DRUG INTERACTIONS Drug Interactions
Since renal function may be reduced by INDOCIN I.V., consideration should be given to reduction in dosage of those medications that rely on adequate renal function for their elimination. Because the half-life of digitalis (given frequently to pre-term infants with patent ductus arteriosus and associated cardiac failure) may be prolonged when given concomitantly with indomethacin, the neonate should be observed closely; frequent ECGs and serum digitalis levels may be required to prevent or detect digitalis toxicity early. Furthermore, in one study of premature infants treated with INDOCIN I.V. and also receiving either gentamicin or amikacin, both peak and trough levels of these aminoglycosides were significantly elevated.
Therapy with indomethacin may blunt the natriuretic effect of furosemide. This response has been attributed to inhibition of prostaglandin synthesis by non-steroidal anti-inflammatory drugs. In a study of 19 premature infants with patent ductus arteriosus treated with either INDOCIN I.V. alone or a combination of INDOCIN I.V. and furosemide, results showed that neonates receiving both INDOCIN I.V. and furosemide had significantly higher urinary output, higher levels of sodium and chloride excretion, and higher glomerular filtration rates than did those receiving INDOCIN I.V. alone. In this study, the data suggested that therapy with furosemide helped to maintain renal function in the premature infant when INDOCIN I.V. was added to the treatment of patent ductus arteriosus.
Indomethacin usually does not influence the hypoprothrombinemia produced by anticoagulants. When indomethacin is added to anticoagulants, prothrombin time should be monitored closely. In post marketing experience, bleeding has been reported in patients on concomitant treatment with anticoagulants and INDOCIN I.V. Caution should be exercised when INDOCIN I.V. and anticoagulants are administered concomitantly.
In some patients with compromised renal function, the co-administration of an NSAID and an ACE inhibitor or angiotensin II antagonist may result in further deterioration of renal function,including possible acute renal failure, which is usually reversible.
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