Ibuprofen

Dose & administration
Three doses at 24-hour intervals, as intravenous injections over 15 minutes, or by oro-gastric administration:

• 1st dose: 10 mg/kg
• 2nd and 3rd dose: 5 mg/kg

Indications
Closure of the patent ductus arteriosus.

Contraindications and special considerations (incl incompatibilities)
Contraindications include:

• duct-dependent cardiovascular malformation
• active bleeding, including intracranial, gastrointestinal or lung bleeding
• necrotizing enterocolitis (confirmed or suspected)
• significant thrombocytopenia or coagulation defects
• significantly reduced renal function
• significant hyperbilirubinemia

Pulmonary hypertension has been reported when ibuprofen was given within 6 hours after birth.

Concomitant use the following pharmaceuticals products is not recommended:

• diuretics: ibuprofen may reduce the effect of diuretics, and diuretics may increase the risk of renal insufficiency in dehydrated patients.
• anticoagulants: ibuprofen may inhibit platelet function and concomitant use with anticoagulants may increase the risk of bleeding
• corticosteroids: concomitant use with ibuprofen may increase the risk of gastrointestinal bleeding
• nitric oxide: since both nitric oxide and ibuprofen inhibit platelet function, concomitant use may in theory increase the risk of bleeding
• other NSAIDs: concomitant use of more than one NSAID should be avoided because of the increased risk of adverse reactions
• aminoglycosides: ibuprofen may reduce clearance of aminoglycosides, concomitant use may increase the risk of nephrotoxicity and ototoxicity, and surveillance of serum levels of aminoglycides should be performed

Ibuprofen should not be administrated with any acidic solution.

Adverse effects
Oligura and transient renal insufficiency. Ibuprofen has less renal side-effects than indomethacin.

Pharmacological  aspects
Ibuprofen is an anti-inflammatory drug (NSAID) that reduces the synthesis of prostaglandins through a non-selective inhibition of cyclo-oxygenase.

Prostaglandins are involved in the persistence of the ductus arteriosus after birth, through relaxation of the muscle layer of the ductus arteriosus.

The reduction of prostaglandins by ibuprofen is believed to be the main mechanism of action. The estimated T1/2 is 30 (16-43) hours.

References

• Summary of product characteristics. Pedea -EMEA/H/C/000549 -IG/392. (URL)
• Ibuprofen for the treatment of patent ductus arteriosus in preterm or low birth weight infants. Cochrane Database of Systematic Reviews 2015, Issue 2. Art. No.: CD003481. 
PMID: 25692606
• Pulmonary hypertension after ibuprofen prophylaxis in very preterm infants. Lancet 2002; 359: 1486–88. PMID: 11988250

Document version history
2017-02-10  / Stefan Johansson