Diflunisal Pregnancy and Breastfeeding Warnings

Brand names: Dolobid

Medically reviewed by Drugs.com. Last updated on Oct 24, 2023.

Diflunisal Pregnancy Warnings

NSAIDs should be avoided at 20 weeks gestation and later

US FDA pregnancy category: C

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 revealed evidence of embryotoxicity and teratogenicity at higher doses that also produced maternal toxicity. Aspirin and other salicylates have shown evidence of teratogenicity in animal studies at doses ranging from 1 to 8 times the human dose. Administration of nonsteroidal anti-inflammatory drugs (NSAIDs) during the third trimester of pregnancy may cause significant adverse effects, including premature closure of the fetal ductus arteriosus, pulmonary hypertension, prolongation of bleeding time, tricuspid incompetence, intracranial bleeding, fetal renal impairment, oligohydramnios, gastrointestinal bleeding or perforation, and increased risk of necrotizing enterocolitis. Administration during labor and delivery in rat studies caused an increased incidence of dystocia, delayed parturition, and decreased pup survival. 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.

US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

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Diflunisal Breastfeeding Warnings

A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother.

Excreted into human milk: Yes

Comments: The effects in the nursing infant are unknown.

Milk levels range from 2% to 7% of simultaneous maternal serum levels after 7 days of administration of 125 or 250 mg twice a day. This would represent milk levels ranging from 0.3 to 0.9 mg/L with a dose of 125 mg/day and 0.8 to 2.7 mg/L with a dose of 250 mg/day. A shorter-acting agent with more published information available may be preferred, especially while nursing a newborn or preterm infant.

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Further information

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