Pedea 5 mg/ml solution for injection

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.

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);

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?.

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.

If after the second course of treatment, the ductus arteriosus is still not closed, a surgery may then be proposed.

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),
• Bleeding in the lung,
• 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.

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.

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.

BelgiqueBelgiëBelgien Orphan Europe Benelux Koning Albert I laan 48 bus 3 B-1780 Wemmel BelgiqueBelgiëBelgien TélTel32 2 461 01 36 LuxembourgLuxemburg Orphan Europe Benelux Koning Albert I laan 48 bus 3 B-1780 Wemmel BelgiqueBelgiëBelgien TélTel32 2 461 01 36

Orphan Europe Germany GmbH Max-Planck Str. 6 D-63128 Dietzenbach Te. 49 6074 914090 Magyarország Orphan Europe GmbH Max-Planck Str. 6 D - 63128 Dietzenbach Németország Tel 49 06074 914090

eská republika Orphan Europe GmbH Max-Planck Str. 6 D - 63128 Dietzenbach Nmecko Tel 49 06074 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 BelgiqueBelgiëBelgien TélTel32 2 461 01 36

Deutschland Orphan Europe GmbH Max-Planck Str. 6 D - 63128 Dietzenbach Tel 49 06074 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

Polska Orphan Europe GmbH Max-Planck Str. 6 D - 63128 Dietzenbach Niemcy Tel 49 6074 914090 Orphan Europe SARL Immeuble Le Wilson 70 avenue du Général de Gaulle F 92800 Puteaux 33 1 47 73 64 58

España Orphan Europe, S.L. Gran via de les Cortes Catalanes, 649 Despacho n1 E 08010 Barcelona Tel 34 93 244 09 30 Portugal Orphan Europe, S.L. Gran via de les Cortes Catalanes, 649 Despacho n1 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

Slovenija Orphan Europe Germany GmbH Max-Planck Str. 6 D-63128 Dietzenbach Nemija 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

Ísland Orphan Europe Nordic AB Banérgatan 37 S-11522 Stockholm Svíjóð Tel 46 8 545 80 230 Slovenská republika Orphan Europe Germany GmbH Max-Planck Str. 6 D-63128 Dietzenbach Nemecko Tel 49 6074 914090

Italia Orphan Europe Italy Srl Via Cellini 11 I-20090 Segrate Milano Tel 39 02 26 95 01 39 SuomiFinland Orphan Europe Nordic AB Banérgatan 37 S-11522 Stockholm Ruotsi Tel 46 8 545 80 230

Sverige Orphan Europe Nordic AB Banérgatan 37 S-11522 Stockholm Tel 46 8 545 80 230 Orphan Europe SARL Immeuble Le Wilson 70 avenue du Général de Gaulle F 92800 Puteaux 33 1 47 73 64 58

Latvija Orphan Europe Nordic AB Banérgatan 37 S-11522 Stockholm Zviedrija Tel 46 8 545 80 230 United Kingdom Orphan Europe UK Ltd. Isis House, 43 Station road Henley-on-Thames Oxfordshire RG9 1AT, UK Tel 44 1491 414333

Lietuva

Orphan Europe Nordic AB
Banérgatan 37
S-11522 Stockholm
?vedija
Tel: + 46 8 545 80 230

This leaflet was last approved in

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.

Posology and method of administration (see also section 3)

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.

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.