Adenosine: Package Insert and Label Information

ADENOSINE — adenosine injection, solution
NorthStar Rx LLC

1 INDICATIONS AND USAGE

Adenosine injection, USP is indicated as an adjunct to thallium-201 myocardial perfusion scintigraphy in patients unable to exercise adequately.

2 DOSAGE AND ADMINISTRATION

The recommended adenosine injection dose is 0.14 mg/kg/min infused over six minutes (total dose of 0.84 mg/kg) (Table 1).

  • Administer adenosine injection only as a continuous peripheral intravenous infusion
  • Inject Thallium-201 at the midpoint of the adenosine injection infusion (i.e., after the first three minutes of adenosine injection)
  • Thallium-201 is physically compatible with adenosine injection and may be injected directly into the adenosine injection infusion set
  • Inject Thallium-201 as close to the venous access as possible to prevent an inadvertent increase in the dose of adenosine injection (the contents of the intravenous tubing) being administered

Visually inspect adenosine injection for particulate matter and discoloration prior to administration. Do not administer adenosine injection if it contains particulate matter or is discolored.

There are no data on the safety or efficacy of alternative adenosine injection infusion protocols. The safety and efficacy of adenosine injection administered by the intracoronary route have not been established.

Table 1 Dosage Chart for Adenosine Injection
Patient Weight (kilograms) Infusion Rate (mL per minute over 6 minutes for total dose of 0.84 mg/kg)
45 2.1
50 2.3
55 2.6
60 2.8
65 3
70 3.3
75 3.5
80 3.8
85 4
90 4.2

The nomogram displayed in Table 1 was derived from the following general formula:

formula
(click image for full-size original)

3 DOSAGE FORMS AND STRENGTHS

Adenosine injection, USP is supplied as 20 mL and 30 mL single-dose vials containing a sterile, nonpyrogenic, clear solution of adenosine 3 mg/mL.

4 CONTRAINDICATIONS

Adenosine injection is contraindicated in patients with:

5 WARNINGS AND PRECAUTIONS

5.1 Cardiac Arrest, Ventricular Arrhythmias, and Myocardial Infarction

Fatal and nonfatal cardiac arrest, sustained ventricular tachycardia (requiring resuscitation), and myocardial infarction have occurred following adenosine injection infusion. 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 adenosine injection. Appropriate resuscitative measures should be available [see Overdosage (10)].

5.2 Sinoatrial and Atrioventricular Nodal Block

Adenosine injection exerts a direct depressant effect on the SA and AV nodes and may cause first-, second- or third-degree AV block, or sinus bradycardia. In clinical trials, approximately 6% of patients developed AV block following adenosine injection administration (first-degree heart block developed in 3%, second-degree in 3%, and third-degree in 0.8% of patients) [see Clinical Trials Experience (6.1)].

Use adenosine injection with caution in patients with pre-existing first-degree AV block or bundle branch block. Do not use in patients with high-grade AV block or sinus node dysfunction (except in patients with a functioning artificial pacemaker). Discontinue adenosine injection in any patient who develops persistent or symptomatic high-grade AV block.

5.3 Bronchoconstriction

Adenosine injection administration can cause dyspnea, bronchoconstriction, and respiratory compromise. Adenosine injection should be used with caution in patients with obstructive lung disease not associated with bronchoconstriction (e.g., emphysema, bronchitis). Do not use in patients with bronchoconstriction or bronchospasm (e.g., asthma). Discontinue adenosine injection in any patient who develops severe respiratory difficulties. Resuscitative measures should be available prior to adenosine injection administration [see Clinical Trials Experience (6.1), Overdosage (10), and Clinical Pharmacology (12.2)].

5.4 Hypotension

Adenosine injection is a potent peripheral vasodilator and can induce significant hypotension. The risk of serious hypotension may be higher in patients with autonomic dysfunction, hypovolemia, stenotic valvular heart disease, pericarditis or pericardial effusions, or stenotic carotid artery disease with cerebrovascular insufficiency. Discontinue adenosine injection in any patient who develops persistent or symptomatic hypotension.

5.5 Cerebrovascular Accident

Hemorrhagic and ischemic cerebrovascular accidents have occurred. Hemodynamic effects of adenosine injection including hypotension or hypertension can be associated with these adverse reactions. [see Warnings and Precautions (5.4) and (5.9)].

5.6 Seizures

New-onset or recurrence of convulsive seizures has occurred following adenosine injection. Some seizures are prolonged and require emergent anticonvulsive management. Aminophylline may increase the risk of seizures associated with adenosine injection. Methylxanthine use is not recommended in patients who experience seizures in association with adenosine injection administration [see Overdosage (10)].

5.7 Hypersensitivity

Dyspnea, throat tightness, flushing, erythema, rash, and chest discomfort have occurred. Symptomatic treatment may be required. Have personnel and appropriate treatment available. Resuscitative measures may be necessary if symptoms progress. [see Clinical Trials Experience (6.1)].

5.8 Atrial Fibrillation

Adenosine injection can cause atrial fibrillation in patients with or without a history of atrial fibrillation. Atrial fibrillation typically began 1.5 to 3 minutes after initiation of adenosine injection, lasted for 15 seconds to 6 hours, and spontaneously converted to normal sinus rhythm [see Post-Marketing Experience (6.2)].

5.9 Hypertension

Adenosine injection can induce clinically significant increases in systolic and diastolic blood pressure. Most increases resolved spontaneously within several minutes, but in some cases, hypertension lasted for several hours [see Clinical Trials Experience (6.1)].

6 ADVERSE REACTIONS

The following adverse reactions are discussed in more detail in other sections of the prescribing information:

6.1 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.

The following adverse reactions, with an incidence of at least 1%, were reported with adenosine injection among 1,421 patients in clinical trials. 11% of the adverse reactions occurred several hours after adenosine injection administration. 8% of the adverse reactions began with adenosine injection infusion and persisted for up to 24 hours.

The most common (incidence greater than or equal to 10%) adverse reactions to adenosine injection are flushing, chest discomfort, shortness of breath, headache, throat, neck or jaw discomfort, gastrointestinal discomfort, and dizziness (Table 2).

Table 2 Adverse Reactions in Clinical Trials (Frequency Greater Than or Equal To 1%)
Adverse Reactions Adenosine N= 1,421
Flushing 44%
Chest discomfort 40%
Dyspnea 28%
Headache 18%
Throat, neck or jaw discomfort 15%
Gastrointestinal discomfort 13%
Lightheadedness/dizziness 12%
Upper extremity discomfort 4%
ST segment depression 3%
First-degree AV block 3%
Second-degree AV block 3%
Paresthesia 2%
Hypotension 2%
Nervousness 2%
Arrhythmias 1%
Adverse reactions to adenosine injection of any severity reported in less than 1% of patients include:
Body as a Whole: back discomfort, lower extremity discomfort, weakness
Cardiovascular System: myocardial infarction, ventricular arrhythmia, third-degree AV block, bradycardia, palpitation, sinus exit block, sinus pause, T-wave changes, hypertension (systolic blood pressure greater than 200 mm Hg)
Respiratory System: cough
Central nervous System: drowsiness, emotional instability, tremors
Genital/Urinary System: Vaginal pressure, urgency
Special Senses: blurred vision, dry mouth, ear discomfort, metallic taste, nasal congestion, scotomas, tongue discomfort

6.2 Post-Marketing Experience

The following adverse reactions have been reported from marketing experience with adenosine injection. Because these reactions are reported voluntarily from a population of uncertain size, are associated with concomitant diseases and multiple drug therapies and surgical procedures, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiac Disorders: cardiac arrest, atrial fibrillation, cardiac failure, myocardial infarction, tachycardia, ventricular arrhythmia
Gastrointestinal Disorders: nausea and vomiting
General Disorders and Administration Site Conditions: chest pain, injection site reaction, infusion site pain
Immune System Disorders: hypersensitivity
Nervous System Disorders: cerebrovascular accident including intracranial hemorrhage, seizure activity including tonic-clonic (grand mal) seizures, loss of consciousness
Respiratory, Thoracic and Mediastinal Disorders: bronchospasm, respiratory arrest, throat tightness

7 DRUG INTERACTIONS

7.1 Effects of Other Drugs on Adenosine Injection

  • The vasoactive effects of adenosine are inhibited by adenosine receptor antagonists, (such as methylxanthines (e.g., caffeine, aminophylline, and theophylline). The safety and efficacy of adenosine injection in the presence of these agents has not been systematically evaluated [see Overdosage (10)].
  • The vasoactive effects of adenosine are potentiated by nucleoside transport inhibitors such as dipyridamole. The safety and efficacy of adenosine in the presence of dipyridamole has not been systematically evaluated.
  • Whenever possible, drugs that might inhibit or augment the effects of adenosine should be withheld for at least five half-lives prior to the use of adenosine injection.
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