Avoid use starting at 30 weeks gestation (third trimester); Use during the first 2 trimesters is not recommended unless clearly needed

US FDA pregnancy category: Not assigned

Risk Summary: Available data on use of this drug in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage.

Comments:
-Aspirin should be avoided in pregnant women starting at 30 weeks gestation due to risk of premature closure of the fetal ductus arteriosus.
-Prolonged use of opioids during pregnancy can result in physical dependence in the neonate; women should be advised of the risk of neonatal abstinence syndrome and ensure that appropriate treatment will be available.

Animal reproduction studies have not been conducted with this combination product. Barbiturates readily cross the placental barrier. A 2-day old infant whose mother had taken a butalbital-containing product during the last two months of pregnancy experienced withdrawal seizures; butalbital was found in the infant's serum. Aspirin has not been associated with an increased risk of abnormalities when taken during the first trimester of pregnancy; however, use of aspirin during the third trimester increases the risk of premature closure of the fetal ductus arteriosus. Therapeutic doses of aspirin close to term may cause bleeding in mother, fetus, or neonate. Codeine use in pregnant women may lead to neonatal abstinence syndrome. There are no controlled data on this combination product in human pregnancy.

Chronic use of opioids may cause reduced fertility in females and males of reproductive potential; it is unknown if these effects are reversible.

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

Codeine is present in breast milk. For women with normal codeine metabolism (normal CYP450 2D6 activity) the amount of codeine secreted is low and dose-dependent; however, in women who are ultra-rapid metabolizers (those with multiple copies of the gene for CYP450 2D6) higher-than-expected serum levels of morphine (active metabolite) may be present in their breast milk leading to dangerously high serum morphine levels in their breastfed infants. In most cases, a person's specific CYP450 2D6 genotype is unknown. Several small series and 1 small retrospective study suggest that codeine may be causative in episodes of apnea, bradycardia, and cyanosis in the first week of life. A death of a breastfeed infant due to respiratory depression has been reported; the mother was found to be a CYP450 2D6 ultrarapid metabolizer. The significance of small amounts of aspirin, butalbital, and caffeine in human milk has not been reported, but due to the potential for serious adverse reactions in nursing infants, other agents may be preferred.

Not recommended

Excreted into human milk: Yes (aspirin); Yes (barbiturates); Yes (caffeine); Yes (codeine)

Comments:
-Breastfeeding is not recommended due to the potential for serious adverse reactions in the breastfed infant including excess sedation, respiratory depression, and death.

See references