Skip to main content

Naproxen / pseudoephedrine Pregnancy and Breastfeeding Warnings

Naproxen / pseudoephedrine is also known as: Aleve-D Sinus & Cold, Aleve-D Sinus & Headache, Sinus & Cold D, Sudafed 12 Hour Pressure+Pain

Medically reviewed by Drugs.com. Last updated on Jun 14, 2021.

Naproxen / pseudoephedrine Pregnancy Warnings

Animal studies are not available for the combination product. There are no controlled data in human pregnancy.

Naproxen: Animals studies at 0.23 to 0.28 times the expected human dose showed no fetal harm or impaired fertility. An investigation of several nonsteroidal anti-inflammatories (NSAIDs), including naproxen, in mice found they induced cleft palate in mice. Naproxen crosses the placental barrier (molecular weight is about 230). A surveillance study with 1448 first trimester naproxen exposures did not support an association with major birth defects: 70 (4.8%) major birth defects occurred (62 expected). A combined population-based observational cohort and case control study found no association with NSAID use and congenital malformations, prematurity, or low birth weight, but a positive association with miscarriage, while a similar study showed association with cardiac defects and orofacial clefts. A 2003 study found significant association of early pregnancy NSAID exposure and miscarriage.

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.

Pseudoephedrine: A monitoring study of 50, 282 mother/child pairs (3082 first trimester sympathomimetic drug exposures, 9719 any time pregnancy exposures) suggested a link to categories of minor malformations (non-life-threatening, no major cosmetic defects) including inguinal hernia and clubfoot. Pseudoephedrine may be associated with gastroschisis, but this may also be caused by maternal health factors. First trimester oral decongestant exposure or maternal smoking may increase the risk of gastroschisis, small intestinal atresia (SIA), and hemifacial microsomia.

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.

NSAIDs should be avoided at 20 weeks gestation and later

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.

See references

Naproxen / pseudoephedrine Breastfeeding Warnings

Naproxen: One 5-month postpartum patient on 250 mg twice daily had peak milk levels of 1.1 to 1.3 mg/L (2.4 mg/L with 375 mg twice daily); peak occurred at 4 to 5 hours and fell slowly over 12 to 24 hours; estimated maximum intake from milk (exclusively breastfed infant) is about 2.2 to 2.8% of the maternal weight-adjusted dose.

The manufacturer makes no recommendation regarding use during lactation.

Excreted into human milk: Yes (naproxen, pseudoephedrine)

Comments:
-Naproxen levels in milk are low and adverse effects appear uncommon.
-There is a case report of naproxen possibly causing prolonged bleeding time, thrombocytopenia, and acute anemia in a 7-day old; the parent was also on bacampicillin.
-Alternatives to naproxen during breastfeeding may be warranted based on possible bleeding time prolongation and naproxen's long half-life.
-A survey of 20 infants exposed to naproxen during breastfeeding had 2 reports of drowsiness and one report of vomiting in the infants, neither requiring medical care.
-The small amounts of pseudoephedrine (about 4.3 to 5.5% of maternal dose) may cause occasional irritability.
-A single pseudoephedrine dose acutely decreases milk production (average 24%); repeated use interferes with lactation.
-Do not use pseudoephedrine in patients with insufficient milk production or in those just establishing lactation.

See references

References for pregnancy information

  1. US Food and Drug Administration "FDA recommends avoiding use of NSAIDs in pregnancy at 20 weeks or later because they can result in low amniotic fluid. Available from: URL: https://www.fda.gov/media/142967/download." ([2020, Oct 15]):
  2. Briggs GG, Freeman RK. "Drugs in Pregnancy and Lactation. 10th ed." Philadelphia, PA: Wolters Kluwer Health (2015):
  3. "Product Information. Aleve-D Sinus & Cold (naproxen-pseudoephedrine)." Bayer Pharmaceutical Inc, West Haven, CT.

References for breastfeeding information

  1. United States National Library of Medicine "Toxnet. Toxicology Data Network. Available from: URL: http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT." ([cited 2013 -]):
  2. "Product Information. Aleve-D Sinus & Cold (naproxen-pseudoephedrine)." Bayer Pharmaceutical Inc, West Haven, CT.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.