PEDEA 5 mg/ml INJECTABLE SOLUTION

2. Before using Pedea for your baby

Pedea will only be administered to your baby in a neonatal intensive care unit by qualified healthcare 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 that has not been treated;
• if your baby has bleeding, especially if the bleeding is inside the skull or in the intestines;
• if your baby has a decrease in the number of blood cells called platelets (thrombocytopenia) or other blood clotting problems;
• if your baby has kidney problems;
• if your baby has other heart problems that require the ductus arteriosus to remain open to maintain adequate blood circulation;
• if your baby has or is suspected of having certain intestinal problems (a disease called necrotizing enterocolitis).

Be careful with Pedea

• Before starting treatment with Pedea, a heart examination will be performed on the baby to confirm that the ductus arteriosus is open.
• Pedea should not be administered in the first 6 hours of life.
• Treatment with Pedea should not be used if it is suspected that your baby has liver disease, whose signs and symptoms include yellowish skin and eyes.
• If your baby already has an infection that is being treated, the doctor will treat your baby with Pedea only after carefully evaluating your baby's condition.
• Healthcare staff should administer Pedea to your baby with caution in order to avoid damage to the skin and surrounding tissues.
• Ibuprofen may reduce your baby's blood clotting ability. Therefore, your baby should be monitored for signs of prolonged bleeding.
• Your baby may develop some bleeding in the intestines and kidneys. To detect this, your baby's stool and urine may be analyzed to determine the presence of blood in them.
• Pedea may reduce the amount of urine excreted by your baby. If this is significant, your baby's treatment may be interrupted until the urine volume returns to normal levels.
• Pedea may be less effective in very premature babies under 27 weeks of gestational age.

Using other medicines

Tell your doctor or pharmacist if your baby is using or has recently used other medicines, including those obtained without a prescription.

Certain medicines, if given with Pedea, may cause adverse reactions. These are mentioned below:

• your baby may have problems expelling urine and may have been prescribed diuretics. Ibuprofen could reduce the effect of these medicines.
• your baby may be given anticoagulants (medicines that prevent blood clotting). Ibuprofen may increase the anticoagulant effect of this product.
• your baby may be given nitric oxide to improve blood oxygenation. Ibuprofen could increase the risk of bleeding.
• your baby may be given corticosteroids to prevent inflammation. Ibuprofen could increase the risk of bleeding in the stomach and intestines.
• in order to treat an infection, your baby may be given aminoglycosides (a family of antibiotics). Ibuprofen may increase the blood levels of these and thus increase the risk of toxicity to the kidney and ear.

Important information about some of the ingredients of Pedea

This medicine contains less than 1 mmol of sodium (15 mg) per 2 ml, i.e., it is essentially 'sodium-free'.

3. How to use Pedea

Only a qualified healthcare professional will administer Pedea to your baby in a neonatal intensive care unit.

A therapy cycle is defined as three injections of Pedea by intravenous route administered at 24-hour intervals. The dose to be administered will be calculated based on your baby's weight. It is 10 mg/kg for the first administration and 5 mg/kg for the second and third administrations.

This calculated amount will be administered by infusion into a vein over a period of 15 minutes.

If after this first treatment cycle, the ductus arteriosus is not closed or reopens, the doctor may decide to administer a second treatment cycle.

If after the second treatment cycle, the ductus arteriosus is still not closed, 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 that occur in premature babies and complications due to the disease.

The frequency of possible side effects is listed below 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)

frequency not known (cannot be estimated from the available data)

Very common:

• Decrease in the number of platelets in the blood (thrombocytopenia)
• Decrease in the number of white blood cells called neutrophils (neutropenia)
• Increased creatinine level in the blood
• Decrease in sodium level in the blood
• Respiratory problems (bronchopulmonary dysplasia)

Common:

• Bleeding inside the skull (intraventricular hemorrhage) and brain injury (periventricular leukomalacia)
• Pulmonary hemorrhage
• Perforation of the intestines and injury to the intestinal tissue (necrotizing enterocolitis)
• Decrease in urine volume, blood in the urine, fluid retention

Uncommon:

• Acute kidney failure
• Intestinal bleeding
• Oxygen content below normal values in arterial blood (hypoxemia)

Not known:

• Perforation of the stomach

If you think any of the side effects that your baby is getting are serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

5. Storage of Pedea

Keep out of the reach and sight of children.

Do not use Pedea after the expiry date stated on the carton and label after EXP. The expiry date refers to the last day of the month indicated.

No special storage conditions are required.

Once opened, Pedea should be used immediately.

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

6. Further information

Composition of Pedea

• The active substance is ibuprofen. Each ml contains 5 mg of ibuprofen. Each 2 ml ampoule contains 10 mg of ibuprofen.
• The other ingredients are trometamol, sodium chloride, sodium hydroxide (for pH adjustment), 25% hydrochloric acid (for pH adjustment), and water for injections.

Appearance and packaging of the product

Pedea 5 mg/ml solution for injection is a clear, colorless to pale yellow solution.

Pedea 5 mg/ml solution for injection is available in cartons of 4 ampoules of 2 ml.

Marketing authorisation holder

Orphan Europe SARL

Immeuble “Le Wilson”

70, avenue du Général de Gaulle

F-92800 Puteaux,

France

Manufacturer

Orphan Europe SARL

Immeuble “Le Wilson”

70, avenue du Général de Gaulle

92800 Puteaux

France

or

Orphan Europe SARL

Eco River Parc

30, rue des Peupliers

F-92000 Nanterre

France

You can request more information about this medicine from the local representative of the marketing authorisation holder.

This leaflet was approvedin {Month/Year}.

Detailed information on this medicine is available on the European Medicines Agency (EMEA) website http://www.emea.europa.eu/.

This information is intended only for healthcare professionals:

Like all parenteral products, Pedea ampoules should be inspected visually for particles and to check the integrity of the container before use. The ampoules are for single use only; any unused portion should be discarded.

Posology and method of administration (see also section 3)

For intravenous use only. Treatment with Pedea should only be carried out in a neonatal intensive care unit under the supervision of a neonatologist with experience. A therapy cycle is defined as three intravenous doses of Pedea administered at 24-hour intervals.

The dose of ibuprofen is adjusted to the baby's body weight as follows:

• 1st injection: 10 mg/kg,
• 2nd and 3rd injections: 5 mg/kg.

If the ductus arteriosus does not close within 48 hours after the last injection or if it reopens, a second cycle of 3 doses may be administered, as indicated above.

If the condition persists after a second cycle of therapy, surgical intervention of the persistent ductus arteriosus may then be necessary.

In case of manifest anuria or oliguria after the first or second dose, the next dose should be postponed until urine excretion returns to normal levels.

Method of administration:

Pedea should be administered as a short infusion over 15 minutes, preferably undiluted. To facilitate administration, an infusion pump may be used.

If necessary, the volume of the injection may be adjusted with sodium chloride 9 mg/ml (0.9%) injection solution or glucose 50 mg/ml (5%) injection solution. Any unused portion of the solution should be discarded.

The total volume of the injected solution in premature newborns should take into account the total daily fluid volume administered. Normally, the maximum volume of 80 ml/kg/day on the first day of life should be respected; this volume will be gradually increased over the next 1-2 weeks (approximately 20 ml/kg birth weight/day) to a maximum volume of 180 ml/kg birth weight/day.

Incompatibilities

Chlorhexidine should not be used to disinfect the ampoule neck because it is incompatible with the Pedea solution. Therefore, to perform asepsis of the ampoule before use, 60% ethanol or 70% isopropyl alcohol is recommended.

In order to avoid any interaction with the Pedea solution during disinfection of the ampoule neck with an antiseptic, the ampoule should be completely dry before opening.

This medicine should not be mixed with other medicines except with sodium chloride 9 mg/ml (0.9%) injection solution or glucose 50 mg/ml (5%) solution.

In order to avoid any substantial variation in pH due to the presence of acidic medicines that may remain in the infusion line, the line should be flushed before and after administration of Pedea with 1.5 to 2 ml of sodium chloride 9 mg/ml (0.9%) injection solution or glucose 50 mg/ml (5%) solution.