Ibuprofen

Ibuprofen

• Treatment of a hemodynamically significant patent ductus arteriosus in newborns less than 34 weeks gestational age
• Not recommended for prophylactic use within first 3 days of life
• Limited data in neonates <27 weeks  gestation

Pharmacology

• Non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic activity
• Non-selective inhibitor of cyclo-oxygenase, which decreases prostaglandin synthesis
• Inhibition of prostaglandin synthesis (particularly the E series) allows the ductus to constrict and close
• Inhibition of synthesis of thromboxane A2 (an end product of the cyclo-oxygenase pathway) may lead to impaired platelet aggregation
• Apparent volume of distribution (Vd): 200 mL/kg (range, 62 – 350 mL/kg)
• Elimination half-life is approximately 30 hours (range, 16 – 43 hours)
• Clearance increases with increasing gestational age
• highly bound (95%) to plasma albumin
  • In vitro studies have shown that ibuprofen, at high concentrations, may displace bilirubin binding to albumin.  However, this has not been observed at the recommended dosing range
• eliminated primarily by the liver

Side Effects

• Cardiorespiratory: case reports of pulmonary hypertension have been described, especially when ibuprofen is used prophylactically
• GI: GI hemorrhage, intestinal perforation, necrotizing enterocolitis (NEC)
• Renal: transient oliguria, hyponatremia and elevation in blood creatinine; acute renal failure is uncommon

Drug Interactions

• Ibuprofen may reduce the effect of diuretics
• ibuprofen may enhance the effects of anticoagulants
• Ibuprofen and steroids may increase the risk of GI bleeding
• Ibuprofen and nitric oxide, which both inhibit platelet function, may theoretically increase the risk of bleeding
• Ibuprofen may decrease the clearance of aminoglycosides and other drugs that are eliminated through renal excretion

Contraindications

• life-threatening infection
• active bleeding, especially intracranial or gastrointestinal hemorrhage
• severe thrombocytopenia or coagulation defects
• significant impairment of renal function
• known or suspected NEC
• “duct-dependent” congenital heart diseases in which patency of the ductus arteriosus is necessary for satisfactory pulmonary or systemic blood flow (e.g., pulmonary atresia, pulmonary stenosis, transposition of the great arteries, coarctation of the aorta, hypoplastic left heart)

Precautions

• Before administration of the drug, the following studies should be considered:  electrolytes, bilirubin, creatinine, CBC, hemoglobin
• Continue to monitor serum sodium, infant’s weight, accurate fluid intake and output
• If anuria or severe oliguria occurs, the next dose may be withheld or postponed, until renal function improves
  • N.B. Transient renal impairment is an expected pharmacologic effect of ibuprofen.  It is generally reversible upon completion of treatment
• The need for fluid restriction should be anticipated with a course of ibuprofen treatment
• May decrease clearance of aminoglycosides; serum aminoglycoside levels are recommended during co-administration with ibuprofen

Dose and Administration

• Prior and subsequent to administration: the infusion line should be flushed over 15 minutes with 1.5 to 2 mL of 0.9% normal saline or glucose 5% solution
• a course of therapy consists of 3 doses, administered as an IV infusion q24h
  • first dose: 10 mg/kg
  • second and third doses: 5 mg/kg
• Each infusion should be administered over 15 minutes, preferably undiluted
• If necessary, the preparation can be diluted, using either sodium chloride 0.9% solution for injection or glucose 5% solution for injection
• a 2nd course may be considered if the ductus arteriosus fails to close or if it re-opens
• Do not mix with any other medication, including TPN and lipids

Supplied As

• 5 mg / mL ampoule (2 mL)
• clear, colourless to slightly yellow solution