Dose:  0.1 to 0.2 mg/kg/dose IV

Frequency: Q 8 to 12 hours

Comments: Indomethacin is a non-steroidal anti-inflammatory agent used in newborns to close a patent ductus arteriosus (PDA). The starting dose is 0.2 mg/kg, with following doses of 0.2 mg/kg or 0.1 mg/kg based on the infant's response (particularly urine output).  Indomethacin is cleared mainly by hepatic metabolism; however, after intravenous administration, over 50% undergoes extensive enterohepatic circulation thus prolonging the half-live. Serum half-live varies from 27 + 8 hours in infants less than 1 week to 12 hours in infants greater than 1 year of age.  Treatment strategies have evolved with prophylactic treatment and early symptomatic treatment of PDAs having significantly reduced need for later surgical ligation. Infants who received early indomethacin therapy also were reported to have significantly lower incidence of BPD, duration of mechanical ventilation, and incidence of NEC. 

Recent reports have also suggested that it may be useful as prophylaxis against PDAs as well. Though a study by Ment showed a decrease in the incidence of grade 3/4 intraventricular hemorrhages following indomethacin prophylaxis, the results of the international trial (TIPP) reported by Barbara Schmidt at Hot Topics, December 2000 and in Pediatr Res 2000; 47:431A did not show an improvement in survival without neurosensory impairment in very low birth weight infants who received prophylactic indomethacin. For more information see comments on indomethacin.

The manufacturer lists the following as contraindications:
1. Infants with untreated infections.
2. Infants who are bleeding, especially GI or renal bleeding.
3. Infants with thrombocytopenia.
4. Infants with coagulation defects.
5. Infants with NEC.
6. Infants with significantly impaired renal function.

Toxicity: Although use of the drug may be associated with serious side effects in premature infants, it is unclear whether these are due to the underlying condition of these sick infants or to effects of the drug itself. The most frequent adverse effect that is clearly due to indomethacin is renal dysfunction. Indomethacin has been shown to prolong the bleeding time in infants which may last for several days beyond the last dose or the drug. Only minor clinical signs of bleeding have been observed (transient occult hematuria). There is no evidence to suggest that use of indomethacin is associated with extension of an IVH or the occurrence of other serious bleeding diathesis.  However, infusions of indomethacin have been associated with decreased cerebral, mesenteric, and renal blood flow. Potential gastrointestinal complications include hemorrhage, NEC, and focal areas of bowel perforation. The latter appears to be increased following the use of corticosteroids. Some infants receiving indomethacin have developed a transient ileus manifested by abdominal distension and vomiting.  Metabolic effects occurring with indomethacin include hyponatremia,   hyperkalemia, and fluid retention.  Finally, the use of indomethacin has been shown to increase peak and trough levels of aminoglycosides which paralleled decreased urine output.  See adverse effects associated with indomethacin.

Preparation: Indomethacin (Indocin) will be sent up from the pharmacy in a 0.1 mg/ml concentration. The drug is infused over 1/2 hour on a pump. An oral preparation may be used when IV indomethacin is unavailable, though ibuprofen may be a better alternative. (Scanlon. Pediatr 1982; 69:507).  Reconstituted indomethacin 0.5 milligrams per milliliter was stable in its original glass vial for 14 days when stored at 2 to 6 degrees Celsius (Walker et al, 1998).  Indomethacin will not be subject to standard times.   The first dose should be given promptly on receiving orders.  The usual course of therapy is three doses of 0.1-0.25 mg/kg, given 12 hours apart.    The pharmacist should schedule all three doses based on when they are prepared and delivered to the NICU.    Prescribers will want to be particularly clear in their orders if it is necessary to hold a dose for an adverse reaction, or to cancel subsequent doses based on patient response or repeat echocardiogram.  

Compatibility: Not compatible with TPN information about filter is unknown.   It is compatible with sterile water for injection, normal saline, D2.5W and D5W, as well as furosemide, insulin, potassium chloriede, sodium bicarbonate, and sodium nitroprusside.  Incompatible with D7.5W, D10W, calcium gluconate, dobutamine, dopamine, gentamicin, tobramycin, and tolazoline.