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Acetaminophen / dextromethorphan / doxylamine / phenylephrine Pregnancy and Breastfeeding Warnings

Acetaminophen / dextromethorphan / doxylamine / phenylephrine is also known as: Alka-Seltzer Plus Maximum Strength Day & Night Cold & Flu Liquid Gels (Night Formula), Alka-Seltzer Plus Maximum Strength Night Cold & Flu Liquid Gels, Alka-Seltzer Plus Multi-Symptom Cold & Flu (Night Formula), Alka-Seltzer Plus Multi-Symptom Cold & Flu Day & Night Liquid Gels (Night Formula), Alka-Seltzer Plus Night Cold Formula Liquid, Alka-Seltzer Plus Night Severe Cold+Flu Hot Drink Mix, Alka-Seltzer Plus Severe Sinus Congestion & Cough (Night Formula), Alka-Seltzer Plus Severe Sinus Congestion, Allergy & Cough Liquid Gels, Delsym Night Time Multi-Symptom, Mucinex Fast-Max Night Time Cold & Flu Liquid Gels, Tylenol Cold Multi-Symptom Nighttime Liquid, Vicks NyQuil Severe Cold & Flu

Medically reviewed by Drugs.com. Last updated on Sep 21, 2018.

Acetaminophen / dextromethorphan / doxylamine / phenylephrine Pregnancy Warnings

The manufacturer makes no recommendation regarding use during pregnancy.

US FDA pregnancy category: Not assigned

Comments:
-Acetaminophen is commonly used during pregnancy and has been assumed safe; recent data questions the safety, especially with routine use or varying genetics.
-Routine use of acetaminophen during pregnancy is not advised.
-Available human data does not demonstrate major teratogenicity with dextromethorphan.
-Fetuses of mothers with slow dextromethorphan metabolism may be exposed to higher concentrations, but the clinical significance is unknown.
-According to some authorities dextromethorphan is compatible with pregnancy; low birth defect incidences were seen in surveillance studies.
-According to some authorities doxylamine is probably compatible with pregnancy including the first trimester; associations with congenital anomalies were thought to be from chance or due to the consequences of the nausea and vomiting being treated.
-Phenylephrine is a sympathomimetic used in emergencies to treat hypotension and alleviate eye and ear allergic symptoms.
-Phenylephrine could cause constriction in uterine vessels (that are normally maximally dilated during pregnancy), reducing uterine blood flow, potentially causing fetal hypoxia.
-Phenylephrine may interact with oxytocic or ergot derivatives to cause persistent maternal hypertension; cerebral vessel rupture is possible.
-Sympathomimetic amines are teratogenic in some animal models, but are not suspected to cause human teratogenicity.

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

Acetaminophen: Routinely used during all stages of pregnancy, it appears safe for short-term use. This drug crosses the placenta.

Dextromethorphan: Available data does not indicate a major teratogenic risk, and a survey study did not show a relationship with congenital malformations.

Doxylamine: Animal studies of doxylamine alone or as a combination product (doxylamine, pyridoxine, dicyclomine) did not show an increase in fetal abnormalities, but 3 studies showed a small dose-related decrease in fetal weight. A combination product of doxylamine and pyridoxine was used in over 30 million women for prevention and treatment of pregnancy related nausea and vomiting, and was discontinued over litigation alleging an association with congenital limb defects (including skeletal, limb, and cardiac abnormalities, and cleft lip or palate), however many large studies have found no association between the combination product and birth weight or length, head circumference, gestational age, or congenital malformations.

Phenylephrine: A monitoring study including 1249 mother-child pairs that had first trimester phenylephrine exposure showed an increase in malformation, with association greater with minor defects than major defects (8 eye and ear defects, 6 syndactyly, 4 preauricular skin tags, and 3 clubfoot cases); 4149 any time pregnancy exposures were associated with 15 congenital dislocation of the hip, 6 umbilical hernia, and 4 other musculoskeletal defects. Placental transfer is likely with phenylephrine's low molecular weight (about 167).

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

Acetaminophen / dextromethorphan / doxylamine / phenylephrine Breastfeeding Warnings

The manufacturer makes no recommendation regarding use during lactation.

Excreted into human milk: Yes (acetaminophen) /Data not available (dextromethorphan, doxylamine, phenylephrine)
Excreted into animal milk: Data not available (dextromethorphan, doxylamine, phenylephrine)

Comments:
-The amount of acetaminophen in breast milk is much less than typical infant doses.
-One study calculated that infants receive about 0.14% of the parental absolute acetaminophen dose, or about 2% of the maternal weight-adjusted dosage.
-Given dextromethorphan's low molecular weight, excretion into breastmilk is probable.
-Given doxylamine's low molecular weight (about 389), excretion into breastmilk is probable.
-Adverse events are not expected with occasional small doxylamine doses, but large doses or prolonged use may have adverse effects (e.g. drowsiness) on the infant or decrease milk production, particularly in combination with sympathomimetics (e.g. pseudoephedrine) or before lactation is established.
-Phenylephrine oral bioavailability is about 40%, making it unlikely an infant would receive large doses from breast milk.
-Phenylephrine may decrease milk production.

See references

References for pregnancy information

  1. "Product Information. NyQuil Severe Cold & Flu (acetaminophen/dextromethorphan/doxylamine/PE)." Procter and Gamble Pharmaceuticals, Mason, OH.
  2. Briggs GG, Freeman RK. "Drugs in Pregnancy and Lactation. 10th ed." Philadelphia, PA: Wolters Kluwer Health (2015):

References for breastfeeding information

  1. "Product Information. NyQuil Severe Cold & Flu (acetaminophen/dextromethorphan/doxylamine/PE)." Procter and Gamble Pharmaceuticals, Mason, OH.
  2. 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 -]):
  3. Briggs GG, Freeman RK. "Drugs in Pregnancy and Lactation. 10th ed." Philadelphia, PA: Wolters Kluwer Health (2015):

Further information

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

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