From the Guidelines
Indocin (Indomethacin) is not entirely safe during pregnancy, particularly in the third trimester.
Risks and Precautions
- The use of Indocin (Indomethacin) during pregnancy is generally considered safe in low doses, intermittently, and when discontinued six to eight weeks before term 1.
- However, potential maternal effects when NSAIDs, including Indocin, are used close to term include prolonged gestation and labor, increased peripartum blood loss, and increased anemia 1.
- Potential fetal effects close to term include increased cutaneous and intracranial bleeding, premature closure of the ductus arteriosus, pulmonary hypertension, impaired renal function, reduced urine output, and reduced amniotic fluid volume 1, 2.
- The American College of Rheumatology strongly recommends against the use of NSAIDs, including Indocin, in the third trimester due to the risk of premature closure of the ductus arteriosus 3.
Safe Usage
- Indocin may be considered during the first and second trimesters, but the lowest effective dose should be used and discontinued at gestational week 32 2.
- The American Academy of Pediatrics considers Indocin safe in breastfeeding women, as only trace amounts are found in breast milk 1.
- However, breastfeeding mothers should avoid large doses of aspirin due to the potential risk of salicylate intoxication and bleeding problems in the neonate 1.
From the FDA Drug Label
Teratogenic Effects. Pregnancy Category C Teratogenic studies were conducted in mice and rats at dosages of 0. 5, 1, 2, and 4 mg/kg/day. Except for retarded fetal ossification at 4 mg/kg/day considered secondary to the decreased average fetal weights, no increase in fetal malformations was observed as compared with control groups Other studies in mice reported in the literature using higher doses (5 to 15 mg/kg/day) have described maternal toxicity and death, increased fetal resorptions, and fetal malformations. There are no adequate and well controlled studies in pregnant women. Indomethacin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus Because of the known effects of non-steroidal anti-inflammatory drugs on the fetal cardiovascular system (closure of ductus arteriosus), use during pregnancy (particularly late pregnancy) should be avoided The known effects of indomethacin and other drugs of this class on the human fetus during the third trimester of pregnancy include: constriction of the ductus arteriosus prenatally, tricuspid incompetence, and pulmonary hypertension; nonclosure of the ductus arteriosus postnatally which may be resistant to medical management; myocardial degenerative changes, platelet dysfunction with resultant bleeding, intracranial bleeding, renal dysfunction or failure, renal injury/dysgenesis which may result in prolonged or permanent renal failure, oligohydramnios, gastrointestinal bleeding or perforation, and increased risk of necrotizing enterocolitis.
Indomethacin is not safe during pregnancy, particularly in the third trimester, due to the potential risk of fetal cardiovascular effects and other adverse outcomes. The drug should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus 4. Key concerns include:
- Constriction of the ductus arteriosus
- Tricuspid incompetence
- Pulmonary hypertension
- Myocardial degenerative changes
- Platelet dysfunction
- Intracranial bleeding
- Renal dysfunction or failure
From the Research
Safety of Indomethacin During Pregnancy
- The safety of indomethacin during pregnancy has been studied in several research papers 5, 6, 7, 8, 9.
- A study published in 1993 found that indomethacin was effective in prolonging gestation in 10 cases of premature labor, but 5 neonates developed renal insufficiency attributed to indomethacin 5.
- Another study published in 2007 found that prolonged indomethacin therapy was rarely associated with ductal constriction and oligohydramnios, and that composite morbidity occurred in 29% of neonates 6.
- A 2022 study used physiologically based pharmacokinetic (PBPK) modeling to predict the maternal and fetal pharmacokinetics of indomethacin during pregnancy, and found that fetal exposures increased by approximately 30% from the second trimester to the third trimester of pregnancy 7.
- A 1990 study found that indomethacin was safe and effective for long-term tocolysis, with no increase in neonatal complications compared to infants exposed to intravenous tocolytics only 8.
- A 1994 study found that indomethacin can be safely used for treatment of premature labor, provided that its administration is carefully monitored, and that there were no adverse effects in the women and babies 9.
Adverse Effects
- Renal insufficiency in neonates has been reported as a potential adverse effect of indomethacin use during pregnancy 5.
- Ductal constriction and oligohydramnios have also been reported as potential adverse effects of prolonged indomethacin therapy 6.
- Increased fetal exposures to indomethacin in the third trimester of pregnancy may pose safety risks to the fetus 7.