Oral medications regarding their safety and efficacy in the management of patent ductus arteriosus

Table 1 Summary of the studies comparing oral ibuprofen and others (IV ibuprofen/indomethacin, oral paracetamol)

Ref.	Comparison (n)	Gestational age (wk)	Method	Ductal closure rates		Comparison of adverse effects	Conclusion
Aly et al[30] (LOE 1A)	IV INDO (9) Oral IBU (12)	IV INDO: 32.9 ± 1.6 Oral IBU: 31.2 ± 2.5	Prospective, randomized, single mask	Oral IBU 83%	IV INDO 78%	Oral IBU = IV INDO	Oral IBU could be an easy to administer and efficacious alternative treatment.
Cherif et al[31] (LOE 1A)	IV IBU (32) Oral IBU (32)	IV IBU: 28.3 ± 1.1 Oral IBU: 29.3 ± 1.2	Prospective, randomized, single mask	Oral IBU 70.30%	IV IBU 70%	Oral IBU < IV IBU	Early ductal closure with oral IBU is as good as IV route
Gokmen et al[10] (LOE 1A)	IV IBU (50) Oral IBU (52)	IV IBU: 28.7 ± 2.1 Oral IBU: 28.5 ± 1.9	Prospective, randomized	Oral IBU 84.6%1	IV IBU 62%	IV IBU = Oral IBU	Oral IBU is more effective than IV IBU for ductal closure in VLBW infants
Erdeve et al[11] (LOE 1A)	IV IBU (34) Oral IBU (36)	IV IBU: 26.3 ± 1.3 Oral IBU: 26.4 ± 1.1	Prospective, randomized	Oral IBU 83.3%1	IV IBU 61.70%	BPD is lower with oral IBU	Oral IBU is as effective as IV IBU for PDA closure even in < 1000 g preterm infants.
Keady et al[42] (LOE 1B)	Oral PARA (80) Oral IBU (80)	Oral PARA: 31.2 ± 1.8 Oral IBU: 30.9 ± 2.2	Prospective, randomized	Oral PARA 81.20%	Oral IBU 78.80%	Oral PARA < Oral IBU	Oral PARA was comparable to IBU in terms of the rate of ductal closure and even showed a decreased risk of hyperbilirubinemia or gastrointestinal bleeding.
Oncel et al[21] (LOE 1B)	Oral PARA (40) Oral IBU (40)	Oral PARA: 27.3 ± 1.7 Oral IBU: 27.3 ± 2.1	Prospective, randomized	Oral PARA 72.50%	Oral IBU 77.50%	Oral PARA = Oral IBU	Oral PARA is as effective as oral IBU for PDA closure.

¹Differences were statistically significant (P < 0.05). LOE: Levels of evidence; IBU: Ibuprofen; INDO: Indomethacin; IV: Intravenous; PARA: Paracetamol; PDA: Patent ductus arteriosus; BPD: Bronchopulmonary dysplasia; VLBW: Very low birth weight.

Table 2 Comparison of adverse effects of oral ibuprofen and paracetamol[3]

	Oral ibuprofen	Oral paracetamol
Renal side effects	+/-	-
NEC	+	-
Spontaneous intestinal perforation	+	-
Gastrointestinal system bleeding	++	-
IVH	+	-
BPD	+/-	-
Alteration of platelet function	+	-
Decrease in cerebral blood flow	-	-
Hyperbilirubinemia	+/-	-
Hypertransaminasemia	-	+

NEC: Necrotizing enterocolitis; IVH: Intraventricular hemorrhage; BPD: Bronchopulmonary dysplasia.