adenosine

Indications and 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 AND 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 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 intravenous 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 intravenous 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.

CONTRAINDICATIONS Intravenous adenosine injection is contraindicated in: 1. Second- or third-degree A-V block (except in patients with a functioning artificial pacemaker). 2. Sinus node disease, such as sick sinus syndrome or symptomatic bradycardia (except in patients with a functioning artificial pacemaker). 3. Known hypersensitivity to adenosine.

ADVERSE REACTIONS 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. 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. To report SUSPECTED ADVERSE REACTIONS, contact Mylan Pharmaceuticals Inc. at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

Drug Interactions Intravenous adenosine injection has been effectively administered in the presence of other cardioactive drugs, such as quinidine, beta-adrenergic blocking agents, calcium channel blocking agents, and angiotensin converting enzyme inhibitors, without any change in the adverse reaction profile. Digoxin and verapamil use may be rarely associated with ventricular fibrillation when combined with adenosine injection (see WARNINGS ). Because of the potential for additive or synergistic depressant effects on the SA and AV nodes, however, adenosine injection should be used with caution in the presence of these agents. The use of adenosine injection in patients receiving digitalis may be rarely associated with ventricular fibrillation (see WARNINGS ). The effects of adenosine are antagonized by methylxanthines such as caffeine and theophylline. In the presence of these methylxanthines, larger doses of adenosine may be required or adenosine may not be effective. Adenosine effects are potentiated by dipyridamole. Thus, smaller doses of adenosine may be effective in the presence of dipyridamole. Carbamazepine has been reported to increase the degree of heart block produced by other agents. As the primary effect of adenosine is to decrease conduction through the A-V node, higher degrees of heart block may be produced in the presence of carbamazepine.

Mechanism of Action Adenosine Injection slows conduction time through the A-V node, can interrupt the reentry pathways through the A-V node, and can restore normal sinus rhythm in patients with paroxysmal supraventricular tachycardia (PSVT), including PSVT associated with Wolff-Parkinson-White Syndrome. Adenosine Injection is antagonized competitively by methylxanthines such as caffeine and theophylline, and potentiated by blockers of nucleoside transport such as dipyridamole. Adenosine Injection is not blocked by atropine.

DESCRIPTION Adenosine is an endogenous nucleoside occurring in all cells of the body. It is chemically 6-amino-9-β-D-ribofuranosyl-9-H-purine and has the following structural formula: C 10 H 13 N 5 O 4 267.25 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, USP is a sterile solution for rapid bolus intravenous injection. Each mL contains 3 mg adenosine, USP and 9 mg sodium chloride, USP in water for injection, USP. The pH of the solution is between 4.5 and 7.5. Structural Formula

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.

HOW SUPPLIED ADENOSINE INJECTION, USP is supplied in the following dosage forms. NDC 51662-1511-1 ADENOSINE INJECTION, USP 12mg PER 4mL (3mg PER mL) 4mL SYR HF Acquisition Co LLC, DBA HealthFirst Mukilteo, WA 98275 Also supplied in the following manufacture supplied dosage forms Adenosine Injection, USP is supplied as a sterile solution in normal saline as follows: Storage Conditions Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Do not freeze. 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. Sterile, Nonpyrogenic, Preservative-free, PVC-free, DEHP-free. The container closure is not made with natural rubber latex. Discard unused portion. May require needle or blunt. To prevent needle-stick injuries, needles should not be recapped, purposely bent or broken by hand. HOW SUPPLIED