ADENOCOR Solution for injection Ref.[6080] Active ingredients: Adenine Deoxy Nucleoside

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 (see section 4.2).

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. There have been reports of cerebrovascular accident/transient ischemic attack, secondary to the haemodynamic effects of adenosine.

There have been reports of myocardial infarction shortly after use of Adenocor. 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 (see section 4.5).

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 (see section 4.3).

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

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.

Paediatric population

Adenosine may trigger atrial arrhythmias and thus might lead to ventricular acceleration in children with Wolff-Parkinson-White (WPW) syndrome (see section 5.1).

The efficacy of intraosseus administration has not been established.

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 (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.

Adenocor 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.

Breast-feeding

It is unknown whether adenosine metabolites are excreted in human milk. Adenocor should not be used during breast-feeding.

Not applicable.

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).

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).

Immune system disorders

Not known: anaphylactic reaction (including angioedema and skin reactions such as urticaria and rash).

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

Not known: asystole/cardiac arrest, sometimes fatal especially in patients with underlying ischemic heart disease/cardiac disorder (see section 4.4)

Vascular disorders

Very common: flushing

Not known: hypotension (sometimes severe) (see section 4.4)

Nervous system disorders

Common: headache, dizziness, light-headedness, paraesthesia

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)

Eye disorders

Uncommon: blurred vision

Respiratory, thoracic and mediastinal disorders

Very common: dyspnea (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), apnea/respiratory arrest

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

Gastrointestinal disorders

Common: nausea

Uncommon: metallic taste

Not known: vomiting

Psychiatric disorders

Common: nervousness

General disorders and administration site conditions

Very common: chest pain or pressure, feeling of thoracic constriction/oppression

Uncommon: sweating, discomfort in the leg, arm or back, feeling of general discomfort, weakness/pain

Very rare: injection site reactions

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme at: www.mhra.go.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Compatibility with other medicines is not known.