To view the fulltext, please log in
To view the pdf, please log in
Background: Pharmacological closure of patent ductus arteriosus (PDA) is commonly achieved by intravenous (IV) administration of ibuprofen or indomethacin. Occasionally, oral ibuprofen is used for PDA treatment although its efficacy and safety are unclear. Objectives: To systematically review randomized and quasi-randomized trials comparing oral ibuprofen with IV ibuprofen or IV indomethacin for closure of PDA in preterm infants. Methods: The standard search methods of the Cochrane Neonatal Review Group were used. Results: We identified two studies (n = 166) of good methodological quality comparing oral ibuprofen with IV ibuprofen and three small trials (n = 92) of moderate methodological quality comparing oral ibuprofen to IV indomethacin. Meta-analysis showed higher PDA closure rate of oral ibuprofen versus IV ibuprofen but no difference between oral ibuprofen and IV indomethacin. Meta-analysis did not indicate a significant difference in adverse effects. Conclusion: Oral ibuprofen for PDA closure appears to be as effective as IV ibuprofen and IV indomethacin. Due to small sample size, lack of data in extremely preterm neonates, and methodological limitations of reviewed trials, definitive conclusions cannot be drawn. Randomized trials with a low risk of bias and adequate sample size in extremely preterm infants are urgently needed.
Copyright / Drug Dosage
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
- Hamrick SE, Hansmann G: Patent ductus arteriosus of the preterm infant. Pediatrics 2010;125:1020–1030.
- Ohlsson A, Walia R, Shah S: Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight infants. Cochrane Database Syst Rev 2010;CD003481.
- Koehne PS, Bein G, Alexi-Meskhishvili V, Weng Y, Bührer C, Obladen M: Patent ductus arteriosus in very low birthweight infants: complications of pharmacological and surgical treatment. J Perinat Med 2001;29:327–334.
- Keating P, Verhagen E, van Hoften J, ter Horst H, Bos AF: Effect of indomethacin infused over 30 minutes on cerebral fractional tissue oxygen extraction in preterm newborns with a patent ductus arteriosus. Neonatology 2010;98:232–237.
- Jobe AH: Drug pricing in pediatrics: the egregious example of indomethacin. Pediatrics 2007;119:1197–1198.
- Sharma PK, Garg SK, Narang A: Pharmacokinetics of oral ibuprofen in premature infants. J Clin Pharmacol 2003;43:968–973.
- Cherif A, Jabnoun S, Khrouf N: Oral ibuprofen in early curative closure of patent ductus arteriosus in very premature infants. Am J Perinatol 2007;24:339–345.
- Heyman E, Morag I, Batash D, Keidar R, Baram S, Berkovitch M: Closure of patent ductus arteriosus with oral ibuprofen suspension in premature newborns: a pilot study. Pediatrics 2003;112:e354.
- Guimarães H, Rocha G, Tome T, Anatolitou F, Sarafidis K, Fanos V: Non-steroid anti-inflammatory drugs in the treatment of patent ductus arteriosus in European newborns. J Matern Fetal Neonatal Med 2009;22:77–80.
- Aly H, Lotfy W, Badrawi N, Ghawas M, Abdel-Meguid IE, Hammad TA: Oral ibuprofen and ductus arteriosus in premature infants: a randomized pilot study. Am J Perinatol 2007;24:267–270.
- Cherif A, Khrouf N, Jabnoun S, Mokrani C, Amara M, Guellouze N, Kacem S: Randomized pilot study comparing oral ibuprofen with intravenous ibuprofen in very low birth weight infants with patent ductus arteriosus. Pediatrics 2008;122:e1256–1261.
- Chotigeat U, Jirapapa K, Layangkool T: A comparison of oral ibuprofen and intravenous indomethacin for closure of patent ductus arteriosus in preterm infants. J Med Assoc Thai 2003;86:S563–S569.
- Salama H, Alisi A, Al-Rifai H, Shaddad A, Samawal L, Habboub L, Masoud A: A randomized controlled trial on the use of oral ibuprofen to close patent ductus arteriosus in premature infants. J Neonatal Perinatal Med 2008;1:153–158.
- Gokmen T, Erdeve O, Altug N, Oguz SS, Uras N, Dilmen U: Efficacy and safety of oral versus intravenous Ibuprofen in very low birth weight preterm infants with patent ductus arteriosus. J Pediatr 2011;158:549–554.
- Higgins JP, Thompson SG, Deeks JJ, Altman DG: Measuring inconsistency in meta-analyses. BMJ 2003;327:557–560.
- Akisu M, Ozyurek AR, Dora C: Enteral ibuprofen versus indomethacin in the treatment of patent ductus arteriosus in preterm newborn infants. Çocuk Sağlığı ve Hastalıkları Dergisi 2001;44:56–60.
- Fakhraee SH, Badiee Z, Mojtahedzadeh S, Kazemian M, Kelishadi R: Comparison of oral ibuprofen and indomethacin therapy for patent ductus arteriosus in preterm infants. Zhongguo Dang Dai Er Ke Za Zhi 2007;9:399–403.
- Pourarian S, Pishva N, Madani A, Rastegari M: Comparison of oral ibuprofen and indomethacin on closure of patent ductus arteriosus in preterm infants. East Mediterr Health J 2008;14:360–365.
- Supapannachart S, Limrungsikul A, Khowsathit P: Oral ibuprofen and indomethacin for treatment of patent ductus arteriosus in premature infants: a randomized trial at Ramathibodi Hospital. J Med Assoc Thai 2002;85 S1252–S1258.
- Sangtawesin C, Sangtawesin V, Lertsutthiwong W, Kanjanapattanakul W, Khorana M, Ayudhaya JK: Prophylaxis of symptomatic patent ductus arteriosus with oral ibuprofen in very low birth weight infants. J Med Assoc Thai 2008;91:S28–S34.
- Teksam O, Yigit S, Karagoz T, Korkmaz A, Yurdakok M, Tekinalp G: Oral ibuprofen and intravenous indomethacin for treatment of patent ductus arteriosus in newborn infants: a retrospective study. Çocuk Sağlığı ve Hastalıkları Dergisi 2004;47:96–102.
- Tiker F, Yildirim SV: Acute renal impairment after oral ibuprofen for medical closure of patent ductus arteriosus. Indian Pediatr 2007;44:54–55.
- Erdeve O, Sarici SU, Sari E, Gok F: Oral-ibuprofen-induced acute renal failure in a preterm infant. Pediatr Nephrol 2008;23:1565–1567.
- Pereira-da-Silva L, Pita A, Virella D, Serelha M: Oral ibuprofen for patent ductus arteriosus closure in preterm infants: does high osmolality matter? Am J Perinatol 2008;25:319–320.
- Ohlsson A, Shah SS: Ibuprofen for the prevention of patent ductus arteriosus in preterm and/or low birth weight infants. Cochrane Database Syst Rev 2011;CD004213.
- Barzilay B, Youngster I, Batash D, Keidar R, Baram S, Goldman M, Berkovich M, Heyman E: Pharmacokinetics of oral ibuprofen for patent ductus arteriosus closure in preterm infants. Arch Dis Child Fetal Neonatal Ed 2011 (E-pub ahead of print).
- Su BH: Comparison of oral and intravenous ibuprofen for PDA Treatment in premature infants. ClinicalTrials.gov registration number: NCT01149564.
- Erdeve O, Yurtuttan S, Dilmen U: Efficacy and safety of oral versus intravenous ibuprofen for PDA treatment in EBLW infants. ClinicalTrials.gov registration number: NCT01261117.