ETODOLAC

Fetal Risk Summary

The nonsteroidal anti-inflammatory drug (NSAID), etodolac, is used in the treatment of arthritis, and acute and chronic pain. Etodolac is in an NSAID subclass (pyranocarboxylic acid) that contains no other members.

In reproduction studies with rats the drug produced isolated occurrences of alterations in limb development (polydactyly, oligodactyly, syndactyly, and unossified phalanges) at doses close to human clinical doses (2 to 14 mg/kg/day) (1). These same doses produced oligodactyly and synostosis of metatarsals in rabbits. However, a clear drug or dose-response relationship was not established (1). Similar to other agents in this class, etodolac increased the incidence of dystocia, prolonged gestation, and decreased pup survival in rats (1).

It is not known if etodolac crosses the human placenta. The molecular weight (about 287) 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 (2). 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 late pregnancy, as is inhibition of labor, prolongation of pregnancy, and suppression of fetal renal function (see also Indomethacin) (3). Persistent pulmonary hypertension of the newborn may occur if these agents are used in the 3rd trimester close to delivery (3). Women attempting to conceive should not use any prostaglandin synthesis inhibitor, including etodolac, because of the findings in a variety of animal models that indicate these agents block blastocyst implantation (4,5). 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 etodolac during lactation have been located. Because of the relatively low molecular weight (about 287), the excretion of etodolac into breast milk should be expected. Moreover, because of its long termination adult plasma half-life (7.3 hours), other agents may be preferred during lactation. One reviewer listed several low-risk alternatives (diclofenac, fenoprofen, flurbiprofen, ibuprofen, ketoprofen, ketorolac, and tolmetin) if a nonsteroidal anti-inflammatory agent is required while nursing (6).

References

1. Product information. Lodine. Wyeth-Ayerst Laboratories, 2000.
2. Nielsen GL, Sorensen HT, Larsen H, Pedersen L. Risk of adverse birth outcome and miscarriage in pregnant users of nonsteroidal antiinflammatory drugs: population based observational study and case-control study. Br Med J 2001;322:266–70.
3. Levin DL. Effects of inhibition of prostaglandin synthesis on fetal development, oxygenation, and the fetal circulation. Semin Perinatol 1980;4:35–44.
4. Matt Dw, Borzelleca JF. Toxic effects on the female reproductive system during pregnancy, parturition, and lactation. In Witorsch RJ, editor. Reproductive Toxicology. 2nd ed. New York, NY:Raven Press, 1995:175–93.
5. Dawood MY. Nonsteroidal antiinflammatory drugs and reproduction. Am J Obstet Gynecol 1993;169:1255–65.
6. Anderson PO. Medication use while breast feeding a neonate. Neonatal Pharmacol Q 1993;2:3–14.