Dose and Administration

1. 1st dose: 200 micrograms/kg as IV infusion by syringe pump over 30 minutes.
   Subsequent doses: 100 micrograms/kg/dose every 24 hours for a further 5 doses.

Indications

1. Closure of persistent patent ductus arteriosus.

Contraindications and Precautions

1. Anuria or oliguria (<0.5-1.0ml/kg/hour).
2. Serum creatinine >150 micromol/L.
3. Thrombocytopenia <80 x 10⁹/L.
4. Bleeding phenomena.
5. Necrotising enterocolitis.

Clinical Pharmacology

Indomethacin, an indole derivative, is one of the most potent inhibitors of the cyclo-oxygenase pathway. Inhibits the action of prostaglandin synthetase, and thus inhibits the synthesis of the prostaglandin E series. Indomethacin is a potent vasoconstrictor and decreases cerebral, gastrointestinal, and renal blood flow.

Very variable absorption from gastrointestinal tract (10-90%). Indomethacin solutions very susceptible to chemical decomposition. High binding (95%) to human plasma protein. No displacement of bilirubin from albumin at usual therapeutic levels. Hepatic metabolism, elimination via biliary tract and kidneys. Elimination half-life is approximately 30 hours (range 15-50 hours). Individual differences in rate of distribution, drug metabolism, rate of renal and biliary excretion, and re-entry of drug into the circulation by enterohepatic recirculation all contribute to the variability in plasma clearance.

Possible Adverse Effects

1. Renal impairment
2. Gastrointestinal dysfunction (abdominal distension, gastrointestinal bleeding, necrotising enterocolitis, gastric perforation, gastric ulceration).
3. Platelet dysfunction and bleeding tendency.

Special Considerations

1. Rapid infusions of intravenous indomethacin have been associated with significant reductions in cerebral blood flow.
2. Careful monitoring of gastrointestinal and renal status is required during a course of therapy.