Adenosine (Page 2 of 3)

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies in animals have not been performed to evaluate the carcinogenic potential of adenosine. 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. Fertility studies in animals have not been conducted with adenosine.

Pregnancy Category C

Animal reproduction studies have not been conducted with adenosine; nor have studies been performed in pregnant women. As adenosine is a naturally occurring material, widely dispersed throughout the body, no fetal effects would be anticipated. However, since it is not known whether adenosine can cause fetal harm when administered to pregnant women, adenosine should be used during pregnancy only if clearly needed.

Pediatric Use

No controlled studies have been conducted in pediatric patients to establish the safety and efficacy of adenosine for the conversion of paroxysmal supraventricular tachycardia (PSVT). However, intravenous adenosine has been used for the treatment of PSVT in neonates, infants, children and adolescents (see DOSAGE AND ADMINISTRATION).1

Geriatric Use

Clinical studies of adenosine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, adenosine in geriatric patients should be used with caution since this population may have a diminished cardiac function, nodal dysfunction, concomitant diseases or drug therapy that may alter hemodynamic function and produce severe bradycardia or AV block.

ADVERSE REACTIONS

The following reactions were reported with intravenous adenosine used in controlled U.S. clinical trials. The placebo group had a less than 1% rate of all of these reactions.

Cardiovascular	Facial flushing (18%), headache (2%), sweating, palpitations, chest pain, hypotension (less than 1%).
Respiratory	Shortness of breath/dyspnea (12%), chest pressure (7%), hyperventilation, head pressure (less than 1%).
Central Nervous System	Lightheadedness (2%), dizziness, tingling in arms, numbness (1%), apprehension, blurred vision, burning sensation, heaviness in arms, neck and back pain (less than 1%).
Gastrointestinal	Nausea (3%), metallic taste, tightness in throat, pressure in groin (less than 1%).

Post Marketing Experience

(see WARNINGS)

The following adverse events have been reported from marketing experience with adenosine. Because these events 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. Decisions to include these events in labeling are typically based on one or more of the following factors: (1) seriousness of the event, (2) frequency of the reporting, (3) strength of causal connection to the drug, or a combination of these factors.

CARDIOVASCULAR

Prolonged asystole, ventricular tachycardia, ventricular fibrillation, transient increase in blood pressure, bradycardia, atrial fibrillation, and Torsade de Pointes.

RESPIRATORY

Bronchospasm

CENTRAL NERVOUS SYSTEM

Seizure activity, including tonic clonic (grand mal) seizures, and loss of consciousness.

OVERDOSAGE

The half-life of adenosine injection is less than 10 seconds. Thus, adverse effects are generally rapidly self-limiting. Treatment of any prolonged adverse effects should be individualized and be directed toward the specific effect. Methylxanthines, such as caffeine and theophylline, are competitive antagonists of adenosine.

DOSAGE AND ADMINISTRATION

For rapid bolus intravenous use only.

Adenosine injection should be given as a rapid bolus by the peripheral intravenous route. To be certain the solution reaches the systemic circulation, it should be administered either directly into a vein or, if given into an IV line, it should be given as close to the patient as possible and followed by a rapid saline flush.

Adult Patients

The dose recommendation is based on clinical studies with peripheral venous bolus dosing. Central venous (CVP or other) administration of adenosine has not been systematically studied.

The recommended intravenous doses for adults are as follows:

Initial dose: 6 mg given as a rapid intravenous bolus (administered over a 1 to 2 second period).

Repeat administration: If the first dose does not result in elimination of the supraventricular tachycardia within 1 to 2 minutes, 12 mg should be given as a rapid intravenous bolus. This 12 mg dose may be repeated a second time if required.

Pediatric Patients

The dosages used in neonates, infants, children and adolescents were equivalent to those administered to adults on a weight basis.

Pediatric Patients with a Body Weight < 50 kg:

Initial dose: Give 0.05 to 0.1 mg/kg as a rapid IV bolus given either centrally or peripherally. A saline flush should follow.

Repeat administration: If conversion of PSVT does not occur within 1 to 2 minutes, additional bolus injections of adenosine can be administered at incrementally higher doses, increasing the amount given by 0.05 to 0.1 mg/kg. Follow each bolus with a saline flush. This process should continue until sinus rhythm is established or a maximum single dose of 0.3 mg/kg is used.

Pediatric Patients with a Body Weight > 50 kg:

Administer the adult dose.

Doses greater than 12 mg are not recommended for adult and pediatric patients.

NOTE: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.

HOW SUPPLIED

Adenosine Injection, USP is supplied as a sterile, nonpyrogenic solution in normal saline.

NDC 0641-6113-10 6 mg/2 mL (3 mg/mL) in 2 mL flip-top vials, packaged in shelf packs of ten.

Storage

Store at 20°-25°C (68°-77°F), excursions permitted to 15°-30°C (59°-86°F). [See USP Controlled Room Temperature.]

DO NOT REFRIGERATE as crystallization may occur. If crystallization has occurred, dissolve crystals by warming to room temperature. The solution must be clear at the time of use.

Contains no preservatives. Discard unused portion.

To report SUSPECTED ADVERSE REACTIONS, contact West-Ward Pharmaceutical Corp. at 1-877-845-0689, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

For Product Inquiry call 1-877-845-0689.

REFERENCE

1. Paul T, Pfammatter. J-P. Adenosine: an effective and safe antiarrhythmic drug in pediatrics. Pediatric Cardiology 1997; 18:118-126.

Manufactured by:
Baxter Pharmaceutical Solutions LLC
Bloomington, IN 47403

Distributed by:

WEST-WARD
PHARMACEUTICALS
Eatontown, NJ 07724 USA

Revised October 2011

462-633-00

3-3609-443