Lexiscan Information
Lexiscan (Regadenoson) Indications And Usage
Lexiscan (Regadenoson) injection is a pharmacologic stress agent indicated for radionuclide myocardial perfusion imaging (MPI) in patients unable to undergo adequate exercise stress.
Lexiscan (Regadenoson) Dosage And Administration
The recommended intravenous dose of Lexiscan (Regadenoson) is 5 mL (0.4 mg regadenoson)
NOTE: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer Lexiscan (Regadenoson) if it contains particulate matter or is discolored.
Lexiscan (Regadenoson) Contraindications
Do not administer Lexiscan (Regadenoson) to patients with:
unless these patients have a functioning artificial pacemaker [].
Lexiscan (Regadenoson) Warnings And Precautions
Anaphylaxis, angioedema, cardiac or respiratory arrest, respiratory distress, decreased oxygen saturation, hypotension, throat tightness, urticaria and rashes have occurred. In clinical trials, hypersensitivity reactions were reported in fewer than 1 percent of patients [s]. Have personnel and resuscitative equipment immediately available.
Adenosine receptor agonists, including Lexiscan (Regadenoson) , may cause dyspnea, bronchoconstriction, and respiratory compromise. Appropriate bronchodilator therapy and resuscitative measures should be available prior to Lexiscan (Regadenoson) administration [].
Lexiscan (Regadenoson) Adverse Reactions
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 subjects were exposed to Lexiscan (Regadenoson) , with most receiving 0.4 mg as a rapid (≤ 10 seconds) intravenous injection. Most of these subjects received Lexiscan (Regadenoson) 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 Lexiscan (Regadenoson) (N = 1,337) or Adenoscan(N = 678). The population was 26–93 years of age (median 66 years), 70% male and primarily Caucasian (76% Caucasian, 7% African American, 9% Hispanic, 5% Asian). shows the most frequently reported adverse reactions.
Overall, any adverse reaction occurred at similar rates between the study groups (80% for the Lexiscan (Regadenoson) group and 83% for the Adenoscan group). Aminophylline was used to treat the reactions in 3% of patients in the Lexiscan (Regadenoson) 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.
ECG Abnormalities
The frequency of rhythm or conduction abnormalities following Lexiscan (Regadenoson) or Adenoscan is shown in [see ()].
Respiratory Abnormalities
In a randomized, placebo-controlled trial (Study 3) of 999 subjects with asthma (n=532) or stable chronic obstructive pulmonary disease (n=467), the overall incidence of pre-specified respiratory adverse reactions was greater in the Lexiscan (Regadenoson) group compared to the placebo group (p < 0.001). Most respiratory adverse reactions resolved without therapy; a few subjects received aminophylline or a short acting bronchodilator. No differences were observed between treatment arms in the reduction of >15% from baseline at two-hours in FEV ()
Renal Impairment
In a randomized, placebo-controlled trial of 504 subjects (Lexiscan (Regadenoson) n=334 and placebo n=170) with a diagnosis or risk factors for coronary artery disease and NKFK/DOQI Stage III or IV renal impairment (defined as GFR 15-59 mL/min/1.73 m), no serious adverse events were reported through the 24-hour follow-up period.
Cardiovascular
Heart block (including third degree block), asystole, marked hypertension, symptomatic hypotension in association with transient ischemic attack, seizures and syncope [
], requiring intervention with fluids and/or aminophylline have occurred. QTc prolongation shortly after Lexiscan (Regadenoson) administration has been reported.
Central Nervous System
Tremor, seizure (particularly with a history of seizure)
Gastrointestinal
Abdominal pain, occasionally severe, has been reported a few minutes after Lexiscan (Regadenoson) administration, in association with nausea, vomiting, or myalgias; administration of aminophylline, an adenosine antagonist, appeared to lessen the pain. Diarrhea and fecal incontinence have also been reported following Lexiscan (Regadenoson) administration.
Hypersensitivity
Anaphylaxis, angioedema, cardiac or respiratory arrest, respiratory distress, decreased oxygen saturation, hypotension, throat tightness, urticaria, rashes have occurred and have required treatment including resuscitation [].
Musculoskeletal
Musculoskeletal pain has occurred, typically 10-20 minutes after Lexiscan (Regadenoson) administration; the pain was occasionally severe, localized in the arms and lower back and extended to the buttocks and lower legs bilaterally. Administration of aminophylline appeared to lessen the pain.
Respiratory
Respiratory arrest, dyspnea and wheezing have been reported following Lexiscan (Regadenoson) administration.
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 Lexiscan (Regadenoson) exposure.
Lexiscan (Regadenoson) Drug Interactions
No formal pharmacokinetic drug interaction studies have been conducted with Lexiscan (Regadenoson) .
Lexiscan (Regadenoson) Overdosage
Lexiscan (Regadenoson) overdosage may result in serious reactions []. In a study of healthy volunteers, symptoms of flushing, dizziness and increased heart rate were assessed as intolerable at Lexiscan (Regadenoson) doses greater than 0.02 mg/kg.
Lexiscan (Regadenoson) Description
Regadenoson is an A adenosine receptor agonist that is a coronary vasodilator []. Regadenoson is chemically described as adenosine, 2-[4-[(methylamino)carbonyl]-1-pyrazol-1-yl]-, monohydrate. Its structural formula is:
The molecular formula for regadenoson is CHNO• HO and its molecular weight is 408.37.
Lexiscan (Regadenoson) is a sterile, nonpyrogenic solution for intravenous injection. The solution is clear and colorless. Each pre-filled syringe contains 0.084 mg of regadenoson monohydrate, corresponding to 0.08 mg regadenoson on an anhydrous basis, 10.9 mg dibasic sodium phosphate dihydrate or 8.7 mg dibasic sodium phosphate anhydrous, 5.4 mg monobasic sodium phosphate monohydrate, 150 mg propylene glycol, 1 mg edetate disodium dihydrate, and Water for Injection, with pH between 6.3 and 7.7.
Lexiscan (Regadenoson) Clinical Pharmacology
In healthy volunteers, 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 Lexiscan (Regadenoson) 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 []. Within the dose range of 0.3–20 µg/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.
Lexiscan (Regadenoson) Nonclinical Toxicology
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 Lexiscan (Regadenoson) 's carcinogenic potential or potential effects on fertility.
Lexiscan (Regadenoson) Clinical Studies
The efficacy and safety of Lexiscan (Regadenoson) were determined relative to Adenoscan in two randomized, double-blind studies (Studies 1 and 2) in 2,015 patients with known or suspected coronary artery disease who were indicated for pharmacologic stress MPI. A total of 1,871 of these patients had images considered valid for the primary efficacy evaluation, including 1,294 (69%) men and 577 (31%) women with a median age of 66 years (range 26–93 years of age). Each patient received an initial stress scan using Adenoscan (6-minute infusion using a dose of 0.14 mg/kg/min, without exercise) with a radionuclide gated SPECT imaging protocol. After the initial scan, patients were randomized to either Lexiscan (Regadenoson) or Adenoscan, and received a second stress scan with the same radionuclide imaging protocol as that used for the initial scan. The median time between scans was 7 days (range of 1–104 days).
The most common cardiovascular histories included hypertension (81%), CABG, PTCA or stenting (51%), angina (63%), and history of myocardial infarction (41%) or arrhythmia (33%); other medical history included diabetes (32%) and COPD (5%). Patients with a recent history of serious uncontrolled ventricular arrhythmia, myocardial infarction, or unstable angina, a history of greater than first-degree AV block, or with symptomatic bradycardia, sick sinus syndrome, or a heart transplant were excluded. A number of patients took cardioactive medications on the day of the scan, including β-blockers (18%), calcium channel blockers (9%), and nitrates (6%). In the pooled study population, 68% of patients had 0–1 segments showing reversible defects on the initial scan, 24% had 2–4 segments, and 9% had ≥ 5 segments.
Lexiscan (Regadenoson) How Supplied/storage And Handling
Lexiscan (Regadenoson) is supplied as a sterile, preservative-free solution containing 0.08 mg/mL regadenoson in the following package:
Lexiscan (Regadenoson) Patient Counseling Information
Patients with COPD or asthma should be informed to discuss their respiratory history and administration of pre-and post-study bronchodilator therapy with their clinician before scheduling an MPI study with Lexiscan (Regadenoson) .
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Syringes Manufactured by:
Only Lexiscan (Regadenoson) is the trademark of Astellas US, LLC. Other trademarks listed belong to their respective owners.
Revised: October 2011
11H061-LEX-SPL
Lexiscan (Regadenoson) Principal Display Panel
