Current evidence on the safety profile of NSAIDs for the treatment of PDA

Abstract

Patent ductus arteriosus (PDA) complicates the clinical course of preterm infants. Nonsteroidal anti-inflammatory drugs, especially Indomethacin and Ibuprofen, have been widely used for both prevention and treatment of PDA. Short-term efficacy of Indomethacin or Ibuprofen is equivalent, while Ibuprofen results show a higher safety profile. Ibuprofen is associated with fewer clinical gastrointestinal and renal side effects with respect to Indomethacin even if subclinical potential effects are reported. When administered as prophylaxis, Ibuprofen has no effects on prevention of intraventricular haemorrhage unlike Indomethacin. Considering the potential adverse effects of both these drugs, a careful monitoring during and after the treatment period is highly recommended.

Nonsteroidal anti-inflammatory administration and patent ductus arteriosus ligation, a survey of practice preferences at US children’s hospitals

“…However, it has not been shown to improve long-term outcomes including neurodevelopment at 18-36 months, respiratory outcomes, and mortality [10, 32] and there are concerns about the potential adverse effects of indomethacin in preterm neonates including nephrotoxicity, acute renal failure [31, 33], and decreased cerebral and intestinal blood flow [26, 27]. Our survey demonstrated the lack of evidence for improved neurodevelopmental outcomes and concern for adverse effects as leading reasons for avoiding indomethacin prophylaxis.…”

“…These therapies are efficacious in preventing IVH and closing PDA, respectively, but have not been shown to improve long term respiratory, neurodevelopmental, or mortality outcomes [8, 10, 15, 19, 23, 25]. In addition, the risk for long-term adverse effects following treatment of developing preterm infants with NSAIDs has not been fully evaluated [31, 33] and surgical ligation of PDA has been associated with increased bronchopulmonary dysplasia (BPD) and neurodevelopmental delay [4, 5, 16, 18, 22]. …”

Evidence-Based Use of Indomethacin and Ibuprofen in the Neonatal Intensive Care Unit

“…Indomethacin first became available in 1963 17 and belongs to a group of drugs called indoleacetic acids. Synthetically derived from arylacetic acid, 18 indomethacin inhibits COX in a competitive, time-dependent, slowly reversible manner. 15,16,18 Indomethacin nonselectively inhibits COX enzymes, resulting in decreased synthesis of all prostaglandin types.…”

“…Synthetically derived from arylacetic acid, 18 indomethacin inhibits COX in a competitive, time-dependent, slowly reversible manner. 15,16,18 Indomethacin nonselectively inhibits COX enzymes, resulting in decreased synthesis of all prostaglandin types. The nonselective mechanism of COX inhibition is responsible for the various unwanted side effects that can occur with administration.…”

“…17 It is a chiral compound derived from arylpropionic acid. 18 Ibuprofen exerts its effect in a simple, competitive, rapidly reversible manner. 15,16,18 Like indomethacin, ibuprofen inhibits COX in a nonselective manner.…”