PERSANTIN AMPOULES 10MG/2ML SOLUTION FOR INFUSION

Active substance: DIPYRIDAMOLE

View full screen / Print PDF » Download PDF ⇩

Transcript
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.
PHARMACEUTICAL FORM
Solution for infusion.
CLINICAL PARTICULARS
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.
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 circulation.
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.

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.
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 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.

Contraindications
Hypersensitivity to any of the components of the
product.

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.

Patients with dysrhythmias, second- or thirddegree 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.

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 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 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.

Patients with bronchial asthma or a tendency to
bronchospasm.
Patients with myasthenia gravis. (See Interactions.)
Pregnancy and lactation.

Caution should be exercised in patients with
known pre-existing first-degree heart block.
22DXXX

1

Mandatory in

Technical information

TD

File information

Printfile

a = Batch No.

b = Expiry date

Issue date of TD:

20-05-2011

Yes

Yes

c = Manufacturing date

d = Price/Sample/Clinic

PPM SKU:

P003236

No

Yes

Technical colors

PPM SKU version: 

006

No

Yes

BI-Diecut-Legendcase

Issue date of artwork:

27-09-2012

No

Yes

Print colors:

PAN Black

No

Yes

Free area

Gluepoints

Additional Requirements of Packaging site
* Registration mark: Use the darkest print color or use the same color of text.

Mat. No. Pack. Site:

22DXXX

Legend case version:

V3.0 01/JUN/2010 (please do not change or remove it)

No

Yes

** Page number: Use the darkest print color or use the same color of text.
TD file: TMP_PI_155x250_6c_AMP
Template number: 0000-49 / 0000-50 / 0000-51 / 0000-52 / 0000-53 / 0000-54

Interaction 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.
Pregnancy and lactation
Use of intravenous dipyridamole for cardiac
stress testing in pregnancy and lactation is not
recommended.
Effect on ability to drive and use machines
None stated.
Undesirable effects
Approximately 47% of patients given intravenous
dipyridamole will experience an adverse event, of
which 0.26% would be expected to be severe.
When using PERSANTIN as an adjunct to
myocardial imaging, the following adverse events
have been reported: cardiac death, cardiac arrest,
myocardial infarction (rarely fatal), chest pain/
angina pectoris, electrocardiographic changes
(most commonly ST-T changes), arrhythmias (e.g.
sinus node arrest, heart block, tachycardia,
bradycardia, fibrillation), syncope and
cerebrovascular events (e.g. stroke, TIA, seizures).
PERSANTIN may cause severe hypotension and
hot flushes.
Hypersensitivity reactions such as rash, urticaria,
angioedema, laryngospasm, severe
bronchospasm, and very rarely anaphylactoid
reactions have been reported.
Other adverse reactions include: abdominal pain,
vomiting, diarrhoea, nausea, dizziness, headache,
paraesthesia, myalgia, hypertension, blood
pressure lability, fatigue and dyspepsia. A bitter
taste has been experienced after i.v. injection.
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.

2

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.
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).

22DXXX

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.
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.
3

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.
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
None
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
Cartons containing 5 x 2 ml colourless glass
(Type I) ampoules.
Instructions for use, handling and disposal
None stated.
Marketing authorisation number
PL 00015/0119
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 October
2012.
© Boehringer Ingelheim Limited 2012

22DXXX

4

22DXXX

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 ischemic 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
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.
5

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 the 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.
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.
22DXXX

4. POSSIBLE SIDE EFFECTS
Like all medicines, PERSANTIN Ampoules can
cause side effects although not everybody gets
them. The following side effects may happen with
this medicine:
Allergic reactions
• Rash or itching

• Swelling of the face or mouth or wheezing
• In a few cases this could be sudden and severe
(anaphylactoid reaction)
Heart problems
• Heart beat problems
• Chest pain
• Cardiac arrest and heart attack (in a few cases
fatal)

Other side effects
• Higher or lower blood pressure than normal
• Hot flushes or fainting
• Feeling sick (nausea), being sick (vomiting),
indigestion or diarrhoea
• Feeling dizzy, tired (fatigue) or having a
headache
• Gut (abdominal ) or muscle (myalgia) pain
• Pins and needles (paraesthesia)
• A bitter taste is sometimes experienced
immediately after the injection of PERSANTIN
Ampoules
• Stroke
• Fits (seizures)
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.

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 October 2012.
© Boehringer Ingelheim Limited 2012

5. HOW TO STORE PERSANTIN AMPOULES
• 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
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.
6. FURTHER INFORMATION
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

20020725

What PERSANTIN Ampoules looks 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.

6

22DXXX

Expand view ⇕

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
(web2)