General MedicationsINTRAVENOUSHigh Alert

Indomethacin

INDOMETHACIN

Standard Dose

2 DOSAGE AND ADMINISTRATION • Dosage is dependent on the age of the infant at time of therapy. A course of therapy requires intravenous doses of Indomethacin for Injection given at 12 to 24 hour intervals. AGE at 1st dose DOSAGE (mg/kg) Less than 48 hours 1st 0.2 2nd 0.1 3rd 0.1 2 to 7 days 0.2 0.2 0.2 Over 7 days 0.2 0.25 0.25 • If anuria or marked oliguria (urinary output <0.6 mL/kg/hr) is evident at the scheduled time of the second or third dose of Indomethacin for Injection, do not give additional doses until laboratory studies indicate that renal function has returned to normal • If the ductus arteriosus closes or is significantly reduced in size after an interval of 48 hours or more from completion of the first course of Indomethacin for Injection, no further doses are necessary • If the neonate remains unresponsive to therapy with Indomethacin for Injection after 2 courses, surgery may be necessary for closure of the ductus arteriosus. ( 2.1 ) For intravenous administration only . Dosage recommendations for closure of the ductus arteriosus depend on the age of the infant at the time of therapy. A course of therapy is defined as three intravenous doses of Indomethacin for Injection given at 12 to 24 hour intervals, with careful attention to urinary output. If anuria or marked oliguria (urinary output <0.6 mL/kg/hr) is evident at the scheduled time of the second or third dose of Indomethacin for Injection, do not give additional doses until laboratory studies indicate that renal function has returned to normal [see Warnings and Precautions ( 5.7 )] . Dosage according to age is as follows: AGE at 1st dose DOSAGE (mg/kg) Less than 48 hours 1st 0.2 2nd 0.1 3rd 0.1 2 to 7 days 0.2 0.2 0.2 Over 7 days 0.2 0.25 0.25 If the ductus arteriosus closes or is significantly reduced in size after an interval of 48 hours or more from completion of the first course of Indomethacin for Injection, no further doses are necessary. If the ductus arteriosus re-opens, a second course of 1 to 3 doses may be given, each dose separated by a 12 to 24 hour interval as described above. If the neonate remains unresponsive to therapy with Indomethacin for Injection after 2 courses, surgery may be necessary for closure of the ductus arteriosus. 2.1 Directions for Use Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. The reconstituted solution, pH 6.0 to 7.5, is clear, slightly yellow and essentially free from visible particles. Prepare the solution with 1 to 2 mL of preservative-free Sterile Sodium Chloride Injection, 0.9 percent or preservative-free Sterile Water for Injection. Benzyl alcohol as a preservative has been associated with toxicity in neonates. Therefore, do not use diluents that contain preservatives. If 1 mL of diluent is used, the concentration of indomethacin in the solution will equal approximately 0.1 mg/0.1 mL; if 2 mL of diluent are used, the concentration of the solution will equal approximately 0.05 mg/0.1 mL. Discard any unused portion of the solution as it does not contain a preservative. Prepare a fresh solution just prior to each administration. Once reconstituted, the indomethacin solution may be injected intravenously. While the optimal rate of injection has not been established, published literature suggests an infusion rate over 20 to 30 minutes. Further dilution with intravenous infusion solutions is not recommended.

Max Dose

See official label

Primary Use

1 INDICATIONS AND USAGE Indomethacin for Injection is indicated to close a hemodynamically significant patent ductus arteriosus in premature infants weighing between 500 and 1,750 g when 48 hours usual medical management (e.g., fluid restriction, diuretics, digitalis, respiratory support, etc.) is ineffective.

Summary

Clear-cut clinical evidence of a hemodynamically significant patent ductus arteriosus should be present, such as respiratory distress, a continuous murmur, a hyperactive precordium, cardiomegaly, or pulmonary plethora on chest x-ray.

Structured Monograph

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE Indomethacin for Injection is indicated to close a hemodynamically significant patent ductus arteriosus in premature infants weighing between 500 and 1,750 g when 48 hours usual medical management (e.g., fluid restriction, diuretics, digitalis, respiratory support, etc.) is ineffective. Clear-cut clinical evidence of a hemodynamically significant patent ductus arteriosus should be present, such as respiratory distress, a continuous murmur, a hyperactive precordium, cardiomegaly, or pulmonary plethora on chest x-ray. Indomethacin for Injection is a cardiovascular drug indicated: • To close a hemodynamically significant patent ductus arteriosus in premature infants weighing between 500 and 1,750 g. ( 1 ) Dosage and administration 2 DOSAGE AND ADMINISTRATION • Dosage is dependent on the age of the infant at time of therapy. A course of therapy requires intravenous doses of Indomethacin for Injection given at 12 to 24 hour intervals. AGE at 1st dose DOSAGE (mg/kg) Less than 48 hours 1st 0.2 2nd 0.1 3rd 0.1 2 to 7 days 0.2 0.2 0.2 Over 7 days 0.2 0.25 0.25 • If anuria or marked oliguria (urinary output <0.6 mL/kg/hr) is evident at the scheduled time of the second or third dose of Indomethacin for Injection, do not give additional doses until laboratory studies indicate that renal function has returned to normal • If the ductus arteriosus closes or is significantly reduced in size after an interval of 48 hours or more from completion of the first course of Indomethacin for Injection, no further doses are necessary • If the neonate remains unresponsive to therapy with Indomethacin for Injection after 2 courses, surgery may be necessary for closure of the ductus arteriosus. ( 2.1 ) For intravenous administration only . Dosage recommendations for closure of the ductus arteriosus depend on the age of the infant at the time of therapy. A course of therapy is defined as three intravenous doses of Indomethacin for Injection given at 12 to 24 hour intervals, with careful attention to urinary output. If anuria or marked oliguria (urinary output <0.6 mL/kg/hr) is evident at the scheduled time of the second or third dose of Indomethacin for Injection, do not give additional doses until laboratory studies indicate that renal function has returned to normal [see Warnings and Precautions ( 5.7 )] . Dosage according to age is as follows: AGE at 1st dose DOSAGE (mg/kg) Less than 48 hours 1st 0.2 2nd 0.1 3rd 0.1 2 to 7 days 0.2 0.2 0.2 Over 7 days 0.2 0.25 0.25 If the ductus arteriosus closes or is significantly reduced in size after an interval of 48 hours or more from completion of the first course of Indomethacin for Injection, no further doses are necessary. If the ductus arteriosus re-opens, a second course of 1 to 3 doses may be given, each dose separated by a 12 to 24 hour interval as described above. If the neonate remains unresponsive to therapy with Indomethacin for Injection after 2 courses, surgery may be necessary for closure of the ductus arteriosus. 2.1 Directions for Use Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. The reconstituted solution, pH 6.0 to 7.5, is clear, slightly yellow and essentially free from visible particles. Prepare the solution with 1 to 2 mL of preservative-free Sterile Sodium Chloride Injection, 0.9 percent or preservative-free Sterile Water for Injection. Benzyl alcohol as a preservative has been associated with toxicity in neonates. Therefore, do not use diluents that contain preservatives. If 1 mL of diluent is used, the concentration of indomethacin in the solution will equal approximately 0.1 mg/0.1 mL; if 2 mL of diluent are used, the concentration of the solution will equal approximately 0.05 mg/0.1 mL. Discard any unused portion of the solution as it does not contain a preservative. Prepare a fresh solution just prior to each administration. Once reconstituted, the indomethacin solution may be injected intravenously. While the optimal rate of injection has not been established, published literature suggests an infusion rate over 20 to 30 minutes. Further dilution with intravenous infusion solutions is not recommended. Warnings and cautions 5 WARNINGS AND PRECAUTIONS • Indomethacin may mask the usual signs of infection. ( 5.1 ) • Monitor for signs of hepatic reactions. Indomethacin for Injection may need to be discontinued. ( 5.2 ) • Indomethacin for Injection may inhibit platelet aggregation. ( 5.3 ) • Gastrointestinal Effects: Monitor neonates for blood in stool. ( 5.4 ) • Central Nervous System Effects: Monitor neonates for intraventricular hemorrhage. ( 5.5 ) • Renal Effects: Monitor renal function and serum electrolytes. ( 5.6 ) 5.1 Infection Indomethacin may mask the usual signs and symptoms of infection. Therefore, the physician must be continually on the alert for this and should use the drug with extra care in the pre

Monitoring

• 5 WARNINGS AND PRECAUTIONS • Indomethacin may mask the usual signs of infection.
• ( 5.1 ) • Monitor for signs of hepatic reactions.
• Indomethacin for Injection may need to be discontinued.
• ( 5.2 ) • Indomethacin for Injection may inhibit platelet aggregation.

Interaction Notes

• 7 DRUG INTERACTIONS As renal function may be reduced by Indomethacin for Injection, consider reducing the dosage of those medications that rely on adequate renal function for their elimination.
• • When used concomitantly with digoxin, monitor neonates for the development of digoxin toxicity.
• ( 7.1 ) • Monitor prothrombin time when indomethacin is added to anticoagulants.
• ( 7.2 ) 7.1 Digoxin Because the half-life of digoxin (given frequently to pre-term infants with patent ductus arteriosus and associated cardiac failure) may be prolonged when given concomitantly with indomethacin, observe neonates receiving concomitant digoxin closely; frequent ECGs and serum digoxin levels may be required to prevent or detect digoxin toxicity early.