Prolonged indomethacin treatment in preterm infants with symptomatic patent ductus arteriosus: efficacy, drug level monitoring, and patient selection.

Indomethacin treatment for 1 week monitored by drug level determinations was evaluated in 32 preterm infants with symptomatic patent ductus arteriosus (sPDA). Inter- and intra-individual indomethacin dispositions varied considerably with the need for marked dosage adjustments to maintain the drug level within the proposed therapeutic range. The overall success rate of this prolonged treatment was 63%. There were no significant differences between the groups of responders (n = 20), relapsers (n = 5) and non-responders (n = 7) with respect to postnatal age, sex, total indomethacin dose, and indomethacin serum concentrations. The responders, however, had significantly higher birth weights. Eighty-five percent of infants weighing more than 1000 g (n = 20) were treated successfully. Only four of these children experienced adverse reactions. The benefit-to-risk ratio was lowest in the group of infants weighing 1000 g or less (n = 12) with a success rate of only 25% and, potentially, severe adverse reactions in ten infants. In conclusion, prolonged indomethacin treatment is an alternative to conventional short-term treatment and appears to be particularly efficacious and safe in infants weighing more than 1000 g. In infants weighing 1000 g or less and suffering from severe pulmonary diseases, this treatment cannot generally be recommended. The advantage of on-line drug level monitoring during indomethacin treatment deserves further investigation.