Pregnancy & Lactation : הריון/הנקה

4.6   Fertility, pregnancy and breastfeeding
Piroxicam is contraindicated during ascertained or suspected pregnancy, and during breastfeeding (see section 4.3).
Pregnancy
Inhibition of prostaglandin synthesis can adversely affect pregnancy and/or embryo/foetal development.
Results from epidemiological studies suggest an increased risk of miscarriage, cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor during early pregnancy. The absolute risk of cardiac malformations increased from less than 1% up to approximately 1.5%. It was considered that the risk is dose-related and also increases with duration of therapy.

Studies on animals have shown reproductive toxicity (see section 5.3). In animals, the administration of prostaglandin synthesis inhibitors has been shown to cause an increase in pre- and post-implantation losses and in embryo-foetal mortality.
Moreover, an increased incidence of various malformations, including cardiovascular malformation, was reported in animals given prostaglandin synthesis inhibitors during organogenesis.

From Week 20 onwards of pregnancy, the use of NSAIDs can cause oligohydramnios arising from fetal renal dysfunction. This condition may be found shortly after the start of treatment and is generally reversible with treatment interruption. Cases of closure of the ductus arteriosus following treatment in the second trimester have also been reported, the majority of which resolved after discontinuation of treatment.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors can expose the foetus to:
− cardiopulmonary toxicity (with premature constriction/closure of the ductus arteriosus and pulmonary hypertension);
− renal dysfunction, (see above)
Both mother and newborn child, at the end of pregnancy, to:
− possible prolongation of bleeding time and anti-aggregating effect that can even occur at very low doses;
− inhibition of uterine contractions resulting in delayed or prolonged labour.

As a consequence, BREXIN is contraindicated during pregnancy (see sections 4.3 and 5.3).

Oligohydramnios/Neonatal Renal Impairment
Use of NSAIDs, including Brexin, 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. 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.

Breastfeeding
Data show that piroxicam concentration in breast milk lies between 1% and 3% of maternal plasma concentration. Piroxicam is contraindicated during breastfeeding because safety in newborns has not yet been established (see section 4.3).

Fertility
The use of piroxicam could compromise female fertility and it is not recommended in women who are trying to conceive. In women with difficulty conceiving or who are undergoing fertility investigations, discontinuation of piroxicam therapy should be considered.