Clinical Experience with Intravenous Ibuprofen Lysine in the Pharmacologic Closure of Patent Ductus Arteriosus

Patent ductus arteriosus (PDA) is the failure of the ductus that arises from the distal dorsal aortic arch to close during the first few days of life. The treatment options for PDA include “watchful waiting,” pharmacologic therapy with cyclooxygenase (COX) inhibitors (COX-1 and COX-2), such as indomethacin or intravenous (IV) ibuprofen lysine, and surgery when medical interventions have proved ineffective. The clinical trials evaluating the utilization of IV ibuprofen lysine focus on either preventing the persistence of a PDA or treating the PDA in premature infants in whom the ductus does not close within 48 hours of birth. Although the role of COX inhibitors in prophylaxis of PDA has been studied, it has not been clearly delineated. Treatment of PDA in preterm low birth weight infants from the second day of life on with IV ibuprofen lysine has been studied in 4 major and 3 smaller clinical trials. Overall, in 7 studies with 492 patients, the closure rate of PDA was 75.1% with IV ibuprofen lysine compared to 73.5% with indomethacin. In addition, neonates treated with IV ibuprofen lysine had significantly better creatinine clearance, urine output, serum creatinine, and blood urea nitrogen (BUN) profiles than indomethacin-treated patients. Overall, IV ibuprofen lysine is as effective as indomethacin for closure of PDA, yet is associated with a better safety profile with fewer negative side effects when compared to indomethacin.

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High Dose Indomethacin for Patent Ductus Arteriosus Closure Increases Neonatal Morbidity

American Journal of Perinatology ◽

10.1055/s-0039-3400996 ◽

2019 ◽

Cited By ~ 1

Author(s):

Salome Waldvogel ◽

Andrew Atkinson ◽

Mélanie Wilbeaux ◽

Mathias Nelle ◽

Markus R. Berger ◽

...

Keyword(s):

Patent Ductus Arteriosus ◽

Preterm Infants ◽

Necrotizing Enterocolitis ◽

Standard Dose ◽

Ductus Arteriosus ◽

Treatment Options ◽

Univariate Analysis ◽

High Dose ◽

Closure Rate ◽

Patent Ductus

Abstract Objective Symptomatic patent ductus arteriosus (sPDA) is the most common heart abnormality in preterm infants. Optimal duration and dose of medical treatment is still unclear. We assessed undesired effects and closure rate of high-dose indomethacin (HDI) for pharmacological closure of sPDA. Study Design Retrospective single center analysis of 248 preterm infants born between January 2006 and December 2015 with a birth weight <2,000 g and sPDA which was treated with indomethacin. Patients were treated with either standard dose indomethacin (SDI; n = 196) or HDI (n = 52). Undesired effects and PDA closure were compared between patients treated with SDI and HDI. Results In univariate analysis, patients receiving HDI had a significant increase in gastrointestinal hemorrhage (32.7 vs.11.7%, p = 0.001), bronchopulmonary dysplasia (BPD) (77.8 vs. 55.1%, p = 0.003), and retinopathy of prematurity (13.5 vs. 2.6%, p = 0.004). Moreover, HDI patients needed longer mechanical ventilation (2.5 vs. 1.0 days, p = 0.01). Multivariate analyses indicated that necrotizing enterocolitis (17 vs. 7%, p = 0.01) and BPD (79 vs. 55%, p = 0.02) were more frequent in HDI patients. PDA closure rate was 79.0% with HDI versus 65.3% with SDI. Conclusion HDI used for PDA closure is associated with an increase in necrotizing enterocolitis and BPD. Risks of HDI should be balanced against other treatment options.

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

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-12.3.147 ◽

2007 ◽

Vol 12 (3) ◽

pp. 147-157

Author(s):

Karen E. Corff ◽

Kris C. Sekar

Keyword(s):

Clinical Trials ◽

Blood Flow ◽

Patent Ductus Arteriosus ◽

Premature Infants ◽

Ductus Arteriosus ◽

Arterial Blood Flow ◽

Medical Decision ◽

Cox Inhibitors ◽

Clinical Considerations ◽

Patent Ductus

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.12 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.

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