Label: Information for the User

Ibuprofen Gen.Orph 5 mg/ml injectable solution

Ibuprofen

Read this label carefully before starting to take this medicine, as it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this label. See section 4.

While the baby is inside the mother's uterus, it does not need to use the lungs. Fetus have a blood vessel called the ductus arteriosus near the heart that allows the baby's blood not to enter the lungs and circulate through the rest of the body.

When the baby is born, and begins to use the lungs, the ductus arteriosus normally closes. However, in some cases, this does not occur. The medical term for this condition is "ductus arteriosus persistent", that is, an open ductus arteriosus. This can produce heart problems in the baby. This condition is much more frequent in premature newborns than in those born at term.

Ibuprofeno Gen.Orph, when administered to the baby, may help to close the ductus arteriosus.

The active ingredient of Ibuprofeno Gen.Orph is ibuprofen. Ibuprofeno Gen.Orph closes the ductus arteriosus by inhibiting the production of prostaglandin, a naturally occurring chemical in the body that keeps the ductus arteriosus open.

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

Do not use Gen.Orph Ibuprofen

• if your baby is allergic (hypersensitive) to ibuprofen or any of the other components of Gen.Orph Ibuprofen;
• 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 platelet cells (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 to have certain intestinal problems (a disease called necrotizing enterocolitis).

Warnings and precautions

• Before starting treatment with Gen.Orph Ibuprofen, an echocardiogram of the baby will be performed to confirm that the ductus arteriosus is open.
• Gen.Orph Ibuprofen should not be administered in the first 6 hours of life
• if liver disease is suspected, with signs and symptoms including yellow skin and eyes.
• If your baby already has an infection being treated, the doctor will only treat your baby with Gen.Orph Ibuprofen after carefully evaluating your baby's condition.
• Healthcare personnel should administer Gen.Orph Ibuprofen with caution to your baby, 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.
• Gen.Orph Ibuprofen may reduce the amount of urine your baby expels. If this is significant, treatment may be interrupted until your baby's urine output returns to normal levels.
• Gen.Orph Ibuprofen may be less effective in very premature babies less than 27 weeks of gestational age.
• Severe skin reactions associated with Gen.Orph Ibuprofen treatment have been reported.
• Stop taking Gen.Orph Ibuprofen and seek medical attention immediately if you experience any skin rash, mucous membrane lesions, blisters, or other signs of allergy, as these may be the first signs of a severe skin reaction. See section 4.

Use of Gen.Orph Ibuprofen with other medications

Inform your doctor or pharmacist if your baby is taking, has taken recently, or may need to take any other medication.

Certain medications, if administered with Gen.Orph Ibuprofen, may cause adverse reactions. These are listed below:

• Your baby may have difficulty expelling urine and may have been prescribed diuretics.
• Ibuprofen may reduce the effect of these medications.
• Your baby may be taking anticoagulants (medications that prevent blood from clotting). Ibuprofen may increase the anticoagulant effect of this medication.
• 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.
• To treat an infection, your baby may be given aminoglycosides (a family of antibiotics). Ibuprofen may increase the blood concentrations of these and thus increase the risk of kidney and ear toxicity.

Gen.Orph Ibuprofen contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per 2 ml, which is essentially "sodium-free".

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

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

The calculated amount will be administered via infusion into a vein over a period of 15 minutes.

If after the first treatment cycle, the arterial duct is not closed or reopens, your baby's doctor may decide to administer a second treatment cycle.

If after the second treatment cycle, the arterial duct remains open, a surgical procedure may then be proposed.

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

Like all medications, this medication may produce adverse effects, although not all people will experience them.

However, it is difficult to distinguish them from frequent complications that occur in premature babies and complications due to the disease.

The possible adverse effects are listed below.

Very Frequent (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 level of creatinine in the blood
• Decrease in the level of sodium in the blood
• Respiratory problems (bronchopulmonary dysplasia)

Frequent (may affect up to 1 in 10 people)

• Internal head hemorrhage (intraventricular hemorrhage) and brain injury (periventricular leukomalacia)
• Pulmonary hemorrhage
• Intestinal perforation and intestinal tissue injury (necrotizing enterocolitis)
• Decreased urine output, blood in the urine, fluid retention

Rare (may affect up to 1 in 100 people)

• Acute renal insufficiency
• Intestinal hemorrhage
• Arterial blood oxygen levels below normal values (hypoxemia)

Unknown frequency (cannot be estimated from available data)

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

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is an adverse effect that does not appear in this prospectus. You can also report them directly through the national notification system included in theAppendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

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

Do not use this medication after the expiration date that appears on the label and the box after CAD. The expiration date is the last day of the month indicated.

No special storage conditions are required.

Once opened, Ibuprofeno Gen.Orph must be administered immediately.

Do not use this medication if you observe visible signs of deterioration of the solution.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of medications that you no longer need. This will help protect the environment.

What Ibuprofeno Gen.Orph contains

• The active substance is ibuprofen. Each milliliter contains 5 mg of ibuprofen. Each 2 ml ampoule contains 10 mg of ibuprofen.
• The other components are trometamol, sodium chloride, sodium hydroxide (to adjust the pH), hydrochloric acid (to adjust the pH), and water for injection. See point 2. Ibuprofeno Gen.Orph contains sodium.

Appearance of Ibuprofeno Gen.Orph and contents of the pack

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

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

Marketing authorisation holder

Gen.Orph

185 Bureaux de la Colline

92213 Saint Cloud Cedex

France

Responsible person

Haupt Pharma

1 rue Comte de Sinard

26250 Livron-sur-Drôme

France

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

Last update of this leaflet:

The detailed information on this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu.

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This information is intended solely for healthcare professionals:

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

Dosage and administration (see also section 3)

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

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

The dose of ibuprofen is adjusted according to the following body weight:

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

If the patent 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 in the same way.

If the condition persists after a second cycle of treatment, surgical intervention on the persistent patent ductus arteriosus may be necessary.

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

Administration:

Ibuprofeno Gen.Orph should be administered as a short infusion over 15 minutes, preferably undiluted. To facilitate administration, a syringe pump may be used.

If necessary, the injection volume may be adjusted with a 9 mg/ml sodium chloride solution (0.9%) or a 50 mg/ml glucose solution (5%) in a PVC-free bag. Discard any unused portion of the solution.

The total volume of the injected solution in preterm infants should take into account the total daily volume of administered liquids. Normally, a maximum volume of 80 ml/kg/day should be respected on the first day of life; this volume should 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 not compatible with the Ibuprofeno Gen.Orph solution. Therefore, to perform the asepsis of the ampoule before use, it is recommended to use 60% ethanol or 70% isopropyl alcohol.

To avoid any interaction with the Ibuprofeno Gen.Orph solution during the disinfection of the ampoule neck with an antiseptic, the ampoule should be completely dry before opening.

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

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