PIROXICAM

Fetal Risk Summary

Piroxicam is a nonsteroidal anti-inflammatory drug (NSAID) used for relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis. It is in the same NSAID subclass (oxicams) as meloxicam.

Animal reproduction studies in rabbits and rats have not shown drug-related embryotoxicity or teratogenicity (1,2 and 3). However, decreased fetal growth was observed in some species (2).

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 161 newborns had been exposed to piroxicam during the 1st trimester (F. Rosa, personal communication, FDA, 1993). Six (3.7%) major birth defects were observed (seven expected). Specific data were available for six defect categories, including (observed/expected) 1/2 cardiovascular defects, 1/0 oral clefts, 1/0 spina bifida, 1/0.5 polydactyly, 0/0 limb reduction defects, and 0/0 hypospadias. These data do not support an association between the drug and congenital defects.

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 (4). 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 (see also Indomethacin) (5). Persistent pulmonary hypertension of the newborn may occur if these agents are used in the 3rd trimester close to delivery (5). These drugs also have been shown to inhibit labor and prolong pregnancy, both in humans (6) (see also Indomethacin) and in animals (7). Women attempting to conceive should not use any prostaglandin synthesis inhibitor, including piroxicam, 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

Piroxicam is excreted into breast milk. A nursing woman, 9 months postpartum, was treated with piroxicam 20 mg/day for 4 months (10). Maternal serum concentrations of the drug 2.5 and 15.0 hours after a dose were 5.85 and 4.79 µg/mL, respectively. Milk levels varied between 0.05 and 0.17 µg/mL. Based on an ingested volume of 600 mL/day, the investigators estimated the infant would have received a daily dose of about 0.05 mg. However, no drug was detectable in the infant's serum. A second woman stopped nursing her 8-month-old infant when she was treated with piroxicam 40 mg/day (10). Milk concentrations of the drug ranged from 0.11 to 0.22 µg/mL, with the highest level measured 2.5 hours after the second dose. In both cases, the concentration of the drug in milk was approximately 1% of the mother's serum levels. These amounts probably do not present a risk to the nursing infant (11). The American Academy of Pediatrics considers piroxicam to be compatible with breast feeding (12).

References

1. Product information. Feldene. Pfizer, 2001.
2. Sakai T, Ofsuki I, Noguchi F. Reproduction studies on piroxicam. Yakuri to Chiryo 1980;8:4655–71. As cited in Shepard TH. Catalog of Teratogenic Agents. 6th ed. Baltimore, MD: Johns Hopkins University Press, 1989:513.
3. Perraud J, Stadler J, Kessedjian MJ, Monro AM. Reproductive studies with the anti-inflammatory agent, piroxicam: modification of classical protocols. Toxicology 1984;30:59–63.
4. 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.
5. Levin DL. Effects of inhibition of prostaglandin synthesis on fetal development, oxygenation, and the fetal circulation. Semin Perinatol 1980;4:35–44.
6. Fuchs F. Prevention of prematurity. Am J Obstet Gynecol 1976;126:809–20.
7. Powell JG, Cochrane RL. The effects of a number of non-steroidal anti-inflammatory compounds on parturition in the rat. Prostaglandins 1982;23:469–88.
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. Ostensen M. Piroxicam in human breast milk. Eur J Clin Pharmacol 1983;25:829–30.
11. Ostensen M, Husby G. Antirheumatic drug treatment during pregnancy and lactation. Scand J Rheumatol 1985;14:1–7.
12. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137–50.