ADENOSINE

Adenosine is an endogenous nucleoside occurring in all cells of the body. It is chemically 6-amino-9-ß-D-ribofuranosyl-9-H-purine and has the following structural formula: Adenosine is a white crystalline powder. It is soluble in water and practically insoluble in alcohol. Solubility increases by warming and lowering the pH. Adenosine is not chemically related to other antiarrhythmic drugs. Adenosine Injection is a sterile, nonpyrogenic solution for rapid bolus intravenous injection. Each mL contains 3 mg adenosine and 9 mg sodium chloride in water for injection. The pH of the solution is between 4.5 and 7.5. STRUCTURE

INDICATIONS & USAGE Intravenous adenosine injection is indicated for the following: Conversion to sinus rhythm of paroxysmal supraventricular tachycardia (PSVT), including that associated with accessory bypass tracts (Wolff-Parkinson-White Syndrome). When clinically advisable, appropriate vagal maneuvers (e.g., Valsalva maneuver), should be attempted prior to adenosine injection administration. It is important to be sure the adenosine injection solution actually reaches the systemic circulation (see DOSAGE & ADMINISTRATION . Adenosine injection does not convert atrial flutter, atrial fibrillation, or ventricular tachycardia to normal sinus rhythm. In the presence of atrial flutter or atrial fibrillation, a transient modest slowing of ventricular response may occur immediately following adenosine injection administration.

DOSAGE & ADMINISTRATION For rapid bolus intravenous use only. Adenosine Injection, USP 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 Injection, USP 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 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.

Intravenous adenosine injection is contraindicated in: Second- or third-degree A-V 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 hypersensitivity to adenosine.

The following reactions were reported with intravenous adenosine injection 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 injection. 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 Torsades de Pointes. Respiratory Bronchospasm. Central Nervous System Seizure activity, including tonic clonic (grand mal) seizures, and loss of consciousness.