Pregnancy & Lactation : הריון/הנקה

4.6          Fertility, pregnancy and lactation
Pregnancy
There are no adequate data available from the use of Excedrin in pregnant women. Animal studies have not been performed with acetylsalicylic acid, paracetamol and caffeine in combination (see section 5.3).
Acetylsalicylic acid
Due to the presence of acetylsalicylic acid in Excedrin, its use is contraindicated in the 3rd trimester of pregnancy (see section 4.3), and caution should be exercised when used in the first 2 terms of pregnancy.
Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The risk is believed to increase with dose and duration of therapy. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryo-foetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period. During the first and second trimester of pregnancy, acetylsalicylic acid should not be given unless clearly necessary. If acetylsalicylic acid is used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the dose should be kept as low and duration of treatment as short as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may have the following effects:
On the foetus:
• cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
• renal dysfunction, which may progress to renal failure with oligo-hydroamniosis; On the mother and the neonate:
• at the end of pregnancy, possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses;
• inhibition of uterine contractions resulting in delayed or prolonged labour. Consequently, acetylsalicylic acid is contraindicated during the third trimester of pregnancy.
Rarely, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) after 20 weeks gestation in pregnancy may cause fetal renal dysfunction leading to oligohydramnios.
These effects are seen 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.
The use of NSAIDs after week 20 of gestation should be restricted. If the benefit of NSAID treatment is considered greater than the risk, limit use to the lowest effective dose and shortest duration possible.
Consider ultrasound monitoring of amniotic fluid if NSAID treatment of this medicine at the full treatment dosage extends beyond five days. Discontinue the NSAID if oligohydramnios occurs.

Paracetamol

Epidemiological studies indicate that under normal therapeutically conditions paracetamol can be used during pregnancy. Nevertheless, it should be used only after a careful benefit-risk assessment has been done.
Caffeine
Pregnant women are advised to limit their intake of caffeine to a minimum as the available data on the effect of caffeine on the human fetus suggests a potential risk.

Breast-feeding
Salicylate, paracetamol and caffeine are excreted into breast milk. Due to the content of caffeine, the behaviour of the suckling child may be influenced (excitement, poor sleeping pattern). Due to the salicylate, there may also be a potential for adverse effects on platelet function in the infant (could cause slight bleeding), though none have been reported. Also, there are concerns with the use of ASA in case of potential development of Reye's Syndrome in infants. Therefore, Excedrin is not recommended during breastfeeding.

Fertility
Acetylsalicylic acid
There is some evidence that medicinal products that inhibit cyclo-oxygenase / prostaglandin synthesis may cause impairment of female fertility by an effect on ovulation. This is reversible on withdrawal of treatment.