Arbutamine (Systemic)

Primary: AU100
Secondary: CV053

Commonly used brand name(s): GenESA.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

Not commercially available in Canada.


Diagnostic aid, coronary artery disease—



Coronary artery disease (CAD) (diagnosis)—Arbutamine, administered through a closed-loop, computer-controlled drug-delivery system, is indicated to elicit acute cardiovascular responses, similar to those produced by exercise, in order to aid in diagnosing the presence or absence of CAD in patients who cannot exercise adequately {01}. Arbutamine must not be administered without the use of the approved computer-controlled device {01}. Cardiac stress testing with arbutamine always must be performed under the direct supervision of a physician, and cardiac emergency equipment and supplies, such as a defibrillator and intravenous beta-adrenergic blocking agents, must be available {01}.


Physicochemical characteristics:

Chemical group—
    Catecholamine {01}.
Molecular weight—
    353.85 {01}

Mechanism of action/Effect:

Arbutamine is a synthetic catecholamine with positive chronotropic and inotropic properties {01}. The chronotropic (increase in heart rate [HR]) and inotropic (increase in force of contraction) effects of arbutamine serve to mimic exercise by increasing cardiac work (producing stress) and provoke myocardial ischemia in patients with compromised coronary arteries {01}. The increase in HR caused by arbutamine is thought to limit regional subendocardial perfusion, thereby limiting tissue oxygenation {01}. In functional assays, arbutamine is more selective for beta-adrenergic receptors than for alpha-adrenergic receptors {01}. The beta-agonist activity of arbutamine provides cardiac stress by increasing HR, cardiac contractility, and systolic blood pressure {01}. The degree of hypotension that occurs for a given chronotropic activity is less with arbutamine than, for example, with isoproterenol because alpha receptor activity is retained {01}.


Volume of distribution (Vol D)—0.74 liters per kg (L/kg) {01}.

Protein binding:

Moderate (approximately 58%) {01}.


Arbutamine is primarily metabolized to methoxyarbutamine {01}. Another possible metabolite is ketoarbutamine {01}. The metabolites of arbutamine appear to have a longer half-life and less pharmacological activity than arbutamine {01}.



Approximately 8 minutes {01}.

    Renal—84% {01}.
    Fecal—9% {01}.

In dialysis—
        Arbutamine is rapidly eliminated and in cases of overdose, peritoneal or hemodialysis may not be required {01}.

Precautions to Consider


No carcinogenicity tests have been performed with arbutamine {01}.


Arbutamine was not found to be genotoxic in the Ames microbial mutagen test with or without S9 mix, nor in the mouse micronucleus test {01}. However, arbutamine was found to be genotoxic in the human lymphocyte chromosomal aberration assay (> 66 mcg per mL [mcg/mL]) and in the mouse lymphoma cell assay (> 39 mcg/mL) {01}.

Adequate and well-controlled studies in humans to determine the effect of arbutamine on fertility have not been done {01}.

Although no adequate and well-controlled studies in pregnant women have been done, reproduction studies performed in rats and rabbits given intravenous doses of arbutamine of up to 0.9 and 0.36 mg per kg of body weight (mg/kg) per day, respectively, revealed no evidence of harm to the fetus {01}. These doses represent 4 and 12 times, respectively, the maximum recommended human dose (MRHD) on a mg per square meter of body surface area (mg/m 2) basis {01}.

FDA Pregnancy Category B {01}.


Problems in humans have not been documented.


No information is available on the relationship of age to the effects of arbutamine in pediatric patients. Safety and efficacy have not been established.


No information is available on the relationship of age to the effects of arbutamine in geriatric patients.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

» Beta-adrenergic blocking agents {01}    (concurrent use may blunt the response to arbutamine {01}; beta-adrenergic blocking agents should be withdrawn at least 48 hours before conducting an arbutamine-mediated stress test {01})

» Antiarrhythmic agents, class I {01} , such as:
» Flecainide {01} or
» Lidocaine {01} or
» Quinidine {01}    (concurrent use with arbutamine may have a proarrhythmic effect and is not recommended {01})

» Antidepressants, tricyclic {01} or
» Atropine or other anticholinergic agents {01} or
» Digitalis glycosides {01}    (concurrent use with arbutamine may produce additive inotropic and/or chronotropic effects {01})

Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Potassium, serum {01}    (transient decreases have occurred, but hypokalemia is rare {01})

Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).

Except under special circumstances, this medication should not be used when the following medical problems exist:
» Congestive heart failure, New York Heart Association (NYHA) class III or IV {01} or
» Hypertrophic subaortic stenosis, idiopathic {01} or
» Ventricular tachycardia, recurrent sustained, history of {01}    (the inotropic and/or chronotropic effects of arbutamine in these patients may worsen the existing condition or, in the case of a history of recurrent sustained ventricular tachycardia, may precipitate ventricular arrhythmias {01})

» Cardiac pacemaker, implanted {01} or
» Cardioverter/defibrillator, automated, present {01}
» Hypersensitivity to arbutamine {01}
Risk-benefit should be considered when the following medical problems exist
Angina, unstable {01} or
Cardiac transplant {01} or
Cerebrovascular accident, history of {01} or
Glaucoma, narrow-angle {01} or
Hypertension, uncontrolled {01} or
Hyperthyroidism, uncontrolled {01} or
Left ventricular outflow obstruction, mechanical, such as
Aortic stenosis, valvular, severe {01} or
Peripheral vascular disorder resulting in cerebral or aortic aneurysm, history of {01}    (the inotropic and chronotropic effects of arbutamine may exacerbate the existing condition and its use in these patients is not recommended {01})

Arrhythmias, supraventricular or ventricular, sustained, history of {01}    (use of arbutamine in these patients is not recommended because it may precipitate the arrhythmia {01})

Myocardial infarction, recent (within 30 days) {01}    (use of arbutamine in these patients has not been evaluated {01})

Sensitivity to sulfites {01}    (arbutamine injection contains sodium metabisulfite, which may cause allergic- or anaphylactic-type reactions and life-threatening or less severe asthmatic episodes in individuals who are sensitive to sulfites {01}; sensitivity to sulfites is more common in asthmatic patients than in nonasthmatic patients {01})

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

» Blood pressure, systolic {01}    (monitored continuously by the computerized drug-delivery device {01}; arbutamine may cause rapid increases or paradoxical decreases in systolic blood pressure {01})

» Electrocardiogram (ECG) {01}    (continuous monitoring is recommended {01}; although the device provides monitoring capabilities, it is not designed to detect arrhythmias and a diagnostic-quality ECG machine also must be used {01}; arbutamine infusion has been associated with a transient increase in the corrected QT interval [QTc], as measured from the surface ECG; however, this effect does not appear to be associated with an increased incidence of arrhythmias {01})

» Heart rate (HR) {01}    (the HR response of the patient is measured by the device {01}; the HR slope [rate of rise] and target HR are chosen by the physician and are based on the desired duration of the test and the desired rate of HR rise {01}; following the completion of the test after the HR target has been reached or after a total of 10 mcg per kg of body weight [mcg/kg] of arbutamine has been administered, the patient's HR should be monitored until it has returned to an acceptable level {01}; in clinical trials, after termination of the infusion, HR decreased by 50% within 13 to 16 minutes {01}. Arbutamine may cause rapid increases or paradoxical decreases in HR {01}; it is possible that upon the occurrence of an arrhythmia, the device may record an inaccurate heart rate {01})

Side/Adverse Effects

Note: Supraventricular and ventricular arrhythmias, most commonly, isolated premature ventricular and atrial contractions, have occurred with administration of arbutamine {01}. In clinical trials, most of the arrhythmias that occurred were self-limiting and all arrhythmias resolved without further effects {01}. Although the overall incidence of serious adverse events was low (0.5%), 10 serious adverse events occurred: three episodes of ventricular fibrillation, one episode of sustained ventricular tachycardia, three episodes of atrial fibrillation, one event of myocardial infarction, and two cases of severe angina {01}. Two of the three cases of ventricular fibrillation occurred after the delivery device had detected a plateau in heart rate (HR) response and had terminated the arbutamine infusion, but the physician restarted the infusion {01}. No deaths occurred {01}.
Arbutamine may cause rapid increases or paradoxical decreases in heart rate and systolic blood pressure {01}.
Arbutamine injection contains sodium metabisulfite, which may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain individuals {01}.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention

Note: Many side/adverse effects are similar to those of arbutamine toxicity. See Clinical effects of overdose section.

Incidence more frequent
Angina pectoris{01} (chest pain, severe)—incidence 12%{01}
cardiac arrhythmias, ventricular and supraventricular{01} —incidence 12%
headache{01} —incidence 9%{01}
hypotension{01} (dizziness, lightheadedness, or fainting)—incidence 6%{01}
tremor{01} —incidence 15%{01}

Incidence less frequent
chest pain{01} —incidence 4%{01}
dizziness{01} —incidence 4%
dry mouth{01}
dyspnea{01} (difficult or labored breathing)—incidence 4%
fatigue{01} (unusual tiredness)
flushing or hot flushes{01} (redness of face)—incidence 3%
hypoesthesia{01} (decreased touch sensation)
nausea{01} —incidence 3%
pain, nonspecific{01}
palpitations{01} (heartbeat sensations)—incidence 4%
paresthesia{01} (burning or tingling skin sensation)
sweating, increased{01}
taste perversion{01} (change in sense of taste)

Incidence rare
myocardial ischemia{01}
skin rash{01}
ST segment depression{01}

For specific information on the agents used in the management of arbutamine overdose, see:    • Esmolol (Systemic) monograph; and/or
   • Metoprolol or Propranolol in Beta-adrenergic Blocking Agents (Systemic) monograph; and/or
   • Nitroglycerin or Isosorbide Dinitrate in Nitrates (Systemic) monograph.

For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Angina pectoris {01}
anxiety {01}
dizziness {01}
flushing or hot flushes {01}
headache {01}
hypertension {01}
hypotension {01}
myocardial infarction {01}
nausea {01}
paresthesia {01}
ST segment abnormalities {01}
sweating, increased {01}
tachyarrhythmias {01}
tremor {01}
ventricular fibrillation {01}

Treatment of overdose
The maximum total dose of arbutamine permitted by the drug delivery device is 10 mcg per kg of body weight (mcg/kg) {01}. Arbutamine is metabolized and eliminated rapidly; therefore, an overdosage should be of short duration and forced diuresis, peritoneal dialysis, hemodialysis, or charcoal hemoperfusion is unlikely to be required {01}. If arbutamine is ingested, absorption from the mouth and gastrointestinal tract may be unpredictable {01}.

Initial treatment—Arbutamine should be discontinued and an airway established to ensure adequate oxygenation and ventilation {01}.

Specific treatment—Severe signs or symptoms, such as angina, tachyarrhythmias, ST segment abnormalities, or hypotension, may be treated with an intravenous beta-adrenergic blocking agent, such as esmolol, metoprolol, or propranolol {01}. Other treatment, such as sublingual nitrates, should be used if appropriate and necessary {01}.

General Dosing Information
Arbutamine is intended for direct intravenous infusion only with the approved drug delivery device {01}. The device has a single-channel electrocardiogram (ECG) (R wave) detector, a noninvasive blood pressure monitor, computer software (closed-loop algorithm) that controls drug delivery, an intravenous syringe pump, display functions, and an operator key pad {01}. ECG, heart rate (HR), blood pressure, and dosing information are displayed continuously {01}. The device uses visual and auditory alerts and alarms to warn of conditions that may require attention and can stop drug delivery if a potential safety hazard is detected {01}.

The drug delivery device is not designed to detect arrhythmias, and appropriate monitoring equipment, such as a diagnostic-quality ECG machine, must be used during a patient test {01}.

For treatment of adverse effects
Recommended treatment consists of the following:    • If any arrhythmia occurs that is of clinical concern, administration of arbutamine should be stopped immediately and appropriate therapy administered, if necessary {01}.

Parenteral Dosage Forms


Note: Refer to the manufacturer's labeling for complete operating instructions and directions for use of the drug delivery system for administration of arbutamine {01}.

Usual adult dose
Diagnostic aid, coronary artery disease (CAD)
Intravenous infusion, up to a maximum of 10 mcg per kg of body weight as administered by the drug delivery device {01}.

Drug delivery by the device:
The delivery device, using a closed-loop algorithm, individualizes the dosing regimen of arbutamine according to the heart rate (HR) response of the patient {01}. Initially, the device administers a small dose of arbutamine (0.1 mcg per kg of body weight [mcg/kg] per minute for one minute) and measures the patient's HR response {01}. The device calculates the difference between the desired and actual HR response, and maintains or modifies, as necessary, the infusion rate {01}. The physician conducting the test may manually interrupt the delivery of arbutamine at any time, if clinically appropriate {01}. The infusion of arbutamine may be restarted by the operator if the condition resulting in the interruption of infusion has been corrected, a diagnostic end point has not been reached, and it is considered safe and appropriate to do so {01}.

Heart rate selection and monitoring:
The physician selects the desired rate of HR rise (HR slope) and the maximum HR to be achieved (HR target) for each patient test {01}:

HR slope—
Low (four beats per minute per minute [bpm/min]), medium (eight bpm/min), or high (twelve bpm/min) (or any value from four to twelve bpm/min may be selected), based upon the desired duration of the test and the rate of HR rise that is determined by the physician to be most appropriate {01}. Clinical data, obtained using an HR slope of eight bpm/min, support the use of a medium slope in a majority of patients {01}.

HR target—
Estimated by the device as 85% of (220 - age), or adjusted manually by the operator {01}.

The device has a feature (“Hold HR”) that allows the HR to be maintained at an approximate level for up to five minutes {01}. The maximal HR response to arbutamine, determined by a flattening or plateau of the HR response to increasing doses of arbutamine (“HR saturation”), is an end point of the stress test {01}. If such a flattening or plateau is detected when the HR is £ forty bpm above the baseline level, restart of the infusion is allowed by the device {01}. If the HR is > forty bpm above baseline and an “HR saturation” alarm occurs, restart of the arbutamine infusion is prevented by the device because any further clinically significant increases in HR are unlikely to occur following restart and there is a potential risk for serious cardiac arrhythmias {01}.

Termination of the infusion:
The infusion of arbutamine should be terminated when a diagnostic end point (e.g., ST segment deviation on ECG) has been reached, if clinically significant symptoms or arrhythmias occur, or if clinically appropriate for any other reason {01}. The device will stop drug delivery when the HR target has been reached or after a total 10 mcg/kg of arbutamine has been delivered {01}. Following completion of the infusion, the patient should be monitored (using the device or other means), until HR and blood pressure have returned to acceptable levels {01}.

Usual adult prescribing limits
The maximum infusion rate delivered by the device is 0.8 mcg per kg of body weight per minute (mcg/kg/min) and the maximum total dose permitted by the device is 10 mcg/kg {01}.

Usual pediatric dose
Diagnostic aid, CAD
Safety and efficacy have not been established.

Strength(s) usually available

0.05 mg per mL (Rx) [GenESA (20 mL prefilled syringe. Each syringe contains 1 mg of arbutamine hydrochloride)]

Packaging and storage:
Store between 2 and 8 ºC (36 and 46 ºF) {01}. Protect from light {01}. Protect from freezing.

Preparation of dosage form:
Arbutamine must be administered from the prefilled syringe and must not be diluted or transferred to another syringe {01}.

Arbutamine injection should be inspected visually for particulate matter and discoloration prior to administration {01}.

Developed: 04/26/1998

  1. GenESA package insert (Gensia Automedics—U.S.), New 8/97, Rec 2/98.