OXAPROZIN

Fetal Risk Summary

Oxaprozin is a nonsteroidal anti-inflammatory drug (NSAID) used in the treatment of acute and chronic arthritis. It is in the same subclass (propionic acids) as five other NSAIDs (fenoprofen, flurbiprofen, ibuprofen, ketoprofen, and naproxen).

The drug produced infrequent congenital malformations in rabbits treated with doses in the usual human range, but not in mice and rats (1). No teratogenic effects were observed in two other studies of pregnant rats and rabbits (2,3,4 and 5). A dose-dependent constriction of the ductus arteriosus, similar to that produced by other nonsteroidal antiinflammatory agents, was observed in fetal rats (5).

It is not known if oxaprozin crosses the human placenta. The molecular weight (about 293) is low enough, however, that passage to the fetus should be expected.

A combined 2001 population-based observational cohort study and a case-control study estimated the risk of adverse pregnancy outcome from the use of NSAIDs (6). The use of NSAIDs during pregnancy was not associated with congenital malformations, preterm delivery, or low birth weight, but a positive association was discovered with spontaneous abortions (SABs) (see Ibuprofen for details).

Constriction of the ductus arteriosus in utero is a pharmacologic consequence arising from the use of prostaglandin synthesis inhibitors during pregnancy, as is inhibition of labor, prolongation of pregnancy, and suppression of fetal renal function (see also Indomethacin) (7). Persistent pulmonary hypertension of the newborn may occur if these agents are used in the 3rd trimester close to delivery (7). Women attempting to conceive should not use any prostaglandin synthesis inhibitor, including oxaprozin, because of the findings in a variety of animal models that indicate these agents block blastocyst implantation (8,9). Moreover, as noted above, NSAIDs have been associated with SABs.

[*Risk Factor D if used in 3rd trimester or near delivery.]

Breast Feeding Summary

No reports describing the use of oxaprozin during human lactation have been located. The molecular weight (about 293) is low enough that excretion into breast milk should be expected. The drug has been found in the milk of lactating rats (1).

One reviewer listed several NSAIDs (diclofenac, fenoprofen, flurbiprofen, ibuprofen, ketoprofen, ketorolac, and tolmetin) that were considered safer alternatives to other agents (oxaprozin not mentioned) if a NSAID was required while nursing (10). Because of the long terminal elimination half-life (approximately 42 hours or longer) in adults and the unknown amount of oxaprozin that is excreted into milk, any of these choices are probably preferable.

References

1. Product information. Daypro. G.D. Searle, 2001.
2. Yamada T, Nishiyama T, Sasajima M, Nakane S. Reproduction studies of oxaprozin in the rat and rabbit. Iyakuhin Kenkyu 1984;15:207–92. As cited in Shepard TH. Catalog of Teratogenic Agents. 7th ed. Baltimore, MD: Johns Hopkins University Press, 1992:299–300.
3. Yamada T, Norariya T, Sasajima M, Nakane S. Reproduction studies of oxaprozin. II. Teratology study in rats. Iyakuhin Kenkyu 1984;15:225–49. As cited in Schardein JL. Chemically Induced Birth Defects. 2nd ed. New York, NY: Marcel Dekker, 1993:132–3.
4. Yamada T, Uchida H, Sasajima M, Nakane S. Reproduction studies of oxaprozin. III. Teratogenicity study in rabbits. Iyakuhin Kenkyu 1984;15:250–64. As cited in Schardein JL. Chemically Induced Birth Defects. 2nd ed. New York, NY: Marcel Dekker, 1993:132–3.
5. Yamada T, Inoue T, Hara M, Ohba Y, Nakame S, Uchida H. Reproductive studies of oxaprozin and studies on the fetal ductus arteriosus. Clin Report 1984;18:514–25, 528–36. As cited in Shepard TH. Catalog of Teratogenic Agents. 7th ed. Baltimore, MD: Johns Hopkins University Press, 1992:299–300.
6. Nielsen GL, Sorensen HT, Larsen H, Pedersen L. Risk of adverse birth outcome and miscarriage in pregnant users of non-steroidal anti-inflammatory drugs: population based observational study and case-control study. Br Med J 2001;322:266–70.
7. Levin DL. Effects of inhibition of prostaglandin synthesis on fetal development, oxygenation, and the fetal circulation. Semin Perinatol 1980;4:35–44.
8. Matt DW, Borzelleca JF. Toxic effects on the female reproductive system during pregnancy, parturition, and lactation. In Witorsch RJ, ed. Reproductive Toxicology. 2nd ed. New York, NY: Raven Press, 1995:175–93.
9. Dawood MY. Nonsteroidal antiinflammatory drugs and reproduction. Am J Obstet Gynecol 1993;169:1255–65.
10. Anderson PO. Medication use while breast feeding a neonate. Neonatal Pharmacol Q 1993;2:3–14.