Adenosine 3mg/ml Solution for Injection

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

For a full list of excipients, see Section 6.1.

Solution for injection (injection).

A clear, colourless solution free from visible particles.

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 adenosine injection 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.

Adenosine injection 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 intravenous (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.

Adenosine injection 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

Adults:

Initial dose: 3mg 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 to 2 minutes, 6mg 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 to 2 minutes 12mg should be given also as a rapid intravenous bolus.

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.

Adenosine injection 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. (section 4.2).

Because it has the potential to cause significant hypotension, adenosine injection 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- 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, adenosine injection'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 adenosine injection. It is therefore suggested that adenosine injection should not be administered to patients receiving dipyridamole; if use of Adenosine Injection is essential, dipyridamole should be stopped 24 hours before hand, or the dose of Adenosine Injection should be greatly reduced. (see Section 4.5 Interactions with other Medicaments and other forms of Interaction).

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 injection should be used with caution in patients with a prolonged QT interval, whether this is drug induced or of metabolic origin. Adenosine injection is contraindicated in patients with Long QT syndrome (see section 4.3).

Adenosine may precipitate or aggravate bronchospasm (see sections 4.3 and 4.8)..

Adenosine injection contains approximately 7mg sodium per injection vial (2ml) i.e. essentially 'sodium-free'.

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 injection should not be administered to patients receiving dipyridamole; if use of adenosine injection is essential, dipyridamole should be stopped 24 hours before hand, or the dose of adenosine should be greatly reduced (see section 4.4).

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 injection.

Adenosine 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.

Lactation:

It is unknown whether adenosine metabolites are excreted in human milk

Adenosine Injection should not be used during breast-feeding.

Not applicable.

Adverse events are ranked under the heading of the frequency:

Very common (>1/10), Common (>1/100, <1/10), Uncommon (>1/1,000, <1/100), Rare (>1/10,000, <1/1,000), Very rare (<1/10,000), 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).

Overdosage 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.

ATC Code: Other Cardiac Preparations C01EB 10

Endogenous nucleoside with peripheral vasodilator/antiarrhythmic effect

Antiarrhythmic drug.

Adenosine is a purine nucleoside which is present in all cells of the body. Animal pharmacology studies have in several species shown that Adenosine has a negative dromotropic effect on the atrioventricular (AV) node.

In man adenosine 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.

One acute interruption of the circuit is usually sufficient to arrest the tachycardia.

Since atrial fibrillation and atrial flutter do not involve the AV node as part of a re-entry circuit, Adenosine will not terminate these arrhythmias.

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

Adenosine 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.

It is impossible to study adenosine in classical pharmacokinetic studies. It is present in various forms in all cells of the body where it plays an important role in energy production and utilisation systems. An efficient salvage and recycling system exists in the body, primarily in the erythrocytes and blood vessel endothelial cells. The half life in vitro is estimated to be less than 10 seconds. The in vivo half life may be even shorter.

There are no pre-clinical data of relevance to the prescriber that are additional to those already included in other sections of the SPC.

Sodium chloride

Water for injections

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

Unopened: 24 months.

The product should be used immediately after opening.

Do not refrigerate.

Clear, neutral type I glass vials (2ml) sealed with chlorobutyl rubber closures. Packs of 6 vials packed in a PVC tray in a cardboard carton.

Do not use if any particles or discolouration are noticed in the solution.

Any unused product or waste material should be disposed of in accordance with local requirements.

Wockhardt UK Ltd

Ash Road North

Wrexham

LL13 9UF

UK

UK: PL 29831/0457

UK: 02/09/2011