Ibuprofen Gen.Orph: detailed information

Package leaflet: Information for the user

Ibuprofene Gen.Orph 5 mg/mL injection solution

ibuprofen
Please read all of this leaflet carefully before you are given this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor, pharmacist or nurse.
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of this leaflet

What Ibuprofene Gen.Orph is and what it is used for
What you need to know before being given Ibuprofene Gen.Orph
How Ibuprofene Gen.Orph is given
Possible side effects
How to store Ibuprofene Gen.Orph
Contents of the pack and other information

1. What Ibuprofene Gen.Orph is and what it is used for

While in the mother's womb, the fetus does not need to use its lungs. The fetus has a blood vessel near the heart called the ductus arteriosus, which allows blood to bypass the pulmonary circulation and flow to the rest of the body.
At birth, the newborn begins to use its lungs, and normally the ductus arteriosus closes. However, in some cases this does not happen. The medical term for this condition is "patent ductus arteriosus", meaning an open ductus arteriosus. This condition, which may cause heart problems in the child, is much more common in premature infants than in full-term infants.
Ibuprofene Gen.Orph, administered to your baby, can help close the ductus arteriosus.
The active substance contained in Ibuprofene Gen.Orph is ibuprofen. Ibuprofene Gen.Orph closes the ductus arteriosus by inhibiting the production of prostaglandin, a chemical substance naturally produced by the body that keeps the ductus arteriosus open.

2. What you should know before taking Ibuprofene Gen.Orph

Ibuprofene Gen.Orph will be administered to your baby exclusively by a qualified healthcare professional in a specialized neonatal intensive care unit.
Do not use Ibuprofene Gen.Orph.

if your baby is allergic (hypersensitive) to ibuprofen or to any of the other components of Ibuprofene Gen.Orph;
if your baby has a life-threatening infection that has not been treated;
if your baby has ongoing bleeding, particularly intracranial (inside the skull) or intestinal haemorrhage;
if your baby has a reduced number of blood cells called platelets (thrombocytopenia) or other blood clotting disorders;
if your baby has kidney problems;
if your baby has other heart conditions in which the ductus arteriosus must 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 treatment with Ibuprofene Gen.Orph, your baby will undergo a heart examination to confirm that the ductus arteriosus is open.
Ibuprofene Gen.Orph must not be administered within the first 6 hours of life.
If liver disease is suspected in your baby, signs and symptoms of which include yellowing of the skin and eyes.
If your baby has an infection for which treatment is ongoing, the doctor will administer Ibuprofene Gen.Orph only after carefully evaluating the baby's condition.
Ibuprofene Gen.Orph must be administered carefully by healthcare personnel to avoid damage to the skin and surrounding tissues.
Since ibuprofen may reduce blood clotting ability, your baby should be closely monitored for signs of prolonged bleeding.
Intestinal and renal bleeding may occur in the baby; therefore, tests on stools and urine may be performed to detect the presence of blood.
Ibuprofene Gen.Orph may reduce the amount of urine produced by the baby. If this occurs significantly, treatment may be interrupted until urine output returns to normal.
The effectiveness of Ibuprofene Gen.Orph may be reduced in very premature infants with a gestational age of less than 27 weeks.
Serious skin reactions have been reported with treatment using Ibuprofene Gen.Orph. Discontinue treatment with Ibuprofene Gen.Orph and consult your doctor immediately if rash, mucosal lesions, blisters or other signs of allergy appear, as these may be early signs of a severe skin reaction. See section 4.

Other medicines and Ibuprofene Gen.Orph
Inform the doctor or pharmacist if your baby is taking, has recently taken or might take any other medicines.
Some medicines, when administered together with Ibuprofene Gen.Orph, may cause unwanted effects. These are described below:

your baby may have urinary problems for which diuretics have been prescribed. Ibuprofen may reduce the effect of these medicines;
your baby may be given anticoagulants (medicines that prevent blood clotting). Ibuprofen may enhance the anticoagulant effect of these products;
your baby may be administered 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 gastrointestinal and intestinal bleeding;
your baby may be given other NSAIDs: concomitant use of more than one NSAID should be avoided due to increased risk of adverse reactions;
your baby may be given aminoglycosides (a class of antibiotics) for the treatment of infections. Ibuprofen may increase their blood concentration, thereby increasing the risk of kidney and ear toxicity.

Ibuprofene Gen.Orph contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per 2 mL, i.e. essentially ‘sodium-free’.

3. How to take Ibuprofene Gen.Orph

Ibuprofene Gen.Orph must be administered to neonates only by a qualified healthcare professional in a specialised neonatal intensive care unit.
A treatment cycle is defined as three intravenous doses of Ibuprofene Gen.Orph given at 24-hour intervals. The dose to be administered will be calculated according to the neonate's body weight. It is 10 mg/kg for the first dose and 5 mg/kg for the second and third doses.
The calculated volume will be administered by infusion into a vein over 15 minutes.
If, after this first treatment cycle, the ductus arteriosus has not closed or has reopened, the physician may decide to administer a second treatment cycle to the neonate.
If the ductus arteriosus remains open after the second treatment cycle, surgical intervention may be considered.
If you have any doubts about the use of this medicine, please consult the child'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 the frequent complications occurring in premature infants and from complications induced by the underlying 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 white blood cells called neutrophils (neutropenia)
Increased blood creatinine levels
Decreased blood sodium levels
Breathing problems (bronchopulmonary dysplasia)

Common (may affect up to 1 in 10 people)

Bleeding within the skull (intraventricular haemorrhage) and brain damage (periventricular leukomalacia)
Lung bleeding
Intestinal perforation and damage to intestinal tissue (necrotising enterocolitis)
Reduced urine volume, blood in urine, fluid retention

Uncommon (may affect up to 1 in 100 people)

Acute kidney failure
Intestinal bleeding
Arterial blood oxygen levels below normal (hypoxaemia)

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

Stomach perforation
Widespread red, scaly rash with pustules under the skin and blisters mainly located in skin folds, trunk, and upper limbs, accompanied by fever at the beginning of treatment (generalised exanthematous pustulosis). Stop using Ibuprofene Gen.Orph if these symptoms develop and contact your doctor immediately. See also section 2.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Ibuprofene Gen.Orph

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label after Exp. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
After opening, Ibuprofene Gen.Orph must be administered immediately.
Do not use this medicine if you notice any visible signs of deterioration of the solution.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer used. This will help protect the environment.

6. Package contents and other information

What Ibuprofene Gen.Orph contains

The active substance is ibuprofen. Each mL contains 5 mg of ibuprofen. Each 2 mL vial contains 10 mg of ibuprofen.
The other components are trometamol, sodium chloride, sodium hydroxide (for pH adjustment), hydrochloric acid 25% (for pH adjustment), water for injections. See section 2. Ibuprofene Gen.Orph contains sodium.

Description of the appearance of Ibuprofene Gen.Orph and contents of the pack
Ibuprofene Gen.Orph 5 mg/mL solution for injection is a clear, colourless to slightly yellow solution.
Ibuprofene Gen.Orph 5 mg/mL solution for injection is supplied in packs of four 2 mL vials.

Marketing Authorisation 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

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder.

België/Belgique/Belgien Lietuva
Gen.Orph Gen.Orph
Tél/Tel: +32 (0)496 85 87 49 Tel: +33 (0)1 47 71 04 50
e-mail: [email protected] e-mail: [email protected]

България Luxembourg/Luxemburg
Диакомерс ЕООД Gen.Orph
Тел.: +359 2 807 50 00 Tél/Tel.: +33 (0)1 47 71 04 50
Е-mail: [email protected] email: [email protected]

Česká republika Magyarország
Gen.Orph Gen.Orph
Tel: +33 (0)1 47 71 04 50 Tel.: +33 (0)1 47 71 04 50
e-mail: [email protected] e-mail: [email protected]

Danmark Malta
Gen.Orph Gen.Orph
Tlf: +46 (0)8 21 54 45 Tel: +33 (0)1 47 71 04 50
e-mail: [email protected] e-mail: [email protected]

Deutschland Nederland
Gen.Orph Gen.Orph
Tel: +49 30 8560687897 Tel: +32 (0)496 85 87 49
email: [email protected] e-mail: [email protected]

Eesti Norge
Gen.Orph Gen.Orph
Tel: +33 (0)1 47 71 04 50 Tlf: +46 (0)8 21 54 45
email: [email protected] e-mail: [email protected]

Ελλάδα Österreich
Gen.Orph Gen.Orph
Τηλ: +33 (0)1 47 71 04 50 Tel: +33 (0)1 47 71 04 50
email: [email protected] e-mail: [email protected]

España Polska
Pharma International S.A. Gen.Orph
Tel: +34 915 635 856 Tel.: +33 (0)1 47 71 04 50
e-mail: [email protected] e-mail: [email protected]

France Portugal
Gen.Orph Biojam, S.A.
Tél.: +33 (0)1 47 71 04 50 Tel: +351 212 697 912
e-mail: [email protected] e-mail: [email protected]

Hrvatska România
Gen.Orph Gen.Orph
Tel: +33 (0)1 47 71 04 50 Tel: +33 (0)1 47 71 04 50
e-mail: [email protected] e-mail: [email protected]

Ireland Slovenija
Gen.Orph Gen.Orph
Tel: +33 (0)1 47 71 04 50 Tel: +33 (0)1 47 71 04 50
e-mail: [email protected] e-mail: [email protected]

Ísland Slovenská republika
Gen.Orph Gen.Orph
Simi: +33 (0)1 47 71 04 50 Tel: +33 (0)1 47 71 04 50
e-mail: [email protected] e-mail: [email protected]

Italia Suomi/Finland
Gen.Orph Gen.Orph
Tel: +33 (0)1 47 71 04 50 Puh/Tel: +46 (0)8 21 54 45
e-mail: [email protected] e-mail: [email protected]

Κύπρος Sverige
Gen.Orph Gen.Orph
Tel: +33 (0)1 47 71 04 50 Tel: +46 (0)8 21 54 45
e-mail: [email protected] e-mail:
[email protected]

Latvija United Kingdom
Gen.Orph Gen.Orph
Tel: +33 (0)1 47 71 04 50 Tel: +33 (0)1 47 71 04 50
email: [email protected] email: [email protected]

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

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The following information is intended for healthcare professionals only:

As with all parenteral products, visually inspect the vials of Ibuprofene Gen.Orph before use to exclude the presence of particulate matter and to check container integrity. The vials are for single use only; any unused residual solution must be discarded.

Dosage and method of administration (see also section 3)

For intravenous use only. Treatment with Ibuprofene Gen.Orph must be administered exclusively in a neonatal intensive care unit under the supervision of an experienced neonatologist.

A therapeutic cycle is defined as three doses of Ibuprofene Gen.Orph administered intravenously at 24-hour intervals.

Determine the ibuprofen dose according to body weight as follows:

1st dose: 10 mg/kg,
2nd and 3rd doses: 5 mg/kg.

If the patent ductus arteriosus has not closed within 48 hours after the last dose, or if re-opening occurs, a second cycle of three doses may be administered as described above.

If no improvement is observed even after the second treatment cycle, surgical closure of the patent ductus arteriosus may be required.

If anuria or marked oliguria occurs after the first or second dose, the subsequent dose must not be administered until urine output has returned to normal.

Method of administration

Ibuprofene Gen.Orph must be administered as a short 15-minute infusion, preferably undiluted. An infusion pump may be used to facilitate administration.

If necessary, adjust the injection volume with 9 mg/mL (0.9%) sodium chloride solution for injection or 50 mg/mL (5%) glucose solution for injection in a PVC-free bag. Any unused residual solution must be discarded.

In preterm neonates, the total volume of injected solution must be taken into account in relation to the total daily fluid volume administered. A maximum of 80 mL/kg/day should generally be administered on the first day of life; this volume should then be progressively increased over the following 1–2 weeks (approximately 20 mL/kg of birth weight/day) up to a maximum of 180 mL/kg of birth weight/day.

Incompatibilities

Chlorhexidine is incompatible with Ibuprofene Gen.Orph solution and therefore must not be used to disinfect the vial. For aseptic preparation of the vial before use, a 60% ethanol solution or 70% isopropyl alcohol solution is recommended.

When disinfecting the vial with an antiseptic, the vial must be completely dry before opening to avoid any contact with the Ibuprofene Gen.Orph solution.

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

To avoid significant pH variations due to acidic medicinal products that may remain in the infusion line, flush the line with 1.5–2 mL of 9 mg/mL (0.9%) sodium chloride solution for injection or 50 mg/mL (5%) glucose solution for injection in a PVC-free bag before and after administration of Ibuprofene Gen.Orph.