IBUPROFEN GEN.ORPH 5 mg/ml INJECTABLE SOLUTION

2. What you need to know before your baby takes Ibuprofeno Gen.Orph

Ibuprofeno Gen.Orph will only be administered to your baby by a qualified healthcare professional in a neonatal intensive care unit.

Do not use Ibuprofeno Gen.Orph

• if your baby is allergic (hypersensitive) to ibuprofen or any of the other ingredients of Ibuprofeno Gen.Orph;
• 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 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).

Warnings and precautions

• Before starting treatment with Ibuprofeno Gen.Orph, a heart examination will be performed on the baby to confirm that the ductus arteriosus is open.
• Ibuprofeno Gen.Orph should not be administered in the first 6 hours of life.
• If your baby already has an infection being treated, the doctor will only treat your baby with Ibuprofeno Gen.Orph after carefully evaluating your baby's condition.
• Healthcare staff should administer Ibuprofeno Gen.Orph to your baby with caution 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.
• Ibuprofeno Gen.Orph may reduce the amount of urine your baby expels. If this is significant, your baby's treatment may be interrupted until the urine volume returns to normal levels.
• Ibuprofeno Gen.Orph may be less effective in very premature babies under 27 weeks of gestational age.
• Severe skin reactions associated with Ibuprofeno Gen.Orph treatment have been reported.
• Stop taking Ibuprofeno Gen.Orph and go to the doctor immediately if you experience any skin rash, lesions on the mucous membranes, blisters, or other signs of allergy, as these may be the first signs of a very severe skin reaction. See also section 2.

Using Ibuprofeno Gen.Orph with other medicines

Tell your doctor or pharmacist if your baby is taking, has recently taken, or might take any other medicines.

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

• your baby may have problems expelling urine and may have been prescribed diuretics.
• Ibuprofen may 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 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 other NSAIDs: concomitant use of more than one NSAID should be avoided due to the increased risk of adverse reactions.
• 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 kidney and ear toxicity.

Ibuprofeno Gen.Orph contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per 2 ml, i.e., it is essentially "sodium-free".

3. How to take Ibuprofeno Gen.Orph

Your baby will only be given Ibuprofeno Gen.Orph by a qualified healthcare professional in a neonatal intensive care unit.

A therapy cycle is defined as three injections of Ibuprofeno Gen.Orph administered intravenously 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, your baby's doctor may decide to administer a second treatment cycle.

If after the second treatment cycle, the ductus arteriosus still does not close, surgery may then be proposed.

If you have any further questions about the use of this medicine, ask your baby's doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine 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 possible side effects are listed below.

Very common (may affect more than 1 in 10 people)

• 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
• Decreased sodium level in the blood
• Respiratory problems (bronchopulmonary dysplasia)

Common (may affect up to 1 in 10 people)

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

Uncommon (may affect up to 1 in 100 people)

• Acute kidney failure
• Intestinal hemorrhage
• Low oxygen levels in the blood (hypoxemia)

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

• Stomach perforation
• Widespread red scaly rash, with bumps under the skin and blisters mainly on the skin folds, trunk, and upper limbs, accompanied by fever at the start of treatment (acute generalized exanthematous pustulosis). Stop using Ibuprofeno Gen.Orph if you experience these symptoms and seek medical attention immediately. See also section 2.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Ibuprofeno Gen.Orph

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the label and carton after EXP. The expiry date is the last day of the month shown.

No special storage conditions are required.

Once opened, Ibuprofeno Gen.Orph should be used immediately.

Do not use this medicine if you notice visible signs of deterioration of the solution.

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. Container contents and additional information

What Ibuprofeno Gen.Orph contains

• The active ingredient is ibuprofen. Each ml contains 5 mg of ibuprofen. Each 2 ml ampoule contains 10 mg of ibuprofen.
• The other components are trometamol, sodium chloride, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment), and water for injectables. See section 2. Ibuprofeno Gen.Orph contains sodium.

Appearance of Ibuprofeno Gen.Orph and container contents

Ibuprofeno Gen.Orph 5 mg/ml injectable solution is a clear, colorless to pale yellow solution.

Ibuprofeno Gen.Orph 5 mg/ml injectable solution is presented in boxes of four 2 ml ampoules.

Marketing authorization holder

Gen.Orph

185 Bureaux de la Colline

92213 Saint Cloud Cedex

France

Manufacturer

Haupt Pharma

1 rue Comte de Sinard

26250 Livron-sur-Drôme

France

You can request more information about this medication by contacting the local representative of the marketing authorization holder.

Date of last revision of this prospectus:

Detailed information on this medication is available on the European Medicines Agency website: http://www.ema.europa.eu.

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This information is intended only for healthcare professionals:

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

Dosage and administration (see also section 3)

For intravenous use only. Treatment with Ibuprofeno Gen.Orph can only be performed in a neonatal intensive care unit under the supervision of an experienced neonatologist.

A therapy cycle is defined as three intravenous doses of Ibuprofeno Gen.Orph administered at 24-hour intervals.

The dose of ibuprofen is adjusted according to body weight as follows:

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

If the arterial duct 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 disorder persists after a second cycle of therapy, surgical intervention of the persistent arterial duct may be necessary.

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

Administration method:

Ibuprofeno Gen.Orph 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 a 9 mg/ml (0.9%) sodium chloride injectable solution or a 50 mg/ml (5%) glucose injectable solution in a PVC-free bag. Any unused portion of the solution should be discarded.

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

Incompatibilities

Chlorhexidine should not be used to disinfect the ampoule neck because it is incompatible with the Ibuprofeno Gen.Orph 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 Ibuprofeno Gen.Orph solution during disinfection of the ampoule neck with an antiseptic, the ampoule should be completely dry before opening.

This medication should not be mixed with other medications except with a 9 mg/ml (0.9%) sodium chloride injectable solution or a 50 mg/ml (5%) glucose solution in a PVC-free bag.

In order to avoid any substantial variation in pH due to the presence of acidic medications that may remain in the infusion line, the line should be flushed before and after administration of Ibuprofeno Gen.Orph with 1.5 to 2 ml of a 9 mg/ml (0.9%) sodium chloride injectable solution or a 50 mg/ml (5%) glucose solution in a PVC-free bag.