Adeno-Avenir

/ BioAvenir Ltd.

This medicinal product is intended for hospital use only with monitoring and cardiorespiratory resuscitation equipment available for immediate use.
This medicinal product should only be used when facilities exist for cardiac monitoring. Patients who develop high-level AV block at a particular dose should not be given further dosage increments.
Therapeutic dose for adult:
Initial dose: 3 mg given as a rapid intravenous bolus (over 2 seconds).
Second dose: If the first dose does not result in elimination of the supraventricular tachycardia within 1 – 2 minutes, 6 mg should be given also as a rapid intravenous bolus.
Third dose: If the second dose does not result in elimination of the supraventricular tachycardia within 1 – 2 minutes. 12 mg should be given also as a rapid intravenous bolus.
Additional or higher doses are not recommended. See prescribing information for full details.

Rapid conversion to a normal sinus rhythm of paroxysmal supraventricular tachycardias, including those associated with accessory by-pass tracts (Wolff- Parkinson-White Syndrome).

• Hypersensitivity to the active substance or to any of the excipients.
• Sick sinus syndrome, second- or third-degree Atrio-Ventricular (AV) block (except in patients with a functioning artificial pacemaker).
• Chronic obstructive lung disease with evidence of bronchospasm (e.g. asthma
bronchiale).
• Long QT syndrome.
• Severe hypotension.
• Decompensated states of heart failure.

Special warnings
Due to the possibility of transient cardiac arrhythmias arising during conversion of the
supraventricular tachycardia to normal sinus rhythm, administration should be carried
out in a hospital setting with monitoring and cardio-respiratory resuscitation equipment available for immediate use if necessary. During administration, continuous ECG monitoring is necessary as life-threatening arrhythmia might occur.
Because it has the potential to cause significant hypotension, adenosine should be used with caution in patients with left main coronary stenosis, uncorrected hypovolemia, stenotic valvular heart disease, left to right shunt, pericarditis or pericardial effusion, autonomic dysfunction or stenotic carotid artery disease with cerebrovascular insufficiency. There have been reports of cerebrovascular accident/transient ischemic attack, secondary to the haemodynamic effects of adenosine.
There have been reports of myocardial infarction shortly after use of this drug.
Adenosine should be used with caution in patients with recent myocardial infarction,
severe heart failure, or in patients with minor conduction defects (first degree A-V block, bundle branch block) that could be transiently aggravated during infusion.
Adenosine should be used with caution in patients with atrial fibrillation or flutter and
especially in those with an accessory by-pass tract since particularly the latter may
develop increased conduction down the anomalous pathway.
Rare cases of severe bradycardia have been reported. Some occurred in early post
heart transplant patients; in the other cases, occult sino-atrial disease was present. The
occurrence of severe bradycardia should be taken as a warning of underlying disease
and could potentially favour the occurrence of Torsades de pointes, especially in
patients with prolonged QT intervals.
In patients with recent heart transplantation (less than 1 year) an increased sensitivity of the heart to adenosine has been observed.
Since neither the kidney nor the liver are involved in the degradation of exogenous
adenosine, the product’s efficacy should be unaffected by hepatic or renal
insufficiency. As dipyridamole is a known inhibitor of adenosine uptake, it may
potentiate the action of this medicinal product. It is therefore suggested that this medicinal product should not be administered to patients receiving dipyridamole; if use of adenosine is essential, dipyridamole should be stopped 24 hours before hand, or the dose of adenosine should be greatly reduced.
Precautions
The occurrence of angina, severe bradycardia, severe hypotension, respiratory failure
(potentially fatal), or asystole/cardiac arrest (potentially fatal), should lead to immediate discontinuation of administration.
Adenosine may trigger convulsions in patients who are susceptible to convulsions. In
patients with history of convulsions/seizures, the administration of adenosine should be carefully monitored.
Because of the possible risk of Torsades de pointes, adenosine should be used
with caution in patients with a prolonged QT interval, whether this is drug induced or of metabolic origin. This medicinal product is contraindicated in patients with Long QT syndrome.
Adenosine may precipitate or aggravate bronchospasm.
See prescribing information for full details.

Very common: Bradycardia, sinus pause, skipped beats, atrial extrasystoles, Atrio- Ventricular block, ventricular excitability disorders such as ventricular extrasystoles, non-sustained ventricular tachycardia, flushing, dyspnea (or the urge to take a deep breath), chest pain or pressure, feeling of thoracic constriction/oppression.
Common: Headache, dizziness, light-headedness, paraesthesia, nausea, nervousness.
See prescribing information for full details.

Dipyridamole inhibits adenosine cellular uptake and metabolism and potentiates the
action of adenosine. In one study dipyridamole was shown to produce a 4-fold increase in adenosine actions. Asystole has been reported following concomitant administration. It is therefore suggested that adenosine should not be administered to patients receiving dipyridamole; if use of adenosine is essential, dipyridamole should be stopped 24 hours before hand, or the dose of adenosine should be greatly reduced.
Aminophylline, theophylline and other xanthines are competitive adenosine antagonists and should be avoided for 24 hours prior to use of adenosine.
Food and drinks containing xanthines (tea, coffee, chocolate and cola) should be
avoided for at least 12 hours prior to use of adenosine.
This medicinal product may interact with drugs tending to impair cardiac conduction.

Pregnancy
There are no or limited amount of data from the use of adenosine in pregnant women.
Animal studies are insufficient with respect to reproductive toxicity. Adenosine is not
recommended during pregnancy unless the physician considers the benefits to
outweigh the potential risks.
Breast-feeding
It is unknown whether adenosine metabolites are excreted in human milk. This medicinal product should not be used during breast-feeding.

Overdose would cause severe hypotension, bradycardia or asystole. The half-life of adenosine in blood is very short, and side effects (when they occur) would quickly resolve. Administration of IV aminophylline or theophylline may be needed.
Pharmacokinetic evaluation indicates that methyl xanthines are competitive antagonists to adenosine, and that therapeutic concentrations of theophylline block its exogenous effects.

Store below 25°C.
Once opened, the product should be used immediately. Any portion of the vial not used at once should be discarded.