1990; 335:827-38. [IDIS 264836] [PubMed 1969567]

267. Alderman MH. Which antihypertensive drugs first—and why! JAMA. 1992; 267:2786-7. Editorial.

268. MacMahon S, Peto R, Cutler J et al. Blood pressure, stroke, and coronary heart disease. Part 1, prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet. 1990; 335:765-74. [PubMed 1969518]

269. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA. 1991; 265:3255-64. [IDIS 282107] [PubMed 2046107]

270. Dahlof B, Lindholm LH, Hansson L et al. Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-hypertension). Lancet. 1991; 338:1281-5. [IDIS 289158] [PubMed 1682683]

271. MRC Working Party. Medical Research Council trial of treatment of hypertension in older adults: principal results. BMJ. 1992; 304:405-12. [IDIS 292411] [PubMed 1445513]

272. Drake WM, Gordon GD. Heart block in a patient on propranolol and fluoxetine. Lancet. 1994; 343:425-6. [IDIS 325792] [PubMed 7905586]

273. Beta-adrenergic blocker interactions: fluoxetine (Prozac). In: Hansten PD, Horn JR. Drug interactions and updates. Vancouver, WA: Applied Therapeutics, Inc; 1994:771.

274. National Heart, Lung, and Blood Institute. NHLBI panel reviews safety of calcium channel blockers. Rockville, MD; 1995 Aug 31. Press release.

275. National Heart, Lung, and Blood Institute. New analysis regarding the safety of calcium-channel blockers: a statement for health professionals from the National Heart, Lung, and Blood Institute. Rockville, MD; 1995 Sep 1.

276. Psaty BM, Heckbert SR, Koepsell TD et al. The risk of myocardial infarction associated with antihypertensive drug therapies. JAMA. 1995; 274:620-5. [IDIS 352203] [PubMed 7637142]

277. Yusuf S. Calcium antagonists in coronary artery disease and hypertension: time for reevaluation? Circulation. 1995; 92:1079-82. Editorial.

278. Roche. Posicor (mibefradil hydrochloride) tablets prescribing information. Nutley, NJ; 1997 Dec.

279. Ellison RH. Dear doctor letter regarding appropriate use of Posicor. Nutley, NJ: Roche Laboratories; 1997 Dec.

280. Sidmak Laboratories. Propranolol hydrochloride and hydrochlorothiazide tablets prescribing information. East Hanover, NJ; 1995 Jan.

281. Swislocki A. Insulin resistance and hypertension. Am J Med Sci. 1990; 300:104-15. [IDIS 272104] [PubMed 2206054]

282. White J Jr, Harman J, Campbell K. Drug interactions in diabetic patients. Postgrad Med. 1993; 93:131-9.

283. Joseph J, Schuna A. Management of hypertension in the diabetic patient. Clin Pharm. 1990; 9:864-73. [IDIS 273967] [PubMed 2272152]

284. Houston M. The effects of antihypertensive drugs on glucose intolerance in hypertensive nondiabetics and diabetics. Am Heart J. 1988; 115:640-56. [IDIS 242151] [PubMed 3278578]

285. Hurel S, Taylor R. Drugs and glucose tolerance. Adverse Drug React Bull. 1995; 174:659-62.

286. Holland B, Kaplan N. Propranolol in the treatment of hypertension. N Engl J Med. 1976; 294:930-6. [PubMed 1256484]

287. Chan JCN, Cockram CS. Drug-induced disturbances of carbohydrate metabolism. Adv Drug React Toxicol Rev. 1991; 10:1-29.

288. Reviewers’ comments (personal observations) on metformin 68:20.92.

289. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). Bethesda, MD: National Institutes of Health; 1997 Nov. (NIH publication No. 98-4080.)

290. Kaplan NM. Choice of initial therapy for hypertension. JAMA. 1996; 275:1577-80. [IDIS 365188] [PubMed 8622249]

291. Psaty BM, Smith NL, Siscovich DS et al. Health outcomes associated with antihypertensive therapies used as first-line agents: a systematic review and meta-analysis. JAMA. 1997; 277:739-45. [IDIS 380501] [PubMed 9042847]

292. Ryan TJ, Antman EM, Brooks NH et al. ACC/AHA guidelines for the management of patients with acute myocardial infarction: 1999 update: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). From website.

293. Whelton PK, Appel LJ, Espeland MA et al. for the TONE Collaborative Research Group. Sodium reduction and weight loss in the treatment of hypertension in older persons: a randomized controlled trial of nonpharmacologic interventions in the elderly (TONE). JAMA. 1998; 279:839-46. [PubMed 9515998]

294. American Diabetes Association. Clinical Practice Recommendations 2001. Position Statement. Diabetic nephropathy. Diabetes Care. 2001; 24(Suppl 1):S69-72.

295. Genuth P. United Kingdom prospective diabetes study results are in. J Fam Pract. 1998; 47:(Suppl 5):S27.

296. American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care. 2001; 24(Suppl 1):S33-43.

297. Watkins PJ. UKPDS: a message of hope and a need for change. Diabet Med. 1998; 15:895-6. [PubMed 9827842]

298. Bretzel RG, Voit K, Schatz H et al. The United Kingdom Prospective Diabetes Study (UKPDS): implications for the pharmacotherapy of type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes. 1998; 106:369-72. [PubMed 9831300]

299. UK Prospective Diabetes Study Group. Efficacy of atenolol and captopril in reducing risk of macrovascular complications in type 2 diabetes: UKPDS 39. BMJ. 1998; 317:713-20. [IDIS 412065] [PubMed 9732338]

300. American Diabetes Association. The United Kingdom Prospective Diabetes Study (UKPDS) for type 2 diabetes: what you need to know about the results of a long-term study. Washington, DC; 1998 Sep 15 from American Diabetes Association web site.

301. UK Prospective Diabetes Study Group. Efficacy of atenolol and captopril in reducing risk of macrovascular complications in type 2 diabetes: UKPDS 39. BMJ. 1998; 317:713-20. [IDIS 412065] [PubMed 9732338]

302. Davis TME. United Kingdom Prospective Diabetes Study: the end of the beginning? Med J Aust. 1998; 169:511-2.

303. American Diabetes Association. Clinical Practice Recommendations 1999. Position statement. Implications of the United Kingdom propective Diabetes Study. Diabetes Care. 1999; 22(Suppl 1):S27-31.

304. Anon. Consensus recommendations for the management of chronic heart failure. On behalf of the membership of the advisory council to improve outcomes nationwide in heart failure. Part II. Management of heart failure: apporaches to the prevention of heart failure. Am J Cardiol. 1999; 83:9-38A.

305. Lim PO, MacDonald TM. Antianginal and β-adrenergic blocking drugs. In: Dukes MNG, ed. Meyler’s side effects of drugs. 13th ed. New York: Elsevier/North Holland Inc; 1996:488-535.

306. Gress TW, Nieto FJ, Shahar E et al. Hypertension and antihypertensive therapy as risk factors for type 2 diabetes mellitus. N Engl J Med. 2000; 342:905-12. [IDIS 442916] [PubMed 10738048]

307. Sower JR, Bakris GL. Antihypertensive therapy and the risk of type 2 diabetes mellitus. N Engl J Med. 2000; 342:969-70. [IDIS 442921] [PubMed 10738057]

308. Izzo JL, Levy D, Black HR. Importance of systolic blood pressure in older Americans. Hypertension. 2000; 35:1021-4. [PubMed 10818056]

309. Frohlich ED. Recognition of systolic hypertension for hypertension. Hypertension. 2000; 35:1019-20. [PubMed 10818055]

310. Novartis Pharmaceuticals Corporation. Mellaril, Mellaril-S (thioridazine) tablets, oral solutions, and oral suspensions prescribing information. East Hanover, NJ; 2000 Jun.

311. Bakris GL, Williams M, Dworkin L et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. Am J Kidney Dis. 2000; 36:646-61. [IDIS 452007] [PubMed 10977801]

312. Hansson L, Zanchetti A, Carruthers SG et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet. 1998; 351:1755-62. [IDIS 409003] [PubMed 9635947]

313. American Heart Association in collaboration with the International Liaison Committee on Resuscitation. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. Part 6: advanced cardiovascular life support. Circulation. 2000;102(Suppl I):I86-171.

314. Ayerst Laboratories Inc. InderalLA (propranolol hydrochloride) long acting capsules prescribing information. Philadelphia, PA; 2002 Jan 23.

315. Roxane Laboratories. Propranolol hydrochloride oral solution and oral solution concentrate prescribing information. Columbus, OH; 1995 Sept.

316. American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care. 2002; 25(Suppl. 1):S71-S73.

317. American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care. 2002; 25(Suppl 1):S33-43.

318. ACC/AHA/ACP-ASIM guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients with Chronic Stable Angina). J Am Coll Cardiol. 1999; 33:2092-7.

319. Fuster V, Ryden LE, Asinger RW et al. ACC/AHA/ESC guidelines for the management of atrial fibrillation. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients with Atrial Fibrillation). J Am Coll Cardiol. 2001; 38:1266i-lxx.

320. Williams CL, Hayman LL, Daniels SR et al. Cardiovascular health in childhood: a statement for health professional from the Committee on Atherosclerosis, Hypertension, and Obesity in the Young (AHOY) of the Council on Cardiovascular Disease in the Young, American Heart Association. Circulation. 2002; 106:143-60. [PubMed 12093785]

321. Braunwald E, Antman EM, Beasley JW et al. ACC/AHA guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients with Unstable Angina). 2002. From ACC website. Accessed Sep. 10, 2002.

322. Hunt SA, Baker DW, Chin MH et al. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure). 2001. From ACC website. Accessed July 25, 2002.

323. Ayerst Laboratories Inc. Inderide (propranolol hydrochloride and hydrochlorothiazide) tablets prescribing information. Philadelphia, PA; 2001 May 8.

324. Braunwald E, Antman EM, Beasley JW et al. ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). J Am Coll Cardiol. 2002; 40:1366-74. [IDIS 488261] [PubMed 12383588]

325. American Heart Association in collaboration with the International Liaison Committee on Resuscitation. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. Part 7: the era of reperfusion. Circulation. 2000;102(Suppl I):I172-I203.

326. Ramadan NM, Silberstein SD, Freitag FG et al. Evidence-based guidelines for migraine headache in the primary care setting: pharmacological management for prevention of migraine. St. Paul, MN; 2001. From the American Academy of Neurology web site.

327. Appel LJ. The verdict from ALLHAT—thiazide diuretics are the preferred initial therapy for hypertension. JAMA. 2002; 288:3039-42. [IDIS 490723] [PubMed 12479770]

328. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-riskhypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002; 288:2981-97. [IDIS 490721] [PubMed 12479763]

329. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII) Express. Bethesda, MD: May 14 2003. From NIH website. (Also published in JAMA. 2003; 289.

330. Douglas JG, Bakris GL, Epstein M et al. Management of high blood pressure in African Americans: Consensus statement of the Hypertension in African Americans Working Group of the International Society on Hypertension in Blacks. Arch Intern Med. 2003; 163:525-41.

331. Guidelines Committee. 2003 European Society of Hypertension–European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertension. 2003; 21:1011-53.

332. The Guidelines Subcommitee of the WHO/ISH Mild Hypertension Liaison Committee. 1999 guidelines for the management of hypertension. J Hypertension. 1999; 17:392-403.

333. American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care. 2003; 26(Suppl 1):S80-2.

335. National High Blood Pressure Education Program Working Group on Hypertension Control in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004; 114(Suppl 2):555-76. [PubMed 15286277]

336. Wright JT, Dunn JK, Cutler JA et al. Outcomes in hypertensive black and nonblack patients treated with chlorthalidone, amlodipine, and lisinopril. JAMA. 2005; 293:1595-607. [IDIS 531054] [PubMed 15811979]

337. Neaton JD, Kuller LH. Diuretics are color blind. JAMA. 2005; 293:1663-6. [IDIS 531056] [PubMed 15811986]

338. Baxter Healthcare Corporation. Propranolol hydrochloride injection prescribing information. Deerfield, IL; 2006.

339. Thadani U. Beta blockers in hypertension. Am J Cardiol. 1983; 52:10-5D.

340. Conolly ME, Kersting F, Dollery CT. The clinical pharmacology of beta-adrenoceptor-blocking drugs. Prog Cardiovasc Dis. 1976; 19:203-34. [PubMed 10600]

341. Shand DG. State-of-the-art: comparative pharmacology of the β-adrenoceptor blocking drugs. Drugs. 1983; 25(Suppl 2):92-9.

342. Breckenridge A. Which beta blocker? Br Med J. 1983; 286:1085-8.

343. Anon. Choice of a beta-blocker. Med Lett Drugs Ther. 1986; 28:20-2. [PubMed 2869400]

344. Wallin JD, Shah SV. β-Adrenergic blocking agents in the treatment of hypertension: choices based on pharmacological properties and patient characteristics. Arch Intern Med. 1987; 147:654-9. [IDIS 227948] [PubMed 2881524]

345. McDevitt DG. β-Adrenoceptor blocking drugs and partial agonist activity: is it clinically relevant? Drugs. 1983; 25:331-8.

346. McDevitt DG. Clinical significance of cardioselectivity: state-of-the-art. Drugs. 1983; 25(Suppl 2):219-26.

347. Frishman WH. β-Adrenoceptor antagonists: new drugs and new indications. N Engl J Med. 1981; 305:500-6. [IDIS 136600] [PubMed 6114433]

348. Thadani U, Davidson C, Chir B et al. Comparison of the immediate effects of five β-adrenoceptor-blocking drugs with different ancillary properties in angina pectoris. N Engl J Med. 1979; 300:750-5. [PubMed 581782]

349. Lewis RV, McDevitt DG. Adverse reactions and interactions with β-adrenoceptor blocking drugs. Med Toxicol. 1986; 1:343-61. [IDIS 239050] [PubMed 2878346]

350. Frishman WH. Clinical differences between beta-adrenergic blocking agents: implications for therapeutic substitution. Am Heart J. 1987; 113:1190-8. [IDIS 229873] [PubMed 2883867]

351. Clonidine/beta blockers. In: Tatro DS, Olin BR, Hebel SK, eds. Drug interaction facts. St. Louis: JB Lippincott Co; 1992 (July):200.

352. The American Heart Association. Guidelines 2005 for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2005; 112(Suppl I): IV1-211.

HID. Trissel LA. Handbook on injectable drugs. 17th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2013:995-6.

a. AHFS Drug Information 2004. McEvoy GK, ed. Propranolol. Bethesda, MD: American Society of Health-System Pharmacists; 2004:1777-84.

b. Ayerst Laboratories Inc. Inderal (propranolol hydrochloride) tablets and injection prescribing information. Philadelphia, PA; 2003 Nov.

c. Ayerst Laboratories Inc. Inderal LA (propranolol hydrochloride) long-acting capsules prescribing information. Philadelphia, PA; 2003 Nov.

d. Ayerst Laboratories Inc. Inderide (propranolol hydrochloride and hydrochlorothiazide) tablets prescribing information. Philadelphia, PA; 2003 Nov.

Hide
(web5)