MELOXICAM

Fetal Risk Summary

The nonsteroidal anti-inflammatory drug (NSAID), meloxicam, shares the same mechanism of action and uses as other agents in this class. It is an oxicam derivative in the same subclass as piroxicam. No published reports linking meloxicam to human congenital malformations have been located.

Reproduction studies have been conducted in the rat and rabbit. In rabbits, oral doses 64.5 times the human dose (HD) at 15 mg/day for a 50-kg adult based on body surface area given throughout organogenesis resulted in an increased incidence of cardiac septal defects (1). Embryo lethality was observed at ³5.4 times the HD. In pregnant rats, no teratogenicity was noted at doses up to 2.2 times the HD. An increase in stillbirths, however, occurred at oral doses about ³0.5 times the HD, and a decrease in pup survival at 2.1 times the HD, when these doses were administered throughout organogenesis (1). At ³0.5 times the HD in late gestation, meloxicam was associated with stillbirths, an increased length of delivery time, and delayed parturition. At doses ³0.07 times the HD during late gestation and lactation, reductions in birth index, live births, and neonatal survival were seen in rats.

It is not known if meloxicam crosses the human placenta. The molecular weight (about 351), however, is low enough that transfer to the fetus should be expected. Meloxicam does cross the rat placenta (1).

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 pregnancy (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). These drugs have also been shown to inhibit labor and prolong gestation, both in humans (4) (see also Indomethacin) and in animals (1,5). Women attempting to conceive should not use any prostaglandin synthesis inhibitor, including meloxicam, because of the findings in a variety of animal models that indicate these agents block blastocyst implantation (6,7). Moreover, as noted above, NSAIDs have been associated with SABs (2).

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

Breast Feeding Summary

No reports describing the use of meloxicam during human lactation have been located. The drug is excreted into the milk of lactating rats at concentrations higher than those in the plasma (1). The molecular weight (about 351) is low enough that excretion into human breast milk should be expected. The effects of this exposure on a nursing infant are unknown, but a similar agent, piroxicam, is classified as compatible with breast feeding by the American Academy of Pediatrics (see Piroxicam).

References

1. Product information. Mobic. Boehringer Ingelheim Pharmaceuticals, 2001.
2. 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.
3. Levin DL. Effects of inhibition of prostaglandin synthesis on fetal development, oxygenation, and the fetal circulation. Semin Perinatol 1980;4:35–44.
4. Fuchs F. Prevention of prematurity. Am J Obstet Gynecol 1976;126:809–20.
5. 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.
6. Matt DW, Borzelleca JF. Toxic effects on the female reproductive system during pregnancy, parturition, and lactation. In Wilorsch RJ, ed. Reproductive Toxicology. 2nd ed. New York, NY: Raven Press, 1995:175–93.
7. Dawood MY. Nonsteroidal anti-inflammatory drugs and reproduction. Am J Obstet Gynecol 1993;169:1255–65.