Adenocor

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

For excipients, see 6.1

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. 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.

Therapeutic dose

Adult:

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.

Children

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.

Adenocor is contraindicated for patients presenting:

− Known hypersensitivity to adenosine.

− Sick sinus syndrome, second or third degree Atrio-Ventricular block (except in patients with a functioning artificial pacemaker).

− Chronic obstructive lung disease (such as asthma)

− 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 hospital with electrocardiographic monitoring.

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, 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.

Some 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.

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, its dosage should be 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.

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 (see section 4.3).

Adenosine may precipitate or aggravate bronchospasm.

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. 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, its dosage should be reduced. See Section 4.4 Special Warnings and Precautions for Use.

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

Adenocor may interact with drugs tending to impair cardiac conduction.

Pregnancy: In the absence of evidence that adenosine does not cause foetal harm, Adenocor should only be used during pregnancy where absolutely necessary.

Lactation: In the absence of clinical experience use of Adenocor during lactation should be considered only if essential.

Not applicable.

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.

•Nervous System disorders

Common:

- Headache

- Dizziness / lightheadedness

Uncommon:

- Head pressure

Very rare:

- Transient, and spontaneously and rapidly reversible worsening of intracranial hypertension

Not known:

- Loss of consciousness / syncope

- Convulsions, especially in predisposed patients (see section 4.4)

•Psychiatric disorders

Common:

- Apprehension

•Eye disorders

Uncommon:

- Blurred vision

•Gastrointestinal disorders

Common:

- Nausea

Uncommon:

- Metallic taste

Not known:

- Vomiting

•Cardiac Disorders:

Very common:

- Asystole

- Bradycardia

- Sinus pause

- Atrioventricular block

- Atrial extrasystoles

- Skipped beats

- Ventricular excitability disorders such as ventricular extrasystoles, non-sustained ventricular tachycardia

Uncommon:

- Sinus tachycardia

- Palpitations

Very rare:

- Severe bradycardia which is not corrected by atropine and may require temporary pacing

- Atrial fibrillation

- Ventricular excitability disorders, including ventricular fibrillation and torsade de pointes (see section 4.4)

Not known:

- Hypotension sometimes severe

- Cardiac arrest, sometimes fatal especially in patients with underlying ischemic heart disease /cardiac disorder (see section 4.4)

•Respiratory, thoracic and mediastinal disorders

Very common:

- Dyspnoea (or the urge to take a deep breath)

Uncommon:

- Hyperventilation

Very rare:

- Bronchospasm (see section 4.4)

Not known:

- Respiratory failure (see section 4.4)

- Apnoea/Respiratory arrest

Cases with fatal outcome of respiratory failure, of bronchospasm, and of apnea / respiratory arrest have been reported.

•Vascular disorders:

Very common:

- Flushing

•General disorders and Administration Site conditions

Very Common:

- Chest pressure/pain, feeling of thoracic constriction / oppression

Common:

- Burning sensation

Uncommon:

- Sweating

- Feeling of general discomfort / weakness / pain

Very rare:

- Injection site reactions

No cases of overdosage have been reported. As the half life of adenosine in blood is very short, the duration of any effects is expected to be limited. 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 Adenocor (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.

Adenosine is impossible to study via classical ADME protocols. 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 <10 seconds. The in vivo half life may be even shorter.

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

Sodium Chloride

Water for Injections

Compatibility with other medicines is not known.

36 months.

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

Do not refrigerate.

Clear, type I glass vials with chlorobutyl rubber closures secured with aluminium caps. Packs of 6 vials in plastic trays in cardboard cartons.

None.

Sanofi-aventis

One Onslow Street

Guildford

Surrey

GU1 4YS

UK

PL 11723/0005

12th March 2002

10 March 2009

POM