Principal Display Panel - 5 Ml Syringe Box Label

Regadenoson injection is a pharmacologic stress agent indicated for radionuclide myocardial perfusion imaging (MPI) in patients unable to undergo adequate exercise stress.

The recommended dose of regadenoson injection is 5 mL (0.4 mg regadenoson) administered as an intravenous injection within 10 seconds. Patients should be instructed to avoid consumption of any products containing methylxanthines, including caffeinated coffee, tea or other caffeinated beverages, caffeine-containing drug products, aminophylline and theophylline for at least 12 hours before a scheduled radionuclide MPI [see Drug Interactions (7.1) and Clinical Pharmacology (12.2) ] . Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer regadenoson injection if it contains particulate matter or is discolored. Administer regadenoson injection as an intravenous 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 injection. 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 injection.

Regadenoson injection is supplied as a sterile, preservative-free, clear and colorless solution containing 0.08 mg/mL regadenoson in the following package: Single-dose 5 mL pre-filled plastic syringes with luer-lock fitting (NDC 0407-5034-05)

Do not administer regadenoson injection to patients with: Second- or third-degree AV block, or sinus node dysfunction unless these patients have a functioning artificial pacemaker [see Warnings and Precautions (5.2) ] .

Regadenoson is an A 2A adenosine receptor agonist that is a coronary vasodilator [see Clinical Pharmacology (12.1) ] . Regadenoson is chemically described as adenosine, 2-[4- [(methylamino)carbonyl]-1 H -pyrazol-1-yl]. Its structural formula is: The molecular formula for regadenoson is C 15 H 18 N 8 O 5 and its molecular weight is 390.35. Regadenoson injection is a sterile, nonpyrogenic solution for intravenous injection. The solution is clear and colorless. Each 1 mL in the 5 mL pre-filled syringe contains 0.08 mg regadenoson on an anhydrous basis, 21.93 mg dibasic sodium phosphate dodecahydrate, 6.11 mg monobasic sodium phosphate dihydrate, 150 mg propylene glycol, 1 mg edetate disodium dihydrate, and water for injection, with pH between 6.3 and 7.7.

No formal pharmacokinetic drug interaction studies have been conducted with regadenoson injection.

Safety and effectiveness in pediatric patients have not been established.

Of the 1,337 patients receiving regadenoson injection in Studies 1 and 2, 56% were 65 years of age and over and 24% were 75 years of age and over. Older patients (≥ 75 years of age) had a similar adverse event profile compared to younger patients ( < 65 years of age), but had a higher incidence of hypotension (2% vs. ≤ 1%).

Regadenoson was negative in the Ames bacterial mutation assay, chromosomal aberration assay in Chinese hamster ovary (CHO) cells, and mouse bone marrow micronucleus assay. Long-term animal studies have not been conducted to evaluate regadenoson injection's carcinogenic potential or potential effects on fertility.

The following adverse reactions are discussed in more detail in other sections of the labeling. Myocardial Ischemia [see Warnings and Precautions (5.1) ] Sinoatrial and Atrioventricular Nodal Block [see Warnings and Precautions (5.2) ] Atrial Fibrillation/Atrial Flutter [see Warnings and Precautions (5.3) ] Hypersensitivity, Including Anaphylaxis [see Warnings and Precautions (5.4) ] Hypotension [see Warnings and Precautions (5.5) ] Hypertension [see Warnings and Precautions (5.6) ] Bronchoconstriction [see Warnings and Precautions (5.7) ] Seizure [see Warnings and Precautions (5.8) ] Cerebrovascular Accident (Stroke) [see Warnings and Precautions (5.9) ]

Regadenoson injection overdosage may result in serious reactions [see Warnings and Precautions (5) ] . In a study of healthy volunteers, symptoms of flushing, dizziness and increased heart rate were assessed as intolerable at regadenoson injection doses greater than 0.02 mg/kg.

Fatal and nonfatal myocardial infarction (MI), ventricular arrhythmias, and cardiac arrest have occurred following regadenoson injection. Avoid use in patients with symptoms or signs of acute myocardial ischemia, for example unstable angina or cardiovascular instability; these patients may be at greater risk of serious cardiovascular reactions to regadenoson injection. Cardiac resuscitation equipment and trained staff should be available before administering regadenoson injection. Adhere to the recommended duration of injection [see Dosage and Administration (2) ] . As noted in an animal study, longer injection times may increase the duration and magnitude of increase in coronary blood flow [see Clinical Pharmacology (12.2) ] . If serious reactions to regadenoson injection occur, consider the use of aminophylline, an adenosine antagonist, to shorten the duration of increased coronary blood flow induced by regadenoson injection [see Overdosage (10) ] .

Single-dose pre-filled syringe: clear, colorless solution containing regadenoson 0.4 mg/5 mL (0.08 mg/mL)

Regadenoson is a low affinity agonist (K i ≈ 1.3 µM) for the A 2A adenosine receptor, with at least 10-fold lower affinity for the A 1 adenosine receptor (K i > 16.5 µM), and weak, if any, affinity for the A 2B and A 3 adenosine receptors. Activation of the A 2A adenosine receptor by regadenoson produces coronary vasodilation and increases coronary blood flow (CBF).

In healthy subjects, the regadenoson plasma concentration-time profile is multi-exponential in nature and best characterized by 3-compartment model. The maximal plasma concentration of regadenoson is achieved within 1 to 4 minutes after injection of regadenoson injection and parallels the onset of the pharmacodynamic response. 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 coinciding with loss of the pharmacodynamic effect. The terminal phase consists of a decline in plasma concentration with a half-life of approximately 2 hours [see Clinical Pharmacology (12.2) ] . Within the dose range of 0.3 to 20 mcg/kg in healthy subjects, clearance, terminal half-life or volume of distribution do not appear dependent upon the dose. A population pharmacokinetic analysis including data from subjects and patients demonstrated that regadenoson clearance decreases in parallel with a reduction in creatinine clearance and clearance increases with increased body weight. Age, gender, and race have minimal effects on the pharmacokinetics of regadenoson.

Myocardial Ischemia. Fatal cardiac events have occurred. Avoid use in patients with symptoms or signs of acute myocardial ischemia, for example unstable angina or cardiovascular instability, who may be at greater risk. Cardiac resuscitation equipment and trained staff should be available before administration ( 5.1 ). Sinoatrial (SA) and Atrioventricular (AV) Nodal Block. Adenosine receptor agonists, including regadenoson injection, can depress the SA and AV nodes and may cause first-, second- or third-degree AV block, or sinus bradycardia ( 5.2 ). Atrial Fibrillation/Atrial Flutter. New-onset or recurrent atrial fibrillation with rapid ventricular response and atrial flutter have been reported ( 5.3 ). Hypersensitivity, including anaphylaxis, angioedema, cardiac or respiratory arrest, respiratory distress, decreased oxygen saturation, hypotension, throat tightness, urticaria, and rashes have occurred. Have personnel and resuscitative equipment immediately available ( 5.4 ). Hypotension. Adenosine receptor agonists, including regadenoson injection, induce vasodilation and hypotension. The risk of serious hypotension may be higher in patients with autonomic dysfunction, stenotic valvular heart disease, pericarditis or pericardial effusions, stenotic carotid artery disease with cerebrovascular insufficiency, or hypovolemia ( 5.5 ). Hypertension. Adenosine receptor agonists, including regadenoson injection, may induce clinically significant increases in blood pressure particularly in patients with a history of hypertension and when the MPI includes low level exercise ( 5.6 ). Bronchoconstriction. Adenosine receptor agonists, including regadenoson injection, may induce dyspnea, bronchoconstriction and respiratory compromise in patients with chronic obstructive pulmonary disease (COPD) or asthma. Resuscitative measures should be available ( 5.7 ). Seizure. Regadenoson injection may lower the seizure threshold. New onset or recurrence of convulsive seizures has occurred. Some seizures are prolonged and require urgent anticonvulsive management. Methylxanthine use is not recommended in patients who experience a seizure in association with regadenoson injection ( 5.8 ). Cerebrovascular Accident (Stroke). Hemorrhagic and ischemic cerebrovascular accidents have occurred ( 5.9 ).

Store at controlled room temperature, 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature].

GE Healthcare NDC 0407-5034-05 Rx Only Regadenoson Injection 0.4 mg/5 mL (0.08 mg/mL) For Intravenous Use Only 10 x 5 mL Single-dose Pre-filled Syringes Pharmacologic Stress Agent For Diagnostic Purpose Only Inject 5 mL intravenously within 10 seconds. Follow immediately with saline flush and radiopharmaceutical. Syringe may require needle or blunt. Each mL contains: 0.08 mg regadenoson, 21.93 mg dibasic sodium phosphate dodecahydrate, 6.11 mg monobasic sodium phosphate dihydrate, 150 mg propylene glycol, 1 mg edetate disodium dihydrate, and water for injection. Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Medication and fluid path are sterile and nonpyrogenic if protective cover is undisturbed and package is intact. Preservative-free. Discard unused portion. Distributed by GE Healthcare Inc. Marlborough, MA 01752 USA For inquiries call 1-800-654-0118 USE ASEPTIC TECHNIQUE Remove luer cover. Hold plunger and push barrel forward to relieve any resistance that may be present. Pull the barrel down until air is expelled from the syringe.

No dose adjustment is needed in patients with renal impairment including patients with end stage renal disease and/or dependent on dialysis [see Pharmacokinetics (12.3) ].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. During clinical development, 1,651 patients were exposed to regadenoson injection, with most receiving 0.4 mg as a rapid (≤ 10 seconds) intravenous injection. Most of these patients received regadenoson injection in two clinical studies that enrolled patients who had no history of bronchospastic lung disease as well as no history of a cardiac conduction block of greater than first-degree AV block, except for patients with functioning artificial pacemakers. In these studies (Studies 1 and 2), 2,015 patients underwent myocardial perfusion imaging after administration of regadenoson injection (N = 1,337) or Adenoscan (N = 678). The population was 26 to 93 years of age (median 66 years), 70% male and primarily Caucasian (76% Caucasian, 7% African American, 9% Hispanic, 5% Asian). Table 1 shows the most frequently reported adverse reactions. Overall, any adverse reaction occurred at similar rates between the study groups (80% for the regadenoson injection group and 83% for the Adenoscan group). Aminophylline was used to treat the reactions in 3% of patients in the regadenoson injection group and 2% of patients in the Adenoscan group. Most adverse reactions began soon after dosing, and generally resolved within approximately 15 minutes, except for headache which resolved in most patients within 30 minutes. Table 1 Adverse Reactions in Studies 1 and 2 Pooled (Frequency ≥ 5%) Regadenoson Injection N = 1,337 Adenoscan N = 678 Dyspnea 28% 26% Headache 26% 17% Flushing 16% 25% Chest Discomfort 13% 18% Angina Pectoris or ST Segment Depression 12% 18% Dizziness 8% 7% Chest Pain 7% 10% Nausea 6% 6% Abdominal Discomfort 5% 2% Dysgeusia 5% 7% Feeling Hot 5% 8%

The following adverse reactions have been reported from worldwide marketing experience with regadenoson. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Regadenoson injection is a pharmacologic stress agent indicated for radionuclide myocardial perfusion imaging (MPI) in patients unable to undergo adequate exercise stress.

The recommended dose of regadenoson injection is 5 mL (0.4 mg regadenoson) administered as an intravenous injection within 10 seconds. Patients should be instructed to avoid consumption of any products containing methylxanthines, including caffeinated coffee, tea or other caffeinated beverages, caffeine-containing drug products, aminophylline and theophylline for at least 12 hours before a scheduled radionuclide MPI [see Drug Interactions (7.1) and Clinical Pharmacology (12.2) ] . Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer regadenoson injection if it contains particulate matter or is discolored. Administer regadenoson injection as an intravenous 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 injection. 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 injection.

Regadenoson injection is supplied as a sterile, preservative-free, clear and colorless solution containing 0.08 mg/mL regadenoson in the following package: Single-dose 5 mL pre-filled plastic syringes with luer-lock fitting (NDC 0407-5034-05)

Do not administer regadenoson injection to patients with: Second- or third-degree AV block, or sinus node dysfunction unless these patients have a functioning artificial pacemaker [see Warnings and Precautions (5.2) ] .

No formal pharmacokinetic drug interaction studies have been conducted with regadenoson injection.

Safety and effectiveness in pediatric patients have not been established.

Of the 1,337 patients receiving regadenoson injection in Studies 1 and 2, 56% were 65 years of age and over and 24% were 75 years of age and over. Older patients (≥ 75 years of age) had a similar adverse event profile compared to younger patients ( < 65 years of age), but had a higher incidence of hypotension (2% vs. ≤ 1%).

Regadenoson was negative in the Ames bacterial mutation assay, chromosomal aberration assay in Chinese hamster ovary (CHO) cells, and mouse bone marrow micronucleus assay. Long-term animal studies have not been conducted to evaluate regadenoson injection's carcinogenic potential or potential effects on fertility.

The following adverse reactions are discussed in more detail in other sections of the labeling. Myocardial Ischemia [see Warnings and Precautions (5.1) ] Sinoatrial and Atrioventricular Nodal Block [see Warnings and Precautions (5.2) ] Atrial Fibrillation/Atrial Flutter [see Warnings and Precautions (5.3) ] Hypersensitivity, Including Anaphylaxis [see Warnings and Precautions (5.4) ] Hypotension [see Warnings and Precautions (5.5) ] Hypertension [see Warnings and Precautions (5.6) ] Bronchoconstriction [see Warnings and Precautions (5.7) ] Seizure [see Warnings and Precautions (5.8) ] Cerebrovascular Accident (Stroke) [see Warnings and Precautions (5.9) ]

Regadenoson injection overdosage may result in serious reactions [see Warnings and Precautions (5) ] . In a study of healthy volunteers, symptoms of flushing, dizziness and increased heart rate were assessed as intolerable at regadenoson injection doses greater than 0.02 mg/kg.

Regadenoson is an A 2A adenosine receptor agonist that is a coronary vasodilator [see Clinical Pharmacology (12.1) ] . Regadenoson is chemically described as adenosine, 2-[4- [(methylamino)carbonyl]-1 H -pyrazol-1-yl]. Its structural formula is: The molecular formula for regadenoson is C 15 H 18 N 8 O 5 and its molecular weight is 390.35. Regadenoson injection is a sterile, nonpyrogenic solution for intravenous injection. The solution is clear and colorless. Each 1 mL in the 5 mL pre-filled syringe contains 0.08 mg regadenoson on an anhydrous basis, 21.93 mg dibasic sodium phosphate dodecahydrate, 6.11 mg monobasic sodium phosphate dihydrate, 150 mg propylene glycol, 1 mg edetate disodium dihydrate, and water for injection, with pH between 6.3 and 7.7.

Fatal and nonfatal myocardial infarction (MI), ventricular arrhythmias, and cardiac arrest have occurred following regadenoson injection. Avoid use in patients with symptoms or signs of acute myocardial ischemia, for example unstable angina or cardiovascular instability; these patients may be at greater risk of serious cardiovascular reactions to regadenoson injection. Cardiac resuscitation equipment and trained staff should be available before administering regadenoson injection. Adhere to the recommended duration of injection [see Dosage and Administration (2) ] . As noted in an animal study, longer injection times may increase the duration and magnitude of increase in coronary blood flow [see Clinical Pharmacology (12.2) ] . If serious reactions to regadenoson injection occur, consider the use of aminophylline, an adenosine antagonist, to shorten the duration of increased coronary blood flow induced by regadenoson injection [see Overdosage (10) ] .

Single-dose pre-filled syringe: clear, colorless solution containing regadenoson 0.4 mg/5 mL (0.08 mg/mL)

Regadenoson is a low affinity agonist (K i ≈ 1.3 µM) for the A 2A adenosine receptor, with at least 10-fold lower affinity for the A 1 adenosine receptor (K i > 16.5 µM), and weak, if any, affinity for the A 2B and A 3 adenosine receptors. Activation of the A 2A adenosine receptor by regadenoson produces coronary vasodilation and increases coronary blood flow (CBF).

In healthy subjects, the regadenoson plasma concentration-time profile is multi-exponential in nature and best characterized by 3-compartment model. The maximal plasma concentration of regadenoson is achieved within 1 to 4 minutes after injection of regadenoson injection and parallels the onset of the pharmacodynamic response. 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 coinciding with loss of the pharmacodynamic effect. The terminal phase consists of a decline in plasma concentration with a half-life of approximately 2 hours [see Clinical Pharmacology (12.2) ] . Within the dose range of 0.3 to 20 mcg/kg in healthy subjects, clearance, terminal half-life or volume of distribution do not appear dependent upon the dose. A population pharmacokinetic analysis including data from subjects and patients demonstrated that regadenoson clearance decreases in parallel with a reduction in creatinine clearance and clearance increases with increased body weight. Age, gender, and race have minimal effects on the pharmacokinetics of regadenoson.

Myocardial Ischemia. Fatal cardiac events have occurred. Avoid use in patients with symptoms or signs of acute myocardial ischemia, for example unstable angina or cardiovascular instability, who may be at greater risk. Cardiac resuscitation equipment and trained staff should be available before administration ( 5.1 ). Sinoatrial (SA) and Atrioventricular (AV) Nodal Block. Adenosine receptor agonists, including regadenoson injection, can depress the SA and AV nodes and may cause first-, second- or third-degree AV block, or sinus bradycardia ( 5.2 ). Atrial Fibrillation/Atrial Flutter. New-onset or recurrent atrial fibrillation with rapid ventricular response and atrial flutter have been reported ( 5.3 ). Hypersensitivity, including anaphylaxis, angioedema, cardiac or respiratory arrest, respiratory distress, decreased oxygen saturation, hypotension, throat tightness, urticaria, and rashes have occurred. Have personnel and resuscitative equipment immediately available ( 5.4 ). Hypotension. Adenosine receptor agonists, including regadenoson injection, induce vasodilation and hypotension. The risk of serious hypotension may be higher in patients with autonomic dysfunction, stenotic valvular heart disease, pericarditis or pericardial effusions, stenotic carotid artery disease with cerebrovascular insufficiency, or hypovolemia ( 5.5 ). Hypertension. Adenosine receptor agonists, including regadenoson injection, may induce clinically significant increases in blood pressure particularly in patients with a history of hypertension and when the MPI includes low level exercise ( 5.6 ). Bronchoconstriction. Adenosine receptor agonists, including regadenoson injection, may induce dyspnea, bronchoconstriction and respiratory compromise in patients with chronic obstructive pulmonary disease (COPD) or asthma. Resuscitative measures should be available ( 5.7 ). Seizure. Regadenoson injection may lower the seizure threshold. New onset or recurrence of convulsive seizures has occurred. Some seizures are prolonged and require urgent anticonvulsive management. Methylxanthine use is not recommended in patients who experience a seizure in association with regadenoson injection ( 5.8 ). Cerebrovascular Accident (Stroke). Hemorrhagic and ischemic cerebrovascular accidents have occurred ( 5.9 ).

Store at controlled room temperature, 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature].

GE Healthcare NDC 0407-5034-05 Rx Only Regadenoson Injection 0.4 mg/5 mL (0.08 mg/mL) For Intravenous Use Only 10 x 5 mL Single-dose Pre-filled Syringes Pharmacologic Stress Agent For Diagnostic Purpose Only Inject 5 mL intravenously within 10 seconds. Follow immediately with saline flush and radiopharmaceutical. Syringe may require needle or blunt. Each mL contains: 0.08 mg regadenoson, 21.93 mg dibasic sodium phosphate dodecahydrate, 6.11 mg monobasic sodium phosphate dihydrate, 150 mg propylene glycol, 1 mg edetate disodium dihydrate, and water for injection. Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Medication and fluid path are sterile and nonpyrogenic if protective cover is undisturbed and package is intact. Preservative-free. Discard unused portion. Distributed by GE Healthcare Inc. Marlborough, MA 01752 USA For inquiries call 1-800-654-0118 USE ASEPTIC TECHNIQUE Remove luer cover. Hold plunger and push barrel forward to relieve any resistance that may be present. Pull the barrel down until air is expelled from the syringe.

No dose adjustment is needed in patients with renal impairment including patients with end stage renal disease and/or dependent on dialysis [see Pharmacokinetics (12.3) ].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. During clinical development, 1,651 patients were exposed to regadenoson injection, with most receiving 0.4 mg as a rapid (≤ 10 seconds) intravenous injection. Most of these patients received regadenoson injection in two clinical studies that enrolled patients who had no history of bronchospastic lung disease as well as no history of a cardiac conduction block of greater than first-degree AV block, except for patients with functioning artificial pacemakers. In these studies (Studies 1 and 2), 2,015 patients underwent myocardial perfusion imaging after administration of regadenoson injection (N = 1,337) or Adenoscan (N = 678). The population was 26 to 93 years of age (median 66 years), 70% male and primarily Caucasian (76% Caucasian, 7% African American, 9% Hispanic, 5% Asian). Table 1 shows the most frequently reported adverse reactions. Overall, any adverse reaction occurred at similar rates between the study groups (80% for the regadenoson injection group and 83% for the Adenoscan group). Aminophylline was used to treat the reactions in 3% of patients in the regadenoson injection group and 2% of patients in the Adenoscan group. Most adverse reactions began soon after dosing, and generally resolved within approximately 15 minutes, except for headache which resolved in most patients within 30 minutes. Table 1 Adverse Reactions in Studies 1 and 2 Pooled (Frequency ≥ 5%) Regadenoson Injection N = 1,337 Adenoscan N = 678 Dyspnea 28% 26% Headache 26% 17% Flushing 16% 25% Chest Discomfort 13% 18% Angina Pectoris or ST Segment Depression 12% 18% Dizziness 8% 7% Chest Pain 7% 10% Nausea 6% 6% Abdominal Discomfort 5% 2% Dysgeusia 5% 7% Feeling Hot 5% 8%

The following adverse reactions have been reported from worldwide marketing experience with regadenoson. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.