Purine nucleosides (anti- arrhythmics / antiarrhythmics).

Adenosine

Each vial contains 6mg of adenosine per 2ml (3mg/ml).

Solution for injection Clear, colourless solution

Rapid conversion to a normal sinus rhythm of paroxysmal supraventricular tachycardias, including those associated with accessory by-pass tracts (Wolff-Parkinson-White Syndrome). Diagnostic Indications Aid to diagnosis of broad or narrow complex supraventricular tachycardias. Although Adenocor will not convert atrial flutter, atrial fibrillation or ventricular tachycardia to sinus rhythm, the slowing of AV conduction helps diagnosis of atrial activity. Sensitisation of intra-cavitary electrophysiological investigations.

Adenocor is intended for hospital use only with monitoring and cardiorespiratory resuscitation equipment available for immediate use.

Method of administration

It should be administered by rapid IV bolus injection according to the ascending dosage schedule below. To be certain the solution reaches the systemic circulation administer either directly into a vein or into an IV line. If given into an IV line it should be injected as proximally as possible, and followed by a rapid saline flush.

Adenocor 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.

Posology

Adult:

Additional or higher doses are not recommended.

Paediatric population

The safety and efficacy of adenosine in children aged 0-18 years old have not been established. No data are available. No controlled paediatric study has been undertaken. Published uncontrolled studies show similar effects of adenosine in adults and children: effective doses for children were between 0.0375 and 0.25mg/kg.

Elderly

See dosage recommendations for adults.

Diagnostic dose

The above ascending dosage schedule should be employed until sufficient diagnostic information has been obtained.

Method of administration: Rapid intravenous injection only.

No controlled paediatric study has been undertaken. Published uncontrolled studies show similar effects of adenosine in adults and children: effective doses for children were between 0.0375 and 0.25mg/kg.

See dosage recommendations for adults.

Adenocor is contraindicated for patients presenting:

- Known hypersensitivity to adenosine 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.

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, Adenocor'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 Adenocor. It is therefore suggested that Adenocor should not be administered to patients receiving dipyridamole; if use of Adenocor is essential, dipyridamole should be stopped 24 hours before hand, or the dose of Adenocor 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, Adenocor should be used with caution in patients with a prolonged QT interval, whether this is drug induced or of metabolic origin. Adenocor is contraindicated in patients with Long QT syndrome.

Adenosine may precipitate or aggravate bronchospasm.

Adenosine contains 9 mg sodium chloride per ml. (corresponding to 3.54 mg sodium per ml). To be taken into consideration by patients on a controlled sodium diet.

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 Adenocor should not be administered to patients receiving dipyridamole; if use of Adenocor is essential, dipyridamole should be stopped 24 hours before hand, or the dose of Adenocor 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.

Adenocor may interact with drugs tending to impair cardiac conduction.

Adverse events are ranked under the heading of the frequency:

Very common (>1/10), Common (>1/100, <1/10), Uncommon (>1/1000, <1/100), Rare (>1/10000, <1/1000), Very rare (<1/10000), Not known (cannot be estimated from available data).

These side effects are generally mild, of short duration (usually less than 1 minute) and well tolerated by the patient. However severe reactions can occur.

Methylxanthines, such as IV aminophylline or theophylline have been used to terminate persistent side effects (50-125 mg by slow intravenous injection).

sanofi-aventis

(POM)

10 November 2011