ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS
1.
Pedea 5 mg/ml solution for injection
2.
Each ml of the solution contains 5 mg ibuprofen.
Each ampoule of 2 ml contains 10 mg ibuprofen.
Excipients: each ml contains 7.5 mg of sodium.
For a full list of excipients, see section 6.1.
3.
Solution for injection.
Clear, colourless to slightly yellow solution.
4.
Treatment of a haemodynamically significant patent
ductus arteriosus
in preterm newborn infants less
than 34 weeks of gestational age.
Treatment with Pedea should only be carried out in a neonatal intensive care unit under the
supervision of an experienced neonatologist.
Posology
A course of therapy is defined as three intravenous injections of Pedea given at 24-hour intervals. The
first injection should be given after the first 6 hours of life.
The ibuprofen dose is adjusted to the body weight as follows:
- 1
st
injection: 10 mg/kg,
- 2
nd
and 3
rd
injections: 5 mg/kg.
If anuria or manifest oliguria occurs after the first or second dose, the next dose should be withheld
until urine output returns to normal levels.
If the
ductus arteriosus
does not close 48 hours after the last injection or if it re-opens, a second course
of 3 doses, as above, may be given.
If the condition is unchanged after the second course of therapy, surgery of the patent
ductus
arteriosus
may then be necessary.
Method of administration
For intravenous use only.
Pedea should be administered as a short infusion over 15 minutes, preferably undiluted. If necessary,
the injection volume may be adjusted with either sodium chloride 9 mg/ml (0.9%) solution for
injection or glucose 50 mg/ml (5%) solution for injection. Any unused portion of the solution should
be discarded.
The total volume of solution injected should take into account the total daily fluid volume
administered.
2
-
Hypersensitivity to the active substance or to any of the excipients;
-
Life-threatening infection;
-
Active bleeding, especially intracranial or gastrointestinal haemorrhage;
-
Thrombocytopenia or coagulation defects;
-
Significant impairment of renal function;
-
Congenital heart disease in which patency of the
ductus arteriosus
is necessary for satisfactory
pulmonary or systemic blood flow (e.g. pulmonary atresia, severe tetralogy of Fallot, severe
coarctation of the aorta);
-
Known or suspected necrotising enterocolitis;
Before administration of Pedea an adequate echocardiographic examination should be performed in
order to detect a haemodynamically significant patent
ductus arteriosus
and to exclude pulmonary
hypertension and ductal-dependent congenital heart disease.
Since prophylactic use in the first 3 days of life (starting within 6 hours of birth) in preterm newborn
infants less than 28 weeks of gestational age was associated with increased pulmonary and renal
adverse events, Pedea should not be used prophylactically at any gestational age (see sections 4.8 and
5.1). In particular, severe hypoxemia with pulmonary hypertension was reported in 3 infants within
one hour of the first infusion and was reversed within 30 min after start of inhaled nitric oxide therapy.
Since ibuprofen was shown
in vitro
to displace bilirubin from its binding site to albumin, the risk of
bilirubin encephalopathy in premature newborn infants may be increased (see section 5.2). Therefore,
ibuprofen should not be used in infants with marked elevated bilirubin concentration.
As a non-steroidal anti-inflammatory drug (NSAID), ibuprofen may mask the usual signs and
symptoms of infection. Pedea must therefore be used cautiously in the presence of an infection (see
also section 4.3).
Pedea should be administered carefully to avoid extravasation and potential resultant irritation to
tissues.
As ibuprofen may inhibit platelet aggregation, premature neonates should be monitored for signs of
bleeding.
As ibuprofen may decrease the clearance of aminoglycosides, strict surveillance of their serum levels
is recommended during co-administration with ibuprofen.
Careful monitoring of both renal and gastrointestinal function is recommended.
In preterm newborn infants less than 27 weeks of gestational age, the closure rate of the
ductus
arteriosus
(33 to 50%) was shown to be low at the recommended dose regimen (see section 5.1).
This medicinal product contains less than 1 mmol sodium (15 mg) per 2 ml, i.e. essentially ‘sodium-
free’.
The concomitant use of Pedea with the following medicinal products is not recommended:
-
diuretics: ibuprofen may reduce the effect of diuretics; diuretics can increase the risk of
nephrotoxicity of NSAIDs in dehydrated patients.
-
anticoagulants: ibuprofen may increase the effect of anticoagulants and enhance the risk of
bleeding.
-
corticosteroids: ibuprofen may increase the risk of gastrointestinal bleeding.
3
-
nitric oxide: since both medicinal products inhibit platelet function, their combination may in
theory increase the risk of bleeding.
-
other NSAIDs: the concomitant use of more than one NSAID should be avoided because of the
increased risk of adverse reactions.
-
aminoglycosides:
s
ince ibuprofen may decrease the clearance of aminoglycosides, their co-
administration may increase the risk of nephrotoxicity and ototoxicity (see section 4.4).
Not relevant
Not relevant
Data are currently available on approximately 1,000 preterm newborn from both the literature
concerning ibuprofen and clinical trials with Pedea. Causality of adverse events reported in the
preterm newborn is difficult to assess since they may be related to the haemodynamic consequences of
the patent
ductus arteriosus
as well as to direct effects of ibuprofen.
Reported adverse reactions are listed below, by system organ class and by frequency. Frequencies are
defined as: very common (≥ 1/10), common (≥1/100, <1/10) and uncommon (≥1/1,000, <1/100).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Blood and lymphatic system disorders
Very common
: Thrombocytopenia, Neutropenia
Nervous system disorders
Common
: Intraventricular haemorrhage,
Periventricular leukomalacia
Respiratory, thoracic and mediastinal
disorders
Very common:
Bronchopulmonary dysplasia*
Common
: Pulmonary haemorrhage
Uncommon:
Hypoxemia*
Gastrointestinal disorders
Common
: Necrotizing enterocolitis, Intestinal
perforation
Uncommon
: Gastrointestinal haemorrhage
Renal and urinary disorders
Common
: Oliguria, Fluid retention, Haematuria
Uncommon: Acute renal failure
Investigations
Very Common:
Blood creatinine increased, Blood
sodium decreased
* see below
In a clinical curative trial involving 175 preterm newborn infants less than 35 weeks of gestational
age, the incidence of bronchopulmonary dysplasia at 36 weeks post-conceptional age was 13/81 (16%)
for indomethacin versus 23/94 (24%) for ibuprofen.
In a clinical trial where Pedea was administered prophylactically during the first 6 hours of life, severe
hypoxemia with pulmonary hypertension was reported in 3 newborn infants less than 28 weeks of
gestational age. This occurred within one hour of the first infusion and was reversed within 30 minutes
after the inhalation of nitric oxide.
No case of overdose has been reported with intravenous ibuprofen in preterm newborn infants.
4
However, overdose has been described in infants and children administered oral ibuprofen: CNS
depression, seizures, gastrointestinal disturbances, bradycardia, hypotension, apnoea, abnormal renal
function, haematuria have been observed.
Massive overdose (up to more than 1000 mg/kg) has been reported to induce coma, metabolic
acidosis, and transient renal failure. All patients recovered with conventional treatment. Only one
recorded death has been published: after an overdose of 469 mg/kg, a 16-month old child developed
an apnoeic episode with seizures and a fatal aspiration pneumonia.
The management of ibuprofen overdose is primarily supportive.
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: other cardiac preparations, ATC code: C01 EB16
Ibuprofen is a NSAID that possesses anti-inflammatory, analgesic and antipyretic activity. Ibuprofen
is a racemic mixture of S(+) and R(-) enantiomers.
In vivo
and
in vitro
studies indicate that the S(+)
isomer is responsible for the clinical activity. Ibuprofen is a non selective inhibitor of cyclo-
oxygenase, leading to reduced synthesis of prostaglandins.
Since prostaglandins are involved in the persistence of the
ductus arteriosus
after birth, this effect is
believed to be the main mechanism of action of ibuprofen in this indication.
In a dose-response study of Pedea in 40 preterm newborn infants, the
ductus arteriosus
closure rate
associated to the 10-5-5 mg/kg dose regimen was 75% (6/8) in neonates of 27-29 weeks’ gestation and
33% (2/6) in neonates of 24-26 weeks’ gestation.
Prophylactic use of Pedea in the first 3 days of life (starting within 6 hours of birth) in preterm
newborn infants less than 28 weeks of gestational age was associated with increased incidence of renal
failure and pulmonary adverse events including hypoxia, pulmonary hypertension, pulmonary
haemorrhage, as compared to curative use. Conversely, a lower incidence of neonatal grade III-IV
intraventricular haemorrhage and of surgical ligation was associated with prophylactic use of Pedea.
5.2 Pharmacokinetic properties
Distribution
Although a great variability is observed in the premature population, peak plasma concentrations are
measured around 35-40 mg/l after the initial loading dose of 10 mg/kg as well as after the last
maintenance dose, whatever gestational and postnatal age. Residual concentrations are around 10-
15 mg/l 24 hours after the last dose of 5 mg/kg.
Plasma concentrations of the S-enantiomer are much higher than those of the R-enantiomer, which
reflects a rapid chiral inversion of the R- to the S-form in a proportion similar to adults (about 60%).
The apparent volume of distribution is on average 200 ml/kg (62 to 350 according to various studies).
The central volume of distribution may depend on the status of the ductus and decrease as the ductus
closes.
In vitro
studies suggest that, similarly to other NSAIDs, ibuprofen is highly bound to plasma albumin,
although this seems to be significantly lower (95 %) compared with adult plasma (99 %). Ibuprofen
competes with bilirubin for albumin binding in newborn infant serum and, as a consequence, the free
fraction of bilirubin may be increased at high ibuprofen concentrations.
Elimination
Elimination rate is markedly lower than in older children and adults, with an elimination half-life
estimated at approximately 30 hours (16–43). The clearance of both enantiomers increases with
gestational age, at least in the range of 24 to 28 weeks.
5
PK-PD relationship
In preterm newborns ibuprofen significantly reduced plasma concentrations of prostaglandins and
their metabolites, particularly PGE2 and 6-keto-PGF-1-alpha. Low levels were sustained up to
72 hours in neonates who received 3 doses of ibuprofen, whereas subsequent re-increases were
observed at 72 hours after only 1 dose of ibuprofen.
5.3 Preclinical safety data
There are no preclinical data considered relevant to clinical safety beyond data included in other
sections of this Summary of Product Characteristics. With the exception of an acute toxicity study, no
further studies have been carried out in juvenile animals with Pedea.
6.
6.1 List of excipients
Trometamol,
sodium chloride,
sodium hydroxide (for pH adjustment),
hydrochloric acid 25% (for pH adjustment),
water for injections.
6.2 Incompatibilities
This medicinal product must not be mixed with other medicinal products except those mentioned in
section 6.6.
Pedea solution must not be in contact with any acidic solution such as certain antibiotics or diuretics.
A rinse of the infusion line must be performed between each product administration (see section 6.6).
6.3 Shelf life
4 years.
To avoid any possible microbiological contamination, the product should be used immediately after
first opening.
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 Nature and contents of container
2 ml solution in a colourless type 1 glass ampoule.
Pedea is supplied in packs of 4 x 2 ml ampoules.
6.6 Special precautions for disposal and other handling
As for all parenteral products, ampoules of Pedea should be visually inspected for particulate matter
and the integrity of the container prior to use. Ampoules are intended for single use only, any unused
portions must be discarded.
Chlorhexidine must not be used to disinfect the neck of the ampoule as it is not compatible with the
Pedea solution. Therefore, for asepsis of the ampoule before use, ethanol 60% or isopropyl alcohol
70% is recommended.
6
When disinfecting the neck of the ampoule with an antiseptic, to avoid any interaction with the Pedea
solution, the ampoule must be completely dry before it is opened.
The required volume to be given to the infant should be determined according to body weight, and
should be injected intravenously as a short infusion over 15 minutes, preferably undiluted.
Use only sodium chloride 9 mg/ml (0.9%) solution for injection or glucose 50 mg/ml (5%) solution to
adjust injection volume.
The total volume of solution injected to preterm infants should take into account the total daily fluid
volume administered. A maximal volume of 80 ml/kg/day on the first day of life should usually be
respected; this should be progressively increased in the following 1-2 weeks (about 20 ml/kg
birthweight/day) up to a maximal volume of 180 ml/kg birthweight/day.
Before and after administration of Pedea, to avoid contact with any acidic solution, rinse the infusion
line over 15 minutes with 1.5 to 2 ml of either sodium chloride 9 mg/ml (0.9%) or glucose 50 mg/ml
(5%), solution for injection.
After first opening of an ampoule, any unused portions must be discarded.
Any unused product or waste material should be disposed of in accordance with local requirements.
7.
Orphan Europe SARL
Immeuble “Le Wilson”
70, avenue du Général de Gaulle
F-92800 Puteaux
France
8.
EU/1/04/284/001
9.
Date of first authorisation: 29 July 2004
Date of latest renewal: 2 August 2009
Detailed information on this product is available on the web site of threEuropean medicines Agency
(EMEA) http://www.emea.europa.eu”
7
ANNEX II
A.
MANUFACTURING AUTHORISATION HOLDER
RESPONSIBLE FOR BATCH RELEASE
B.
CONDITIONS OF THE MARKETING AUTHORISATION
8
A
MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH
RELEASE
Name and address of the manufacturer responsible for batch release
Orphan Europe S.A.R.L.,
Immeuble “Le Wilson”
70 avenue du Général de Gaulle
F- 92800 Puteaux,
France
B
CONDITIONS OF THE MARKETING AUTHORISATION
Medicinal product subject to restricted medical prescription (See Annex I: Summary of Product
Characteristics, 4.2).
OTHER CONDITIONS
The holder of this marketing authorisation must inform the European Commission about the marketing
plans for the medicinal product authorised by this decision.
9
ANNEX III
LABELLING AND PACKAGE LEAFLET
10
A. LABELLING
11
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON TEXT
1.
Pedea 5 mg/ml solution for injection
Ibuprofen
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each ml contains 5 mg ibuprofen
Each ampoule of 2 ml contains 10 mg ibuprofen
3.
LIST OF EXCIPIENTS
Excipients: trometamol, sodium chloride, sodium hydroxide, hydrochloric acid 25%, water for
injections.
4.
Solution for injection
4 x 2 ml ampoules
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Intravenous use as short infusion
Read the package leaflet before use
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
From a microbiological point of view, the product should be used immediately
9.
SPECIAL STORAGE CONDITIONS
12
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
After first opening of an ampoule any unused portions must be discarded.
Any unused product or waste material should be disposed of in accordance with local requirements.
11.
Orphan Europe S.A.R.L.,
Immeuble “Le Wilson”
70 avenue du Général de Gaulle
F- 92800 Puteaux,
France
12.
EU/1/04/284/001
13.
BATCH NUMBER
Batch
14.
GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription
15.
INSTRUCTIONS ON USE
16.
INFORMATION IN BRAILLE
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
GLASS AMPOULE LABEL
1.
Pedea 5 mg/ml solution for injection
Ibuprofen
IV use
13
2.
METHOD OF ADMINISTRATION
See leaflet
3.
EXPIRY DATE
EXP
4.
BATCH NUMBER
Batch
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
10 mg / 2 ml
6.
OTHER
14
B. PACKAGE LEAFLET
15
PACKAGE LEAFLET: INFORMATION FOR THE USER
Pedea 5mg/ml solution for injection
Ibuprofen
Read all of this leaflet carefully before this medicine is administered to your baby.
-
If you have further questions, please ask your doctor or your pharmacist.
-
This medicine has been prescribed for your baby. Do not pass it on to others. It may harm
them, even if their symptoms are the same as your baby’s.
-
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor or your pharmacist.
In this leaflet
:
1.
What Pedea is and what it is used for
2.
Before Pedea is administered to your baby
4.
Possible side effects
5.
How to store Pedea
6.
Further information
1.
WHAT PEDEA IS AND WHAT IT IS USED FOR
While a baby is inside its mother’s womb it does not need to use its lungs. An unborn baby has a blood
vessel called the
ductus arteriosus
near the heart which allows the baby’s blood to bypass the lungs
and circulate to the rest of the body.
When the baby is born and starts using its lungs the
ductus arteriosus
normally closes. However, in
some cases this does not happen. The medical term for this condition is ‘patent
ductus arteriosus’
, i.e.
an open
ductus arteriosus
. This can cause heart problems in your baby. This condition is much more
frequent in premature newborn than in full-term newborn infants.
Pedea, when given to your baby, can help to close the
ductus arteriosus
.
The active substance in Pedea is ibuprofen. Pedea closes the
ductus arteriosus
by inhibiting the
production of prostaglandin, a naturally occurring chemical in the body which keeps the
ductus
arteriosus
open.
2.
BEFORE PEDEA IS ADMINISTERED TO YOUR BABY
Pedea will only be given to your baby in a special neonatal intensive care unit by qualified health care
professionals.
Do not use Pedea
-
if your baby is allergic (hypersensitive) to ibuprofen or any of the other ingredients of Pedea;
-
if your baby has a life-threatening infection which has not been treated;
-
if your baby is bleeding, especially if the bleeding is inside the skull or in the intestines;
-
if your baby has a decrease of blood cells called platelets (thrombocytopenia) or other problems
with their blood clotting;
-
if your baby has kidney problems;
-
if your baby has other problems with their heart which require the
ductus arteriosus
to remain
open so that adequate circulation of the blood is maintained;
-
if your baby has or is suspected to have certain problems with their intestines (a condition called
necrotising enterocolitis);
16
-
Keep this leaflet. You may need to read it again.
3.
How Pedea is used
Take special care with Pedea
-
Before treatment with Pedea, your baby’s heart will be examined to confirm that the
ductus
arteriosus
is open.
-
Pedea should not be given in the first 6 hours of life.
-
If your baby is suspected of having liver disease, signs and symptoms of which include yellowing
of the skin and eyes.
-
If your baby is already suffering from an infection that is being treated, the doctor will treat your
baby with Pedea only after careful consideration of your baby’s condition.
-
Pedea should be carefully administered to your baby by the healthcare professional, to avoid
damage to the skin and surrounding tissues.
-
Ibuprofen may reduce the ability of your baby’s blood to clot. Your baby should therefore be
watched for signs of prolonged bleeding.
-
Your baby may develop some bleeding from the intestines and the kidneys. To detect this, your
baby’s stools and urine may be tested to determine if there is any blood present in them.
-
Pedea may reduce the amount of urine your baby passes. If this is significant, your baby’s
treatment may be stopped until the volume of urine returns to normal.
-
Pedea may be less effective in very premature babies less than 27 weeks of gestational age.
Using other medicines
Please tell your doctor or pharmacist if your baby is taking or has recently taken any other medicines,
including medicines obtained without a prescription.
Certain medicines, if given together with Pedea, may cause side effects. These are detailed below:
-
your baby may have problems passing urine and may have been prescribed diuretics. Ibuprofen
may reduce the effect of these medicines.
-
your baby may be given anticoagulants (medicine preventing blood clotting). Ibuprofen may
increase the anti-clotting effect of this product.
-
your baby may be given nitric oxide to improve blood oxygenation. Ibuprofen may increase the
risk of bleeding.
-
your baby may be given corticosteroids to prevent inflammation. Ibuprofen may increase the
risk of bleeding in the stomach and intestines.
-
your baby may be given aminosides (one family of antibiotics) to treat infection. Ibuprofen may
increase blood concentrations and thus increase the risk of toxicity on kidney and ear
Important information about some of the ingredients of Pedea
This medicinal product contains less than 1 mmol sodium (15 mg) per 2 ml, i.e. essentially ‘sodium-
free’.
3.
HOW PEDEA IS USED
Pedea will only be given to your baby in a special neonatal intensive care unit by qualified healthcare
professional.
A course of therapy is defined as three intravenous injections of Pedea given at 24 hour intervals. The
dose to be administered will be calculated from the weight of your baby. It is 10 mg/kg for the first
administration and 5 mg/kg for the second and the third administrations.
This calculated amount will be given by infusion in a vein over a period of 15 minutes.
If after this first course of treatment, the
ductus arteriosus
is not closed or re-opens, your baby’s
doctor may decide to give a second course of treatment.
17
If after the second course of treatment, the
ductus arteriosus
is still not closed, a surgery may then be
proposed.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, Pedea can cause side effects, although not everybody gets them. However, it is
difficult to distinguish them from frequent complications occurring in premature babies and
complications due to the disease.
The frequency of possible side effects listed below is defined using the following convention:
very common (affects more than 1 user in 10)
common (affects 1 to 10 users in 100)
uncommon (affects 1 to 10 users in 1,000)
very rare (affects less than 1 user in 10,000)
not known (frequency cannot be estimated from the available data)
Very common:
-
Decrease in the number of platelets in the blood (thrombocytopenia),
-
Decrease in white blood cells called neutrophils (neutropenia),
-
Increase in creatinine level in the blood,
-
Decrease in sodium level in the blood,
-
Breathing problems (bronchopulmonary dysplasia),
Common:
-
Bleeding inside the skull (intraventricular haemorrhage) and brain injury (periventricular
leukomalacia),
-
Perforation of the intestine and injury of intestinal tissue (necrotizing enterocolitis),
-
Reduced volume of urine passed, blood in the urine, fluid retention
Uncommon:
-
Acute failure of the kidney’s functions
-
Bleeding in the intestine
-
Below normal oxygen content in the arterial blood (hypoxemia)
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please
tell your baby’s doctor or your pharmacist.
5.
HOW TO STORE PEDEA
Keep out of reach and sight of children.
Do not use Pedea after the expiry date which is stated on the carton and label after EXP. The expiry
date refers to the last day of that month.
This medicinal product does not require any special storage conditions.
After opening, Pedea should be administered immediately.
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.
18
-
Bleeding in the lung,
6.
FURTHER INFORMATION
What Pedea contains
-
The active substance is ibuprofen. Each ml contains 5 mg ibuprofen. Each 2 ml ampoule
contains 10 mg ibuprofen.
-
The other ingredients are trometamol, sodium chloride, sodium hydroxide (for pH adjustment),
hydrochloric acid 25% (for pH adjustment) and water for injections.
What Pedea looks like and contents of the pack
Pedea 5mg/ml solution for injection is a clear, colourless to slightly yellow solution.
Pedea 5mg/ml solution for injection is supplied in cartons of four 2 ml ampoules.
Marketing Authorisation Holder and Manufacturer
Orphan Europe S.A.R.L.
Immeuble “Le Wilson”
70 avenue du Général de Gaulle
F- 92800 Puteaux,
France
For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder.
Belgique/België/Belgien
Orphan Europe Benelux
Koning Albert I laan 48 bus 3
B-1780 Wemmel
Belgique/België/Belgien
Tél/Tel:+32 2 461 01 36
Luxembourg/Luxemburg
Orphan Europe Benelux
Koning Albert I laan 48 bus 3
B-1780 Wemmel
Belgique/België/Belgien
Tél/Tel:+32 2 461 01 36
България
Orphan Europe (Germany) GmbH
Max-Planck Str. 6
D-63128 Dietzenbach
Германия
Teл.: + 49 6074 914090
Magyarország
Orphan Europe GmbH
Max-Planck Str. 6
D - 63128 Dietzenbach
Németország
Tel : +49 (0)6074 914090
Česká republika
Orphan Europe GmbH
Max-Planck Str. 6
D - 63128 Dietzenbach
Německo
Tel : +49 (0)6074 914090
Malta
Orphan Europe SARL
Immeuble “Le Wilson”
70 avenue du Général de Gaulle
F – 92800 Puteaux
France
Tel : +33 1 47 73 64 58
Danmark
Orphan Europe Nordic AB
Banérgatan 37
S- 11522 Stockholm
Sverige
Tel : +46 8 545 80 230
Nederland
Orphan Europe Benelux
Koning Albert I laan 48 bus 3
B-1780 Wemmel
Belgique/België/Belgien
Tél/Tel:+32 2 461 01 36
19
Deutschland
Orphan Europe GmbH
Max-Planck Str. 6
D - 63128 Dietzenbach
Tel : +49 (0)6074 914090
Norge
Orphan Europe Nordic AB
Banérgatan 37
S- 11522 Stockholm
Sverige
Tel : +46 8 545 80 230
Eesti
Orphan Europe Nordic AB
Banérgatan 37
S- 11522 Stockholm
Rootsi
Tlf : +46 8 545 80 230
Österreich
Orphan Europe GmbH
Max-Planck Str. 6
D - 63128 Dietzenbach
Deutschland
Tel : +49 6074 914090
Ελλαδα
Orphan Europe SARL
Immeuble “Le Wilson”
70 avenue du Général de Gaulle
F – 92800 Puteaux
Γαλλία
Τηλ : +33 1 47 73 64 58
Polska
Orphan Europe GmbH
Max-Planck Str. 6
D - 63128 Dietzenbach
Niemcy
Tel : +49 6074 914090
España
Orphan Europe, S.L.
Gran via de les Cortes Catalanes, 649
Despacho n°1
E – 08010 Barcelona
Tel : +34 93 244 09 30
Portugal
Orphan Europe, S.L.
Gran via de les Cortes Catalanes, 649
Despacho n°1
E – 08010 Barcelona - Espanha
Tel : +34 93 244 09 30
France
Orphan Europe SARL
Immeuble “Le Wilson”
70 avenue du Général de Gaulle
F – 92800 Puteaux
Tél. : +33 1 47 73 64 58
România
Orphan Europe (Germany) GmbH
Max-Planck Str. 6
D-63128 Dietzenbach
Germania
Tel: + 49 6074 914090
Ireland
Orphan Europe (UK) Ltd.
Isis House, 43 Station road
Henley-on-Thames
Oxfordshire RG9 1AT, UK
United Kingdom
Tel: +44 1491 414333
Slovenija
Orphan Europe (Germany) GmbH
Max-Planck Str. 6
D-63128 Dietzenbach
Nemčija
Tel: +49 6074 914090
Ísland
Orphan Europe Nordic AB
Banérgatan 37
S-11522 Stockholm
Svíþjóð
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20
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This leaflet was last approved in
Detailed information on this medicine is available on the European medicines Agency website:
http://emea.europa.eu
The following information is intended for medical or healthcare professionals only:
As for all parenteral products, ampoules of Pedea should be visually inspected for particulate matter
and the integrity of the container prior to use. Ampoules are intended for single use only, any unused
portions must be discarded.
For intravenous use only. Treatment with Pedea can only be carried out in a neonatal intensive care
unit under the supervision of an experienced neonatologist.
A course of therapy is defined as three intravenous doses of Pedea given at 24-hour intervals.
The ibuprofen dose is adjusted to the body weight as follows:
- 1
st
injection: 10 mg/kg,
- 2
nd
and 3
rd
injections: 5 mg/kg.
If the
ductus arteriosus
does not close 48 hours after the last injection or if it re-opens, a second course
of 3 doses, as above, may be given.
If the condition is unchanged after the second course of therapy, surgery of the PDA may then be
necessary.
If anuria or manifest oliguria occurs after the first or second dose, the next dose should be withheld
until urine output returns to normal levels.
Method of administration:
Pedea should be administered as a short infusion over 15 minutes, preferably undiluted. To facilitate
the administration an infusion pump may be used.
If necessary, the injection volume may be adjusted with either sodium chloride 9 mg/ml (0.9%)
solution for injection or glucose 50 mg/ml (5%) solution for injection. Any unused portion of the
solution should be discarded.
21
The total volume of solution injected to preterm infants should take into account the total daily fluid
volume administered. A maximal volume of 80 ml/kg/day on the first day of life should usually be
respected; this should be progressively increased in the following 1-2 weeks (about 20 ml/kg
birthweight/day) up to a maximal volume of 180 ml/kg birthweight/day.
Incompatibilities
Chlorhexidine must not be used to disinfect the neck of the ampoule as it is not compatible with the
Pedea solution. Therefore, for asepsis of the ampoule before use, ethanol 60% or isopropyl alcohol
70% is recommended.
When disinfecting the neck of the ampoule with an antiseptic, to avoid any interaction with the Pedea
solution, the ampoule must be completely dry before it is opened.
This medicinal product must not be mixed with other medicinal products except sodium chloride
9 mg/ml (0.9%) solution for injection or glucose 50 mg/ml (5%) solution.
In order to avoid any substantial variation of pH due to the presence of acidic medicinal products that
could remain in the infusion line, the latter must be rinsed before and after administration of Pedea
with 1.5 to 2 ml of either sodium chloride 9 mg/ml (0.9%) solution for injection or glucose 50 mg/ml
(5%) solution.
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Source: European Medicines Agency
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