Indomethacin Pregnancy and Breastfeeding Warnings

Brand names: Indocin, Indocin IV, Indocin SR, Tivorbex

Medically reviewed by Drugs.com. Last updated on Aug 3, 2023.

Indomethacin Pregnancy Warnings

Contraindicated last trimester of pregnancy
NSAIDs should be avoided at 20 weeks gestation and later

AU TGA pregnancy category: C
US FDA pregnancy category: Not assigned

Risk Summary: Nonsteroidal anti-inflammatory drugs (NSAIDs) use in pregnant women at 30 weeks gestation and later may cause premature closure of the fetal ductus arteriosus; NSAID use at 20 weeks gestation or later may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment.

Comments:
-NSAID use in pregnancy prior to 20 weeks gestation should be based on a benefit-risk assessment; some authorities recommend avoiding NSAIDs throughout pregnancy whenever possible.
-If NSAID use is necessary between 20- and 30-weeks' gestation, limit use to the lowest effective dose for the shortest duration possible; ultrasound monitoring of amniotic fluid should be considered if NSAID use extends beyond 48 hours; if oligohydramnios occurs, discontinue NSAID and treat appropriately.
-NSAID use is not recommended in women attempting to conceive as it may impair female fertility.

Animal studies have shown prostaglandins play an important role in endometrial vascular permeability, blastocyst implantation, and decidualization; administration of prostaglandin synthesis inhibitors has resulted in increased pre-and post-implantation loss. Data from observational studies in women during the first or second trimester of pregnancy are inconclusive regarding potential embryofetal risks. Epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation increased from less than 1%, up to approximately 1.5 %; this risk is believed to increase with dose and duration of therapy. Use of nonsteroidal anti-inflammatory drugs (NSAIDs) during the third trimester of pregnancy increases the risk of premature closure of the fetal ductus arteriosus. There are no controlled data in human pregnancy.

US FDA Drug Safety Communication (10-2020): The FDA is requiring a new warning be added to NSAID labeling describing the risk of fetal kidney problems that may result in low amniotic fluid. The FDA is recommending pregnant women avoid NSAID use at 20 weeks gestation or later. Through 2017, the FDA has received 35 reports of low amniotic fluid levels or kidney problems in mothers who took NSAIDs while pregnant. Five newborns died; 2 had kidney failure and confirmed low amniotic fluid, 3 had kidney failure without confirmed low amniotic fluid. The low amniotic fluid started as early as 20 weeks of pregnancy. There were 11 reports of low amniotic fluid levels during pregnancy and the fluid volume returned to normal after the NSAID was stopped. The medical literature has reported low amniotic fluid levels with use of NSAIDs for varying amounts of time, ranging from 48 hours to multiple weeks. Complications of prolonged oligohydramnios may include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required. In other cases, the condition was reversible within 3 to 6 days of stopping the NSAID and in these cases reappeared when the same NSAID was restarted.

NSAIDs may impair female fertility; withdrawal of NSAID therapy should be considered in women with difficulties conceiving or who are undergoing investigation of infertility.

AU TGA pregnancy category C: Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

See references

Indomethacin Breastfeeding Warnings

Benefit should outweigh risk

Excreted into human milk: Yes

Comments:
-Some authorities recommend against maternal use during breastfeeding.
-The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for this drug; other agents with more published information may be preferable, especially when nursing a newborn or preterm infant.

Due to low levels in breastmilk and therapeutic administration directly to infants, use is considered acceptable in nursing mothers; however, according to some manufacturers, use is not recommended. In a small study where 11 out of 15 women received doses ranging from 75 mg orally to 300 mg rectally once a day, the average concentration in breast milk was estimated to be 0.27% of the maternal weight adjusted dose. One study reported a plasma level of 47 mcg/L in 1 infant 1.2 hours after the midpoint of breastfeeding in a mother receiving 2.94 mg/kg once a day.

In a single case report in which a mother was taking 200 mg from the fourth to sixth day postpartum, the infant experienced a generalized seizure when this drug was stopped in the nursing mother, followed by a second seizure the next day. No metabolic findings accounted for convulsions and no levels of this drug were measured in mother or infant. Initially it was thought that this drug was possibly responsible for causing the seizures, however, later studies and established therapeutic use in newborns makes it unlikely that this drug caused the seizures. Due to lack of published clinical experience in newborns and preterm infants, other agents may be preferred.

See references

Further information

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