Adenosine

Name: Adenosine

Uses for Adenosine

Treatment of Supraventricular Tachyarrhythmias

Termination of paroxysmal supraventricular tachycardia (PSVT), including that associated with accessory bypass tracts (e.g., Wolff-Parkinson-White syndrome).1 14 24 26 300 403

Drug of choice for terminating stable, regular narrow-complex tachycardias, including PSVT due to AV nodal reentrant tachycardia (AVNRT) and AV reentrant tachycardia (AVRT).7 26 300 400 401 403

Attempt appropriate vagal maneuvers (e.g., Valsalva maneuver, carotid sinus massage) when clinically indicated prior to adenosine use.1 24 300

May consider adenosine in selected patients with unstable, narrow-complex tachycardia while preparing for cardioversion†.400 401 (See Cardiovascular and Cerebrovascular Effects under Cautions.)

May be useful for diagnosis and treatment of stable, regular monomorphic wide-complex tachycardias† if the etiology of the rhythm cannot be determined.400 401

Not effective in terminating arrhythmias not due to reentry involving the AV or sinus node (e.g., atrial flutter, atrial fibrillation, ventricular tachycardia).1 4 14 24 Risk of serious arrhythmias and/or hypotension in patients with preexcited arrhythmias.18 19 26 27 29 (See Cardiovascular and Cerebrovascular Effects under Cautions.)

Some clinicians state that adenosine is contraindicated in patients with atrial fibrillation or flutter associated with Wolff-Parkinson-White syndrome; risk of dramatically accelerating ventricular rate.28

Considered drug of choice for conversion of supraventricular tachycardia (SVT) in pediatric patients when pharmacologic therapy indicated.403 Also may be useful in pediatric patients for diagnosis and treatment of wide-complex tachycardias of supraventricular origin if rhythm is regular and monomorphic.403

Thallium Stress Test

Adjunct to thallous (thallium) chloride TI 201 myocardial perfusion scintigraphy (thallium stress test) in patients unable to undergo adequate stress testing with exercise.2 10 17

Diagnosis of Supraventricular Tachycardias

Used to aid diagnosis of stable, regular narrow-complex SVTs†.15 16 26 300 Transient AV block may occur following administration of the drug, which can unmask atrial activity in certain arrhythmias (e.g., atrial tachycardia, atrial flutter).401

Also has been used diagnostically in patients with stable, regular wide-complex tachycardias; if tachycardia is a result of SVT with aberrancy, adenosine will likely be effective in slowing or converting the arrhythmia to normal sinus rhythm.400 401 403

Some experts discourage overuse for diagnostic purposes; use only in suspected arrhythmias of supraventricular origin.27 28 (See Cardiovascular and Cerebrovascular Effects under Cautions.)

Adenosine Dosage and Administration

Administration

Administer by peripheral IV injection 1 or IV infusion depending on use.2 17

Also has been administered via a central vein†13 or by intraosseous (IO) injection† in pediatric patients without reliable/immediate IV access.6 21 403

Safety and efficacy of intracoronary administration (as adjunct to thallium stress test) not established.2

For solution compatibility information, see Compatibility under Stability.

IV Injection

Supraventricular tachyarrhythmias (e.g., PSVT): Administer by rapid IV (“bolus”) injection into a peripheral vein.1

To ensure the drug reaches the systemic circulation, inject directly into a vein.1 If given through an IV line, inject as closely as possible to the patient’s venous access, then follow each dose with a rapid flush of 0.9% sodium chloride injection (e.g., flush with ≥5 mL for pediatric patients and 20 mL for adults).1

Rate of Administration

Supraventricular tachyarrhythmias (e.g., PSVT): Administer over 1–2 seconds.1

IV Infusion

Thallium Stress Test: Administer by continuous infusion into a peripheral vein.2 17

Rate of Administration

Administer over 6 minutes.2 17

Dosage

Pediatric Patients

Supraventricular Tachyarrhythmias PSVT IV

Children <50 kg: Initially, 0.05–0.1 mg/kg.1 If conversion of PSVT does not occur within 1–2 minutes, increase subsequent doses by 0.05–0.1 mg/kg until sinus rhythm is established or a maximum single dose of 0.3 mg/kg (not exceeding 12 mg) has been given.1

Children ≥50 kg: Initially, 6 mg.1 If conversion does not occur within 1–2 minutes, a 12-mg dose may be administered and repeated once, if necessary.1 Maximum single dose is 12 mg.1

A lower initial dose (50% of the usual recommended initial dose for children)27 28 may be effective if given via a central vein, because the rhythm effects of adenosine are concentration dependent.4 8 28

Adults

Supraventricular Tachyarrhythmias PSVT IV

Initially, 6 mg.1 If conversion does not occur within 1–2 minutes, administer a 12-mg dose; may repeat 12-mg dose once, if necessary.1

If recurs after conversion, additional doses of adenosine or a longer-acting AV nodal blocking agent (e.g., diltiazem, β-adrenergic blocking agent) may be used.401 If adenosine fails to convert PSVT, rate control may be attempted with a nondihydropyridine calcium-channel blocking agent (e.g., diltiazem, verapamil) or a β-adrenergic blocking agent.300 400 401

A lower initial dose of adenosine (3 mg for adults)27 28 may be effective if given via a central vein because the rhythm effects of adenosine are concentration dependent.4 8 28

Thallium Stress Test IV

0.14 mg/kg per minute for 6 minutes (total dose of 0.84 mg/kg).2 17

Administer required dose of thallous (thallium) chloride TI 201 at the midpoint (i.e., after the first 3 minutes) of the adenosine infusion2 17 and as close as possible to the venous access site to prevent an inadvertent increase in the dose of adenosine (the contents of the IV tubing) being administered.2

Prescribing Limits

Pediatric Patients

Supraventricular Tachyarrhythmias PSVT IV

Children <50 kg: Manufacturer recommends maximum single dose of 0.3 mg/kg (do not exceed 12 mg).1

Children ≥50 kg: Manufacturer recommends maximum single dose of 12 mg.1

Some experts recommend maximum single dose of 6 mg for initial injection.403

Adults

Supraventricular Tachyarrhythmias PSVT IV

Maximum recommended single dose is 12 mg.1

Special Populations

Cardiac Transplant Patients

Administer with caution because of risk of cardiac denervation-related hypersensitivity.28 (See Cardiovascular and Cerebrovascular Effects under Cautions.)

Consumer Information Use and Disclaimer

  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
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  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.
  • Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about adenosine, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about adenosine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using adenosine.

Review Date: October 4, 2017

Adenosine 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:

Warnings and Precautions

Cardiac Arrest, Ventricular Arrhythmias, and Myocardial Infarction

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

Sinoatrial and Atrioventricular Nodal Block

Adenosine 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 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 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 in any patient who develops persistent or symptomatic high-grade AV block.

Bronchoconstriction

Adenosine administration can cause dyspnea, bronchoconstriction, and respiratory compromise. Adenosine 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 in any patient who develops severe respiratory difficulties. Resuscitative measures should be available prior to Adenosine administration [see Clinical Trials Experience (6.1), Overdosage (10), and Clinical Pharmacology (12.2)].

Hypotension

Adenosine 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 in any patient who develops persistent or symptomatic hypotension.

Cerebrovascular Accident

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

Seizures

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

Hypersensitivity, Including Anaphylaxis

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 Post-Marketing Experience (6.2)].

Atrial Fibrillation

Adenosine 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, lasted for 15 seconds to 6 hours, and spontaneously converted to normal sinus rhythm [see Post-Marketing Experience (6.2)].

Hypertension

Adenosine 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)].

Adverse Reactions

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

• Fatal Cardiac Arrest, Ventricular Arrhythmias, and Myocardial Infarction [see Warnings and Precautions (5.1)] • Sinoatrial and Atrioventricular Nodal Block [see Warnings and Precautions (5.2)] • Bronchoconstriction [see Warnings and Precautions (5.3)] • Hypotension [see Warnings and Precautions (5.4)] • Cerebrovascular Accident [see Warnings and Precautions (5.5)] • Seizures [see Warnings and Precautions (5.6)] • Hypersensitivity [see Warnings and Precautions (5.7)] • Atrial fibrillation [see Warnings and Precautions (5.8)] • Hypertension [see Warnings and Precautions (5.9)]

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 among 1,421 patients in clinical trials. 11% of the adverse reactions occurred several hours after Adenosine administration. 8% of the adverse reactions began with Adenosine infusion and persisted for up to 24 hours.

The most common (incidence ≥ 10%) adverse reactions to Adenosine 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 ≥ 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 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 > 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

Post-Marketing Experience

The following adverse reactions have been reported from marketing experience with Adenosine. 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

Overdosage

The half-life of Adenosine is less than 10 seconds and adverse reactions of Adenosine usually resolve quickly when the infusion is discontinued, although delayed or persistent reactions have been observed. Methylxanthines, such as caffeine, aminophylline, and theophylline, are competitive Adenosine receptor antagonists and theophylline has been used to terminate persistent adverse reactions. In clinical trials, theophylline (50 to 125 mg slow intravenous injection) was used to attenuate Adenosine adverse reactions in approximately 2% of patients. Methylxanthine use is not recommended in patients who experience seizures in association with Adenosine [see Drug Interactions (7.1)].

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies in animals have not been performed to evaluate Adenosine's carcinogenic potential or potential effects on fertility. Adenosine was negative for genotoxic potential in the Salmonella (Ames Test) and Mammalian Microsome Assay.

Adenosine, however, like other nucleosides at millimolar concentrations present for several doubling times of cells in culture, is known to produce a variety of chromosomal alterations.

Patient Counseling Information

• Advise patients that they may be at increased risk of fatal and nonfatal heart attacks, abnormal heart rhythms, cardiac arrest, heart block, significant increase or decrease in blood pressure, bronchoconstriction, hypersensitivity reactions, seizures, or cerebrovascular accidents with the use of Adenosine [see Warnings and Precautions (5.1-5.9)]. • Advise patients with COPD or asthma to discuss their respiratory history with their clinician before scheduling a myocardial perfusion imaging study with Adenosine [see Warnings and Precautions (5.3)]. • Methylxanthines have the potential to impact the effects of Adenosine. Instruct patients to avoid consumption of any products containing methylxanthines, including caffeinated coffee, tea or other caffeinated beverages, caffeine-containing drug products, aminophylline, and theophylline prior to the myocardial perfusion imaging study. Question patients about a history of seizures [see Warnings and Precautions (5.6), Drug Interactions (7.1), and Overdosage (10)].

Manufactured for:

Mylan Institutional LLC

Rockford, IL 61103 U.S.A.

Manufactured by:

Mylan Laboratories Limited

Bangalore, India

JUNE 2017

Pronunciation

(a DEN oh seen)

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience abdominal pain or flushing. Have patient report immediately to prescriber signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), vision changes, shortness of breath, angina, severe dizziness, passing out, tachycardia, bradycardia, abnormal heartbeat, seizures, severe headache, neck pain, jaw pain, or throat pain (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Uses of Adenosine

Adenosine is used in the treatment of:

  • Tachycardia, Atrioventricular Nodal Reentry
  • Tachycardia, Paroxysmal
  • Wolff-Parkinson-White Syndrome

Adenosine is used in the prevention of:

  • Nutritional and Metabolic Diseases

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

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