HYDROCODONE

Fetal Risk Summary

Hydrocodone is a centrally-acting narcotic agent that is related to codeine. It is combined with other drugs for use an analgesic or as an antitussive. In a reproductive study in hamsters, a single SC injection (102 mg/kg) during the critical period of central nervous system organogenesis produced malformations (cranioschisis and various other lesions) in 3.4% of the offspring (1). Because of its narcotic properties, withdrawal could theoretically occur in infants exposed in utero to prolonged maternal ingestion of hydrocodone.

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 332 newborns had been exposed to hydrocodone during the 1st trimester (F. Rosa, personal communication, FDA, 1993). A total of 24 (7.2%) major birth defects were observed (14 expected), five of which were cardiovascular defects (three expected). No anomalies were observed in five other defect categories (oral clefts, spina bifida, polydactyly, limb reduction defects, and hypospadias) for which specific data were available. The total number of malformations is suggestive of a possible association, but other factors, including the mother's disease, concurrent drug use, and chance, may be involved.

At a 1996 meeting, data on 118 women using hydrocodone (N=40) or oxycodone (N=78) during the 1st trimester for postoperative pain, general pain, or upper respiratory infection were matched with a similar group using codeine for these purposes (2). Six (5.1%) of the infants exposed to hydrocodone or oxycodone had malformations, an odds ratio of 2.61 (95% confidence interval 0.6–11.5) (p=0.13). There was no pattern evident among the six malformations.

[*Risk Factor D if used for prolonged periods or in high doses at term.]

Breast Feeding Summary

No reports describing the use of hydrocodone during human lactation or measuring the amount, if any, excreted into breast milk have been located. Because of the relatively low molecular weight (about 381), passage into milk should be expected. Although occasional maternal doses of hydrocodone probably present a minimal risk for adverse effects during nursing, infants should be monitored for gastrointestinal effects, sedation, and changes in feeding patterns.

References

1. Geber WF, Schramm LC. Congenital malformations of the central nervous system produced by narcotic analgesics in the hamster. Am J Obstet Gynecol 1975;123:705–13.
2. Schick B, Hom M, Tolosa J, Librizzi R, Donnfeld A. Preliminary analysis of first trimester exposure to oxycodone and hydrocodone (abstract). Presented at the Ninth International Conference of the Organization of Teratology Information Services, Salt Lake City, Utah, May 2–4, 1996. Reprod Toxicol 1996;10:162.