Indomethacin (indomethacin sodium)

The lowest possible effective dosage and shortest duration of therapy consistent with treatment goals of the patient should be employed. Dosage of indomethacin must be carefully adjusted according to individual requirements and response, using the lowest possible effective dosage. Indomethacin 50-mg suppositories can be substituted for indomethacin capsules; however, there will be significant differences between the two dosage regimens in indomethacin blood levels.

Dosage of indomethacin sodium injection, is expressed in terms of anhydrous indomethacin; the IV injection is labeled for use only in premature infants with PDA.

The potential benefits and risks of indomethacin therapy as well as alternative therapies should be considered prior to initiating indomethacin therapy.

Indomethacin is administered orally or rectally. Indomethacin sodium is administered by IV injection for the treatment of patent ductus arteriosus (PDA).

Commercially available indomethacin oral suspension is supplied as a 25 mg/5 mL (5 mg/mL) concentration.

No dosing information is available for this tab.

No dosing information is available for this tab.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*Indomethacin is contraindicated in patients with known hypersensitivity to the drug or any ingredient in the formulation.

*Nonsteroidal anti-inflammatory agents (NSAIAs), including indomethacin, generally are contraindicated in patients in whom asthma, urticaria, or other sensitivity reactions are precipitated by aspirin or other NSAIAs, since there is potential for cross-sensitivity between NSAIAs and aspirin, and severe, potentially fatal, anaphylactic reactions may occur in such patients.

*Indomethacin is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.

*Indomethacin sodium for injection is contraindicated in neonates with congenital heart disease when patency of the ductus arteriosus is necessary for adequate pulmonary or systemic blood flow (e.g., neonates with pulmonary atresia, severe tetralogy of Fallot, or severe coarctation of the aorta).

*Indomethacin sodium for injection is contraindicated in neonates with proven or suspected, untreated infection.

*Indomethacin sodium for injection is contraindicated in neonates with active bleeding, such as those with intraventricular hemorrhage or GI bleeding, and in neonates with thrombocytopenia or underlying coagulation defect.

*Indomethacin sodium for injection is contraindicated in neonates with substantially impaired renal function.

*Indomethacin sodium for injection is contraindicated in neonates with known or suspected necrotizing enterocolitis.

*Indomethacin suppositories are contraindicated in patients with a history of proctitis or recent rectal bleeding.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

Adverse effects reported in >=3% of patients receiving indomethacin in clinical trials include headache, dizziness, dyspepsia, and nausea.

The most common adverse effects reported in neonates receiving indomethacin sodium for injection for PDA include bleeding issues, a greater incidence of transient oliguria, and elevations in serum creatinine.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

No enhanced messaging available.

Safety and efficacy of oral or rectal indomethacin have not been established in children <=14 years of age. Therefore, the drug should not be administered to children 2-14 years of age except under circumstances when inefficacy or toxicity associated with other drugs warrants the risk; such children should be monitored closely. The manufacturers state that experience with indomethacin in these children has been limited to use of conventional capsules of the drug. Adverse effects associated with use of conventional capsules of the drug in children <=14 years of age have been similar to those associated with use of this dosage form in adults. Hepatotoxicity (sometimes fatal) has occurred in children receiving the drug for juvenile rheumatoid arthritis. If the drug is used in children 2-14 years of age, liver function should be monitored periodically.

Use of NSAIAs during pregnancy at about 30 weeks' gestation or later can cause premature closure of the fetal ductus arteriosus, and use at about 20 weeks' gestation or later has been associated with fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, use of NSAIAs should be avoided in pregnant women at about 30 weeks' gestation or later; if NSAIA therapy is necessary between about 20 and 30 weeks' gestation, the lowest effective dosage and shortest possible duration of treatment should be used. Monitoring of amniotic fluid volume via ultrasound examination should be considered if the duration of NSAIA treatment exceeds 48 hours; if oligohydramnios occurs, the drug should be discontinued and follow-up instituted according to clinical practice. Pregnant women should be advised to avoid use of NSAIAs beginning at 20 weeks' gestation unless otherwise advised by a clinician; they should be informed that NSAIAs should be avoided beginning at 30 weeks' gestation because of the risk of premature closure of the fetal ductus arteriosus and that monitoring for oligohydramnios may be necessary if NSAIA therapy is required for longer than 48 hours' duration between about 20 and 30 weeks' gestation.

Fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment has been observed, on average, following days to weeks of maternal NSAIA use, although oligohydramnios has been observed infrequently as early as 48 hours after initiation of NSAIA therapy. Oligohydramnios is often, but not always, reversible following discontinuance of NSAIA therapy. Complications of prolonged oligohydramnios may include limb contracture and delayed lung maturation. A limited number of case reports have described maternal NSAIA use and neonatal renal dysfunction, in some cases irreversible, without oligohydramnios. Some cases of neonatal renal dysfunction have required treatment with invasive procedures such as exchange transfusion or dialysis. Methodologic limitations of these postmarketing studies and case reports include lack of a control group; limited information regarding dosage, duration, and timing of drug exposure; and concomitant use of other drugs. These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal NSAIA use. Available data on neonatal outcomes generally involved preterm infants, and the extent to which certain reported risks can be generalized to full-term infants is uncertain.

Animal data indicate that prostaglandins have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, inhibitors of prostaglandin synthesis, such as indomethacin, were associated with increased pre- and post-implantation losses. Prostaglandins also have an important role in fetal kidney development. In animal studies, inhibitors of prostaglandin synthesis impaired kidney development at clinically relevant doses.

Reproduction studies in mice and rats at dosages of 0.5-4 mg/kg daily have revealed no increase in fetal malformations other than retarded fetal ossification, which was observed at the highest dosage and was attributed to decreased average fetal weight. Administration of indomethacin to mice and rats during the last 3 days of gestation at a dosage of 4 mg/kg daily was associated with an increased incidence of neuronal necrosis in the diencephalon in live-born fetuses; no increase in neuronal necrosis was observed at a dosage of 2 mg/kg daily, and administration of the drug to the offspring during the first 3 days of life at a dosage of 0.5 or 4 mg/kg daily did not result in an increase in neuronal necrosis.

The effects of indomethacin on labor and delivery are unknown. In studies with rats, drugs that inhibit prostaglandin synthesis, including NSAIAs, increased the incidence of dystocia, delayed parturition, and increased the incidence of stillbirth.

Based on available data, indomethacin may be present in human milk. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for indomethacin and any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.

Indomethacin should be used with caution in geriatric individuals >=65 years of age since increasing age may be associated with increased serious risk of cardiovascular, gastrointestinal and/or renal adverse reactions. If the anticipated benefits of the drug outweigh the potential risks, indomethacin should be initiated at the lower end of the dosage range and patients should be monitored for adverse reactions.

Indomethacin is eliminated mainly by the kidneys and individuals with renal impairment may be at increased risk for toxic reactions to the drug. Because geriatric patients frequently have decreased renal function, particular attention should be paid to indomethacin dosage, and it may be useful to monitor renal function in these patients.

Indomethacin should be used with caution in geriatric individuals >=65 years of age since increasing age may be associated with increased risk of adverse reactions. Geriatric individuals appear to be at a greater risk for fatal adverse GI effects (See Cautions: GI Effects). Indomethacin may cause confusion or, rarely, psychosis; clinicians should remain alert to the possibility of such adverse reactions in geriatric individuals.

Indomethacin is eliminated mainly by the kidneys and individuals with renal impairment may be at increased risk for toxic reactions to the drug. Because geriatric patients frequently have decreased renal function, particular attention should be paid to indomethacin dosage and it may be useful to monitor renal function in these patients.