Pregnancy & Lactation : הריון/הנקה

4.6    Fertility, pregnancy and lactation

Pregnancy and Fertility:
The use of Mesulid is contraindicated in the third trimester of pregnancy (see section 4.3).

Like other NSAIDs, Mesulid is not recommended in women attempting to conceive (see section 4.4).

Inhibition of prostaglandin synthesis may have a negative impact on pregnancy and/or embryonic/fetal development. Results of epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after the use of an inhibitor of prostaglandin synthesis in the first stage of pregnancy. The absolute risk for cardiac malformations was increased from less than 1% to approximately 1.5%. The risk has been considered to increase with the dose and duration of treatment.

In animals, administration of inhibitors of prostaglandin synthesis has been shown to provoke an increase in pre- and post-implantation loss and in embryonic-fetal mortality. Furthermore, an increased incidence of various malformations, including the cardiovascular one, has been reported in animals to which inhibitors of prostaglandin synthesis were administered during the period of organogenesis.

Studies in rabbits have shown an atypical reproductive toxicity (see section 5.3) and no adequate data from the use of nimesulide-containing medicinal products in pregnant women are available.

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Oligohydramnios/Neonatal Renal Impairment and Premature Constriction/ Closure of Ductus Arteriosus: Use of NSAIDs, including Mesulid, 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 post-marketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required.

In addition, there have been reports of ductus arteriosus constriction following treatment in the second trimester, most of which resolved after treatment cessation.

Therefore, during the first and second trimesters of pregnancy, Mesulid should not be given unless clearly necessary.

If Mesulid is used by a woman who is trying to conceive, or during the first and second trimesters of pregnancy, the dose and duration of treatment should be kept as low as possible.

If NSAID treatment is necessary between about 20 weeks and 28 weeks gestation, consider ultrasound monitoring of amniotic fluid if Mesulid treatment extends beyond 5 days, and also consider antenatal monitoring for ductus arteriosus constriction after exposure to Mesulid for several days from gestational week 20 onward. Discontinue Mesulid if oligohydramnios or ductus arteriosus constriction occurs and follow up according to clinical practice.

During the third trimester of pregnancy, all inhibitors of prostaglandin synthesis may expose
• the fetus to: - cardiopulmonary toxicity (premature constriction/closure of the ductus arteriosus and pulmonary hypertension);
- renal dysfunction (see above), which may progress to renal insufficiency with oligohydramnios;
• the mother and the newborn infant, at the end of pregnancy, to: - possible prolongation of bleeding time, and an antiplatelet effect which may occur even at very low doses;
- inhibition of uterine contractions resulting in delay or prolongation of labour.

Consequently, Mesulid is contraindicated during the third trimester of pregnancy.

Breastfeeding:
It is not known whether nimesulide is excreted in human milk. Mesulid is contraindicated when breastfeeding (see sections 4.3 and 5.3).