Clinical Considerations for the Pharmacologic Management of Patent Ductus Arteriosus with Cyclooxygenase Inhibitors in Premature Infants

When medical management is warranted for closure of a persistent patent ductus arteriosus (PDA) in premature infants, treatment with a cyclooxygenase (COX) inhibitor is indicated. Indomethacin, available since 1976, has been the conventional pharmacologic treatment for PDA, but its use is associated with vasoconstrictive effects that impair renal, mesenteric and cerebral blood flow. Intravenous (IV) ibuprofen lysine, approved in the United States in 2006, has less severe vasoconstrictive effects on these vital organs than IV indomethacin. Clinical trials have shown both of these COX inhibitors to be equally effective in closing the PDA in approximately 70%-80% of treated infants, with less vasoconstrictive and adverse renal effects occurring with IV ibuprofen lysine.1,2 Several clinical considerations are important in the process of medical decision-making when faced with the need for PDA treatment with one of these pharmacologic agents in the premature infant. This paper focuses on these clinical considerations, including cerebral, renal and mesenteric blood flow, renal function, pulmonary effects, protein-binding capacity as it relates to hyperbilirubinemia, and platelet aggregation. No differences in chronic lung disease, pulmonary hypertension, hyperbilirubinemia and coagulopathy were observed in clinical trials when comparing these 2 COX inhibitors; however, significant differences have been observed in arterial blood flow to the cerebral, renal and mesenteric organs, suggesting that IV ibuprofen lysine may be the more favorable agent.