Lexiscan & Adenoscan Emerging Litigation

Brand name: Lexiscan

Generic name: Regadenoson

Manufacturer: Astellas Pharma US Inc.

  • Lexiscan is an A2A adenosine receptor agonist indicated for use as a pharmacologic stress agent in radionuclide myocardial perfusion imaging (MPI), a test that detects and characterizes coronary artery disease, in patients unable to undergo adequate exercise stress.
  • An intravenous (IV) medication that is administered to patients undergoing a cardiac stress test. This test measures blood-flow to the heart muscle during exercise and at rest. About 50% of people who need a cardiac stress test are unable to exercise due to an underlying medical condition. For these patients, a medication like Lexiscan is used to stress the heart muscle and simulate exercise. Doctors take pictures of the heart before and after administering Lexiscan. These images can help diagnose coronary artery disease.

What is the problem with Lexiscan? Lexiscan causes blood vessels to dilate, which increases blood-flow through healthy arteries that are not obstructed. The problem is that this can significantly reduce blood-flow through a narrow artery, which can cause a life-threatening or fatal heart attack.

DOSAGE AND ADMINISTRATION: The recommended intravenous dose of Lexiscan is 5 mL (0.4 mg regadenoson)

  • Administer Lexiscan as a rapid (approximately 10 seconds) injection into a peripheral vein using a 22 gauge or larger catheter or needle
  • Administer a 5 mL saline flush immediately after the injection of Lexiscan
  • Administer the radionuclide myocardial perfusion imaging agent 10–20 seconds after the saline flush. The radionuclide may be injected directly into the same catheter as Lexiscan

DOSAGE FORMS AND STRENGTHS: Single-use pre-filled syringe: Injection solution containing regadenoson 0.4 mg/5 mL (0.08 mg/mL).

CONTRAINDICATIONS: Do not administer Lexiscan to patients with: Second- or third- degree AV block, or Sinus node dysfunction; unless these patients have a functioning artificial pacemaker

Drug Interactions:

·         Methylxanthine, e.g., caffeine, aminophylline and theophylline, interfere with the activity of Lexiscan

·         Aminophylline may be used to attenuate severe and/or persistent adverse reactions to Lexiscan

·         Dipyridamole may increase the activity of Lexiscan. When possible, withhold dipyridamole for at least two days prior to Lexiscan administration

Other cardiac nuclear stress test agents include:

    • Intravenous dipyridamole (FDA-approved for use during cardiac stress test)
    • Dobutamine (not FDA-approved for use during cardiac stress test)

FDA:

FDA approved: Yes (First approved April 10th, 2008)

RECENT MAJOR CHANGES

Warnings and Precautions, Myocardial Ischemia – 10/2013: 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

Warnings and Precautions, Atrial Fibrillation/Atrial Flutter 07/2014: New-onset or recurrent atrial fibrillation with rapid ventricular response and atrial flutter have been reported

Warnings and Precautions, Seizure 07/2014: Lexiscan 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 Lexiscan

Warnings and Precautions, Cerebrovascular Accident 07/2014: Hemorrhagic and ischemic cerebrovascular accidents have occurred

Lexiscan (Regadenoson) and Adenoscan (Adenosine): Drug Safety Communication – FDA warns of Rare but Serious Risk of Heart Attack and Death: (Posted on 11/20/2013)

Safety Announcement: The U.S. Food and Drug Administration (FDA) warning health care professionals of the rare but serious risk of heart attack and death with use of the cardiac nuclear stress test agents Lexiscan (regadenoson) and Adenoscan (adenosine). We have approved changes to the drug labels to reflect these serious events and updated our recommendations for use of these agents. Health care professionals should avoid using these drugs in patients with signs or symptoms of unstable angina or cardiovascular instability, as these patients may be at greater risk for serious cardiovascular adverse reactions.

Lexiscan and Adenoscan are FDA approved for use during cardiac nuclear stress tests in patients who cannot exercise adequately. Lexiscan and Adenoscan help identify coronary artery disease. They do this by dilating the arteries of the heart and increasing blood flow to help identify blocks or obstructions in the heart’s arteries. Lexiscan and Adenoscan cause blood to flow preferentially to the healthier, unblocked or unobstructed arteries, which can reduce blood flow in the obstructed artery. In some cases, this reduced blood flow can lead to a heart attack, which can be fatal.

The Warnings & Precautions section of the Lexiscan and Adenoscan labels previously contained information about the possible risk of heart attack and death with use of these drugs. However, recent reports of serious adverse events in the FDA Adverse Event Reporting System (FAERS) database and the medical literature prompted approval changes to the drug labels to include updated recommendations for use.

RECOMMENDATIONS: Screen all nuclear stress test candidates for their suitability to receive Lexiscan or Adenoscan. Avoid using these drugs in patients with signs or symptoms of unstable angina or cardiovascular instability, as these patients may be at greater risk for serious cardiovascular adverse reactions. Cardiac resuscitation equipment and trained staff should be available before administering Lexiscan or Adenoscan.

Adverse Events:

·         Myocardial Ischemia

·         Sinoatrial and Atrioventricular Nodal Block

·         Atrial Fibrillation/Atrial Flutter

·         Hypersensitivity, Including Anaphylaxis

·         Hypotension

·         Hypertension

·         Bronchoconstriction

·         Seizure

·         Cerebrovascular Accident (Stroke)

The most common (incidence ≥5%) adverse reactions to Lexiscan are dyspnea, headache, flushing, chest discomfort, dizziness, angina pectoris, chest pain, and nausea

Lexiscan Evaluation Criteria:

1. Whether the patient underwent cardiac stress test/myocardial perfusion imaging (MPI) using Lexiscan?

2. Reason for Lexiscan administration?

3. Dosage and Administration details

4. Did the patient have any pre-existing conditions, allergies or contraindications for Lexiscan (Other drug interactions)

5. What was the injury due to Lexiscan administration?

6. When and where was the injury diagnosed? Whether hospitalized? Dates of hospitalization?

  • Treatment/management. Any complications
  • Follow-up visits for treatment/management of injury.
  • Outcome/prognosis. Resolution of injury?

Specific Focus

Identify and report cases with the following scenarios:-

  1. No Injuries: Patient underwent cardiac stress test (With Lexiscan administration) but did not develop any injuries
  2. No Lexiscan administration: Patient was given a different drug and not Lexiscan. Hold case and communicate to client.
  3. Lexiscan contraindicated in patient but still prescribed
  4. Any medical/surgical history, social history that could have had an effect on the injury 

Missing Record Communication:

Identify and report on missing medical records

Apart from identifying critical missing records that are important for the case, provide a detailed outline on what records are needed, why we need them, how did we get a clue that these records are missing and whether the records missing are confirmatory/probable. This will also help in following up and retrieving the records.

Missing Records are presented in the following format

lexiscan-records

 

 

Adenoscan (Adenosine) is a medication that is used during cardiac stress tests, which are used to diagnose heart disease by testing blood-flow to the heart during exercise and at rest. About 50% of people who undergo a cardiac stress test are unable to use a treadmill or stationary bike, and they must be given a medication like Adenoscan, which stresses the heart without exercise.

Problems with Adenoscan and Cardiac Stress Tests

Adenoscan significantly increases blood-flow in coronary arteries (vessels that supply the heart muscle with oxygenated blood). In people who have obstructed or narrow coronary arteries, Adenoscan may cause blood to flow preferentially through healthy, unobstructed arteries. This can cut off the blood-flow to a narrow artery, which can cause a heart attack or death.

Generic Name and Formulations: Adenosine 3mg/mL; soln for IV infusion; preservative-free.

Company: Astellas Pharma US, Inc.

Indications for ADENOSCAN: Adjunct to thallium-201 myocardial perfusion scintigraphy in patients unable to undergo adequate exercise stress.

Adult Dose for ADENOSCAN: Give peripherally as a continuous IV infusion. ≥18yrs: 140microgram/kg/min over 6 minutes for a total dose of 0.84mg/kg. Infusion rate (mL/min)= 0.140 (mg/kg/min) x total body weight (kg)/adenosine conc. (3mg/mL)

Children’s Dose for ADENOSCAN: <18yrs: Not recommended.

Contraindications: Sinus bradycardia. 2nd– or 3rd-degree AV block, sick sinus syndrome, unless paced. Bronchospastic disease (eg, asthma)

Interactions: May be potentiated by β-blockers, cardiac glycosides, calcium channel blockers; use caution. Antagonized by methylxanthine (eg, caffeine, theophylline). Potentiated by dipyridamole.

FDA

Initial U.S. Approval: 1995

RECENT MAJOR CHANGES:

Warnings and Precautions: Cardiac Arrest, Ventricular Arrhythmias, and Myocardial Infarction 10/2013: Fatal cardiac events have occurred. Avoid use in patients with symptoms or signs of acute myocardial ischemia. Appropriate resuscitative measures should be available

Warnings and Precautions: Cerebrovascular Accidents 8/2014: Hemorrhagic and ischemic cerebrovascular accidents have occurred

Warnings and Precautions: Seizures 8/2014: New onset or recurrence of convulsive seizures has occurred. Use of methylxanthine (e.g., caffeine, aminophylline and theophylline) is not recommended in patients who experience seizures in association with Adenoscan

Warnings and Precautions: Hypersensitivity 8/2014: Dyspnea, throat tightness, flushing, erythema, rash, and chest discomfort have occurred. Have personnel and resuscitative equipment immediately available

In November 2013, the FDA strengthened warnings about the risk of heart attacks and death from Adenoscan.

 Safety Announcement: [11-20-2013] The U.S. Food and Drug Administration (FDA) is warning health care professionals of the rare but serious risk of heart attack and death with use of the cardiac nuclear stress test agents Lexiscan (Regadenoson) and Adenoscan (Adenosine).  We have approved changes to the drug labels to reflect these serious events and updated our recommendations for use of these agents.  Health care professionals should avoid using these drugs in patients with signs or symptoms of unstable angina or cardiovascular instability, as these patients may be at greater risk for serious cardiovascular adverse reactions.

The Warnings & Precautions section of the Lexiscan and Adenoscan labels previously contained information about the possible risk of heart attack and death with use of these drugs.  However, recent reports of serious adverse events in the FDA Adverse Event Reporting System (FAERS) database and the medical literature1,2 (see Data Summary) prompted us to approve changes to the drug labels to include updated recommendations for use.  Some events occurred in patients with signs or symptoms of acute myocardial ischemia, such as unstable angina or cardiovascular instability.  Cardiac resuscitation equipment and trained staff should be available before administering Lexiscan or Adenoscan.  At this time, data limitations prevent us from determining if there is a difference in risk of heart attack or death between Lexiscan and Adenoscan.

Adverse events:

  • Fatal Cardiac Arrest, Ventricular Arrhythmias, and Myocardial Infarction
  • Sinoatrial and Atrioventricular Nodal Block
  • Bronchoconstriction
  • Hypotension
  • Cerebrovascular Accident
  • Seizures
  • Hypersensitivity
  • Atrial Fibrillation
  • Hypertension

With Adenoscan, the most common adverse events associated with death were cardiorespiratory arrest, dyspnea, cardiac arrest, respiratory arrest, and ventricular tachycardia.

Other adverse reactions: Flushing, chest discomfort, dyspnea, headache, throat/neck/jaw discomfort, GI discomfort, lightheadedness/dizziness, ST segment depression, 1st– or 2nd-degree AV block, paresthesia

Adenoscan Evaluation Criteria:

1. Whether the patient underwent cardiac stress test using Adenoscan?

2. Reason for Adenoscan administration?

3. Dosage and Administration details

4.Did the patient have any pre-existing conditions, allergies or contraindications for Adenoscan (Other drug interactions)

5.What was the injury due to Adenoscan administration?

6.When and where was the injury diagnosed? Whether hospitalized? Dates of hospitalization?

  • Treatment/management. Any complications
  • Follow-up visits for treatment/management of injury.
  • Outcome/prognosis. Resolution of injury?

 

Specific Focus

Identify and report cases with the following scenarios:-

  1. No Injuries: Patient underwent cardiac stress test (With Adenoscan administration) but did not develop any injuries
  2. No Adenoscan administration: Patient was given a different drug and not Adenoscan. Hold case and communicate to client.
  3. Adenoscan contraindicated in patient but still prescribed
  4. Any medical/surgical history, social history that could have had an effect on the injury

Missing Record Communication:

Identify and report on missing medical records

Apart from identifying critical missing records that are important for the case, provide a detailed outline on what records are needed, why we need them, how did we get a clue that these records are missing and whether the records missing are confirmatory/probable. This will also help in following up and retrieving the records.

Missing Records are presented in the following format

adenoscan-records