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

Aid to diagnosis of broad or narrow complex supraventricular tachycardias. Although Adenocor is not effective in converting 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 administered by rapid intravenous injection slows conduction through the AV node. This action can interrupt re-entry circuits involving the AV node and restore normal sinus rhythm in patients with paroxysmal supraventricular tachycardias. Once the circuit has been interrupted, the tachycardia stops and normal sinus rhythm is re-established.

By transiently stowing AV conduction, atrial activity is easier to evaluate from ECG recordings and therefore Adenocor can aid the diagnosis of broad or narrow complex tachycardias.

Adenocor may be useful during electrophysiological studies to determine the site of AV block or to determine, in some cases of pre-excitation, whether conduction is occurring by an accessory pathway or via the AV node.

Adenocor is intended for hospital use only. It should be administered by rapid IV bogus 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.

Initial dose: 3 mg given as a rapid intravenous bogus Lover 2 seconds}.

Second dose: If the first dose does not result in elimination of the supraventricular tachycardia within 1 to 2 minutes, 6 mg should be given also as a rapid intravenous bogus.

Third Dose: If the second dose does not result in elimination of the supraventricular tachycardia within 1 to 2 minutes, 12mg should be given also as a rapid intravenous bogus.

Additional or higher doses are not recommended.

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 0.25 mg/kg.

See dosage recommendations for adults.

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

Adenocor is contra-indicated in patients suffering from:

• second or third degree AV block (except in patients with a functioning artificial pacemaker).
• sick sinus syndrome (except in patients with a functioning artificial pacemaker).

Patients with atrial fibrillation/flutter and an accessory by-pass tract may develop increased conduction down the anomalous pathway.

Since neither the kidney nor the liver are involved in the degradation of exogenous adenosine, the efficacy of Adenocor should be unaffected by hepatic or renal insufficiency.

It has been reported that inhaled adenosine caused bronchial constriction in asthmatic patients but not in healthy individuals. However a limited number of asthmatic patients have received adenosine intravenously without suffering aggravation of symptoms. Nevertheless physicians should be aware of the possibility.

Facial flush, dyspnoea, a feeling of thoracic constriction, nausea and lightheadedness occur commonly. More rarely observed side-effects have been: feeling of discomfort; sweating; palpitations; hyperventilation; head pressure; apprehension; blurred vision; burning sensation; bradycardia; chest pains; headache; dizziness; heaviness in arms; arm, back and neck pains; metallic taste. These side effects were mild, of short duration (usually less than 1 minute) and generally well-tolerated by the patient.

Severe bradycardia has been reported and some patients have required temporary pacing. The effects of Adenocor are not blocked by atropine.

At the time of conversion to normal sinus rhythm, the ECG may show premature ventricular contractions, premature atrial contractions, sinus bradycardia, sinus tachycardia, skipped beats and varying degrees of AV nodal block. These abnormalities generally last only a few seconds and have been self limiting.

As dipyridamole is a known inhibitor of adenosine uptake, it may potentiate the action of Adenocor; in one study dipyridamole was shown to produce a 4 fold increase in adenosine actions. It is therefore suggested that Adenocor should not be administered to patients receiving dipyridamole; if use of Adenocor is essential, dosage should be reduced.

Theophylline and other xanthines such as caffeine are known strong inhibitors of adenosine.

Adenocor may interact with drugs tending to impair cardiac conduction.

Adenosine is a substance which is naturally present in some form in all cells of the body, therefore no effect on the foetus would be expected. In the absence of evidence that adenosine does not cause foetal harm, Adenocor should only be used during pregnancy where absolutely necessary.

No cases of overdosage have been reported. As the half life of adenosine in blood is very short, the duration of any side effects due to overdose is likely to be limited.

Do not refrigerate. Any portion of the vial not used at once should be discarded.

POM

Carton of 6 vials

PL 1 1723/0005

Sanofi Winthrop Limited

One Onslow Street,

Guildford,

Surrey GU1 4YS

April 1992