Pregnancy & Lactation : הריון/הנקה

4.6 Pregnancy and lactation
Pregnancy
Prostaglandin synthesis inhibition may have a harmful effect on pregnancy and/or embryonic or fetal development. Epidemiological data, following the use of a prostaglandin synthesis inhibitor during the early stage of pregnancy, suggest an increased risk of miscarriage, cardiac malformation, and gastroschisis. The absolute risk of cardiac malformation is increased from less than 1% to approximately 1.5%.
This risk would seem to increase with dose and treatment duration.
In animal studies, administration of a prostaglandin synthesis inhibitor induces an increase in pre- and post-implantation losses, and embryo-fetal mortality.
Furthermore, an increased incidence of various malformations, including cardiovascular malformations, has been observed in animals having received a prostaglandin synthesis inhibitor during the organogenesis period.
Unless treatment is clearly shown to be absolutely necessary, the use of ketoprofen should be avoided during the first and second trimesters of pregnancy.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may lead to:
• Kidney function impairment: o in utero which may be observed from 12 weeks of amenorrhea (initiation of fetal diuresis): oligohydramnios (in most cases reversible on treatment discontinuation), or even severe oligohydramnios, particularly during prolonged exposure.
o at birth, kidney failure (reversible or nonreversible) may persist, in particular in cases of late-stage or long term exposure (with a risk of severe, delayed hyperkalemia).
• Risk of cardiopulmonary damage: 
Partial or complete in utero constriction of the ductus arteriosus. This can occur from 5 full months of pregnancy, and can lead to fetal or neonatal right heart failure or even fetal death in utero. This risk is increased when the drug is administered close to term (less reversibility). This effect can even occur following single administration.

• Risk of prolonged bleeding time for the mother and infant (due to the antiplatelet effect which may occur even at very low doses).
• inhibition of uterine contractions which can delay or prolong labor.

Consequently:

• Up to 12 weeks of amenorrhea: use of Profenid should only be considered if necessary.
• Between 12 and 24 weeks of amenorrhea (between the initiation of fetal diuresis and 5 full months of pregnancy): a brief course of treatment should only be prescribed if necessary.
Prolonged use is strongly inadvisable.
• After 24 weeks of amenorrhea (5 full months): any use, even single administration, is contraindicated (see Section 4.3). Accidental use after 24 weeks of amenorrhea (5 full months) warrants cardiac and renal monitoring in the fetus and/or neonate depending on the stage at which exposure occurred. Duration of monitoring should be adjusted to the elimination half-life of the compound.

During use in women hoping to conceive, or in the second trimester of pregnancy, the lowest possible dose should be used for the shortest period possible.

Lactation
Since NSAIDs are excreted in breast milk, as a precaution, administration should be avoided in breast-feeding women.