PERSANTIN AMPOULES 10MG/2ML SOLUTION FOR INFUSION

Active substance: DIPYRIDAMOLE

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PROFESSIONAL LEAFLET



Persantin® Ampoules
10 mg/2 ml Solution
for Infusion

abcd

(dipyridamole)
TRADE NAME OF MEDICINAL PRODUCT
PERSANTIN Ampoules 10 mg / 2 ml Solution for
Infusion
QUALITATIVE AND QUANTITATIVE
COMPOSITION
Dipyridamole 5 mg/ml. Each 2 ml ampoule
contains 10 mg dipyridamole.

Patients with severe coronary artery disease,
including unstable angina and recent myocardial
infarction (within 4 weeks), left ventricular
outflow obstruction or haemodynamic instability
(e.g. decompensated heart failure).
Patients with bronchial asthma or a tendency to
bronchospasm.

PHARMACEUTICAL FORM
Solution for infusion.

CLINICAL PARTICULARS

Patients with myasthenia gravis. (See
Interactions.)

Therapeutic indications
Adults:
As an alternative to exercise stress in
thallium-201 myocardial imaging, particularly in
patients unable to exercise or in those for whom
exercise may be contraindicated.

Special warnings and special precautions for use
The potential clinical information to be gained
through use of intravenous PERSANTIN as an
adjunct in myocardial imaging must be weighed
against the risk to the patient. Comparable
reactions to exercise-induced stress may occur.
Therefore dipyridamole-thallium scanning should
be performed with continuous ECG monitoring of
the patient.

Pregnancy and lactation.

Children:
As an alternative to exercise stress in myocardial
perfusion imaging, particularly in children unable
to exercise or in those for whom exercise may be
contraindicated. More specifically, this may
include children with Kawasaki disease
complicated by coronary artery involvement, or
those with congenitally abnormal coronary
circulations.
Posology and method of administration
The dose of intravenous PERSANTIN as an
adjunct to thallium myocardial perfusion imaging
should be adjusted according to the weight of the
patient. The recommended dose is 0.142 mg/kg/
minute (0.567 mg/kg total) infused over 4
minutes.
Thallium-201 should be injected within 3-5
minutes following the 4-minute infusion of
PERSANTIN.
Contraindications
Hypersensitivity to any of the components of the
product.
Patients with dysrhythmias, second- or third
degree atrioventricular block or with sick sinus
syndrome should not receive intravenous
PERSANTIN (unless they have a functioning
pacemaker). Patients with baseline hypotension
(systolic blood pressure < 90 mmHg), recent
unexplained syncope (within 4 weeks) or with
recent transient ischaemic attacks are not
suitable candidates for dipyridamole testing.

When myocardial imaging is performed with
intravenous PERSANTIN, parenteral
aminophylline should be readily available for
relieving adverse effects such as bronchospasm
or chest pain. Vital signs should be monitored
during and for 10 -15 minutes following the
intravenous infusion of PERSANTIN and an
electrocardiographic tracing should be obtained
using at least one chest lead.
Sedation may be necessary in young children.
Use with caution in young infants with immature
hepatic metabolism.
Should severe chest pain or bronchospasm occur,
parenteral aminophylline may be administered by
slow intravenous injection; for adults, doses
ranging from 75 mg to 100 mg aminophylline,
repeated if necessary, are appropriate; for
children, doses of 3-5 mg/kg aminophylline have
been used.
In the case of severe hypotension, the patient
should be placed in a supine position with the
head tilted down if necessary, before
administration of parenteral aminophylline. If
aminophylline does not relieve chest pain
symptoms within a few minutes, sublingual
nitroglycerin may be administered. If chest pain
continues despite use of aminophylline and
nitroglycerin, the possibility of myocardial
infarction should be considered.

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If the clinical condition of a patient with an
adverse effect permits a one minute delay in the
administration of parenteral aminophylline,
thallium-201 may be injected and allowed to
circulate for one minute before the injection of
aminophylline. This will allow initial thallium
perfusion imaging to be performed before
reversal of the pharmacologic effects of
PERSANTIN on the coronary circulation.
Patients being treated with regular oral doses of
PERSANTIN should not receive additional
intravenous dipyridamole. Clinical experience
suggests that patients being treated with oral
dipyridamole who also require pharmacological
stress testing with intravenous dipyridamole
should discontinue drugs containing oral
dipyridamole for twenty-four hours prior to stress
testing.
Caution should be exercised in patients with
known pre-existing first-degree heart block.
Interactions with other medicinal products and
other forms of interaction
Xanthine derivatives (e.g. caffeine and
theophylline) can potentially reduce the
vasodilating effect of dipyridamole and should
therefore be avoided 24 hours before myocardial
imaging with PERSANTIN. For discontinuation of
oral dipyridamole see section 4.4.
Dipyridamole increases plasma levels and
cardiovascular effects of adenosine.
Dipyridamole may increase the hypotensive effect
of drugs which reduce blood pressure.
Dipyridamole may counteract the anticholinesterase effect of cholinesterase inhibitors
thereby potentially aggravating myasthenia
gravis.
Fertility, pregnancy and lactation
Pregnancy and lactation
Use of intravenous dipyridamole for cardiac stress
testing in pregnancy and lactation is not
recommended.
Fertility
No studies on the effect on human fertility have
been conducted with PERSANTIN. Non-clinical
studies with dipyridamole did not indicate direct
or indirect harmful effects with respect to fertility
(please refer to preclinical safety data).

Effect on ability to drive and use machines
No studies on the effects on the ability to drive
and use machines have been performed.
However, patients should be advised that they
may experience undesirable effects such as
dizziness during treatment with PERSANTIN. If
patients experience dizziness they should avoid
potentially hazardous tasks such as driving or
operating machinery.

2

Undesirable effects
When using as an adjunct to myocardial imaging,
the following adverse events have been reported.
Frequencies have been assigned based on two
clinical trials of 73,806 and 3,911 patients.

Frequencies
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
Immune system disorders
Hypersensitivity
Anaphylactoid reaction
Angioedema

rare
very rare
not known

Nervous system disorders
Headache
Dizziness
Paraesthesia
Transient ischaemic attack
Cerebrovascular accident
Convulsion

very common
very common
common
rare
very rare
very rare

Cardiac disorders
Chest pain/angina pectoris
Arrhythmia
Tachycardia
Myocardial infarction
Bradycardia
Cardiac arrest
Ventricular fibrillation
Syncope
Sinus arrest
Atrioventricular block

very common
common
not known
uncommon
uncommon
very rare
very rare
not known
not known
not known

Vascular disorders
Hypotension
Hot flush

common
common

Respiratory, thoracic and mediastinal disorders
Bronchospasm
uncommon
Laryngospasm
not known
Gastrointestinal disorders
Nausea
Abdominal pain
Diarrhoea
Vomiting

common
uncommon
not known
not known

Skin and subcutaneous tissue disorders
Urticaria
not known
Rash
not known
Musculoskeletal, connective tissue and bone
disorders
Myalgia
not known
General disorders and administration site
conditions
Cardiac death
rare
Oedema
not known
Investigations
Electrocardiogram ST-T
change
Electrocardiogram change

common
not known

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At high doses of intravenous dipyridamole as
used in cardiac imaging, more frequent and
severe side effects have been reported than those
reported during either intravenous or oral
administration of dipyridamole at the
recommended doses. Nevertheless, all available
data suggest that the benefit risk ratio is at least
as favourable as the benefit-risk ratio of
conventional exercise testing.
Overdose
Symptoms:
Although there is no experience of overdose, the
signs and symptoms that might be expected to
occur include cardiac death, cardiac arrest,
myocardial infarction, chest pain, angina pectoris,
electrocardiographic changes, syncope,
cerebrovascular events, hypotension, hot flushes,
hypersensitivity reactions, anaphylactoid
reactions, gastrointestinal symptoms, dizziness,
headache, paraesthesia, myalgia, bitter taste and
blood pressure lability.
Therapy:
Symptomatic therapy is recommended.
Should severe chest pain or bronchospasm occur,
parenteral aminophylline may be administered by
slow intravenous injection; for adults, doses
ranging from 75 to 100 mg aminophylline,
repeated if necessary, are appropriate; for
children, doses of 3-5 mg/kg aminophylline have
been used. If aminophylline does not relieve
chest pain symptoms within a few minutes,
sublingual nitroglycerin may be administered. If
chest pain continues despite use of
aminophylline and nitroglycerin, the possibility of
myocardial infarction should be considered.
Due to its wide distribution to tissues and its
predominantly hepatic elimination, dipyridamole
is not likely to be accessible to enhanced removal
procedures.
PHARMACOLOGICAL PROPERTIES
Pharmacodynamic properties
Dipyridamole inhibits the uptake of adenosine
into erythrocytes, platelets and endothelial cells
in vitro and in vivo; the inhibition amounts to
80% at its maximum and occurs dosedependently at concentrations of 0.5 - 2 µg/mL.
Consequently, there is an increased concentration
of adenosine locally to act on the platelet
A2-receptor, stimulating platelet adenylate
cyclase, thereby increasing platelet cAMP levels.
Thus, platelet aggregation in response to various
stimuli such as PAF, collagen and ADP is
inhibited. Reduced platelet aggregation reduces
platelet consumption towards normal levels. In
addition, adenosine has a vasodilator
effect and this is one of the mechanisms by which
dipyridamole produces vasodilation.
Presumably via a ‘steal effect’ the vasodilation
induced by PERSANTIN administered i.v. in doses
used for cardiac imaging techniques leads to
regional redistribution of coronary blood flow and
may lead to abnormalities in thallium distribution
and ventricular function in patients with coronary
artery disease.
3

The normal vessels dilate with enhanced flow,
leaving relatively reduced pressure and flow
across areas of haemodynamically important
coronary stenoses.
Dipyridamole inhibits phosphodiesterase (PDE) in
various tissues. Whilst the inhibition of cAMPPDE is weak, therapeutic levels inhibit cGMP-PDE,
thereby augmenting the increase in cGMP
produced by EDRF (endothelium-derived relaxing
factor, identified as NO).
Dipyridamole also stimulates the biosynthesis
and release of prostacyclin by the endothelium.
Dipyridamole reduces the thrombogenicity of
subendothelial structures by increasing the
concentration of the protective mediator
13-HODE (13-hydroxyoctadecadienic acid).
Pharmacokinetic properties
Distribution
Owing to its high lipophilicity, log P 3.92
(n-octanol/0.1N, NaOH), dipyridamole distributes
to many organs. After i.v. administration
(60 mg/75 min) fitted by a 3-compartment model
a rapid alpha phase, with a half-life of about 3
min presumably reflecting distribution of the drug
from the central compartment to peripheral
compartments, is observed. The apparent volume
of distribution of the central compartment (Vc) is
about 5 L (similar to plasma volume). The
apparent volume of distribution at steady state is
about 100 L, reflecting distribution to various
compartments.
Non-clinical studies indicate that dipyridamole is
distributed preferentially to the liver, then to the
lungs, kidneys, spleen and heart, it does not cross
the blood-brain barrier to a significant extent and
shows a very low placental transfer. Non-clinical
data have also shown that dipyridamole can be
excreted in breast milk.
Protein binding of dipyridamole is about 97-99%,
primarily it is bound to alpha 1-acid glycoprotein
and albumin.
Metabolism
Metabolism of dipyridamole occurs in the liver.
Dipyridamole is metabolized by conjugation with
glucuronic acid to form mainly a monoglucuronide
and only small amounts of diglucuronide. After
i.v. treatment, glucuronide concentrations are
approx. 10% of total drug.
Elimination
After i.v. administration (60 mg/75 min) fitted by
a 3-compartment model, a beta phase, with a
half-life of about 40 min (dominant half-life) and
a prolonged terminal elimination phase (λZ) with a
half-life of about 15 hours are observed.
According to this model, the beta phase
represents the elimination of most of the
administered drug and accounting for about 70%
(together with the alpha phase) of the total AUC,
whereas the terminal elimination phase (about
30% of the total AUC) probably represents the
rediffusion of a smaller proportion of the
administered dose from remotely accessible
tissues of low capacity back into the central
compartment.
22D626

Renal excretion of parent compound is negligible
(< 0.5%). Urinary excretion of the glucuronide
metabolite is low (< 8%), the metabolites are
mostly (about 95%) excreted via the bile into the
faeces, with some evidence of entero-hepatic
recirculation. Total clearance is approximately
200 mL/min and mean residence time is 6.4
hours.
Elderly subjects
Plasma concentrations (determined as AUC) in
elderly subjects (> 65 years) were about 30-50%
higher with oral treatment than in young (< 55
years) subjects and the difference is caused
mainly by reduced clearance; a slower decrease of
plasma concentrations after i.v. treatment is to be
expected.
Hepatic impairment
Patients with hepatic insufficiency show no
change in plasma concentrations of dipyridamole,
but an increase of (pharmacodynamically low
active) glucuronides. It is suggested to dose
dipyridamole without restriction as long as there
is no clinical evidence of liver failure.

Marketing Authorisation Number
PL 0015/0119
Marketing Authorisation Holder
Boehringer Ingelheim Limited
Ellesfield Avenue
Bracknell
Berkshire
RG12 8YS, England
Manufacturer of the product
Boehringer Ingelheim España S.A.
Prat de la Riba, 50
08174 Sant Cugat del Vallés
Barcelona, Spain
Legal Category
POM
Date of revision of the text
This professional leaflet was revised in March
2013
© Boehringer Ingelheim Limited 2013

Renal impairment
Since renal excretion is very low (5%), no change
in pharmacokinetics is to be expected in cases of
renal insufficiency. In the ESPS2 trial, in patients
with creatinine clearances ranging from about 15
mL/min to >100 mL/min, no changes were
observed in the pharmacokinetics of
dipyridamole or its glucuronide metabolite if data
were corrected for differences in age.
Preclinical Safety Data
Dipyridamole has been extensively investigated in
animal models and no clinically significant
findings have been observed at doses equivalent
to therapeutic doses in humans.
PHARMACEUTICAL PARTICULARS
List of excipients
Tartaric acid
Macrogol 600
Hydrochloric acid
Water for injections
Incompatibilities
None stated.
Shelf life
3 years.
Special precautions for storage
Keep container in the outer carton.
Nature and contents of container
Carton containing 5 x 2 ml colourless Type I glass
ampoules.
Instructions for use, handling and disposal
None stated.

4

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PACKAGE LEAFLET:
INFORMATION FOR THE USER

Persantin® Ampoules
10 mg/2 ml Solution
for Infusion

abcd

(dipyridamole)
Read all of this leaflet carefully before you start
taking this medicine.
• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your
doctor or pharmacist.
• This medicine has been prescribed for you. Do
not pass it on to others. It may harm them, even
if their symptoms are the same as yours.
• If any of the side effects gets troublesome or
serious, or if you notice any side effects not
listed in this leaflet, please tell your doctor or
pharmacist.
In this leaflet:
1. What PERSANTIN Ampoules are and what they
are used for
2. Before you receive PERSANTIN Ampoules
3. How PERSANTIN Ampoules will be given
4. Possible side effects
5. How to store PERSANTIN Ampoules
6. Further information
1. WHAT PERSANTIN AMPOULES ARE AND
WHAT THEY ARE USED FOR
The name of your injection is PERSANTIN
Ampoules 10 mg / 2 ml Solution for Infusion
(called PERSANTIN Ampoules in this leaflet).
• It contains a medicine called dipyridamole. This
belongs to a group of medicines called
‘coronary vasodilators’
• It works by opening up (dilating) the blood
vessels in the heart
PERSANTIN Ampoules are used instead of
exercise during scans to assess heart conditions.
2. BEFORE YOU RECEIVE PERSANTIN AMPOULES
You should not be given PERSANTIN Ampoules
if:
• You are allergic (hypersensitive) to dipyridamole
or any of the other ingredients of PERSANTIN
Ampoules (listed in Section 6 below)
• You have heart problems such as a recent heart
attack (within the last 4 weeks), angina (chest
pain) at rest, irregular heart beat, heart block
(this usually causes a slow heart beat), heart
failure or a problem affecting the heart valves
• You have low blood pressure or have recently
fainted (within the last 4 weeks) for no apparent
reason
• You have had a stroke or something called a
‘transient ischaemic attack’ (a temporary stroke
that lasts less than 24 hours)
• You have breathing problems such as asthma,
shortness of breath or wheezing
• You have myasthenia gravis (a rare muscle
problem)
• You are pregnant, likely to get pregnant or are
breast-feeding
5

You should not receive this medicine if any of the
above apply to you. If you are not sure, talk to
your doctor or pharmacist before having
PERSANTIN Ampoules.
Take special care with PERSANTIN Ampoules
Check with your doctor or pharmacist before
having this medicine if:
• The person having the injection is a young
infant whose liver is not fully grown
Taking other medicines
Please tell your doctor or pharmacist if you are
taking or have recently taken any other medicines.
This includes medicines obtained without a
prescription and herbal medicines. This is because
PERSANTIN Ampoules can affect the way some
other medicines work. Also some other medicines
can affect the way PERSANTIN Ampoules work.
In particular tell your doctor or pharmacist if you
are taking any of the following medicines:
• Medicines used to treat high or low blood
pressure
• Medicines that contain something called
“xanthine derivatives” such as caffeine and
theophylline. This also includes drinks such as
tea, coffee and cola. If you have taken any of
these, you need to wait at least 24 hours before
having PERSANTIN Ampoules. This is because
the caffeine can stop the injection working
properly
• Medicines containing dipyridamole
Having PERSANTIN Ampoules with food and
drink
You need to wait at least 24 hours before
receiving PERSANTIN Ampoules if you have had a
drink with caffeine in it such as tea, coffee or
cola. This is because caffeine can stop the
injection working properly.
Pregnancy and breast-feeding
You should not be given PERSANTIN Ampoules if
you are pregnant, likely to get pregnant or are
breast-feeding.
Driving and using machines
You may feel dizzy while receiving PERSANTIN
Ampoules. If this happens do not drive or use any
tools or machines.

22D626

3. HOW PERSANTIN AMPOULES WILL BE GIVEN
PERSANTIN Ampoules are usually given by a
doctor or nurse. How much you are given
depends on how much you weigh.
Receiving the injection
• PERSANTIN Ampoules are slowly injected into a
vein over 4 minutes
• This process is often called having an infusion
• An injection of something called ‘thallium–201’
is then given within 3-5 minutes of the first
injection
If you have more PERSANTIN Ampoules than you
should
It is unlikely that you will be given too much of
this medicine. However, tell the doctor or nurse if
you think that you have been given too much.
4. POSSIBLE SIDE EFFECTS

Not known
• Serious allergic reaction the signs of which
include swelling of the face or throat, sudden
difficulties in breathing
• Build up of fluid in the body causing swelling
(oedema)
• Rash, urticaria (nettle rash)
• Faster heart rate than normal
• Fainting
• A heart problem called Atroventricular block
• Being sick (vomiting) or diarrhoea
• Muscle pain
If any of the side effects gets troublesome or
serious, or if you notice any side effects not listed
in this leaflet, please tell your doctor or
pharmacist.
5. HOW TO STORE PERSANTIN AMPOULES

Like all medicines, PERSANTIN Ampoules can
cause side effects, although not everybody gets
them. The following side effects may happen with
this medicine:

• Keep out of the reach and sight of children
• PERSANTIN Ampoules should be kept in the
outer carton
• Do not use the ampoules after the expiry date
which is printed on the packaging

The side effects described below have been
experienced by people taking PERSANTIN
Ampoules. They are listed as either very common,
common, uncommon, rare, very rare or not
known.

Medicines should not be disposed of via
wastewater or household waste. Ask your
pharmacist how to dispose of medicines no
longer required. These measures will help to
protect the environment.

Very Common (affects more than 1 in 10 people)
• Headache
• Dizziness
• Chest pain

6. FURTHER INFORMATION

Uncommon (affects less than 1 in 100 people but
more than 1 in 1,000 people)
• Heart attack
• Slower heart beat
• Difficulty in breathing or wheezing
• Gut (abdominal) pain
Rare (affects less than 1 in 1,000 people but more
than 1 in 10,000 people)
• Hypersensitivity
• Stroke like symptoms that start suddenly but
only last a short time
• Heart problems causing shortness of breath or
ankle swelling
Very rare (affects less than 1 in 10,000 people)
• Serious allergic reaction which causes
difficulty in breathing or dizziness
• Stroke
• Fits (convulsions)
• Cardiac arrest
• Severe heart problem which causes abnormal
and irregular heart beats (ventricular fibrillation)

6

What PERSANTIN Ampoules look like and
contents of the pack
PERSANTIN Ampoules are clear glass vials
containing a clear, yellow liquid. They are
supplied in cartons of 5 ampoules.
Marketing Authorisation Holder and
Manufacturer
The Marketing Authorisation for PERSANTIN
Ampoules is held by:
Boehringer Ingelheim Limited
Ellesfield Avenue
Bracknell
Berkshire
RG12 8YS
and the ampoules are manufactured at:
Boehringer Ingelheim España S.A.
Prat de la Riba, 50
08174 Sant Cugat del Vallés
Barcelona, Spain
This leaflet was revised in March 2013.
© Boehringer Ingelheim Limited 2013

20110714

Common (affects less than 1 in 10 people but
more than 1 in 100)
• Irregular heart beats
• Pins and needles (paraesthesia)
• Lower blood pressure than normal
• Hot flushes
• Feeling sick (nausea)

What PERSANTIN Ampoules contain
• The active substance is dipyridamole. One 2 ml
ampoule contains 10 mg dipyridamole
• The other ingredients in the injection are
tartaric acid, macrogol 600, hydrochloric acid
and water for injections

22D626

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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.

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