Adenoscan has been shown to be well tolerated in clinical trials. Initial studies involving 1421 patients in controlled and uncontrolled studies reported frequent but mostly self-limiting side effects (Table 5).
Subsequently, Cerqueira et al
8 published a cumulative review of 9256 patients who underwent adenosine/thallium-201 perfusion imaging in an open-label phase 3 trial using fixed-dose, continuous infusion of adenosine. Interpretable images were obtained in 98.7% of patients, adenosine infusion was completed in 80%, dose reduction was required in 13%, infusion was terminated early in 7%, and aminophylline was given to 0.8%.
Adverse effects were categorized as clinically mild, moderate, and severe in 78.4%, 9.6%, and 4.7%, respectively (Table 5). Though adverse effects occurred frequently, they usually self-terminated following infusion.
|
Table 5. Most Frequent (>5%) Adenoscan Adverse Effects |
|
|
Initial Studies
(n=1421) |
Cumulative
Review8
(n=9256) |
|
Flushing |
44% |
37% |
|
Chest pain |
40% |
35% |
| Shortness of breath |
28% |
35% |
| GI discomfort |
13% |
15% |
| Headache |
18% |
14% |
| Throat/neck/jaw discomfort |
15% |
12% |
| Light-headedness |
12% |
9% |
| AV block |
6% |
8% |
 |
|
|
|
Delayed or Persistent Side Effects
Of 1067 patients who were monitored for 24 hours after the infusion stopped, 10.6% of the side effects occurred not with the infusion of Adenoscan but several hours after the infusion terminated. Also, 8.4% of the side effects that began coincident with the infusion persisted for up to 24 hours after the infusion was complete. In many cases, as in the initial studies, it is not possible to know whether these late adverse events are the result of Adenoscan infusion.
Myocardial Infarction and Ventricular Arrhythmias
Fatal cardiac arrest, sustained ventricular tachycardia (requiring resuscitation), and nonfatal myocardial infarction have been reported coincident with Adenoscan infusion. Patients with unstable angina may be at greater risk.
AV Block
Because adenosine exerts its effects on the sinoatrial (SA) and AV nodes, there is the potential for sinus bradycardia and first-, second-, or third-degree AV block. Frequency of occurrence is 2.9%, 2.6%, and 0.8% in first-, second-, and third-degree AV block, respectively. Most occurrences were self-limiting and did not require intervention; less than 2% required theophylline.
8
Hypotension
As a potent peripheral vasodilator, adenosine may cause hypotension in patients without intact baroreceptor reflexes, though severe hypotension is rare. Therefore, Adenoscan should be used with caution in patients with autonomic dysfunction, stenotic valvular heart disease, pericarditis or pericardial effusions, stenotic carotid artery disease with cerebral insufficiency, or uncorrected hypovolemia. If persistent hypotension occurs, the infusion should be discontinued.
Hypertension
Increases in systolic and diastolic pressure have been observed (as great as 140 mm Hg systolic in 1 case) concomitant with Adenoscan infusion; most increases resolved spontaneously within several minutes, but in some cases hypertension lasted for several hours.
Bronchospasm
Adenoscan should not be used in patients with known or suspected bronchoconstrictive or bronchospastic lung disease. Adenoscan is thought to stimulate carotid receptors,
21 which leads to hyperventilation and reduces arterial pCO
2, causing respiratory alkalosis. When administered to asthmatic patients by inhalation, adenosine has been reported to provoke bronchospasm, probably because of mast cell degranulation and histamine release.
22 Adenoscan should be discontinued in any patient who develops severe respiratory difficulties.
Drug Interactions
Studies have shown that adenosine has been used safely in patients receiving cardioactive drugs such as cardiac glycosides, beta-blockers, and calcium channel blockers. Caution should be taken, however, in the presence of these drugs because of the potential for additive or synergistic depressant effects on the SA and AV nodes. Concomitant use of other drugs by patients receiving Adenoscan always should be evaluated.
Adenoscan should not be used in the presence of methylxanthines or dipyridamole. Methylxanthines (eg, caffeine and theophylline) are competitive inhibitors of adenosine at A
2 cell-surface receptors, inhibiting the vasoactive effects of Adenoscan. Dipyridamole blocks adenosine re-uptake, thereby producing an extracellular accumulation of adenosine, potentiating the vasoactive effects. Whenever possible, drugs that might inhibit or augment the effects of adenosine should be withheld for at least 5 half-lives prior to the use of Adenoscan.
Use During Pregnancy
Neither animal reproduction studies nor human pregnancy studies have been performed with Adenoscan. It has not been established if Adenoscan can cause harm to fetuses. Adenoscan should be used during pregnancy only if clearly needed.
Pediatric Use
The safety and efficacy of Adenoscan have not been established in patients younger than 18 years.
Geriatric Use
Clinical studies of Adenoscan did not include a sufficient number of subjects aged older than 65 years to determine whether they respond differently. Other reported experience has not revealed clinically relevant differences of the response of the elderly in comparison to younger patients. Greater sensitivity of some older individuals, however, cannot be ruled out.
Contraindications
Adenoscan must not be used in patients with second- or third-degree AV block (except in patients with a functioning artificial pacemaker), sinus node disease, such as sick sinus syndrome or symptomatic bradycardia (except in patients with a functioning artificial pacemaker), known or suspected bronchoconstrictive or bronchospastic lung disease (eg, asthma), or known hypersensitivity to adenosine.
Safety
