Propranolol decrease in blood pressure

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propranolol (HIGH ALERT)(PHARMACOGENETICS)

Introduction

(proe-pran-oh-lole)
[Apo-Propranolol], [Betachron E-R], Inderal, Inderal LA, InnoPran XL, [Novopranol], [pms Propranolol]
[] = Available in Canada only.

Classification:

Therapeutic: antianginalsantiarrhythmics (Class II), antihypertensives, vascular.headache.suppressants
Pharmacologic: beta blockers

Pregnancy Category C

Indications

Management of hypertension, angina, arrhythmias, hypertrophic cardiomyopathy, thyrotoxicosis, essential tremors, pheochromocytoma, Also used in the prevention and management of MI, and the prevention of vascular headaches. Unlabeled uses: Also used to manage alcohol withdrawal, aggressive behavior, antipsychotic-associated akathisia, situational anxiety, and esophageal varices, Post-traumatic stress disorder (PTSD)(Ongoing clinical trials at National Institute for Mental Health [NIMH]).

Action

Blocks stimulation of beta1(myocardial) and beta2 (pulmonary, vascular, and uterine)-adrenergic receptor sites. Therapeutic Effects: Decreased heart rate and blood pressure. Suppression of arrhythmias. Prevention of MI.

Pharmacokinetics

Absorbtion: Well absorbed but undergoes extensive first-pass hepatic metabolism
Distribution: Moderate CNS penetration. Crosses the placenta; enters breast milk
Protein Binding: 93%
Metabolism and Excretion: Almost completely metabolized by the liver (primarily for CYP2D6 isoenzyme) (the CYP2D6 enzyme system exhibits genetic polymorphism; ~7% of population may be poor metabolizers and may have significantly propranolol concentrations and an risk of adverse effects)
Half Life: 3.4-6 hr

TIME/ACTION PROFILE (cardiovascular effects)

ROUTE

ONSET

PEAK

DURATION
PO

30 min

60-90 min+

6-12 hr
PO-ER

unknown

6 hr

24 hr
IV

immediate

1 min

4-6 hr

+Following single dose, full effect not seen until several weeks of therapy

Contraindications/Precautions

Contraindicated in: Uncompensated CHF. Pulmonary edema. Cardiogenic shock. Bradycardia or heart block.
Use Cautiously in: Renal or hepatic impairment. Pulmonary disease (including asthma). Diabetes mellitus (may mask signs of hypoglycemia). Thyrotoxicosis (may mask symptoms). History of severe allergic reactions (may intensity of response). OB: Crosses the placenta and may cause fetal/neonatal bradycardia, hypotension, hypoglycemia, or respiratory depression. May also blood supply to the placenta, increase the risk for premature birth or fetal death, and cause intrauterine growth retardation. May risk of cardiac and pulmonary complications in the infant during the neonatal time frame. Lactation: Appears in breast milk; use formula if propranolol must be taken. Pedi: risk of hypoglycemia, especially during periods of fasting such as before surgery, during prolonged exertion, or with coexisting renal insufficiency. Geri: sensitivity to all beta blockers; initial dose reduction and careful titration recommended.

Adverse Reactions/Side Effects*
*CAPITALS indicates life-threatening; underlines indicate most frequent.

CNS: fatigue, weakness, anxiety, dizziness, drowsiness, insomnia, memory loss, mental depression, mental status changes, nervousness, nightmares.
EENT: blurred vision, dry eyes, nasal stuffiness Resp: bronchospasm, wheezing CV: ARRHYTHMIAS, BRADYCARDIA, CHF, PULMONARY EDEMA, orthostatic hypotension, peripheral vasoconstriction GI: constipation, diarrhea, nausea GU: erectile dysfunction, libido Derm: itching, rashes Endo: hyperglycemia, hypoglycemia ( in children) MS: arthralgia, back pain, muscle cramps Neuro: paresthesia Misc: drug-induced lupus syndrome

Interactions

Drug-Drug: General anesthesia, IV phenytoin, and verapamil may cause additive myocardial depression. Additive bradycardia may occur with digoxin. Additive hypotension may occur with other antihypertensives, acute ingestion of alcohol, or nitrates. Concurrent use with amphetamines, cocaine, ephedrine, epinephrine, norepinephrine, phenylephrine, or pseudoephedrine may result in unopposed alpha-adrenergic stimulation (excessive hypertension, bradycardia). Concurrent thyroid administration may effectiveness. May alter the effectiveness of insulin or oral hypoglycemics (dose adjustments may be necessary). May effectiveness of beta-adrenergic bronchodilators and theophylline. May beneficial beta cardiovascular effects of dopamine or dobutamine. Use cautiously within 14 days of MAO inhibitor therapy (may result in hypertension). Cimetidine may blood levels and toxicity. Concurrent NSAIDs may antihypertensive action. Smoking metabolism and effects; smoking cessation may effects.

Route/Dosage

PO (Adults): Antianginal—80-320 mg/day in 2-4 divided doses or once daily as extended/sustained-release capsules. Antihypertensive—40 mg twice daily initially; may be as needed (usual range 120-240 mg/day; doses up to 1 g/day have been used); or 80 mg once daily as extended/sustained-release capsules, as needed up to 120 mg. InnoPran XL dosing form is designed to be given once daily at bedtime. Antiarrhythmic—10-30 mg 3-4 times daily. Prevention of MI—180-240 mg/day in divided doses. Hypertrophic cardiomyopathy—20-40 mg 3-4 times daily. Adjunct therapy of pheochromocytoma—20 mg 3 times daily to 40 mg 3-4 times daily concurrently with alpha-blocking therapy, started 3 days before surgery is planned. Vascular headache prevention—20 mg 4 times daily or 80 mg/day as extended/sustained-release capsules; may be as needed up to 240 mg/day. Management of tremor—40 mg twice daily; may be up to 120 mg/day (up to 320 mg have been used)
PO (Children): Antihypertensive/antiarrhythmic—0.5-1 mg/kg/day in 2-4 divided doses; may be as needed (usual range for maintenance dose is 2-4 mg/kg/day in 2 divided doses)
IV (Adults): Antiarrhythmic—1-3 mg; may be repeated after 2 min and again in 4 hr if needed
IV (Children): Antiarrhythmic—10-100 mcg (0.01-0.1 mg)/kg (up to 1 mg/dose); may be repeated q 6-8 hr if needed

Availability (generic available)

Oral solution: 4 mg/mL, 8 mg/mL Cost: Generic4 mg/mL $38.54/480 mL Tablets: 10 mg, 20 mg, 40 mg, 60 mg, 80 mg Cost: Generic10 mg $8.99/100, 20 mg $7.99/100, 40 mg $12.22/100, 60 mg $86.65/100, 80 mg $15.59/100 Sustained-release capsules (Inderal LA): 60 mg, 80 mg, 120 mg, 160 mg Cost: 60 mg $132.98/90, 80 mg $141.97/90, 120 mg $176.80/90, 120 mg $230.05/90 Extended-release capsules: 60 mg, 80 mg, 120 mg, 160 mg Cost: Generic60 mg $99.99/90, 80 mg $141.97/90, 120 mg $176.80/90, 160 mg $230.05/90 Injection: 1 mg/mL In combination with: hydrochlorothiazide (Inderide). See Appendix B: Combination Drugs

NURSING IMPLICATIONS

Assessment

• Monitor blood pressure and pulse frequently during dose adjustment period and periodically during therapy
• Abrupt withdrawal of propranolol may precipitate life-threatening arrhythmias, hypertension, or myocardial ischemia. Drug should be tapered over a 2-week period before discontinuation. Assess patient carefully during tapering and after medication is discontinued. Consider that patients taking propranolol for non-cardiac indications may have undiagnosed cardiac disease. Abrupt discontinuation or withdrawal over too-short a period of time (less than 9 days) should be avoided
• Pedi: Assess pediatric patients for signs and symptoms of hypoglycemia, particularly when oral foods and fluids are restricted
• Patients receiving propranolol IV must have continuous ECG monitoring and may have pulmonary capillary wedge pressure (PCWP) or central venous pressure (CVP) monitoring during and for several hours after administration.
• Assess for orthostatic hypotension when assisting patient up from supine position.
• Monitor intake and output ratios and daily weight. Assess patient routinely for evidence of fluid overload (peripheral edema, dyspnea, rales/crackles, fatigue, weight gain, jugular venous distention).
• Angina: Assess frequency and characteristics of anginal attacks periodically during therapy.
• Vascular Headache Prophylaxis: Assess frequency, severity, characteristics, and location of vascular headaches periodically during therapy.
• PTSD: Assess frequency of symptoms (flashbacks, nightmares, efforts to avoid thoughts or activities that may trigger memories of the trauma, and hypervigilance) periodically throughout therapy.
• Lab Test Considerations: May cause BUN, serum lipoprotein, potassium, triglyceride, and uric acid levels
• May cause ANA titers
• May cause or in blood glucose levels. In labile diabetic patients, hypoglycemia may be accompanied by precipitous of blood pressure.
• Toxicity and Overdose: Monitor patients receiving beta blockers for signs of overdose (bradycardia, severe dizziness or fainting, severe drowsiness, dyspnea, bluish fingernails or palms, seizures). Notify health care professional immediately if these signs occur
• Hypotension may be treated with modified Trendelenburg position and IV fluids unless contraindicated. Vasopressors (epinephrine, norepinephrine, dopamine, dobutamine) may also be used. Hypotension does not respond to beta agonists
• Glucagon has been used to treat bradycardia and hypotension.

Potential Nursing Diagnoses

Decreased cardiac output (Side Effects).
Noncompliance (Patient/Family Teachings).

Implementation

• High Alert: IV vasoactive medications are inherently dangerous. Before administering intravenously, have second practitioner independently check the original order, dose calculations, and infusion pump settings. Also, patient harm or fatalities have occurred when switching from oral to IV propranolol; oral and parenteral doses are not interchangeable. IV dose is 1/10 of the oral dose. Change to oral therapy as soon as possible. Do not confuse propranolol with pravachol. Do not confuse Inderal (a brand name of propranolol) with Adderall (an amphetamine/dextroamphetamine combination drug).
• PO: Take apical pulse prior to administering. If <50 bpm or if arrhythmia occurs, withhold medication and notify physician or other health care professional
• Administer with meals or directly after eating to enhance absorption
• Extended-release capsules should be swallowed whole; do not crush, open, or chew. Propranolol tablets may be crushed and mixed with food
• Mix propranolol oral solution with liquid or semisolid food (water, juices, applesauce, puddings). To ensure entire dose is taken, rinse glass with more liquid or have patient consume all of the applesauce or pudding. Do not store after mixing.

IV Administration

• Direct IV: Diluent: Administer undiluted or dilute each 1 mg in 10 mL of D5W for injectionConcentration: Undiluted: 1 mg/mL. Diluted in 10 mL of D5W: 0.1 mg/mL. Rate: Administer at 0.5 mg/ min for adults to avoid hypotension and cardiac arrest; do not exceed 1 mg/min. Pedi: Administer over 10 min.
• Intermittent Infusion: Diluent: May be diluted in 50 mL of 0.9% NaCl, D5W, D5/0.45% NaCl, D5/0.9% NaCl, or lactated Ringer's injectionConcentration: Depends on dose. Rate: Infuse over 10-15 min.
• Y-Site Compatibility: acyclovir, alfentanil, alteplase, amikacin, aminophylline, anidulafungin, ascorbic acid, atracurium, atroppine, azathioprine, aztreonam, benztropine, bivalirudin, bumetanide, buprenorphine, butorphanol, calcium chloride, calcium gluconate, carboplatin, caspofungin, cefazolin, cefonocid, cefoperazone, cefotetan, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, chloramphenicol, chlorpromazine, cimetidine, cisplatin, clindamycin, cyanocobalamin, cyclophosphamide, cyclosporine, cytarabine, dactinomycin, daptomycin, dexamethasone, dexmedetomidine, digoxin, diltiazem, diphenhydramine, dobutamine, docetaxel, dopamine, doxacurium, doxorubicin, doxycycline, enalaprilat, ephedrine, epinephrine, epirubicin, epoetin alfa, eptifibatide, ertapenem, erythromycin, esmolol, etoposide, etoposide phosphate, famotidine, fenoldopam, fentanyl, fluconazole, fludarabine, fluorouracil, folic acid, furosemide, ganciclovir, gemcitabine, gentamicin, glycopyrrolate, granisetron, heparin, hetastarch, hydrocortisone, hydromorphone, idarubicin, ifosfamide, imipenem/cilastatin, inamrinone, isoproterenol, ketorolac, labetalol, levofloxacin, lidocaine, linezolid, lorazepam, magnesium sulfate, mannitol, mechlorethamine, meperidine, metaraminol, methotrexate, methoxamine, methyldopate, methylprednisolone, metoclopramide, metoprolol, metronidazole, midazolam, milrinone, mitoxantrone, morphine, multivitamins, nafcillin, nalbuphine, naloxone, nesiritide, nitroglycerin, nitroprusside, norepinephrine, octreotide, ondansetron, oxacillin, oxaliplatin, oxytocin, palonosetron, pancuronium, papaverine, pemetrexed, penicillin G, pentamidine, pentazocine, pentobarbital, phenobarbital, phentolamine, phenylephrine, phytonadione, potassium chloride, procainamide, prochlorperazine, promethazine, propofol, protamine, pyridoxime, quinupristin/dalfopristin, ranitidine, rocuronium, sodium acetate, sodium bicarbonate, streptokinase, succinylcholine, sufentanil, tacrolimus, teniposide, theophylline, thiamine, thiotepa, ticarcillin/clavulanate, tigecycline, tirofiban, tobramycin, tolazoline, trimetaphan, urokinase, vancomycin, vasopressin, vecuronium, verapamil, vincristine, vinorelbine, vitamin B complex with C, voriconazole.
• Y-Site Incompatibility: amphotericin B cholesteryl, amphotericin B colloidal, amphotericin B liposome, dantrolene, diazepam, diazoxide, indomethacin, insulin, paclitaxel, pantoprazole, phenytoin, piperacillin/tazobactam, trimethoprim/sulfamethoxazole.

Patient/Family Teaching

• Instruct patient to take medication as directed, at the same time each day, even if feeling well; do not skip or double up on missed doses. Take missed doses as soon as possible up to 4 hr before next dose (8 hr with extended-release propranolol). Inform patient that abrupt withdrawal can cause life-threatening arrhythmias, hypertension, or myocardial ischemia.
• Advise patient to make sure enough medication is available for weekends, holidays, and vacations. A written prescription may be kept in wallet in case of emergency.
• Teach patient and family how to check pulse daily and blood pressure biweekly. Advise patient to hold dose and contact health care professional if pulse is <50 bpm or blood pressure changes significantly.
• May cause drowsiness or dizziness. Caution patients to avoid driving or other activities that require alertness until response to the drug is known.
• Advise patients to change positions slowly to minimize orthostatic hypotension, especially during initiation of therapy or when dose is increased.
• Caution patient that this medication may increase sensitivity to cold.
• Instruct patient to ask a health care professional before taking any OTC medications or herbal products, especially cold preparations, when taking this medication.
• Diabetic patients should closely monitor blood glucose, especially if weakness, malaise, irritability, or fatigue occurs. May mask tachycardia and increased blood pressure as signs of hypoglycemia, but dizziness and sweating may still occur.
• Advise patient to notify health care professional if slow pulse, difficulty breathing, wheezing, cold hands and feet, dizziness, light-headedness, confusion, depression, rash, fever, sore throat, unusual bleeding, or bruising occurs.
• Instruct patient to inform health care professional of medication regimen prior to treatment or surgery.
• Advise patient to carry identification describing disease process and medication regimen at all times.
• Hypertension: Reinforce the need to continue additional therapies for hypertension (weight loss, sodium restriction, stress reduction, regular exercise, moderation of alcohol consumption, and smoking cessation). Medication controls but does not cure hypertension.
• Angina: Caution patient to avoid overexertion with decrease in chest pain.
• Vascular Headache Prophylaxis: Caution patient that sharing this medication may be dangerous.
• PTSD: Advise patient that medication may relieve distressing symptoms but that psychotherapy is the primary treatment for the disorder. Refer patient and family to a PTSD support group.

Evaluation/desired Outcomes

• Decrease in blood pressure.
• Control of arrhythmias without appearance of detrimental side effects.
• Reduction in frequency of anginal attacks.
• Increase in activity tolerance.
• Prevention of MI.
• Prevention of vascular headaches.
• Management of thyrotoxicosis.
• Management of pheochromocytoma.
• Decrease in tremors.
• Management of hypertrophic cardiomyopathy.
• Decrease in symptoms associated with PTSD.
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Copyright © 2009 by F.A. Davis Company. All rights reserved.
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APRIL HAZARD VALLERAND, PhD, RN, FAAN, JUDITH HOPFER DEGLIN, PharmD, eds. 2009. Davis's Drug Guide for Nurses. Philadelphia, PA. F. A. Davis Company. ISBN-10: 0-8036-1912-X, ISBN-13: 978-0-8036-1912-8. STAT!Ref Online Electronic Medical Library. http://online.statref.com/document.aspx?fxid=58&docid=476. 6/4/2010 1:18:47 AM CDT (UTC -05:00).

* Copyright:
o Copyright © 2009 by F.A. Davis Company. All rights reserved.
* Database Title:
o STAT!Ref Online Electronic Medical Library
* Editor:
o APRIL HAZARD VALLERAND, PhD, RN, FAAN
o JUDITH HOPFER DEGLIN, PharmD
* ISBN:
o ISBN-10: 0-8036-1912-X
o ISBN-13: 978-0-8036-1912-8
* Publication City:
o Philadelphia, PA
* Publication Year:
o 2008
* Publisher:
o F. A. Davis Company
* Title:
o Davis's Drug Guide for Nurses - 11th Ed. (2009)
* Date Posted:
o 6/3/2010 8:52:15 PM CDT (UTC -05:00)
* Electronic Address:
o http://online.statref.com/document.aspx?fxid=58&docid=476
* Date Accessed:
o 6/4/2010 1:18:47 AM CDT (UTC -05:00)
* Location In Title:
o DAVIS'S DRUG GUIDE FOR NURSES - 12th Ed. (2011)
"P" Monographs
propranolol (HIGH ALERT)(PHARMACOGENETICS)

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5/11/2010 6:32:36 PM
Propranolol (Systemic)

Introduction

Nonselective β-adrenergic blocking agent.b,c

Class: beta-Adrenergic Blocking Agents 24:24; CV100 (VA)

Synonyms: Hydrochlorothiazide and Propranolol Hydrochloride

Uses

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

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

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

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

Specific Drugs
Drug Interaction Comments Antipsychotic agents Potential pharmacodynamic interaction (additive (e.g., phenothiazines) hypotensive effect), especially with large doses of phenothiazines [a] Chlorpromazine Potential pharmacokinetic interaction (decreased propranolol clearance) [a] Thioridazine Potential pharmacokinetic interaction (decreased Concomitant use contraindicated [310] thioridazine metabolism). [310] Possible increased risk of serious, potentially fatal cardiac arrhythmias (e.g., torsades de pointes) [310] Haloperidol Potential pharmacodynamic interactions (hypotension and cardiac arrest) [a] Fluoxetine Potential pharmacokinetic interaction (decreased Caution recommended with concomitant propranolol metabolism); [272,273] complete heart use and in those with impaired block reported [272,273] cardiac conduction [272] Sympathomimetics Potential pharmacodynamic interaction (antagonism of Administer epinephrine with caution; β-adrenergic stimulating effects). [a] Very large decreased pulse rate with first- and doses of isoproterenol may be needed to overcome β- second-degree heart block may occur adrenergic blocking effects [a] [a] Drugs with Potential pharmacodynamic interaction (antagonism of anticholinergic cardiac β-adrenergic blocking effects) [a] effects Diuretics Potential pharmacodynamic interaction (increased Careful dosage adjustments recommended hypotensive effect) [a] [a] Reserpine Potential pharmacodynamic interaction (additive effects) [a] Antiarrhythmic drugs Potential pharmacodynamic interaction (additive or (lidocaine, phenytoin, antagonistic cardiac effects and additive toxic procainamide, effects) [a] quinidine, verapamil) Verapamil Serious adverse reactions reported rarely with concomitant IV verapamil, especially in patients with severe cardiomyopathy, CHF, or recent MI [a] Other cardiovascular Potential pharmacodynamic interaction (additive drugs (e.g., cardiac negative effects on SA or AV nodal conduction) [a] glycosides, nondihydropyridine calcium-channel blocking agents) Neuromuscular blocking Potential pharmacodynamic interaction (increased Administer with caution to patients agents effects of neuromuscular blocking agents) [a] receiving or recovering from the effects of neuromuscular blocking agents [a] Antidiabetic agents Potential pharmacologic interaction (altered Close monitoring recommended [a] antidiabetic response) [a] Ergot alkaloids Potential pharmacokinetic interaction (additive Use concomitantly with caution [a] peripheral vasoconstriction) [a] Cimetidine Potential pharmacokinetic interaction (decreased Monitor for signs and symptoms of propranolol clearance) [a] increased β-adrenergic blocking activity [a] Antacids Potential pharmacokinetic interaction (decreased Need to avoid concomitant use or propranolol absorption) [201,235,236,237] stagger dosing of an aluminum hydroxide antacid has not been fully elucidated; [237,238] consider increasing propranolol dosage if interaction suspected [235,237] Levodopa Potential pharmacodynamic interaction (decreased hypotensive and positive inotropic effects of levodopa) [a] Nonsteroidal anti- Potential pharmacodynamic interaction (decreased inflammatory agents hypotensive effects of propranolol) [a] Theophylline Potential pharmacokinetic interaction (decreased theophylline clearance). [a] Potential pharmacologic interaction (decreased theophylline- induced bronchodilation) [a] Myocardial depressant Potential pharmacodynamic interaction (increased risk general anesthetics of myocardial depression, bradycardia, hypotension) [a]

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 Compatibility [HID]
Compatible Dobutamine HCl Verapamil HCl

>Y-Site Compatibility [HID]
Compatible Alteplase Fenoldopam mesylate Heparin sodium Hydrocortisone sodium succinate Inamrinone lactate Linezolid Meperidine HCl Milrinone lactate Morphine sulfate Potassium chloride Propofol Tacrolimus Tirofiban HCl Vitamin B complex with C Incompatible Amphotericin B cholesteryl sulfate complex Diazoxide Lansoprazole

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.

Propranolol Hydrochloride
Routes Dosage Forms Strengths Brand Names Manufacturer Oral Capsules, 60 mg Inderal® LA Wyeth extended- release 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 (with Roxane parabens) 40 mg/5 mL* Propranolol Hydrochloride Solution (with Roxane parabens) Solution, 80 mg/mL* Propranolol Hydrochloride Intensol® (with Roxane concentrate calibrated dropper) Tablets 10 mg* Inderal® (scored) Wyeth Propranolol Hydrochloride Tablets IVAX, Mylan, Pliva, UDL, Watson 20 mg* Inderal® (scored) Wyeth Propranolol Hydrochloride Tablets IVAX, Mylan, Pliva, UDL, Watson 40 mg* Inderal® (scored) Wyeth Propranolol Hydrochloride Tablets IVAX, Mylan, Pliva, UDL, Watson 60 mg* Inderal® (scored) Wyeth Propranolol Hydrochloride Tablets Pliva 80 mg* Inderal® (scored) Wyeth Propranolol Hydrochloride Tablets IVAX, Mylan, Pliva, UDL, Watson Parenteral Injection 1 mg/mL* Inderal® Wyeth Propranolol Hydrochloride Injection Bedford -----------------------------------------------------------------------------------------------------------
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Propranolol Hydrochloride and Hydrochlorothiazide
Routes Dosage Strengths Brand Names Manufacturer Forms Oral Tablets 40 mg Propranolol Hydrochloride Inderide® (scored) Wyeth and Hydrochlorothiazide 25 mg* Propranolol Hydrochloride and Mylan, Pliva, Hydrochlorothiazide Tablets Purepac 80 mg Propranolol Hydrochloride Inderide® (scored) Wyeth and Hydrochlorothiazide 25 mg* Propranolol Hydrochloride and Mylan, Pliva, Hydrochlorothiazide Tablets Purepac ----------------------------------------------------------------------------------------------------
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2010. For the most current and up-to-date pricing information, please visit www.drugstore.com. 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/$157.4 or 90/$441.99

Inderal LA 160MG 24-hr Capsules (AKRIMAX PHARMACEUTICALS): 30/$194.99 or 90/$564.93

Inderal LA 60MG 24-hr Capsules (AKRIMAX PHARMACEUTICALS): 30/$143.84 or 90/$398.59

Inderal LA 80MG 24-hr Capsules (AKRIMAX PHARMACEUTICALS): 30/$132.48 or 90/$354.9

Inderide 40-25MG Tablets (WYETH): 60/$96.92 or 180/$277.47

InnoPran XL 120MG 24-hr Capsules (GLAXO SMITH KLINE): 30/$73.85 or 90/$200.45

InnoPran XL 80MG 24-hr Capsules (GLAXO SMITH KLINE): 30/$71.75 or 90/$202.53

Propranolol HCl 10MG Tablets (PLIVA): 100/$12.99 or 200/$16.98

Propranolol HCl 20MG/5ML Solution (ROXANE): 240/$25.99 or 480/$45.98

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

Propranolol HCl 40MG Tablets (PLIVA): 30/$12.99 or 90/$12.99

Propranolol HCl 60MG Tablets (PLIVA): 60/$55.99 or 180/$139.97

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

Propranolol HCl CR 120MG 24-hr Capsules (PAR): 30/$59.99 or 60/$105.97

Propranolol HCl CR 160MG 24-hr Capsules (PAR): 100/$219.99 or 300/$619.92

Propranolol HCl CR 60MG 24-hr Capsules (PAR): 100/$115.97 or 300/$319.98

Propranolol HCl CR 80MG 24-hr Capsules (PAR): 100/$134.99 or 300/$375.99

--------------------------

AHFS Drug Information. © Copyright, 1959-2010, Selected Revisions September 2009. 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] [Free Fulltext PMC]

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] [Free Fulltext PMC]

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] [Free Fulltext PMC]

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] [Free Fulltext PMC]

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] [Free Fulltext PMC]

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] [Free Fulltext PMC]

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] [Free Fulltext PMC]

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 http://www/acc.org/clinical/guidelines and http://www.americanheart.org.

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. [Free Fulltext PMC]

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. [Free Fulltext PMC]

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] [Free Fulltext PMC]

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 (http://www.diabetes.org/ada/ukpds.asp).

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] [Free Fulltext PMC]

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. Inderal®LA (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. [Web]

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. [Web]

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 ([Web])

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. ([Web]). (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. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1429-32.

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.

Copyright © 2010 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

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Norepinephrine vasoconstrictor

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5/11/2010 6:32:36 PM
Norepinephrine (Systemic)

Introduction

Norepinephrine is identical to the endogenous catecholamine that is synthesized in the adrenal medulla and in sympathetic nervous tissue; norepinephrine predominantly acts by a direct effect on α-adrenergic receptors.b

Class: alpha- and beta-Adrenergic Agonists 12:12.12; AU100 (VA)

Synonyms: l-Arterenol Bitartrate; l-Arterenol Bitartrate; Levarterenol Bitartrate; Noradrenaline Acid Tartrate; (-)-Noradrenaline Acid Tartrate; (-)-Noradrenaline Bitartrate; l-Noradrenaline Bitartrate; l-Noradrenaline Bitartrate; Levophed; Norepinephrine

Uses

Shock

Used to produce vasoconstriction and cardiac stimulation as an adjunct to correct hemodynamic imbalances in the treatment of shock that persists after adequate fluid volume replacement.b (See Hypovolemia under Cautions.)

If severe peripheral vasoconstriction exists, norepinephrine may be ineffective and may have a deleterious effect by causing further reductions in plasma volume and blood flow to vital organs.b

Value of pressor therapy in shock, especially when due to septicemia, burns, trauma, or drug overdosage, is questionable, either because the effectiveness has not been proved or because vasoconstriction caused by the drug may adversely affect the patient.b

May be indicated if patient fails to respond to administration of fluids, a change in position, or other measures directed to the specific cause of shock such as anti-infectives in septicemia, epinephrine in anaphylactic shock, or specific antidotes and/or removal of the drug in cases of drug overdosage.b

Pressor therapy in overdosage of barbiturates or other sedatives is especially controversial; some clinicians have stated that the incidence of mortality may actually be increased when a pressor is given.b

May be useful to control shock following pheochromocytomectomy, but shock generally can be prevented by maintenance of adequate blood volume and/or preoperative administration of an α-adrenergic blocking agent.b

May be used as an adjunct in the management of shock resulting from sympathectomy or poliomyelitis.b

Anaphylactic Shock

Epinephrine is the drug of choice in the emergency treatment of severe acute anaphylactic reactions, including anaphylactic shock.b

Once adequate ventilation is assured, maintenance of blood pressure in patients with anaphylactic shock may be achieved with other pressor agents, such as norepinephrine.b

MI

In hypotension associated with MI, cautious administration of norepinephrine may be of value and some clinicians consider it to be the pressor drug of choice.b

This type of shock generally has a poor prognosis even when pressor agents are used, and norepinephrine-induced increases in myocardial oxygen demand and the work of the heart may outweigh the beneficial effects of the drug.b

Cardiac arrhythmias due to norepinephrine are more likely to occur in patients with MI.b

CPR

May be used for ACLS as an adjunct to maintain adequate BP when severe hypotension (e.g., SBP <70 mm Hg) and low total peripheral resistance persist and renal and cerebral perfusion remain inadequate after an effective heartbeat, palpable pulse, and ventilation have been established by other means.b

Exhibits both positive inotropic and vasoconstrictive activity; therefore, may be particularly useful in elevating systolic arterial pressures to 70-100 mm Hg.b Once such elevations are achieved, dopamine therapy can be initiated.b

Relatively contraindicated in patients with hypovolemia.b

Use cautiously in patients with ischemic heart disease because it may increase myocardial oxygen requirements.b

Hypotension during Anesthesia

May be used to treat hypotension occurring during spinal anesthesia, but other vasopressors having a longer duration of action and which can be administered IM such as metaraminol, methoxamine, or phenylephrine are more commonly used.b

May be used to treat hypotension occurring during general anesthesia; however, the possibility of cardiac arrhythmias should be considered.b (See Anesthetics, general under Interactions.)

If a vasopressor is required, norepinephrine should not be used in obstetric patients (see Pregnancy under Cautions); ephedrine usually is preferred.b

Adjunct to Local Anesthesia

May be added to solutions of some local anesthetics to decrease the rate of vascular absorption of the anesthetic, thereby localizing anesthesia and prolonging the duration of anesthesia.b

Decreases risk of systemic toxicity due to the local anesthetic.b

Not as potent as epinephrine and must be used in higher concentrations to prolong local anesthetic effects; epinephrine is more commonly used for this purpose.b

GI Hemorrhage

Has been used with some success intraperitoneally+ or via a nasogastric tube+ as a hemostatic agent for severe upper GI bleeding+.b

Pericardial Tamponade

Has been used to increase cardiac output by increasing ventricular emptying and temporarily increasing cardiac filling pressure in pericardial tamponade+.b

Dosage and Administration

General

• Observe the effect of the initial dose on BP carefully and adjust the rate of flow to establish and maintain the desired BP.b
• Do not leave the patient unattended; must closely monitor the infusion flow rate.b
• Check BP every 2 minutes from the time the norepinephrine infusion is started until the desired effect is achieved, then every 5 minutes while the drug is being infused.b
• Elevate BP to slightly less than the patient's normal BP.b
• In previously normotensive patients, maintain SBP at 80-100 mm Hg; in previously hypertensive patients, maintain SBP at 30-40 mm Hg below their preexisting BP.b
• Very severe hypotension: Maintenance of even lower BP may be desirable if blood or fluid volume replacement has not been completed.b
• Continue therapy until adequate BP and tissue perfusion are maintained.b
• Discontinuing therapy: Slow infusion rate gradually and avoid abrupt withdrawal; observe patient carefully so that therapy may be resumed if the BP falls too rapidly.b
• In some patients, additional administration of IV fluids may be necessary before norepinephrine can be discontinued.
• Do not reinstate pressor therapy until the SBP falls to 70-80 mm Hg.b

Administration

Administer by IV infusion.b

IV Administration

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

Administer by IV infusion using an infusion pump or other apparatus to control the rate of flow.b

Infuse into the antecubital vein of the arm if possible, although the femoral vein may also be used.b (See Extravasation under Cautions.)

Administer through a plastic catheter inserted deep into the vein.b

A catheter tie-in technique should be avoided if possible because obstruction of blood flow around the tubing may cause stasis and increased local concentration of the drug.b

Care must be taken to avoid extravasation because local necrosis may result.b (See Extravasation and also Extravasation Treatment under Cautions for discussion on the prevention and treatment of the adverse effects of extravasation.)

In prolonged therapy, change the injection site periodically.b

Dilution

Prior to administration, dilute the commercially available concentrate for injection with 5% dextrose injection, with or without sodium chloride.b

Concentration of norepinephrine and the infusion rate depend on the drug and fluid requirements of the individual patient.b

Infusion solution usually prepared by adding 4 mg of norepinephrine (4 mL of the commercially available injection) to 1 L of 5% dextrose injection creating a resultant solution containing 4 mcg/mL;<<011>>a more dilute or concentrated solution may be prepared depending on the fluid volume requirements of the patient.b

Dosage

Available as norepinephrine bitartrate; dosage expressed in terms of norepinephrine (2 mg of norepinephrine bitartrate is equivalent to 1 mg of norepinephrine).b

Pediatric Patients

Shock

Administer in the lowest effective dosage for the shortest possible time.b

>IV

Usually administered at a rate of 2 mcg/minute; alternatively, 2 mcg/m2 per minute.b

Pediatric Advanced Life Support (PALS) during CPR

>IV

Initial infusion rate: 0.1 mcg/kg per minute; ranges up to 2 mcg/kg per minute and should be adjusted to achieve the desired change in BP and perfusion.b

Adults

Shock

Administer in the lowest effective dosage for the shortest possible time.b

>IV

Usual initial dosage: 8-12 mcg/minute; alternatively, some clinicians suggest initiating norepinephrine therapy at a dosage of 0.5-1 mcg/minute titrated to effect.b

Average adult maintenance dosage: 2-4 mcg/minute.b

>Refractory Shock

IV:

May require 8-30 mcg/minute.b

GI Hemorrhage

>Intraperitoneal

8 mg of norepinephrine in 250 mL of 0.9% sodium chloride injection has been administered intraperitoneally+ to control upper GI bleeding+.b

>Nasogastric

8 mg of norepinephrine in 100 mL of 0.9% sodium chloride solution has been instilled through a nasogastric tube+ every hour for 6-8 hours, then every 2 hours for 4-6 hours to control upper GI bleeding+; frequency of administration was then gradually reduced until the drug was discontinued.b

Special Populations

Geriatric Patients

Has not been evaluated systematically in those 65 years of age and older, but the manufacturers currently do not make specific dosage recommendations for geriatric patients.b

If used in geriatric patients, initial dosage usually should be at the low end of the dosage range and caution should be exercised since renal, hepatic, and cardiovascular dysfunction and concomitant disease or other drug therapy are more common in this age group than in younger patients.b

Cautions

Contraindications

• Generally considered contraindicated to use during anesthesia with cyclopropane or halogenated hydrocarbon general anesthetics because of the risk of inducing cardiac arrhythmias.b (See Anesthetics, general under Interactions.)
• Use in patients with profound hypoxia or hypercapnia may be contraindicated for risk of inducing cardiac arrhythmias.b
• In conjunction with local anesthetics, norepinephrine is contraindicated for use in fingers, toes, ears, nose, or genitalia.b

Warnings/Precautions

Warnings

Hypovolemia

Pressor therapy is not a substitute for replacement of blood, plasma, fluids, and/or electrolytes.b

Correct blood volume depletion as fully as possible before administration.b

May be used in an emergency as an adjunct to fluid volume replacement or as a temporary supportive measure to maintain coronary and cerebral artery perfusion until volume replacement therapy can be completed, but norepinephrine must not be used as sole therapy in hypovolemic patients.b

Additional volume replacement also may be required during or after administration of norepinephrine, especially if hypotension recurs.b

Monitoring of central venous pressure or left ventricular filling pressure may be helpful in detecting and treating hypovolemia; in addition, monitoring of central venous or pulmonary arterial diastolic pressure is necessary to avoid overloading the cardiovascular system and precipitating CHF.b

Hypoxia, Hypercapnia, and Acidosis

Hypoxia, hypercapnia, and acidosis, may reduce the effectiveness and/or increase the incidence of adverse effects of norepinephrine, and must be identified and corrected prior to or concurrently with administration of the drug.b

Extravasation

Because severe local adverse effects may occur, extravasation of norepinephrine must be avoided.b

The site of infusion should be checked frequently for free flow and the infused vein should be observed for blanching.b

Risk of tissue damage is apparently very slight if infused through a plastic catheter deep into an antecubital vein.b

Avoid injection into leg veins, especially in geriatric patients or those with occlusive vascular diseases, arteriosclerosis, diabetes mellitus, or Buerger's disease.b

If blanching is observed in the infused vein or if therapy is to be prolonged, changing the injection site periodically may be advisable.b

Extravasation Treatment

If extravasation occurs, 10-15 mL of sodium chloride solution containing 5-10 mg of phentolamine mesylate should be infiltrated (using a syringe with a fine hypodermic needle) liberally throughout the affected area, which is identified by a cold, hard, and pallid appearance.b

Immediate and conspicuous local hyperemic changes occur if the area is infiltrated within 12 hours, but such treatment is ineffective when given >12 hours after extravasation; therefore, phentolamine should be administered as soon as possible after extravasation is noted.b

Addition of 5-10 mg of phentolamine to each L of infusion fluid containing norepinephrine may prevent sloughing of tissue, if extravasation occurs, without altering the pressor effects of norepinephrine; however, IV injection of phentolamine is not an effective antidote after extravasation has occurred.b

In severe hypotension after MI: Thrombosis in the infused vein and perivenous reactions and necrosis may be prevented by adding enough heparin to the norepinephrine infusion to supply 100-200 units of heparin per hour.b

Hypertensive or Hypothryroid Patients

Administer with caution to hypertensive or hyperthyroid patients since adverse reactions are most likely to occur.b

Peripheral or Mesenteric Vascular Thrombosis

Unless necessary as a life-saving procedure, do not use in patients with peripheral or mesenteric vascular thrombosis because ischemia may be increased and the area of infarction extended.b

Sensitivity Reactions

Sulfite Sensitivity

Formulations of norepinephrine bitartrate injection contain sulfites, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.b

General Precautions

Extravasation and Localized Vasoconstriction

Can cause tissue necrosis and sloughing at the site of injection as a result of local vasoconstriction. (See Extravasation under Warnings.)

Impairment of circulation and sloughing of tissue may also occur without obvious extravasation.b

Prolonged Administration

Has caused decreased cardiac output, edema, hemorrhage, focal myocarditis, subpericardial hemorrhage, necrosis of the intestine, or hepatic and renal necrosis.b

Generally occurs in patients with severe shock and it is not clear if the drug or the shock state itself was the cause.b

Cardiovascular and Renal Effects

Can cause severe peripheral and visceral vasoconstriction, reduced blood flow to vital organs, decreased renal perfusion and therefore decreased urine output, tissue hypoxia, and metabolic acidosis; these effects are most likely to occur in hypovolemic patients.b

May cause plasma volume depletion which may result in perpetuation of the shock state or recurrence of hypotension when the drug is discontinued.b

Increases myocardial oxygen consumption and the work of the heart.b

Cardiac output may be decreased following prolonged use of the drug or administration of large doses because venous return to the heart may be diminished because of increased peripheral vascular resistance; decreased cardiac output may be especially harmful to elderly patients or those with initially poor cerebral or coronary circulation.b

Arrhythmias

May cause palpitation and bradycardia as well as potentially fatal cardiac arrhythmias, including ventricular tachycardia, bigeminal rhythm, nodal rhythm, AV dissociation, and fibrillation.b

Arrhythmias are especially likely to occur in patients with AMI, hypoxia, or hypercapnia, or those receiving other drugs that may increase cardiac irritability such as cyclopropane or halogenated hydrocarbon general anesthetics. (See Anesthetics, general under Cautions.)

Specific Populations

Pregnancy

Category C.c

Lactation

Unknown whether norepinephrine is distributed into human milk.b,c Because of norepinephrine's indications, use during breast-feeding is unlikely.c

Pediatric Use

Safety and efficacy not established.b

Geriatric Use

Has not been evaluated systematically in those ≥65 years of age, but the manufacturers currently do not make specific dosage recommendations for geriatric patients.b

If used in geriatric patients, the initial dosage usually should be at the low end of the dosage range and caution should be exercised since renal, hepatic, and cardiovascular dysfunction and concomitant disease or other drug therapy are more common in this age group than in younger patients.b

Norepinephrine infusions should not be administered into leg veins in geriatric patients. (See Extravasation under Cautions.)

Common Adverse Effects

May cause headache, weakness, dizziness, tremor, pallor, respiratory difficulty or apnea, and precordial pain.b

Overdosage or administration of usual doses to patients who are hypersensitive to the effects of norepinephrine (e.g., hyperthyroid patients) may result in photophobia, pallor, intense sweating, vomiting, retrosternal or pharyngeal pain, severe hypertension, cerebral hemorrhage, seizures, and severe headache. Headache may be a symptom of hypertension.

Interactions

Specific Drugs
Drug Interaction Comments α-Adrenergic blocking agents Despite animal evidence of interaction (decreased pressor response), interaction appears unlikely in humans [b] β-Adrenergic blocking agents Possibility that concomitant use might result in Propranolol may be used to treat cardiac higher elevations of BP because of blockade of any arrhythmias occurring during administration of β-mediated arteriolar dilation should be kept in norepinephrine [b] mind [b] In animals, preadministration of a β-adrenergic blocking drug such as propranolol blocks the cardiac stimulating effects of norepinephrine [b] Anesthetics, general Concomitant use with cyclopropane or halogenated If a pressor drug is required when these general (cyclopropane or halogenated hydrocarbon general anesthetics, which increase anesthetics are used, give one with minimal hydrocarbons) cardiac irritability, may result in arrhythmias [b] cardiac stimulating effects such as methoxamine or phenylephrine [b] Antidepressants, tricyclic May potentiate the pressor effects of norepinephrine, Norepinephrine should be given cautiously and in resulting in severe, prolonged hypertension small doses to patients receiving these drugs Antidepressants, MAO Potentiation may result from inhibition of tissue MAO is one of the enzymes responsible for inhibitors uptake of norepinephrine or by increased norepinephrine metabolism; although some adrenoreceptor sensitivity to the drug [b] clinicians have reported that MAO inhibitors do not appear to potentiate the effects ofnorepinephrine to a clinically important extent, the manufacturer states that norepinephrine should be administered with extreme caution to patients receiving an MAO inhibitor because severe, prolonged hypertension may result Antihistamines (especially May potentiate pressor effects, resulting in severe, Use cautiously and in small doses with these drugs diphenhydramine, prolonged hypertension tripelennamine, and dexchlorpheniramine) Atropine Atropine sulfate blocks the reflex bradycardia caused by norepinephrine and enhances the pressor response to norepinephrine Diuretics (furosemide, other Concomitant use may decrease arterial responsiveness diuretics) to pressor drugs such as norepinephrine Ergot alkaloids, parenteral May potentiate the pressor effects of norepinephrine, Use cautiously and in small doses with these drugs resulting in severe, prolonged hypertension Guanethidine May potentiate the pressor effects of norepinephrine, Use cautiously and in small doses with these drugs resulting in severe, prolonged hypertension Methyldopa May potentiate the pressor effects of norepinephrine, Use cautiously and in small doses with these drugs resulting in severe, prolonged hypertension

Pharmacokinetics

Absorption

Bioavailability

Oral: Destroyed in the GI tract.b

Sub-Q: Poorly absorbed.b

Onset

IV: Pressor response occurs rapidly.b

Duration

Short; pressor action stops within 1-2 minutes after the infusion is discontinued.b

Distribution

Extent

Localizes mainly in sympathetic nervous tissue.b

Crosses the placenta.b,c

Not known if distributes into milk.b,c

Does not cross the blood-brain barrier.b

Elimination

Metabolism

Via the liver and other tissues by a combination of reactions involving the enzymes catechol-O-methyltransferase (COMT) and MAO.b

Pharmacologic actions are terminated mainly by uptake and metabolism in sympathetic nerve endings.b

Major metabolites are normetanephrine and 3-methoxy-4-hydroxy mandelic acid (vanillylmandelic acid, VMA), both of which are inactive.b

Elimination Route

Metabolites are excreted in urine mainly as the sulfate conjugates and, to a lesser extent, as the glucuronide conjugates; only small quantities of norepinephrine are excreted unchanged.b

Stability

Storage

Parenteral

Injection

Tight, light-resistant containers.b

Protect from light and air at 25°C (may be exposed to 15-30°C).b

Compatibility

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

Parenteral

IV infusion: Dilute norepinephrine with 5% dextrose injection with or without sodium chloride to protect against loss of potency caused by oxidation during IV infusion; do not use sodium chloride injection alone.b

Following dilution with 5% dextrose, IV infusions containing norepinephrine 2.5 or 4 mcg/mL have been reported to be stable for at least 24 hours at room temperature if the pH is approximately 5.6.b

Norepinephrine solutions containing 2.5 mcg/mL in 5% dextrose have been reported to lose 5% of their potency in 6 hours at pH 6.5 and in 4 hours at pH 7.5.b

Use caution if diluted with 5% dextrose injections with a pH of >5.5-6 or if the drug is mixed with alkaline additives such as sodium bicarbonate, barbiturates, or alkaline buffered antibiotics which will result in pH >6; these solutions should be used immediately after preparation.b

Administer whole blood or plasma, if indicated during therapy with norepinephrine, separately or via a Y-tube.b

Solution CompatibilityHID
Compatible Amino acids 4.25%, dextrose 25% Dextrose 5% in sodium chloride 0.9% Dextrose 5% in water Ringer's injection, lactated Sodium chloride 0.9%

Drug Compatibility

>Admixture Compatibility [HID]
Compatible Amikacin sulfate Calcium chloride Calcium gluconate Cimetidine HCl Ciprofloxacin Corticotropin Dimenhydrinate Dobutamine HCl Heparin sodium Hydrocortisone sodium succinate Magnesium sulfate Meropenem Methylprednisolone sodium succinate Multivitamins Potassium chloride Succinylcholine chloride Verapamil HCl Vitamin B complex with C Incompatible Aminophylline Amobarbital sodium Blood, whole Chlorothiazide sodium Chlorpheniramine maleate Pentobarbital sodium Phenobarbital sodium Phenytoin sodium Sodium bicarbonate Streptomycin sulfate Thiopental sodium Variable Ranitidine HCl

>Y-site Compatibility [HID]
Compatible Alcohol 10% in dextrose 5% Amiodarone HCl Argatroban Bivalirudin Dexmedetomidine HCl Diltiazem HCl Dobutamine HCl Dopamine HCl Epinephrine HCl Esmolol HCl Famotidine Fenoldopam mesylate Fentanyl citrate Furosemide Haloperidol lactate Heparin sodium Hetastarch in lactated electrolyte injection (Hextend) Hydrocortisone sodium succinate Hydromorphone HCl Inamrinone lactate Labetalol HCl Lorazepam Meropenem Midazolam HCl Milrinone lactate Morphine sulfate Nicardipine HCl Nitroglycerin Pantoprazole sodium Potassium chloride Propofol Ranitidine HCl Remifentanil HCl Sodium nitroprusside Vasopressin Vecuronium bromide Vitamin B complex with C Incompatible Drotrecogin alfa (activated) Thiopental sodium

Actions

• Acts predominantly by a direct effect on α-adrenergic receptors.b
• Directly stimulates β-adrenergic receptors of the heart (β1-adrenergic receptors) but not those of the bronchi or peripheral blood vessels (β2-adrenergic receptors).b
• Believed that α-adrenergic effects result from inhibition of the production of cyclic adenosine-3´,5´-monophosphate (AMP) by inhibition of the enzyme adenyl cyclase, whereas β-adrenergic effects result from stimulation of adenyl cyclase activity.b
• Main effects of therapeutic doses are vasoconstriction and cardiac stimulation.b
• Constricts both capacitance and resistance blood vessels by its effect on α-adrenergic receptors.b
• Total peripheral resistance is increased, resulting in increased SBP and DBP.b Blood flow to vital organs, skin, and skeletal muscle is reduced.b
• Local vasoconstriction caused by the drug may result in hemostasis and/or necrosis.b
• May reduce circulating plasma volume (especially with prolonged use) as a result of loss of fluid into extracellular spaces caused by postcapillary vasoconstriction.b
• Acts on β1-adrenergic receptors in the heart, producing a positive inotropic effect on the myocardium.b
• Although norepinephrine has fewer CNS effects than does epinephrine, restlessness, headache, and tremor may occur.
• Can increase glycogenolysis and inhibit insulin release in the pancreas, resulting in hyperglycemia.b
• Increased oxygen consumption and elevation of body temperature may occur.b
• As a result of its effect on α-adrenergic receptors, norepinephrine may cause contraction of the pregnant uterus and constriction of uterine blood vessels; however, the vasoconstrictor effects may be overcome by an increase in maternal blood pressure.

Advice to Patients

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.
• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
• 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.

Norepinephrine Bitartrate
Routes Dosage Forms Strengths Brand Names Manufacturer Parenteral For injection, 1 mg (of Levophed® Bitartrate (with sodium Hospira concentrate, for norepinephrine) metabisulfite and sodium chloride) IV infusion per mL* Norepinephrine Bitartrate Injection (with Bedford, sodium metabisulfite and sodium PharmaForce, chloride) Sicor -----------------------------------------------------------------------------------------------------------------
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

--------------------------

AHFS Drug Information. © Copyright, 1959-2010, Selected Revisions August 2007. 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

b. AHFS drug information 2004. McEvoy GK, ed. Norepinephrine. Bethesda, MD: American Society of Health-System Pharmacists; 2004:1270-3.

c. Briggs GG, Freeman RK, Yaffe SJ. Drug in pregnancy and lactation: a reference guide to fetal and neonatal risk. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2002:1014.

pdh. Schilling McCann JA, Publisher. Pharmacists drug handbook. 2nd ed. Philadelphia, PA: Lippincott Williams and Wilkins and American Society of Health-System Pharmacists; 2003.

HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1231-7.

Copyright © 2010 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

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Copyright © 2010 by the American College of Physicians. All rights reserved.
The information included herein should never be used as a substitute for clinical judgment and does not represent an official position of ACP. Because all PIER modules are updated regularly, printed web pages or PDFs may rapidly become obsolete. Therefore, PIER users should compare the date of the last update on the website with any printout to ensure that the information being referred to is the most current available.
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2010. ACP PIER & AHFS DI® Essentials™. Philadelphia, PA. American College of Physicians. STAT!Ref Online Electronic Medical Library. http://online.statref.com/document.aspx?fxid=92&docid=5268. 6/4/2010 1:11:07 AM CDT (UTC -05:00).

* Copyright:
o Copyright © 2010 by the American College of Physicians. All rights reserved.
The information included herein should never be used as a substitute for clinical judgment and does not represent an official position of ACP. Because all PIER modules are updated regularly, printed web pages or PDFs may rapidly become obsolete. Therefore, PIER users should compare the date of the last update on the website with any printout to ensure that the information being referred to is the most current available.
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AHFS DI® ESSENTIALS™ (2010)
"N" Monographs
Norepinephrine (Systemic)

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