False-positive urine immunoassay screening tests for benzodiazepines have been reported in patients taking oxaprozin. This is due to lack of specificity of the screening tests. False-positive test results may be expected for several days following discontinuation of oxaprozin therapy. Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish oxaprozin from benzodiazepines.
Use of NSAIDs, including oxaprozin, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, limit dose and duration of oxaprozin use between about 20 and 30 weeks of gestation, and avoid oxaprozin use at about 30 weeks of gestation and later in pregnancy (see Clinical Considerations, Data).
Premature Closure of Fetal Ductus Arteriosus
Use of NSAIDs, including oxaprozin, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus.
Oligohydramnios/Neonatal Renal Impairment
Use of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment.
Data from observational studies regarding other potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive. In animal reproduction studies, oral administration of oxaprozin to pregnant rabbits at doses 0.1-times the maximum daily human dose (based on body surface area) resulted in evidence of teratogenicity; however, oral administration of oxaprozin to pregnant mice and rats during organogenesis at doses equivalent to the maximum recommended human dose revealed no evidence of teratogenicity or embryotoxicity. In rat reproduction studies in which oxaprozin was administered through late gestation failure to deliver and a reduction in live birth index was observed at doses equivalent to the maximum recommended human dose. Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, administration of prostaglandin synthesis inhibitors such as oxaprozin, resulted in increased pre- and post-implantation loss. Prostaglandins also have been shown to have an important role in fetal kidney development. In published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses.
The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Avoid use of NSAIDs in women at about 30 weeks gestation and later in pregnancy, because NSAIDs, including oxaprozin, can cause premature closure of the fetal ductus arteriosus (see Data).
Oligohydramnios/Neonatal Renal Impairment:
If an NSAID is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. If oxaprozin treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. If oligohydramnios occurs, discontinue oxaprozin and follow up according to clinical practice (see Data).
Labor or Delivery
There are no studies on the effects of oxaprozin during labor or delivery. In animal studies, NSAIDs, including oxaprozin, inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth.
Premature Closure of Fetal Ductus Arteriosus: Published literature reports that the use of NSAIDs at about 30 weeks of gestation and later in pregnancy may cause premature closure of the fetal ductus arteriosus.
Oligohydramnios/Neonatal Renal Impairment:
Published studies and postmarketing reports describe maternal NSAID use at about 20 weeks gestation or later in pregnancy associated with fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. In many cases, but not all, the decrease in amniotic fluid was transient and reversible with cessation of the drug. There have been a limited number of case reports of maternal NSAID use and neonatal renal dysfunction without oligohydramnios, some of which were irreversible. Some cases of neonatal renal dysfunction required treatment with invasive procedures, such as exchange transfusion or dialysis.
Methodological limitations of these postmarketing studies and reports include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and concomitant use of other medications. These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal NSAID use. Because the published safety data on neonatal outcomes involved mostly preterm infants, the generalizability of certain reported risks to the full-term infant exposed to NSAIDs through maternal use is uncertain.
Animal data
Teratology studies with oxaprozin were performed in mice, rats, and rabbits in pregnant animals administered oral doses up to 200 mg/kg/day, 200 mg/kg/day, and 30 mg/kg/day, respectively, during the period of organogenesis. In rabbits, malformations were observed at doses greater than or equal to 7.5 mg/kg/day of oxaprozin (0.1 times the maximum recommended human daily dose [MRHD] of 1,800 mg based on body surface area). However, in mice and rats, no drug-related developmental abnormalities or embryo-fetal toxicity were observed at doses up to 50 and 200 mg/kg/day of oxaprozin, respectively (0.1 times and 1.1 times the maximum recommended human daily dose of 1,800 mg based on a body surface area comparison, respectively).
In fertility/reproductive studies in rats, 200 mg/kg/day oxaprozin was orally administered to female rats for 14 days prior to mating through lactation day (LD) 2, or from gestation day (GD) 15 through LD 2 and the females were mated with males treated with 200 mg/kg/day oxaprozin for 60 days prior to mating. Oxaprozin administration resulted in failure to deliver and a reduction in live birth index at 200 mg/kg/day (1.1-times the maximum recommended human daily dose of 1,800 mg based on a body surface area comparison).