Skip to Content

UK Edition. Click here for US version.

ADENOSCAN 30 MG/10 ML SOLUTION FOR INFUSION

Active substance(s): ADENOSINE / ADENOSINE / ADENOSINE

View full screen / Print PDF » Download PDF ⇩

PDF Transcript

SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Adenoscan® 30 mg/10 ml, solution for infusion

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 10 ml vial of Adenoscan® contains 30 mg of adenosine (3 mg/ml)
Excipient: each vial contains 90 mg of sodium chloride (9 mg/ml).
For a full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Solution for infusion
Adenoscan® is a sterile clear, colourless solution

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Intravenous (IV) Adenoscan® is a coronary vasodilator for use in conjunction
with radionuclide myocardial perfusion imaging in patients who cannot
exercise adequately or for whom exercise is inappropriate

4.2

Posology and method of administration
Adenoscan® is intended for use in hospitals with monitoring and cardio-respiratory
resuscitation equipment available for immediate use if necessary.
It should be administered following the same procedure as for exercise testing where
facilities for cardiac monitoring and cardio-respiratory resuscitation are available.
During administration of Adenoscan® continuous ECG control is necessary as life-

threatening arrhythmia might occur. Heart rate and blood pressure should be
monitored every minute.
Adults :
1. Adenoscan® should be administered undiluted as a continuous peripheral
intravenous infusion at a dose of 140 µg/kg/min for six minutes using an infusion
pump. Separate venous sites for Adenoscan® and radionuclide administration are
recommended to avoid an adenosine bolus effect.
2. After three minutes of Adenoscan® infusion, the radionuclide is injected to ensure
sufficient time for peak coronary blood flow to occur. The optimal vasodilator
protocol is achieved with six minutes of Adenoscan® infusion.
3. To avoid an adenosine bolus effect, blood pressure should be measured in the arm
opposite to the Adenoscan® infusion.
The table below is given as a guide for adjustment of the infusion rate of undiluted
Adenoscan®, in line with bodyweight (total dose 0.84 mg/kg).
Patient Weight (kg)
45 - 49
50 - 54
55 - 59
60 - 64
65 - 69
70 - 74
75 - 79
80 - 84
85 - 89
90 - 94
95 - 99
100 - 104

Infusion Rate (ml/min)
2.1
2.3
2.6
2.8
3.0
3.3
3.5
3.8
4.0
4.2
4.4
4.7

Paediatric population:
The safety and efficacy of adenosine in children aged 0-18 years old have not been
established. Currently available data are described in section 5.1 but no
recommendation on a posology can be made.
Elderly:
See dosage recommendations for adults.

4.3

Contraindications
Adenoscan® is contra-indicated in patients suffering from:
-

Hypersensitivity to the active substance or to any of the excipients.

-

Second or third degree atrioventricular (AV) block, sick sinus
syndrome except in patients with a functioning artificial pacemaker

-

Long QT syndrome

4.4

-

Severe hypotension

-

Unstable angina not successfully stabilised with medical therapy

-

Decompensated states of heart failure

-

Chronic obstructive lung disease with evidence of bronchospasm (e.g.
asthma bronchiale)

-

Concomitant use of dipyridamole (see section 4.5).

Special warnings and precautions for use
Adenosine is intended for use 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, Adenoscan®
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. Adenoscan® infusion should
be discontinued in any patient who develops persistent or symptomatic
hypotension.
Adenoscan® should be used with caution in patients with recent myocardial
infarction or severe heart failure. Adenoscan® should be used with caution in
patients with minor conduction defects (first degree AV block, bundle branch
block) that could be transiently aggravated during infusion.
Adenosine may trigger convulsions in patients who are susceptible to
convulsions.
Adenoscan® 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 should lead to treatment discontinuation. Severe
bradycardia would favour the occurrence of torsades de pointes, especially in
patients with prolonged QT intervals. But to date, no case of torsades de
pointes has been reported when adenosine is continuously infused.

The occurrence of respiratory failure (potentially fatal), asystole/cardiac arrest
(potentially fatal), angina, severe bradycardia or severe hypotension should
also lead to treatment discontinuation.
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 (see sections 4.3 and
4.8).
Adenoscan® 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.

4.5

Interaction with other medicinal products and other forms of interaction
Dipyridamole inhibits adenosine cellular uptake and metabolism, and
potentiates the action of Adenoscan®. In one study dipyridamole was shown
to produce a 4 fold increase in adenosine actions. It is therefore suggested that
Adenoscan® should not be administered to patients receiving dipyridamole; if
use of Adenoscan® is essential, dipyridamole should be stopped 24 hours
before hand, or the dose of Adenoscan® should be greatly reduced.
Aminophylline, theophylline and other xanthines are competitive adenosine
antagonists and should be avoided for 24 hours prior to use of Adenoscan®.
Food and drinks containing xanthines (tea, coffee, chocolate and cola) should
be avoided for at least 12 hours prior to use of Adenoscan®.
Adenosine may interact with drugs tending to impair cardiac conduction.

4.6

Pregnancy and lactation
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.
Adenoscan should not be used during breast-feeding.

4.7

Effects on ability to drive and use machines
Not relevant.

4.8

Undesirable effects
Effects related to the known pharmacology of adenosine are frequent, but
usually self-limiting and of short duration. Discontinuation of infusion may be
necessary if the effect is intolerable.
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).
Cardiac Disorders:
- common: hypotension, sometimes severe (see section 4.4), ST segment
depression, sustained or non-sustained ventricular tachycardia, AV block
(see section 4.4).
If sustained second or third degree AV block develops the infusion should be
discontinued. If first degree AV block occurs, the patient should be
observed carefully as a quarter of patients will progress to a higher degree of
block.
- uncommon: bradycardia sometimes severe (see section 4.4)
- not known: asystole /Cardiac arrest (sometimes fatal, especially in patients
with underlying ischemic heart disease/cardiac disorders, see section 4.4):
sinus tachycardia, atrial fibrillation, ventricular fibrillation
Nervous system disorders:
- very common: headache
- common: dizziness, light-headedness, paraesthesia,
- rare: tremor, drowsiness
- not known: loss of consciousness / syncope, convulsions, especially in
predisposed patients (see section 4.4)
Eye disorders:
- rare: blurred vision
Ear and labyrinth disorders:
- rare: tinnitus
Respiratory, thoracic and mediastinal disorders:

- very common: dyspnea (or the urge to breathe deeply)
- rare: bronchospasm (see section 4.4), nasal congestion
- very rare: respiratory failure (see section 4.4)
- not known: apnea/respiratory arrest
Cases with fatal outcome of respiratory failure, of bronchospasm, and of
apnea / respiratory arrest have been reported
Gastro-intestinal disorders:
- very common: abdominal discomfort
- common: dry mouth
- uncommon: metallic taste
- not known: nausea, vomiting
Renal and Urinary disorders:
- rare: urinary urgency

Vascular disorders:
- very common: flushing
General disorders and administration site conditions:
- very common: chest pain or pressure, feeling of thoracic
constriction/oppression
- common: throat, neck and jaw discomfort
- uncommon: sweating, discomfort in the leg, arm or back, feeling of general
discomfort, weakness/pain
- very rare: injection site reactions
Reproductive system and breast disorders:
- rare: nipple discomfort
Psychiatric disorders:
- uncommon: nervousness

4.9

Overdose
Overdosage would cause severe hypotension, bradycardia or asystole. The
half-life of adenosine in blood is very short, and side effects of Adenoscan®
(when they occur) would quickly resolve when the infusion is discontinued.
Administration of IV aminophylline or theophylline may be needed.

5.1.

Pharmacodynamic properties
Pharmacotherapeutic group: Other Cardiac Preparations, ATC code: C01EB 10

Endogenous nucleoside with peripheral vasodilator / antiarrhythmic effect
Adenosine is a potent vasodilator in most vascular beds, except in renal afferent
arterioles and hepatic veins where it produces vasoconstriction. Adenosine exerts its
pharmacological effects through activation of purine receptors (cell-surface A1 and
A2 adenosine receptors). Although the exact mechanism by which adenosine
receptor activation relaxes vascular smooth muscle is not known, there is evidence to
support both inhibition of the slow inward calcium current reducing calcium uptake,
and activation of adenylate cyclase through A2 receptors in smooth muscle cells.
Adenosine may reduce vascular tone by modulating sympathetic neurotransmission.
The intracellular uptake of adenosine is mediated by a specific transmembrane
nucleoside transport system. Once inside the cell, adenosine is rapidly
phosphorylated by adenosine kinase to adenosine monophosphate, or deaminated by
adenosine deaminase to inosine. These intracellular metabolites of adenosine are not
vasoactive.
Intracoronary Doppler flow catheter studies have demonstrated that intravenous
Adenoscan® at 140 µg/kg/min produces maximum coronary hyperaemia (relative to
intracoronary papaverine) in approximately 90% of cases within 2-3 minutes of the
onset of the infusion. Coronary blood flow velocity returns to basal levels within 1-2
minutes of discontinuing the Adenoscan® infusion.
The increase in blood flow caused by Adenoscan® in normal coronary arteries is
significantly more than that in stenotic arteries. Adenoscan® redirects coronary blood
flow from the endocardium to the epicardium and may reduce collateral coronary
blood flow thereby inducing regional ischaemia.
Continuous infusion of adenosine in man has been shown to produce a mild dosedependent fall in mean arterial pressure and a dose-related positive chronotropic
effect, most likely caused by sympathetic stimulation. The onset of this reflex
increase in heart rate occurs later than the negative chronotropic/dromotropic effect.
This differential effect is mostly observed after bolus injection thus explaining the
potential use of adenosine as a treatment for supraventricular arrhythmias when
administered as a bolus or as a coronary vasodilator when administered as an
infusion.
Although Adenoscan® affects cardiac conduction, it has been safely and effectively
administered in the presence of other cardioactive or vasoactive drugs such as beta
adrenergic blocking agents, calcium channel antagonists, nitrates, ACE inhibitors,
diuretics, digitalis or anti-arrhythmics.
Paediatric population
Literature review identified three studies where intravenous adenosine infusion was
used in conjunction with radionuclide myocardial perfusion imaging at a dose of 0.14
mg/kg body weight/min for 2-4 minutes in paediatric patients aged 1 month to 18
years. The largest study included 47 patients aged 1 month to 18 years of age and
reported 87% sensitivity (CI 52-97%) and 95% specificity (CI 79-99%) for
cardiovascular magnetic resonance imaging under pharmacological stress with
intravenous adenosine in a dose of 0.14 mg/kg/min for 3 minutes. No adverse events
were reported in the study. However, the currently available data is considered very
limited to support the use of adenosine for diagnostic purposes in the paediatric
population.

5.2

Pharmacokinetic properties
It is impossible to study adenosine in classical pharmacokinetic studies. It is
present in various forms in all the 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 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.
Since neither the kidney nor the liver are involved in the degradation of
exogenous adenosine, the efficacy of Adenoscan® should be unaffected by
hepatic or renal insufficiency.

5.3

Preclinical safety data
Because adenosine is naturally present in all living cells, studies in animals to
evaluate the carcinogenic potential of Adenoscan® (adenosine) have not been
performed.
No controlled reproductive studies were conducted in animals with adenosine.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Sodium Chloride
Water for Injection

6.2

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

6.3

Shelf life
The shelf life of the unopened product is 3 years
The product should be used immediately after opening

6.4

Special precautions for storage
Do not refrigerate.
See section 6.3

6.5

Nature and contents of container
Type I glass vials with chlorobutyl rubber stoppers, packs with 6 vials

6.6

Special precautions for disposal
See section 4.2.
The product is for single use only.
The product should be inspected visually for particulate matter and colouration
prior to administration. Where the visual appearance of the product may have
changed, the vial should be discarded.
Any unused product or waste material should be disposed of in accordance
with local requirements.

7

MARKETING AUTHORISATION HOLDER
Aventis Pharma Limited
One Onslow Street
Guildford
Surrey
GU1 4YS
UK
or trading as
Sanofi-aventis or Sanofi
One Onslow Street
Guildford
Surrey
GU1 4YS
UK

8

MARKETING AUTHORISATION NUMBER(S)
PL 04425/0682

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
03/05/2010

10

DATE OF REVISION OF THE TEXT
28/11/2013

Expand Transcript

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

Hide