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Effects of indomethacin on digoxin pharmacokinetics in preterm infants
Insights
Indomethacin coadministration with digoxin for patent ductus arteriosus (PDA) in preterm infants significantly increases serum digoxin levels and prolongs its half-life. Digoxin dosage should be reduced by 50% when combined with indomethacin.
Area of Science:
- Neonatal pharmacology
- Pediatric cardiology
- Clinical toxicology
Background:
- Patent ductus arteriosus (PDA) is common in preterm infants.
- Digoxin and indomethacin are frequently used for PDA treatment.
- Combining digoxin (renal excretion) and indomethacin (renal function reduction) poses risks.
Purpose of the Study:
- To investigate the effect of indomethacin on serum digoxin levels and pharmacokinetics in preterm infants with PDA.
- To assess the safety and efficacy of combined digoxin and indomethacin therapy.
Main Methods:
- Observational study of 11 preterm infants treated with digoxin for PDA.
- Standard indomethacin therapy administered.
- Serum digoxin levels, urine output, and serum creatinine monitored before and after indomethacin.
- Digoxin half-life compared to an age-matched control group.
Main Results:
- Indomethacin significantly elevated serum digoxin levels (2.2 to 3.2 ng/ml, P < 0.001).
- Urine output decreased significantly (86 to 43 ml/24hr, P < 0.001).
- Digoxin half-life significantly prolonged (97 vs. 43 hours, P < 0.05) post-indomethacin.
Conclusions:
- Indomethacin increases serum digoxin levels and prolongs its half-life in preterm infants with PDA.
- Reduced renal function likely contributes to digoxin accumulation.
- Recommend a 50% reduction in digoxin dosage when coadministered with indomethacin.
Abstract:
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 less than 0.001). This phenomenon correlated well with decreased urine output (from 86 +/- 34 ml to 43 +/- 24 per 24 hour) (P less than 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 less than 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.