Effects of indomethacin on digoxin pharmacokinetics in preterm infants

Indomethacin is commonly coadministered with digoxin for the treatment of patent ductus arteriosus (PDA) in preterm infants. The combination of digoxin that is eliminated almost exclusively by the kidney and indomethacin, which tends to reduce renal function, has potential hazards. We report 11 preterm infants (gestational age 25-33 week) treated with digoxin for PDA in whom a standard indomethacin therapy (mean of total dose = 0.32 mg/kg) resulted in a significant elevation of serum digoxin to potentially toxic levels (from 2.2 ± 0.7 ng/ml to 3.2 ± 0.7) (P < 0.001). This phenomenon correlated well with decreased urine output (from 86 ± 34 ml to 43 ± 24 per hour) (P < 0.001) following indomethacin. No significant change was found in serum creatinine concentration pre- and post-indomethacin. Digoxin half-life was significantly prolonged (mean 97 ± 17 hour) following indomethacin therapy as compared with an age matched control group (mean half-life 43 ± 19 hour) (P < 0.05). Our data suggest that when indomethacin is added to digoxin therapy, the digoxin dosage should be reduced by 50% until urine output and digoxin serum levels can be better assessed.