LEXISCAN SIDE EFFECTS
- Generic Name: regadenoson injection
- Brand Name: Lexiscan
- Drug Class: How Do Diagnosing Imaging Agents Work?
SIDE EFFECTS
The following adverse reactions are discussed in more detail in other sections of the labeling.
- Myocardial Ischemia
- Sinoatrial and Atrioventricular Nodal Block
- Atrial Fibrillation/Atrial Flutter
- Hypersensitivity, Including Anaphylaxis
- Hypotension
- Hypertension
- Bronchoconstriction
- Seizure
- Cerebrovascular Accident (Stroke)
Clinical Trials Experience
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 LEXISCAN, with most receiving 0.4 mg as a rapid (≤ 10 seconds) intravenous injection. Most of these patients received LEXISCAN 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 (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). Table 1 shows the most frequently reported adverse reactions.
Overall, any adverse reaction occurred at similar rates between the study groups (80% for the LEXISCAN group and 83% for the ADENOSCAN group). Aminophylline was used to treat the reactions in 3% of patients in the LEXISCAN 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%)
| LEXISCAN 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% |
ECG Abnormalities
The frequency of rhythm or conduction abnormalities following LEXISCAN or ADENOSCAN is shown in Table 2.
Table 2 Rhythm or Conduction Abnormalities* in Studies 1 and 2
| LEXISCAN N / N evaluable (%) |
ADENOSCAN N / N evaluable (%) |
|
| Rhythm or conduction abnormalities† | 332/1275 (26%) | 192/645 (30%) |
| Rhythm abnormalities | 260/1275 (20%) | 131/645 (20%) |
| PACs | 86/1274 (7%) | 57/645 (9%) |
| PVCs | 179/1274 (14%) | 79/645 (12%) |
| First-degree AV block (PR prolongation > 220 msec) | 34/1209 (3%) | 43/618 (7%) |
| Second-degree AV block | 1/1209 (0.1%) | 9/618 (1%) |
| AV conduction abnormalities (other than AV blocks) | 1/1209 (0.1%) | 0/618 (0%) |
| Ventricular conduction abnormalities | 64/1152 (6%) | 31/581 (5%) |
| * 12-lead ECGs were recorded before and for up to 2 hours after dosing. † includes rhythm abnormalities (PACs, PVCs, atrial fibrillation/flutter, wandering atrial pacemaker, supraventricular or ventricular arrhythmia) or conduction abnormalities, including AV block. |
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Respiratory Abnormalities
In a randomized, placebo-controlled trial of 999 patients 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 group compared to the placebo group (p < 0.001). Most respiratory adverse reactions resolved without therapy; a few patients 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 FEV1 (Table 3).
Table 3 Respiratory Adverse Effects*
| Asthma Cohort | Chronic Obstructive Pulmonary Disease (COPD) Cohort | |||
| LEXISCAN (N=356) |
Placebo (N=176) |
LEXISCAN (N=316) |
Placebo (N=151) |
|
| Overall Pre-specified Respiratory Adverse Reaction† | 12.9% | 2.3% | 19.0% | 4.0% |
| Dyspnea | 10.7% | 1.1% | 18.0% | 2.6% |
| Wheezing | 3.1% | 1.1% | 0.9% | 0.7% |
| FEV1 reduction >15%‡ | 1.1% | 2.9% | 4.2% | 5.4% |
| * All patients continued the use of their respiratory medications as prescribed prior to administration of LEXISCAN. † Patients may have reported more than one type of adverse reaction. Adverse reactions were collected up to 24 hours following drug administration. Pre-specified respiratory adverse reactions included dyspnea, wheezing, obstructive airway disorder, dyspnea exertional, and tachypnea. ‡ Change from baseline at 2 hours. |
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Renal Impairment
In a randomized, placebo-controlled trial of 504 patients (LEXISCAN 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 m2), no serious adverse events were reported through the 24-hour follow-up period.
Inadequate Exercise Stress
In an open-label, multi-center trial evaluating LEXISCAN administration following inadequate exercise stress, 1,147 patients were randomized into one of two groups. Each group underwent two LEXISCAN stress myocardial perfusion imaging (MPI) procedures. Group 1 received LEXISCAN 3 minutes following inadequate exercise in the first LEXISCAN stress (MPI 1). Group 2 rested 1 hour after inadequate exercise to allow hemodynamics to return to baseline prior to receiving LEXISCAN (MPI 1). Both groups returned for a second stress MPI 1-14 days later and received LEXISCAN without exercise (MPI 2).
The most common adverse reactions are similar in type and incidence to those in Table 1 above for both Groups. The timing of the administration of LEXISCAN following inadequate exercise did not alter the common adverse reaction profile.
Table 4 shows a comparison of cardiac events of interest for the two groups. The cardiac events were numerically higher in Group 1.
Table 4 Cardiac Events of Interest in Inadequate Exercise Stress Study
| Cardiac Event* | Group 1 / MPI 1 LEXISCAN 3 minutes following exercise (N=575) |
Group 2 / MPI 1 LEXISCAN 1 hour following exercise (N=567) |
| Holter/12-Lead ECG Abnormality | 17 (3.0%) | 3 (0.5%) |
| ST-T Depression (≥ 2 mm) | 13 (2.3%) | 2 (0.4%) |
| ST-T Elevation (≥ 1 mm) | 3 (0.5%) | 1 (0.2%) |
| Acute coronary syndrome | 1 (0.2%) | 0 |
| Myocardial infarction | 1 (0.2%) | 0 |
| * A clinically significant cardiac event was defined as any of the following events found on the Holter ECG/12-lead ECG within one hour after regadenoson administration: ventricular arrhythmias (sustained ventricular tachycardia, ventricular fibrillation, Torsade de Pointes, ventricular flutter); ST-T depression (≥ 2 mm); ST-T elevation (≥ 1 mm); AV block (2:1 AV block, AV Mobitz I, AV Mobitz II, complete heart block); sinus arrest > 3 seconds in duration Or
Or
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Post-Marketing Experience
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.
Cardiovascular
Myocardial infarction, cardiac arrest, ventricular arrhythmias, supraventricular tachyarrhythmias including atrial fibrillation with rapid ventricular response (new-onset or recurrent), atrial flutter, heart block (including thirddegree block), asystole, marked hypertension, symptomatic hypotension in association with transient ischemic attack, acute coronary syndrome (ACS), seizures and syncope have been reported. Some events required intervention with fluids and/or aminophylline. QTc prolongation shortly after LEXISCAN administration has been reported.
Central Nervous System
Tremor, seizure, transient ischemic attack, and cerebrovascular accident including intracranial hemorrhage [see WARNINGS AND PRECAUTIONS].
Gastrointestinal
Abdominal pain, occasionally severe, has been reported a few minutes after LEXISCAN 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 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 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 administration.
SRC: NLM .