sanofi-aventis

Adenocor 3mg/ml Solution for Injection

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

Each vial also contains 0.3mmol of sodium per 2ml (0.15mmol/ml).

For a full list of excipients, see section 6.1

Solution for injection.

A 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 (injection 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.

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:

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.

Adenosine may precipitate or aggravate bronchospasm.

Precautions:

Adenosine is intended for use by physicians familiar with the product (see Section 4.2 Posology and Method of Administration) in a hospital setting with monitoring and cardio-respiratory resuscitation equipment available for immediate use if necessary.

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.

Use of Adenoscan^® infusion is contraindicated in patients receiving dipyridamole (see Section 4.3 Contraindications of the Adenoscan® Summary of Product Characteristics). If use of adenosine bolus injection is judged to be essential, dipyridamole should be discontinued 24 hours beforehand, or the dose of adenosine should be significantly reduced.

Adenocor contains 18mg sodium per injection vial (2ml). This should 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 dipyridamol was shown to produce a 4 fold increase in adenosine activity. Use of Adenoscan^® infusion (30mg/mL) is contraindicated in patients receiving dipyridamole (see Section 4.3 Contraindications of the Adenoscan® Summary of Product Characteristics). If use of adenosine bolus injection is judged to be essential, dipyridamole should be discontinued 24 hours beforehand, or the dose of adenosine should be significantly 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.

Adenosine may interact with drugs tending to impair cardiac conduction.

Pregnancy: In the absence of evidence that adenosine does not cause foetal harm, Adenocor should not be used during pregnancy unless the physician considers the benefits to outweigh the potential risks.

Lactation: Studies have not been performed in lactating animals or women. Therefore, adenosine should not be used during lactation. If adenosine treatment is considered essential by the physician, another form of infant feeding should be considered.

Not applicable.

Frequencies provided refer to legacy data. For newly included safety items, which are based exclusively on post-marketing experience, the frequency listed is: “Not known”. The following CIOMS frequency rating is used, where applicable:

• Nervous system disorders

Common:

- headache,

- dizziness / lightheadedness

Uncommon:

- head pressure

Very rare:

- transient, and spontaneously rapidly reversible worsening of intracranial hypertension

Not known:

- loss of consciousness/syncope

- convulsions, especially in predisposed patients (see Section 4.4 Special Warnings and Precautions for Use)

• Psychiatric disorders

Common: apprehension

• Eye disorders

Uncommon: blurred vision

• Vascular disorders

Very common: flushing

• Gastro-intestinal disorders

Common: nausea

Uncommon: metallic taste

Not known: vomiting

• Cardiac disorders:

Very common:

- bradycardia

- sinus pause, skipped beats

- atrial extrasystoles

- atrio-ventricular block

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

Uncommon:

- sinus tachycardia

- palpitations

Very rare:

- atrial fibrillation

- severe bradycardia, not corrected by atropine and possibly requiring temporary pacing

- venticular excitability including ventricular fibrillation and torsades de pointes

Not known:

- hypotension sometimes severe

- asystole/cardiac arrest, sometimes fatal especially in patients with underlying ischaemic heart disease/cardiac disorder

• 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 Special Warnings and Precautions for Use)

Not known:

- respiratory failure (see Section 4.4 Special Warnings and Precautions for Use)

- apnoea/respiratory arrest.

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

• 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

As the half life of adenosine is very short (less than 10 seconds), adverse effects are generally rapidly self-limiting.

Treatment of any prolonged adverse effects should be individualised and directed towards the specific symptom.

Methylxanthines, such as caffeine, theophylline, and aminophylline are competitive antagonists of adenosine.

Intravenous aminophylline or theophylline may be needed.

Antiarrhythmic drug.

Adenosine is a purine nucleoside which is present in all cells of the body. Animal pharmacology studies in several species have 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.

A single 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 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.

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 in vitro half life 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.

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

3 years.

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

Do not refrigerate.

Packs of six clear, Type I glass vials with chlorobutyl rubber closures secured with aluminium caps containing 2ml of solution.

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

sanofi-aventis Ireland Ltd.

Citywest Business Campus

Dublin 24

PA 540/139/1

Date of first authorisation: 16^th June 1994

Date of last renewal: 16^th June 2008

March 2010