Isoproterenol

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Isoproterenol®
Adult Indications and Dosage
Pediatric Indications and Dosage
Contraindications
Warnings
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration and Monitoring
IV Compatibility
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Drug Names
Drug Shortage Status
Price

For patient information regarding Isoproterenol, click here.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Gerald Chi

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Overview

Isoproterenol is a vasopressor that is FDA approved for the treatment of heart block, Adams-Stokes attacks, cardiac arrest until electric shock or pacemaker therapy is available, bronchospasm occurring during anesthesia, and as an adjunct to fluid and electrolyte replacement therapy in hypovolemic and septic shock, low cardiac output (hypoperfusion) states, congestive heart failure, and cardiogenic shock. Common adverse reactions include syncope, tachyarrhythmia, confusion, headache, and tremor.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

  • Isoproterenol hydrochloride injection is indicated:
  • Start Isuprel injection at the lowest recommended dose and increase the rate of administration gradually if necessary while carefully monitoring the patient. The usual route of administration is by intravenous infusion or bolus intravenous injection. In dire emergencies, the drug may be administered by intracardiac injection. If time is not of the utmost importance, initial therapy by intramuscular or subcutaneous injection is preferred.
  • There are no well-controlled studies in children to establish appropriate dosing; however, the American Heart Association recommends an initial infusion rate of 0.1 mcg/kg/min, with the usual range being 0.1 mcg/kg/min to 1 mcg/kg/min.
  • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Such solution should not be used.
Heart Block, Adams-Stokes Attacks, and Cardiac Arrest
  • Dosing Information
This image is provided by the National Library of Medicine.
Shock, Hypoperfusion States, and Bronchospasm Occurring During Anesthesia
  • Dosing Information
This image is provided by the National Library of Medicine.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Acute Symptomatic Bradyarrhythmia
  • Developed by: ACC/AHA
  • Class of Recommendation: Class IIb
  • Strength of Evidence: Category C

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Isoproterenol in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

  • Safety and efficacy of isoproterenol in pediatric patients have not been established.
  • Intravenous infusions of isoproterenol in refractory asthmatic children at rates of 0.05‑2.7 mcg/kg/min have caused clinical deterioration, myocardial necrosis, congestive heart failure and death. The risks of cardiac toxicity appear to be increased by some factors (acidosis, hypoxemia, coadministration of corticosteroids, coadministration of methylxanthines or aminophylline that are especially likely to be present in these patients. If I.V. isoproterenol is used in children with refractory asthma, patient monitoring must include continuous assessment of vital signs, frequent electrocardiography, and daily measurements of cardiac enzymes, including CK-MB.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Isoproterenol in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Isoproterenol in pediatric patients.

Contraindications

Warnings

  • Isoproterenol hydrochloride injection, by increasing myocardial oxygen requirements while decreasing effective coronary perfusion, may have a deleterious effect on the injured or failing heart. Most experts discourage its use as the initial agent in treating cardiogenic shock following myocardial infarction. However, when a low arterial pressure has been elevated by other means, isoproterenol hydrochloride injection may produce beneficial hemodynamic and metabolic effects.
  • In a few patients, presumably with organic disease of the AV node and its branches, isoproterenol hydrochloride injection has paradoxically been reported to worsen heart block or to precipitate Adams-Stokes attacks during normal sinus rhythm or transient heart block.

Precautions

  • Isoproterenol hydrochloride injection should generally be started at the lowest recommended dose. This may be gradually increased if necessary while carefully monitoring the patient. Doses sufficient to increase the heart rate to more than 130 beats per minute may increase the likelihood of inducing ventricular arrhythmias. Such increases in heart rate will also tend to increase cardiac work and oxygen requirements which may adversely affect the failing heart or the heart with a significant degree of arteriosclerosis.
  • Adequate filling of the intravascular compartment by suitable volume expanders is of primary importance in most cases of shock and should precede the administration of vasoactive drugs. In patients with normal cardiac function, determination of central venous pressure is a reliable guide during volume replacement. If evidence of hypoperfusion persists after adequate volume replacement, isoproterenol hydrochloride injection may be given.
  • In addition to the routine monitoring of systemic blood pressure, heart rate, urine flow, and the electrocardiograph, monitor the response to therapy by frequent determination of the central venous pressure and blood gases. Closely observe patients in shock during isoproterenol hydrochloride injection administration. If the heart rate exceeds 110 beats per minute, it may be advisable to decrease the infusion rate or temporarily discontinue the infusion. Determinations of cardiac output and circulation time may also be helpful. Take appropriate measures to ensure adequate ventilation. Pay attention to acid-base balance and to the correction of electrolyte disturbances.

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Clinical Trial Experience of Isoproterenol in the drug label.

Postmarketing Experience

  • The following reactions to isoproterenol hydrochloride injection have been reported:
Cardiovascular

Tachycardia, palpitations, angina, Adams-Stokes attacks, pulmonary edema, hypertension, hypotension, ventricular arrhythmias, tachyarrhythmias.

  • In a few patients, presumably with organic disease of the AV node and its branches, isoproterenol hydrochloride injection has been reported to precipitate Adams-Stokes attacks seizures during normal sinus rhythm or transient heart block.
Neurologic

Nervousness, headache, dizziness, nausea, visual blurring.

Respiratory

Dyspnea.

Miscellaneous

Flushing of the skin, sweating, mild tremors, weakness, pallor.


Drug Interactions

  • Isoproterenol hydrochloride injection and epinephrine should not be administered simultaneously because both drugs are direct cardiac stimulants and their combined effects may induce serious arrhythmias. The drugs may, however, be administered alternately provided a proper interval has elapsed between doses.
  • Avoid Isuprel when potent inhalational anesthetics such as halothane are employed because of potential to sensitize the myocardium to effects of sympathomimetic amines.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

  • Pregnancy Category C
  • Animal reproduction studies have not been conducted with isoproterenol hydrochloride. It is also not known whether isoproterenol hydrochloride can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Isoproterenol hydrochloride should be given to a pregnant woman only if clearly needed.

Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Isoproterenol in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Isoproterenol during labor and delivery.

Nursing Mothers

  • It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when isoproterenol hydrochloride injection is administered to a nursing woman.

Pediatric Use

  • Safety and efficacy of isoproterenol in pediatric patients have not been established.
  • Intravenous infusions of isoproterenol in refractory asthmatic children at rates of 0.05‑2.7 mcg/kg/min have caused clinical deterioration, myocardial necrosis, congestive heart failure and death. The risks of cardiac toxicity appear to be increased by some factors acidosis, hypoxemia, coadministration of corticosteroids, or coadministration of methylxanthines that are especially likely to be present in these patients. If I.V. isoproterenol is used in children with refractory asthma, patient monitoring must include continuous assessment of vital signs, frequent electrocardiography, and daily measurements of cardiac enzymes, including CK-MB.

Geriatic Use

  • Clinical studies of Isuprel did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects in clinical circumstances. There are, however, some data that suggest that elderly healthy or hypertensive patients are less responsive to beta-adrenergic stimulation than are younger subjects. In general, dose selection for elderly patients should usually start at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant diseases or other drug therapy.

Gender

There is no FDA guidance on the use of Isoproterenol with respect to specific gender populations.

Race

There is no FDA guidance on the use of Isoproterenol with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Isoproterenol in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Isoproterenol in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Isoproterenol in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Isoproterenol in patients who are immunocompromised.


Administration and Monitoring

Administration

  • Intravenous

Monitoring

  • Isoproterenol hydrochloride injection should generally be started at the lowest recommended dose. This may be gradually increased if necessary while carefully monitoring the patient.
  • In addition to the routine monitoring of systemic blood pressure, heart rate, urine flow, and the electrocardiograph, monitor the response to therapy by frequent determination of the central venous pressure and blood gases.

IV Compatibility

There is limited information regarding IV Compatibility of Isoproterenol in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

  • The acute toxicity of isoproterenol hydrochloride in animals is much less than that of epinephrine. Excessive doses in animals or man can cause a striking drop in blood pressure, and repeated large doses in animals may result in cardiac enlargement and focal myocarditis.
  • The oral LD50 of isoproterenol hydrochloride in mice is 3,850 mg/kg ± 1,190 mg/kg of pure drug in solution.

Management

Chronic Overdose

There is limited information regarding Chronic Overdose of Isoproterenol in the drug label.

Pharmacology

Isoproterenol.png
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Isoproterenol
Systematic (IUPAC) name
(RS)-4-[1-hydroxy-2-(isopropylamino)ethyl]benzene-1,2-diol
Identifiers
CAS number 7683-59-2
ATC code C01CA02 R03AB02
R03CB01
PubChem 3779
DrugBank DB01064
Chemical data
Formula C11H17NO3 
Mol. mass 211.258 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability  ?
Metabolism  ?
Half life  ?
Excretion  ?
Therapeutic considerations
Pregnancy cat.

C

Legal status

Prescription only

Routes inhaled 80-120μg

Mechanism of Action

  • Isoproterenol is a potent nonselective beta-adrenergic agonist with very low affinity for alpha‑adrenergic receptors. Intravenous infusion of isoproterenol in man lowers peripheral vascular resistance, primarily in skeletal muscle but also in renal and mesenteric vascular beds. Diastolic pressure falls. Renal blood flow is decreased in normotensive subjects but is increased markedly in shock. Systolic blood pressure may remain unchanged or rise, although mean arterial pressure typically falls. Cardiac output is increased because of the positive inotropic and chronotropic effects of the drug in the face of diminished peripheral vascular resistance. The cardiac effects of isoproterenol may lead to palpitations, sinus tachycardia, and more serious arrhythmias; large doses of isoproterenol may cause myocardial necrosis in animals.
  • Isoproterenol relaxes almost all varieties of smooth muscle when the tone is high, but this action is most pronounced on bronchial and gastrointestinal smooth muscle. It prevents or relieves bronchoconstriction, but tolerance to this effect develops with overuse of the drug.
  • In man, isoproterenol causes less hyperglycemia than does epinephrine. Isoproterenol and epinephrine are equally effective in stimulating the release of free fatty acids and energy production.

Structure

  • Isoproterenol hydrochloride is 3,4-Dihydroxy-α-[(isopropylamino)methyl] benzyl alcohol hydrochloride, a synthetic sympathomimetic amine that is structurally related to epinephrine but acts almost exclusively on beta receptors. The molecular formula is C11H17NO3 • HCl. It has a molecular weight of 247.72 and the following structural formula:
This image is provided by the National Library of Medicine.
  • Isoproterenol hydrochloride is a racemic compound.
  • The pH is adjusted between 3.5 and 4.5 with hydrochloric acid or sodium hydroxide.
  • The sterile solution is nonpyrogenic and can be administered by the intravenous, intramuscular, subcutaneous or intracardiac routes.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Isoproterenol in the drug label.

Pharmacokinetics

  • Absorption, Fate, and Excretion
  • Isoproterenol is metabolized primarily in the liver and other tissues by COMT. Isoproterenol is a relatively poor substrate for MAO and is not taken up by sympathetic neurons to the same extent as are epinephrine and norepinephrine. The duration of action of isoproterenol may therefore be longer than that of epinephrine, but is still brief.

Nonclinical Toxicology

  • Carcinogenesis, Mutagenesis, Impairment of Fertility
  • Long-term studies in animals to evaluate the carcinogenic potential of isoproterenol hydrochloride have not been done. Mutagenic potential and effect on fertility have not been determined. There is no evidence from human experience that isoproterenol hydrochloride injection may be carcinogenic or mutagenic or that it impairs fertility.

Clinical Studies

There is limited information regarding Clinical Studies of Isoproterenol in the drug label.

How Supplied

This image is provided by the National Library of Medicine.
  • Protect from light. Keep in opaque container until used.
  • Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]
  • Do not use if the injection is pinkish or darker than slightly yellow or contains a precipitate.


Images

Drug Images

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Package and Label Display Panel

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This image of the FDA label is provided by the National Library of Medicine.
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This image of the FDA label is provided by the National Library of Medicine.

Patient Counseling Information

There is limited information regarding Patient Counseling Information of Isoproterenol in the drug label.

Precautions with Alcohol

  • Alcohol-Isoproterenol interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

Look-Alike Drug Names

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

  1. Neumar, Robert W.; Charles W. Otto, Mark S. Link, Steven L. Kronick, Michael Shuster, Clifton W. Callaway, Peter J. Kudenchuk, Joseph P. Ornato, Bryan McNally, Scott M. Silvers, Rod S. Passman, Roger D. White, Erik P. Hess, Wanchun Tang, Daniel Davis, Elizabeth Sinz, Laurie J. Morrison (2010-11-02). "Part 8: adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care". Circulation 122 (18 Suppl 3): –729-767. doi:10.1161/CIRCULATIONAHA.110.970988. ISSN 1524-4539. PMID 20956224.
  2. Isuprel (isoproterenol hydrochloride) injection, solution.
  3. http://www.ismp.org.

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