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Isoproterenol Hydrochloride

Pronunciation

Class: Non-selective beta-Adrenergic Agonists
VA Class: AU100
CAS Number: 51-30-9

Introduction

Nonselective β-agonist.

Uses for Isoproterenol Hydrochloride

Cardiac Arrhythmias and CPR

Used in the treatment of Adams-Stokes syndrome (Stokes-Adams disease).a May be used in ventricular Arrhythmias secondary to AV nodal block and treatment of carotid sinus hypersensitivity.a

Has been used in the treatment of cardiac arrest until defibrillation or emergency pacemaker therapy could be employed.a The drug may be used in ACLS only as a temporary measure until pacemaker therapy is instituted either for refractory atypical ventricular tachycardia (torsades de pointes) or for the immediate temporary control of hemodynamically significant bradycardia (e.g., in the denervated heart of patients undergoing heart transplantation).a

Use of isoproterenol for temporary immediate control of hemodynamically significant bradycardia usually is limited to when atropine and dobutamine have failed and transcutaneous and transvenous pacing are not available.133

Must not be administered to patients with acetylcholinesterase-induced bradycardias; however, may be beneficial at high doses in refractory bradycardia caused by β-adrenergic blocking agents.136

Isoproterenol (at low doses and in patients with a pulse) should be used with extreme caution, if at all, in the management of symptomatic bradycardia since its potential beneficial chronotropic effect may be outweighed by possible deleterious effects on myocardial oxygen consumption and peripheral circulation.a

Slideshow: Flashback: FDA Drug Approvals 2013

Electrical cardiac pacemakers largely have replaced drug therapy in third-degree AV nodal block (complete heart block), but isoproterenol may be used temporarily until a pacemaker can be implanted or if the implanted pacemaker fails.a

Electroshock may be required in the management of ventricular arrhythmias and usually is the treatment of choice.a

Shock

Isoproterenol IV infusion is used as adjunct to correct hemodynamic imbalances in the treatment of shock characterized by low cardiac output and intense vasoconstriction that persists after adequate fluid replacement.a The drug is not useful if the peripheral vascular bed is already dilated.a

The value of isoproterenol therapy in shock has been questioned because the drug increases oxygen demand in the myocardium and other tissues to levels that may not be met by increased blood flow.a The efficacy of isoproterenol in reducing the incidence of mortality in refractory shock has not been convincingly demonstrated.a

Isoproterenol appears to be less effective than norepinephrine or metaraminol in increasing coronary perfusion.a Also, isoproterenol-induced increases in myocardial oxygen consumption and the work of the heart usually outweigh the beneficial effects of the drug, and arrhythmias occur more readily when the drug is administered to patients with cardiogenic shock.a

Isoproterenol generally is not recommended in shock caused by AMI.a Norepinephrine is considered by some clinicians to be the vasopressor of choice for this condition; however, this type of shock generally has a poor prognosis even when vasopressors are used.a If peripheral vascular resistance is elevated, isoproterenol sometimes is used in conjunction with norepinephrine, but dosage of both drugs must be adjusted carefully according to the specific hemodynamic imbalances present.

The efficacy of isoproterenol may be reduced if CHF is present.a

Should not be used in patients with drug-induced distributive shock; may worsen hypotension by further decreasing systemic vascular resistance.136

Bronchospasm

IV isoproterenol may be useful in bronchospasm occurring during anesthesia but must be administered with extreme caution, if at all, in patients receiving cyclopropane or halogenated hydrocarbon general anesthetics.a

Has been used as a bronchodilator in the symptomatic treatment of bronchial asthma and reversible bronchospasm that may occur in association with chronic bronchitis, pulmonary emphysema, bronchiectasis, and other chronic obstructive pulmonary disorders.a However, oral, sublingual, and oral inhalation preparations of the drug no longer are commercially available in the US.a

Pulmonary Embolism

Has been used by IV infusion to reverse decreases in cardiac output and circulating pulmonary blood volume and to reverse increases in pulmonary arterial pressure and pulmonary vascular resistance occurring during pulmonary embolism.a

Diagnosis of CAD and Other Cardiac Abnormalities

Has been used as an aid in the diagnosis of CAD.a Also has been used in the diagnosis of CAD by increasing myocardial oxygen consumption and intensifying symptoms of ischemia.a

Has been used as an aid in diagnosing the etiology of mitral regurgitation.a

Isoproterenol Hydrochloride Dosage and Administration

General

  • Generally, initiate therapy at the lowest recommended dose.132

  • Rate of administration may be gradually increased, if needed.132

  • Dosage must be regulated by monitoring the ECG and by patient’s response.132 a

Administration

Usually administer IV.135

May administer by intracardiac injection in extreme emergencies (in adults).135 In less urgent situations, initial IM or sub-Q injection is preferred.135

IV Administration

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

Administer by IV injection or infusion.135

Dilution

For direct IV injection, diluted solutions containing isoproterenol hydrochloride 20 mcg/mL (1:50,000) are used; these solutions may be prepared by diluting 1 mL of the commercially available injection containing isoproterenol hydrochloride 0.2 mg/mL (1:5000) to a volume of 10 mL with 0.9% sodium chloride injection or 5% dextrose injection.132 a

For IV infusion, solutions may be prepared by diluting 1–10 mL of the injection containing isoproterenol hydrochloride 0.2 mg/mL (1:5000) with 500 mL of 5% dextrose injection to provide infusion solutions containing 0.4–4 mcg/mL;132 a solutions containing 2–4 mcg/mL are most commonly used.a

The injection concentrate (1:5000) must be diluted in large-volume parenteral fluids in a single-use container and administered by slow IV infusion.132 As the injection concentrate contains no bacteriostatic or antimicrobial agent, each vial is intended for single use only; any unused solution should be discarded.132

Rate of Administration

When the drug is administered by IV infusion, especially as an adjunct in the treatment of shock, the rate of infusion should be adjusted on the basis of the patient’s heart rate, central venous pressure, systemic BP, and urine flow.a

If the heart rate exceeds 110 beats/minute or if premature heart beats or changes in the ECG develop, slowing the rate of infusion or discontinuing the infusion temporarily should be considered.a

Dosage

Available as isoproterenol hydrochloride; dosage expressed in terms of the salt.

Pediatric Patients

Cardiac Arrhythmias and CPR
IV Injection and Infusion

Initial doses of isoproterenol hydrochloride in children have been one-half of those in adults; 0.01–0.03 mg (0.5–1.5 mL of a 1:50,000 dilution) has been given as an IV bolus dose.a

For IV infusion, the AHA recommends an initial rate of 0.1 mcg/kg per minute; subsequent dosage generally ranges from 0.1–1 mcg/kg per minute.132 135

In the management of postoperative cardiac patients with bradycardia, children have been given isoproterenol by IV infusion in a dosage of 0.029 mcg/kg per minute.132

For the management of complete heart block following closure of ventricular septal defects, the drug has been administered to infants as an IV bolus in doses of 0.01–0.03 mg (0.5–1.5 mL of a 1:50,000 dilution).a

Adults

Cardiac Arrhythmias and CPR
IV Injection and Infusion

Initially, 0.02–0.06 mg (1–3 mL of a 1:50,000 dilution) as an IV bolus dose; subsequent doses range from 0.01–0.2 mg (0.5–10 mL of a 1:50,000 dilution).a

For IV infusion, the initial rate of administration is 5 mcg/minute (1.25 mL of a 1:250,000 dilution per minute); subsequent dosage generally ranges from 2–20 mcg/minute.a

Doses of isoproterenol hydrochloride used for the treatment of cardiac arrhythmias also may be employed in the treatment of cardiac arrest; however, the drug usually should not be used for the treatment of cardiac arrest.a (See Cardiac Arrhythmias and CPR under Uses.)

Until pacemaker therapy is instituted either for refractory atypical ventricular tachycardia (torsades de pointes) or for the immediate temporary control of hemodynamically significant bradycardia during ACLS, the suggested IV infusion rate is 2–10 mcg/minute.a Higher dosages may be associated with increased myocardial oxygen consumption, increased infarct size, and malignant ventricular arrhythmias.133

For the management of complete heart block following closure of ventricular septal defects, a dose of 0.04–0.06 mg (2–3 mL of a 1:50,000 dilution) has been used.a

IM

Initially, 0.2 mg (1 mL of 1:5000 injection); subsequent doses range from 0.02–1 mg (0.1–5 mL of 1:5000 injection).135

Sub-Q

Initially, 0.2 mg (1 mL of 1:5000 injection); subsequent doses range from 0.15–0.2 mg (0.75–1 mL of 1:5000 injection).135

Shock
IV Infusion

Suggested infusion rate is 0.5–5 mcg (0.25–2.5 mL of a 1:500,000 dilution) per minute.a In advanced stages of shock, rates >30 mcg/minute have been used.a For septic shock, the drug usually should not be administered for longer than 1 hour.a

Bronchospasm
IV

0.01–0.02 mg (0.5–1 mL of a 1:50,000 dilution); dose may be repeated as needed.a

Diagnosis of CAD and Other Cardiac Abnormalities
IV Infusion

Isoproterenol hydrochloride has been administered by IV infusion at a rate of 1–3 mcg/minute in the diagnosis of CAD or lesions or at a rate of 4 mcg/minute as an aid in diagnosing the etiology of mitral regurgitation.a

Prescribing Limits

For septic shock, the drug usually should not be administered for longer than 1 hour.a

Special Populations

Renal Impairment

No specific dosage recommendations.132 a Administer with caution.a

Geriatric Patients

Careful dosage selection recommended due to possible age-related decrease in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy; initiate therapy at low end of dosage range.134

Cautions for Isoproterenol Hydrochloride

Contraindications

  • Angina pectoris.a

  • Preexisting cardiac arrhythmias (particularly ventricular arrhythmias requiring inotropic therapy and tachyarrhythmias) other than those arrhythmias that may respond to treatment with isoproterenol.a

  • Tachycardia or AV block caused by cardiac glycoside intoxication.a

Warnings/Precautions

Warnings

Cardiovascular Effects

In patients with AMI, isoproterenol may increase the extent of ischemic injury to the myocardium.a Use of the drug as initial agent in the treatment of cardiogenic shock following MI is discouraged.132 a May cause focal necrosis of myocardial cells.132 a

Paradoxically, the drug may precipitate Adams-Stokes seizures in some patients with normal sinus rhythm or transient AV block.a It has been suggested that these patients may have had organic disease of the AV node or its branches.132 a

Evidence of transient myocardial ischemia (i.e., ECG changes and elevation of the cardiac [MB] fraction of creatine kinase [CK, creatine phosphokinase, CPK]) or myocardial dysfunction (i.e., abnormal ECG findings) has been reported with the use of isoproterenol IV infusion for the treatment of severe asthma exacerbation in children.132 a In patients with asthma receiving isoproterenol infusion, administer oxygen concomitantly; monitor heart rate, BP, and arterial blood gases (maintaining arterial oxygen pressure [PaO2 ] >60 mm Hg); and monitor ECG. Confirm ECG changes suggestive of myocardial ischemia by determining the MB fraction of CK.132 a

Disturbances of cardiac rhythm and rate produced by isoproterenol may result in palpitation and VT.132 a Isoproterenol can cause potentially fatal ventricular arrhythmias in doses sufficient to increase heart rate above 130 beats/minute.132 a

Administration of isoproterenol to patients who are in shock is not a substitute for replacement of blood, plasma, fluids, and/or electrolytes.a

Blood volume depletion must be corrected as fully as possible before the drug is administered.a

Use with caution in patients with CAD, coronary insufficiency, diabetes, hyperthyroidism, and sensitivity to sympathomimetic amines.a

Sensitivity Reactions

Sulfite Sensitivity

Some formulations contain sulfites, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.132 a

General Precautions

Hypovolemia

Pressor therapy is not a substitute for replacement of blood, plasma, fluids, and/or electrolytes.132 a Correct blood volume depletion as fully as possible before isoproterenol therapy is instituted.132 a

Additional volume replacement also may be required during administration of isoproterenol; fluid administration must be adequate to compensate for isoproterenol-induced vasodilation, or shock may be worsened.132 a

Detecting and treating hypovolemia: Monitor central venous pressure or left ventricular filling pressure; in addition, monitor central venous or pulmonary arterial diastolic pressure to avoid overloading the cardiovascular system, diluting serum electrolyte concentrations, and precipitating CHF.132 a

Monitoring

Monitor ECG, BP, heart rate, urine flow, central venous pressure, blood pH, and blood PCO2 or bicarbonate concentrations.a (See Hypoxia, Hypercapnia, Acidosis, Electrolyte Disturbances under Cautions.) Measure cardiac output and circulation time to determine the patient’s condition and response to therapy.a Ensure adequate ventilation.a Carefully monitor patients who are in shock.a Consider the possibility that isoproterenol may not produce improved capillary perfusion and oxygen delivery while increasing oxygen demand in the myocardium.a

Hypoxia, Hypercapnia, Acidosis, and Electrolyte Disturbances

Must be identified and corrected prior to or during administration of the drug.a May reduce the efficacy and/or increase the incidence of adverse effects of isoproterenol.a

Disease States

Use with caution in geriatric patients, diabetics, patients with renal or cardiovascular disease (including hypertension, CAD, coronary insufficiency, or degenerative heart disease), hyperthyroidism, and/or those with a history of sensitivity to sympathomimetic amines.132 a

Specific Populations

Pregnancy

Category C.132

Lactation

Not known whether isoproterenol is distributed into human milk.132 Caution advised if IV isoproterenol hydrochloride is used.132

Pediatric Use

Safety and efficacy not established.132 Has been used IV in children with asthma or in postoperative cardiac patients with bradycardia.132 Also has been used in the management of cardiac arrhythmias and CPR in children and for the management of complete heart block following closure of ventricular septal defects in infants.a For use during CPR in children, a continuous infusion of isoproterenol may be considered if bradycardia persists or responds only transiently to epinephrine injection, airway support, ventilation, oxygenation, and chest compressions.136 137

IV infusions of 0.05–2.7 mcg/kg per minute in pediatric patients with refractory asthma have caused clinical deterioration, myocardial necrosis, CHF, and death;135 the risk may be increased by acidosis, hypoxia, and/or concomitant use of other agents (e.g., xanthine derivatives, corticosteroids [see Specific Drugs under Interactions]) likely to be used in these children.135 If used in pediatric patients with refractory asthma, monitor vital signs continuously and ECG frequently, and determine cardiac-specific (MB) fraction of serum CK (CPK) daily.135

Geriatric Use

Insufficient experience in patients >65 years of age to determine whether geriatric patients respond differently to isoproterenol hydrochloride than younger patients.134 Geriatric healthy individuals or hypertensive patients may be less responsive to β-adrenergic stimulation than younger adults.134 Use with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.134 Titrate dosage carefully. (See Special Populations under Dosage and Administration.)

Renal Impairment

Use with caution.a

Common Adverse Effects

Nervousness, headache, dizziness, restlessness, insomnia, anxiety, tension, blurring of vision, fear, excitement, tachycardia, palpitations, angina, Adam-Stokes syndrome, pulmonary edema, hypertension, hypotension, ventricular arrhythmias, tachyarrhythmias, flushing of the skin, diaphoresis, mild tremors, weakness.132 135

Interactions for Isoproterenol Hydrochloride

Specific Drugs

Drug

Interaction

Comments

Anesthetics, general (e.g., halogenated hydrocarbons [halothane], cyclopropane)

Potential for arrhythmiasa

Use with caution, if at alla

β-Adrenergic blocking agents

Cardiac effects of isoproterenol are antagonizeda

Sympathomimetic agents (e.g., epinephrine)

Additive effects and increased cardiotoxicitya

Do not administer concomitantly; may use alternately with appropriate intervals between dosesa

Xanthine derivatives (e.g., aminophylline, theophylline)

Potential increased or additive cardiotoxic effects; fatal myocardial necrosis has been reported100 101 102 103 132 135

Isoproterenol Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Readily absorbed following parenteral administration.132

Duration

Effects persist for few minutes after IV administration.a

Distribution

Extent

Not known whether distributed into human milk.132

Elimination

Metabolism

Metabolized in the GI tract, liver, lungs, and other tissues.

Elimination Route

Following IV administration, excreted in urine (40–50%) as unchanged drug and remainder as metabolite.a

Stability

Storage

Parenteral

Injection

Tight, light-resistant containers at 8–15°C.135

Compatibility

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

Parenteral

Solution CompatibilityHID

Compatible

Amino acids 4.25%, dextrose 25%

Dextran 6% in dextrose 5%

Dextran 6% in sodium chloride 0.9%

Dextrose–Ringer’s injection combinations

Dextrose–Ringer’s injection, lactated, combinations

Dextrose 5% in Ringer’s injection, lactated

Dextrose–saline combinations

Dextrose 5% in sodium chloride 0.9%

Dextrose 2½, 5, or 10% in water

Fructose 10% in sodium chloride 0.9%

Fructose 10% in water

Invert sugar 5 and 10% in sodium chloride 0.9%

Invert sugar 5 and 10% in water

Ionosol products

Ringer’s injection

Ringer’s injection, lactated

Sodium chloride 0.45 or 0.9%

Sodium lactate (1/6) M

Incompatible

Sodium bicarbonate 5%

Drug Compatibility
Admixture CompatibilityHID

Compatible

Atracurium besylate

Calcium chloride

Cimetidine HCl

Dobutamine HCl

Heparin sodium

Magnesium sulfate

Multivitamins

Potassium chloride

Ranitidine HCl

Succinylcholine chloride

Verapamil HCl

Vitamin B complex with C

Incompatible

Aminophylline

Furosemide

Sodium bicarbonate

Y-Site CompatibilityHID

Compatible

Amiodarone HCl

Atracurium besylate

Bivalirudin

Bretylium tosylate

Dexmedetomidine HCl

Famotidine

Fenoldopam mesylate

Heparin sodium

Hetastarch in lactated electrolyte injection (Hextend)

Hydrocortisone sodium succinate

Inamrinone lactate

Levofloxacin

Milrinone lactate

Pancuronium bromide

Potassium chloride

Propofol

Remifentanil HCl

Sodium nitroprusside

Tacrolimus

Vecuronium bromide

Vitamin B complex with C

Actions

  • Stimulates β2-adrenergic receptors.132

  • Little or no effect on α-adrenergic receptors.132

  • Cardiac output usually is increased and may be accompanied by an increase in stroke volume.a

  • Increases myocardial oxygen consumption and the work of the heart and decreases cardiac efficiency.a

  • Lowers peripheral vascular resistance, mainly in skeletal muscle and also in renal and mesenteric vascular beds.132

  • Decreases DBP132 by producing vasodilation.a Mean BP usually is decreased slightly but it may remain unchanged or may be increased slightly if the vasculature already is maximally dilated.a

  • Renal blood flow usually is decreased in normotensive patients, but is substantially increased in patients with shock.132

  • SBP may be increased or remain unchanged.132 a

  • In patients with AV block, isoproterenol shortens conduction time and the refractory period of the AV node and increases the rate and strength of ventricular contraction.a

  • Inhibits antigen-induced release of histamine and the slow reacting substance of anaphylaxis.a

Advice to Patients

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.132

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.132

  • Importance of informing patients of other important precautionary information. (See Cautions.)132

Preparations

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

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

Isoproterenol Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection

0.2 mg/mL*

Isoproterenol Hydrochloride Injection 1:5000 (with sulfites)

Hospira

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions May 31, 2011. 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

Only references cited for selected revisions after 1984 are available electronically.

100. Joseph X, Whitehurst VE, Bloom S et al. Enhancement of cardiotoxic effects of beta-adrenergic bronchodilators by aminophylline in experimental animals. Fundam Appl Toxicol. 1981; 1:443-7. [PubMed 6136445]

101. Anon. Interaction between methyl xanthines and beta adrenergic agonists. FDA Drug Bull. 1981; 11:19-20. [PubMed 6119269]

102. Kelly HW. Controversies in asthma therapy with theophylline and the β2-adrenergic agonists. Clin Pharm. 1984; 3:386-95. [IDIS 187701] [PubMed 6147224]

103. Walker SB, Kradjan WA, Bierman CW. Bitolterol mesylate: a beta-adrenergic agent. Chemistry, pharmacokinetics, pharmacodynamics, adverse effects and clinical efficacy in asthma. Pharmacotherapy. 1985; 5:127-37. [IDIS 393481] [PubMed 3895171]

104. Meyer JM, Wenzel CL, Kradjan WA. Salmeterol: a novel, long-acting beta 2-agonist. Ann Pharmacother. 1993; 27:1478-87. [IDIS 323106] [PubMed 7905757]

105. Brogden RN, Faulds D. Salmeterol xinafoate: a review of its pharmacological properties and therapeutic potential in reversible obstructive airways disease. Drugs. 1991; 42:895-912. [PubMed 1723379]

106. Kelly HW. Issues and advances in the pharmacotherapy of asthma. J Clin Pharm Ther. 1992; 17:271-81. [IDIS 304352] [PubMed 1361192]

107. Lipworth BJ. Risks versus benefits of inhaled β2-agonists in the management of asthma. Drug Safety. 1992; 7:54-70. [PubMed 1346963]

108. Sears MR, Taylor DR, Print CG et al. Regular inhaled beta-agonist treatment in bronchial asthma. Lancet. 1990; 336:1391-6. [IDIS 275192] [PubMed 1978871]

109. Anon. Warnings from the CSM. Int Pharm J. 1991; 5:247-8.

110. Spitzer WO, Sussa S, Ernst P et al. The use of β-agonists and the risk of death and near death from asthma. N Engl J Med. 1992; 326:501-6. [IDIS 291894] [PubMed 1346340]

111. Palmer JBD, Jenkins MM. β2-agonists in asthma. Lancet. 1991; 337:43. [IDIS 275815] [PubMed 1670660]

112. Dahl R. β2-agonists in asthma. Lancet. 1991; 337:43. [IDIS 275815] [PubMed 1670660]

113. Löfdahl CG, Svedmyr N. Beta agonists—friends or foes? Eur Respir J. 1991; 4:1161-5. Editorial.

114. Kamada AK, Spahn JD, Blake KV. Salmeterol: its place in asthma management. Ann Pharmacother. 1994; 28:1100-2. [IDIS 335815] [PubMed 7803888]

115. Wanner A. Is the routine use of inhaled β-adrenergic agonists appropriate in asthma treatment? Yes. Am J Respir Crit Care Med. 1995; 151:597-9. [IDIS 344522] [PubMed 7881643]

116. Sears MR. Is the routine use of inhaled β-adrenergic agonists appropriate in asthma treatment? No. Am J Respir Crit Care Med. 1995; 151:600-1. [IDIS 344523] [PubMed 7881644]

117. Lai CKW, Twentyman OP, Holgate ST. The effect of an increase in inhaled allergen dose after rimiterol hydrobromide on the occurrence and magnitude of the late asthmatic response and the asssociated change in nonspecific bronchial responsiveness. Am Rev Respir Dis. 1989; 140:917-23. [IDIS 310468] [PubMed 2572192]

118. Suissa S, Ernst P, Boivin JF et al. A cohort analysis of excess mortality in asthma and the use of inhaled beta-agonists. Am J Respir Crit Care Med. 1994; 149(3 Part 1):604-10. [IDIS 327105] [PubMed 8118625]

119. O’Connor BJ, Aikman SL, Barnes PJ. Tolerance to the nonbronchodilator effects of inhaled beta 2-agonists in asthma. N Engl J Med. 1992; 327:1204-8. [IDIS 304091] [PubMed 1357551]

120. Cockcroft DW, McParland CP, Britto SA et al. Regular inhaled salbutamol and airway responsiveness to allergen. Lancet. 1993; 342:833-7. [IDIS 320479] [PubMed 8104272]

121. Mullen ML, Mullen B, Carey M. The association between β-agonist use and death from asthma: a meta-analytic integration of case-control studies. JAMA. 1993; 270:1842-5. [IDIS 320909] [PubMed 8105113]

122. Reviewers’ comments (personal observations) on Salmeterol 12:12.

123. National Institutes of Health, National Heart, Lung, and Blood Institute. Global Initiative for asthma: global strategy for asthma management and prevention NHLBI/WHO Workshop Report. Bethesda, MD: National Institutes of Health. 1995 Jan:77-100. NIH/NHLBI Publication No. 95-3659.

124. Devoy MAB, Fuller RW, Palmer JBD. Are there any detrimental effects of the use of inhaled long-acting β2-agonists in the treatment of asthma? Chest. 1995; 107:1116-24.

125. McFadden ER Jr. Perspectives in β2-agonist therapy: vox clamantis in deserto vel lux in tenebris? J Allergy Clin Immunol. 1995; 95:641-51.

126. Crane J, Burgess C, Pearce N et al. Asthma deaths in New Zealand. BMJ. 1992; 304:1307. [IDIS 296806] [PubMed 1606438]

127. Crane J, Pearce N, Flatt A et al. Prescribed fenoterol and death from asthma in New Zealand, 1981-83: case-control study. Lancet. 1989; 1:917-22. [IDIS 254874] [PubMed 2565417]

128. Pearlman DS, Chervinsky P, LaForce C et al. A comparison of salmeterol with albuterol in the treatment of mild-to-moderate asthma. N Engl J Med. 1992; 327:1420-5.

129. D’Alonzo GE, Nathan RA, Henochowicz S et al. Salmeterol xinafoate as maintenance therapy compared with albuterol in patients with asthma. JAMA. 1994; 271:1412-6.

130. National Asthma Education and Prevention Program. Expert panel report II: guidelines for the diagnosis and management of asthma. 1997 Feb.

131. Drazen JM, Israel E, Boushey HA et al. Comparison of regularly scheduled with as- needed use of albuterol in mild asthma. N Engl J Med. 1996; 335:841-7.

132. Abbott Laboratories. Isoproterenol hydrochloride injection, USP 1:5000 and 1:50,000 prescribing information. North Chicago, IL; 1998 Oct.

133. The American Heart Association in Collaboration with the International Liaison Committee on Resuscitation. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2000; 102(Suppl I)I-123.

134. Food and Drug Administration. Isuprel (isoproterenol HCl) injection [February 23, 2000: Abbott]. MedWatch drug labeling changes. Rockville, MD; February 2000. From FDA website.

135. Abbott Laboratories. Isuprel (Isoproterenol hydrochloride injection, USP 1:5000) prescribing information. North Chicago, IL; 1999 Feb.

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

137. Eigel B. (American Heart Association, Dallas, TX): Personal communication; 2006 Aug 16.

HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:962-7.

a. AHFS Drug Information 2007. McEvoy GK, ed. Isoproterenol. American Society of Health System Pharmacists; 2007:1296-1300

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