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Premature Closure of Fetal
Ductus Arteriosus
Avoid use of NSAIDs,
including FELDENE, in pregnant women at
about 30 weeks gestation and later. NSAIDs,
including FELDENE, increase the
risk of premature closure of the fetal ductus arteriosus
at approximately
this gestational age.
Oligohydramnios/Neonatal Renal Impairment
Use of NSAIDs, including FELDENE, at about 20 weeks gestation
or later
in pregnancy may cause 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.
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Risk Summary
Use of NSAIDs, including FELDENE, 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 FELDENE use between about 20 and 30 weeks of gestation, and avoid FELDENE 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 FELDENE, 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 in rats and
rabbits, there was
no evidence of teratogenicity at exposures up to 5
and 10 times the maximum recommended
human dose (MRHD), respectively.
In rat studies with piroxicam, fetotoxicity (postimplantation loss) was
observed at exposures 2 times the MRHD, and delayed parturition
and an increased incidence of stillbirth
were noted at doses equivalent
to the MRHD of piroxicam. 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 piroxicam,
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.
Clinical Considerations
Fetal/Neonatal Adverse
Reactions
Premature Closure of Fetal
Ductus Arteriosus:
Avoid use of NSAIDs
in women at about 30 weeks gestation and later
in pregnancy, because NSAIDs, including FELDENE, 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 FELDENE treatment extends beyond
48 hours, consider monitoring with ultrasound for oligohydramnios. If oligohydramnios occurs,
discontinue FELDENE and follow
up according to clinical
practice (see Data).
Labor or Delivery
There are no studies on the effects of
FELDENE during labor or delivery.
In animal studies, NSAIDS, including
piroxicam inhibit prostaglandin
synthesis, cause delayed parturition,
and increase the incidence of stillbirth.
Data
Human Data
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.
Oligohydramnios is often, but not always, reversible with treatment
discontinuation. Complications
of prolonged oligohydramnios may, for
example, include limb contractures
and delayed lung maturation. In some
postmarketing cases of
impaired neonatal renal function,
invasive procedures such as exchange transfusion or dialysis were
required.
If NSAID treatment is necessary between about 20 weeks
and 30 weeks gestation, limit FELDENE
use to the lowest effective dose and shortest duration
possible. Consider ultrasound monitoring of amniotic fluid if
FELDENE treatment extends beyond 48 hours. Discontinue FELDENE if oligohydramnios occurs and follow up according
to clinical
practice [see Use in Specific
Populations (8.1)].