arbutamine hydrochloride
GenESA

Available forms
Available by prescription only
Injection: 20-ml prefilled syringe containing a total of 1 mg (0.05 mg/ml)

Indications and dosages
 Single-dose diagnostic aid in patients with suspected coronary artery disease (CAD) who cannot exercise adequately (stress induction with arbutamine is indicated as an aid in diagnosing the presence or absence of CAD). Adults: Dose is calculated and delivered via the GenESA Device, a closed-loop, computer-controlled, I.V. infusion device. This device initially delivers 0.1 mcg/kg/minute for 1 minute and adjusts dosage until maximal heart rate limit (target heart rate set by user) is achieved or to maximum infusion rate of 0.8 mcg/kg/minute (maximum total dose 10 mcg/kg).

Pharmacodynamics
Sympathomimetic diagnostic aid action: By increasing cardiac work through positive chronotropic and inotropic actions, arbutamine acts as a cardiac stress agent to mimic exercise and provoke myocardial ischemia in patients with compromised coronary arteries. Beta-agonist activity provides cardiac stress by increasing heart rate, contractility and systolic blood pressure; alpha-receptor activity decreases the potential for hypotension.

Pharmacokinetics
Absorption: Administered I.V.
Distribution: Because of sensitivity limitations of drug assay, pharmacokinetics have been characterized for first 20 to 30 minutes after stopping infusion. Apparent volume of distribution is 0.74 L/kg and plasma half-life is about 8 minutes. Drug is 58% bound to plasma proteins.
Metabolism: Drug is metabolized hepatically to methoxyarbutamine.
Excretion: Drug is 75% eliminated by metabolism to methoxyarbutamine, which is then excreted in either a free or conjugated form in the urine. After I.V. infusion, 84% of total dose is excreted in the urine and 9% in the feces within 48 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and in patients with idiopathic hypertrophic subaortic stenosis, a history of recurrent sustained ventricular tachycardia, or heart failure (New York Heart Association class III or IV). Also contraindicated in patients with an implanted cardiac pacemaker or automated cardioverter or defibrillator. Drug contains sodium metabisulfite, a sulfite that may produce an allergic response in susceptible patients.
  Avoid use of drug in patients with unstable angina, mechanical left ventricular outflow obstruction (such as severe valvular aortic stenosis), uncontrolled systemic hypertension, cardiac transplant, history of cerebrovascular disease, angle-closure glaucoma, or uncontrolled hyperthyroidism or in those receiving class I agents such as quinidine, lidocaine, or flecainide.

Interactions
Drug-drug. Atropine, digoxin, tricyclic antidepressants: May interfere with arbutamine’s effect on heart rate. Avoid use together.
Beta blockers: May attenuate arbutamine effects. Discontinue at least 48 hours before giving arbutamine.

Adverse reactions
CNS: anxiety, dizziness, fatigue, headache, hypoesthesia, pain, paresthesia, tremor.
CV: angina pectoris, ARRHYTHMIAS, chest pain, flushing, hypotension, hot flashes, palpitations, vasodilation.
GI: nausea, dry mouth, taste perversion.
Respiratory: dyspnea.
Skin: increased sweating.

Effects on lab test results
• May decrease potassium level.

Overdose and treatment
Risk of drug overdose is low, given the rapid onset and short half-life of drug and controlled administration. Signs and symptoms of overdose are those of catecholamine excess, such as tremor, headache, flushing, hypotension, dizziness, paresthesia, nausea, hot flashes, angina, increased sweating and anxiety, tachyarrhythmias, hypertension, MI, and ventricular fibrillation.
 Management of overdose should include cessation of infusion, establishment of an airway, and adequate oxygenation. Severe signs and symptoms may be treated with I.V. beta blocker such as metoprolol (7.5 to 50 mg), esmolol (10 to 80 mg), or propranolol (0.5 to 2 mg). Sublingual nitrates should be considered if clinically appropriate.

Special considerations
• Don’t dilute drug, and administer only via the prefilled syringe using the GenESA Device.
• Before using the GenESA Device, it is essential to read and understand the manufacturer’s directions for use.
• Don’t administer atropine to enhance drug-induced chronotropic response; coadministration may lead to tachyarrhythmias.
• Monitor blood pressure, heart rate, and a diagnostic quality ECG continuously throughout drug infusion with cardiac emergency supplies available.
• Transient prolongation of corrected QT interval, as measured from surface ECG, occurs with administration. However, this doesn’t appear to be linked with an increased risk of arrhythmias.
• Transient reductions in serum potassium levels can occur but rarely to hypokalemic levels.
• Safety and efficacy of drug in patients with recent history (within 30 days) of an MI haven’t been evaluated; don’t use drug in these patients.
Breast-feeding patients
• It’s unknown whether drug appears in breast milk; avoid use in breast-feeding women.

Patient education
• Tell patient to discontinue use of beta blockers at least 48 hours before test.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use