Lexiscan

Diagnostic Agents, Other

NOTE: Prior to administration of the stress test, screen all candidates for their suitability to receive the drug and have ready access to cardiac resuscitation equipment and a trained medical staff.

Visually inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit. Regadenoson solution is clear and colorless. Do not administer if particulate matter or discoloration is present.
Prefilled syringes are for single use only.

Administer as an IV injection within 10 seconds into a peripheral vein using a 22 gauge or larger catheter or needle.
Administer a 5 mL saline flush immediately after the injection of regadenoson.
Administer the radionuclide myocardial perfusion imaging agent 10 to 20 seconds after the saline flush. The radionuclide may be injected directly into the same catheter as regadenoson.

bronchospasm / Rapid / 4.0-12.0
AV block / Early / 0.1-3.0
anaphylactic shock / Rapid / 0-1.0
anaphylactoid reactions / Rapid / 0-1.0
respiratory arrest / Rapid / 0-1.0
angioedema / Rapid / 0-1.0
myocardial infarction / Delayed / 0.2-0.2
cardiac arrest / Early / Incidence not known
bradycardia / Rapid / Incidence not known
atrial flutter / Early / Incidence not known
atrial fibrillation / Early / Incidence not known
asystole / Rapid / Incidence not known
stroke / Early / Incidence not known
seizures / Delayed / Incidence not known
intracranial bleeding / Delayed / Incidence not known

sinus tachycardia / Rapid / 5.0-22.0
dyspnea / Early / 10.7-18.0
premature ventricular contractions (PVCs) / Early / 14.0-14.0
angina / Early / 12.0-12.0
chest pain (unspecified) / Early / 7.0-7.0
hypotension / Rapid / 2.0-7.0
hypertension / Early / 0.5-4.6
wheezing / Rapid / 0.9-3.1
QT prolongation / Rapid / Incidence not known
tachypnea / Early / Incidence not known
fecal incontinence / Early / Incidence not known

headache / Early / 26.0-26.0
flushing / Rapid / 5.0-16.0
dizziness / Early / 8.0-8.0
premature atrial contractions (PACs) / Early / 7.0-7.0
nausea / Early / 6.0-6.0
abdominal pain / Early / 5.0-5.0
dysgeusia / Early / 5.0-5.0
urticaria / Rapid / 0-1.0
rash / Early / 0-1.0
syncope / Early / Incidence not known
diarrhea / Early / Incidence not known
vomiting / Early / Incidence not known
tremor / Early / Incidence not known
back pain / Delayed / Incidence not known
musculoskeletal pain / Early / Incidence not known
myalgia / Early / Incidence not known

Lexiscan, Regadenoson

Rx

A2A adenosine receptor agonist
Used as pharmacologic stress agent in radionuclide myocardial perfusion imaging
Alternative to adenosine for diagnosing coronary artery disease

0.4 mg IV once.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Acetaminophen; Aspirin, ASA; Caffeine: (Major) Caffeine is a non-specific adenosine receptor antagonist and can interfere with the efficacy of regadenoson. Patients should avoid consumption of any products containing caffeine (including caffeine from foods and beverages such as coffee, green tea, other teas, colas, and chocolate) for at least 12 hours before regadenoson administration.
Acetaminophen; Caffeine: (Major) Caffeine is a non-specific adenosine receptor antagonist and can interfere with the efficacy of regadenoson. Patients should avoid consumption of any products containing caffeine (including caffeine from foods and beverages such as coffee, green tea, other teas, colas, and chocolate) for at least 12 hours before regadenoson administration.
Acetaminophen; Caffeine; Dihydrocodeine: (Major) Caffeine is a non-specific adenosine receptor antagonist and can interfere with the efficacy of regadenoson. Patients should avoid consumption of any products containing caffeine (including caffeine from foods and beverages such as coffee, green tea, other teas, colas, and chocolate) for at least 12 hours before regadenoson administration.
Acetaminophen; Caffeine; Pyrilamine: (Major) Caffeine is a non-specific adenosine receptor antagonist and can interfere with the efficacy of regadenoson. Patients should avoid consumption of any products containing caffeine (including caffeine from foods and beverages such as coffee, green tea, other teas, colas, and chocolate) for at least 12 hours before regadenoson administration.
Aspirin, ASA; Butalbital; Caffeine: (Major) Caffeine is a non-specific adenosine receptor antagonist and can interfere with the efficacy of regadenoson. Patients should avoid consumption of any products containing caffeine (including caffeine from foods and beverages such as coffee, green tea, other teas, colas, and chocolate) for at least 12 hours before regadenoson administration.
Aspirin, ASA; Caffeine: (Major) Caffeine is a non-specific adenosine receptor antagonist and can interfere with the efficacy of regadenoson. Patients should avoid consumption of any products containing caffeine (including caffeine from foods and beverages such as coffee, green tea, other teas, colas, and chocolate) for at least 12 hours before regadenoson administration.
Aspirin, ASA; Caffeine; Orphenadrine: (Major) Caffeine is a non-specific adenosine receptor antagonist and can interfere with the efficacy of regadenoson. Patients should avoid consumption of any products containing caffeine (including caffeine from foods and beverages such as coffee, green tea, other teas, colas, and chocolate) for at least 12 hours before regadenoson administration.
Aspirin, ASA; Dipyridamole: (Major) Dipyridamole may change the effects of regadenoson. Although the effects are not specified, this may be due to dipyridamole's coronary vasodilatory action. When possible, withhold dipyridamole for at least two days prior to the administration of regadenoson.
Butalbital; Acetaminophen; Caffeine: (Major) Caffeine is a non-specific adenosine receptor antagonist and can interfere with the efficacy of regadenoson. Patients should avoid consumption of any products containing caffeine (including caffeine from foods and beverages such as coffee, green tea, other teas, colas, and chocolate) for at least 12 hours before regadenoson administration.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Caffeine is a non-specific adenosine receptor antagonist and can interfere with the efficacy of regadenoson. Patients should avoid consumption of any products containing caffeine (including caffeine from foods and beverages such as coffee, green tea, other teas, colas, and chocolate) for at least 12 hours before regadenoson administration.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Caffeine is a non-specific adenosine receptor antagonist and can interfere with the efficacy of regadenoson. Patients should avoid consumption of any products containing caffeine (including caffeine from foods and beverages such as coffee, green tea, other teas, colas, and chocolate) for at least 12 hours before regadenoson administration.
Caffeine: (Major) Caffeine is a non-specific adenosine receptor antagonist and can interfere with the efficacy of regadenoson. Patients should avoid consumption of any products containing caffeine (including caffeine from foods and beverages such as coffee, green tea, other teas, colas, and chocolate) for at least 12 hours before regadenoson administration. (Major) Regadenoson may cause an increased coronary blood flow without regard to prior caffeine ingestion. Patients should avoid consumption of any products containing caffeine (including caffeine from foods and beverages such as coffee, green tea, other teas, colas, and chocolate) for at least 12 hours before regadenoson administration.
Caffeine; Sodium Benzoate: (Major) Caffeine is a non-specific adenosine receptor antagonist and can interfere with the efficacy of regadenoson. Patients should avoid consumption of any products containing caffeine (including caffeine from foods and beverages such as coffee, green tea, other teas, colas, and chocolate) for at least 12 hours before regadenoson administration.
Digoxin: (Major) Because of the potential for additive or synergistic depressant effects on SA and AV nodes, regadenoson should be used with caution in the presence of agents that slow cardiac conduction, such as digoxin.
Dipyridamole: (Major) Dipyridamole may change the effects of regadenoson. Although the effects are not specified, this may be due to dipyridamole's coronary vasodilatory action. When possible, withhold dipyridamole for at least two days prior to the administration of regadenoson.
Ergotamine; Caffeine: (Major) Caffeine is a non-specific adenosine receptor antagonist and can interfere with the efficacy of regadenoson. Patients should avoid consumption of any products containing caffeine (including caffeine from foods and beverages such as coffee, green tea, other teas, colas, and chocolate) for at least 12 hours before regadenoson administration.
Green Tea: (Major) Caffeine is a non-specific adenosine receptor antagonist and can interfere with the efficacy of regadenoson. Patients should avoid consumption of any products containing caffeine (including caffeine from foods and beverages such as coffee, green tea, other teas, colas, and chocolate) for at least 12 hours before regadenoson administration.
Nicotine: (Major) Nicotine has been reported to enhance the cardiovascular effects of adenosine receptor agonists; an increase in angina-like chest pain, heart rate, or a decrease in blood pressure may be noted. While no special cautions are recommended for regadenoson, it may be advisable for patients to avoid nicotine products or tobacco prior to electrophysiologic studies or stress testing where adenosine receptor agonists will be administered.
Theophylline, Aminophylline: (Major) Methylxanthines, such as theophylline or aminophylline, are non-specific adenosine receptor antagonists and may interfere with the vasodilation activity of adenosine receptor agonists, such as regadenoson. Patients should avoid any drugs containing theophylline, aminophylline for at least 12 hours before regadenoson administration. Methylxanthines attenuate the duration, but not the peak increase of coronary blood flow produced by regadenoson; aminophylline may be used to attenuate severe or persistent adverse reactions of regadenoson. Aminophylline injected 1 minute after regadenoson in subjects undergoing cardiac catheterization was shown to shorten the duration of the coronary blood flow response as measured by pulsed-wave Doppler ultrasonography. In addition, theophylline, aminophylline may increase the risk of seizures associated with regadenoson; avoid methylxanthine use in patients who have experienced a regadenoson-associated seizure.
Trandolapril; Verapamil: (Major) Because of the potential for additive or synergistic depressant effects on SA and AV nodes, regadenoson should be used with caution in the presence of agents that slow cardiac conduction, such as verapamil.
Verapamil: (Major) Because of the potential for additive or synergistic depressant effects on SA and AV nodes, regadenoson should be used with caution in the presence of agents that slow cardiac conduction, such as verapamil.

Lexiscan/Regadenoson Intravenous Inj Sol: 0.08mg, 1mL

0.4 mg IV single dose.

0.4 mg IV single dose.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Regadenoson is a low affinity agonist for the A2A adenosine receptors on arteriolar vascular smooth muscle. Activation of the A2A adenosine receptors by regadenoson produces coronary vasodilation and increases coronary blood flow.
 
Although the exact mechanism by which adenosine receptor activation relaxes vascular smooth muscle is not known, there is evidence to support both inhibition of the slow inward calcium current reducing calcium uptake, and activation of adenylate cyclase through A2 receptors in smooth muscle cells. Activation of these receptors may also lessen vascular tone by modulating sympathetic neurotransmission.
 
Regadenoson causes a rapid increase in coronary blood flow, which is sustained for a short duration due to its low affinity for the A2A adenosine receptors. In a study, increases in blood flow velocity peaked within 0.5 to 2.3 minutes, while the average duration of an increase in blood flow of at least 2-fold was 8.5 minutes (ranging from 0.1 to 31 minutes). Myocardial uptake of the radiopharmaceutical is directly proportional to coronary blood flow. Because regadenoson increases blood flow in normal coronary arteries with little or no increase in stenotic arteries, there is relatively less uptake of the radiopharmaceutical in vascular territories supplied by stenotic arteries as compared to normal arteries.
 
Coronary vasodilation is primarily generated by the activation of the A2A and A2B adenosine receptors. Stimulation of the A1 and A3 adenosine receptors is generally associated with side effects of adenosine vasodilator stress including chest pain, dyspnea, bronchoconstriction, and conduction abnormalities. Regadenoson has increased selectivity for the A2A adenosine receptors with at least 10-fold lower affinity for the A1 adenosine receptors, and weak, if any, affinity for the A2B and A3 adenosine receptors. However, in a phase III trial, patients reported chest pain and dyspnea with regadenoson, suggesting that these side effects may be due to regadenoson-induced sympathetic stimulation rather than solely mediated by A1 adenosine receptor activation.

Regadenoson is administered as a rapid intravenous injection. Terminal half-life and volume of distribution do not appear dependent upon the dose. The metabolism is unknown in humans; incubation with rat, dog, and human liver microsomes as well as human hepatocytes produced no detectable metabolites of regadenoson. In healthy volunteers, 57% (range 19% to 77%) of the dose is excreted unchanged in the urine, with an average plasma renal clearance around 450 mL/minute in excess of the glomerular filtration rate. This indicates that renal tubular secretion plays a role in regadenoson elimination.
 
Affected cytochrome P450 isoenzymes and drug transporters: none
Regadenoson is not known to be a substrate, inhibitor, or inducer of CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4 in human liver microsomes; additionally, renal tubular secretion may be involved in regadenoson elimination, although whether regadenoson interacts with other drugs that also undergo renal tubular secretion is not known.

Following intravenous administration, the plasma concentration-time profile is best characterized by a 3-compartment model. Initially, maximal plasma concentrations are achieved within 1 to 4 minutes. The half-life of this initial phase is approximately 2 to 4 minutes. An intermediate phase follows, with a half-life on average of 30 minutes that coincides with loss of the pharmacodynamic effect. The terminal phase consists of a decline in plasma concentration with a half-life of approximately 2 hours. Terminal half-life and volume of distribution do not appear dependent upon the dose.

There are no data describing regadenoson use in human pregnancy to inform a drug-associated risk. Adverse developmental outcomes were observed in animal reproductive studies. Regadenoson doses at 10- to 20-times the maximum recommended human dose (MRHD) caused reduced fetal body weights, ossification delays in limb phalanges and metatarsals, and maternal toxicity. Maternal toxicity occurred in rabbits at doses 4-times the MRHD; maternal toxicity, increased embryo-fetal loss, and fetal malformations were noted with regadenoson doses 12- and 20-times the MRHD.

There is no information on the presence of regadenoson in human milk or the effects of regadenoson on the breast-fed infant or milk production. Because of the potential risk of serious cardiac reactions in the breast-fed infant, advise the breast-feeding mother to pump and discard breast milk for 10 hours after regadenoson administration.