Acetaminophen / diphenhydramine / phenylephrine Pregnancy and Breastfeeding Warnings

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Medically reviewed by Drugs.com. Last updated on Sep 6, 2023.

Acetaminophen / diphenhydramine / phenylephrine Pregnancy Warnings

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.

Diphenhydramine: Animal studies at doses up to 5 times the human dose showed no fetal toxicity or fertility impairment. Placental transfer was seen in sheep after a 100 mg intravenous dose with a fetal:maternal ratio of 0.85, peaking within 5 minutes. A monitoring study including 595 mother-child pairs that had first trimester diphenhydramine exposure showed no increase in major or minor malformations; 2948 any time pregnancy exposures showed no increase in major or minor malformations; unconfirmed possible associations include 3 hypospadia cases and 5 other genitourinary malformations, 3 eye and ear defects, 3 syndromes other than Down's, 13 inguinal hernias, 5 clubfoot cases, 5 diaphragm malformations, and 5 ventricular septal defects (any, opening or closing). A case control study of 599 first semester diphenhydramine exposures showed a statistical association with cleft palate; other studies have not found an association with cleft palate or have shown a decrease.

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.

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.
-According to some authorities diphenhydramine is compatible with pregnancy and may be the drug of choice if parenteral antihistamines are needed in pregnancy, however one case-controlled study showed association with cleft palate, and premature infants exposed within 2 weeks of birth risk toxicity.
-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.

See references

Acetaminophen / diphenhydramine / phenylephrine Breastfeeding Warnings

The manufacturer makes no recommendation regarding use during lactation.

Excreted into human milk: Yes (acetaminophen, diphenhydramine) /Data not available (phenylephrine)
Excreted into animal milk: Data not available (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.
-One old biologic assay showed diphenhydramine in breast milk in some women after a 100 mg intramuscular dose; no studies using modern assays are available.
-According to some authorities, occasional, small diphenhydramine doses are not expected to adversely effect breastfeeding infants, but large or prolonged dosing may decrease the milk supply, especially in combination with a sympathomimetic amine (e.g. pseudoephedrine) or if lactation is not well established, and may have effects on the infant.
-Administering diphenhydramine after the last feeding of the day may minimize effects on the infant, but non-sedating antihistamines are preferred.
-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