Nonsteroidal Anti-inflammatory
PREGNANCY RECOMMENDATION: Human Data Suggest Risk in 1st and 3rd Trimesters
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
Constriction of the ductus arteriosus in utero is a pharmacologic consequence arising from the use of prostaglandin synthesis inhibitors during pregnancy (see also Indomethacin) (1). Persistent pulmonary hypertension of the newborn may occur if these agents are used in the 3rd trimester close to delivery (1,2). These drugs have also been shown to inhibit labor and prolong gestation, both in humans (3) (see also Indomethacin) and in animals (4,5). 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, nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with spontaneous abortions (SABs) and congenital malformations. The risk for these defects, however, appears to be small.
FETAL RISK SUMMARY
The 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 at 15 mg/day for a 50-kg adult based on BSA (HD) given throughout organogenesis resulted in an increased incidence of cardiac septal defects. Embryo lethality was observed at ≥5.4 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 ≥0.5 times the HD and a decrease in pup survival at 2.1 times the HD, when these doses were administered throughout organogenesis. At ≥0.5 times the HD in late gestation, meloxicam was associated with stillbirths, an increased length of delivery time, and delayed parturition. At doses ≥0.07 times the HD during late gestation and lactation, reductions in birth index, live births, and neonatal survival were seen in rats (4).
It is not known if meloxicam crosses the human placenta. The molecular weight (about 351) 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 (8). 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 SABs. A similar study, also published in 2001, failed to find a relationship, in general, between NSAIDs and congenital malformations, but did find a significant association with cardiac defects and orofacial clefts (9). In addition, a 2003 study found a significant association between exposure to NSAIDs in early pregnancy and SABs (10). (See Ibuprofen for details on these three studies.)
A brief 2003 editorial on the potential for NSAID-induced developmental toxicity concluded that NSAIDs, and specifically those with greater COX-2 affinity, had a lower risk of this toxicity in humans than aspirin (11).
BREASTFEEDING SUMMARY
No reports describing the use of meloxicam during lactation have been located. The molecular weight (about 351) is low enough that excretion into 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 breastfeeding by the American Academy of Pediatrics (see Piroxicam).
References
1.Levin DL. Effects of inhibition of prostaglandin synthesis on fetal development, oxygenation, and the fetal circulation. Semin Perinatol 1980;4:35–44.
2.Van Marter LJ, Leviton A, Allred EN, Pagano M, Sullivan KF, Cohen A, Epstein MF. Persistent pulmonary hypertension of the newborn and smoking and aspirin and nonsteroidal antiinflammatory drug consumption during pregnancy. Pediatrics 1996;97:658–63.
3.Fuchs F. Prevention of prematurity. Am J Obstet Gynecol 1976;126:809–20.
4.Product information. Mobic. Boehringer Ingelheim Pharmaceuticals, 2001.
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 antiinflammatory drugs and reproduction. Am J Obstet Gynecol 1993;169:1255–65.
8.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.
9.Ericson A, Kallen BAJ. Nonsteroidal anti-inflammatory drugs in early pregnancy. Reprod Toxicol 2001;15:371–5.
10.Li DK, Liu L, Odouli R. Exposure to non-steroidal anti-inflammatory drugs during pregnancy and risk of miscarriage: population based cohort study. Br Med J 2003;327:368–71.
11.Tassinari MS, Cook JC, Hurtt ME. NSAIDs and developmental toxicity. Birth Defects Res B Dev Reprod Toxicol 2003;68:3–4.