OXYCODONE

Fetal Risk Summary

Oxycodone is a narcotic analgesic available as a single agent or in combination with nonnarcotic analgesics, such as acetaminophen or aspirin. Reproduction studies in rats and rabbits at doses up to 4 and 60 times the human dose of 120 mg/day in a 60 kg adult (0.7 and 19 times the human dose based on mg/m2), respectively, found no evidence of fetal harm (1).

The Collaborative Perinatal Project monitored 50,282 mother-child pairs, 8 of which had 1st-trimester exposure to oxycodone (2). No evidence was found to suggest a relationship to large categories of major or minor malformations or to individual defects.

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 281 newborns had been exposed to oxycodone during the 1st trimester (F. Rosa, personal communication, FDA, 1993). A total of 13 (4.6%) major birth defects were observed (12 expected), including (observed/expected) 3/3 cardiovascular defects and 1/1 hypospadias. No anomalies were observed in four other defect categories (oral clefts, spina bifida, polydactyly, and limb reduction defects) for which specific data were available. These data do not support an association between the drug and congenital defects.

At a 1996 meeting, data was presented on 118 women using oxycodone (N=78) or hydrocodone (N=40) during the 1st trimester for postoperative pain, general pain, or upper respiratory infection who were matched with a similar group using codeine for these purposes (3). Six (5.1%) of the infants exposed to oxycodone or hydrocodone had malformations, an odds ratio of 2.61 (95% confidence interval [CI] 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

Oxycodone is excreted into human breast milk. Six healthy postpartum women received a combination product of oxycodone and acetaminophen, one or two capsules every 4–7 hours, while breast-feeding their newborn infants (4). Maternal plasma levels were in the expected range of 14 to 35 ng/mL, and milk concentrations ranged from <5 to 226 ng/mL. Peak milk concentrations occurred 1.5–2.0 hours after the first dose, then at variable times after multiple doses. Although a large degree of variability was present, the mean milk:plasma ratio was 3.4:1. No mention was made of any effects observed in the nursing infants.

Although occasional maternal doses of oxycodone for analgesia 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. Product information. Oxycontin. Purdue Frederick, 1997.
2. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA: Publishing Sciences Group, 1977:287.
3. 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.
4. Marx CM, Pucino F, Carlson JD, Driscoll JW, Ruddock V. Oxycodone excretion in human milk in the puerperium (abstract). Drug Intell Clin Pharm 1986;20:474.