Pregnancy: No cases of pregnancy occurred during the Skudexa clinical development. The safety profile of Skudexa during pregnancy has not been established in the clinical studies included in this section. Data reported for dexketoprofen and tramadol as single agents should be taken into account.
Dexketoprofen: Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies raise concern about an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from less than 1%, up to approximately 1.5%. 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. Nevertheless, animal studies with dexketoprofen haven't shown reproductive toxicity (see Pharmacology: Toxicology: Preclinical safety data under Actions).
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to: cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension); renal dysfunction, which may progress to renal failure with oligo-hydroamniosis.
At the end of pregnancy, the mother and the neonate may be exposed to: possible prolongation of bleeding time, an anti platelet effect which may occur even at very low doses; inhibition of uterine contractions resulting in delayed or prolonged labour.
Tramadol: Animal studies with tramadol revealed at very high doses effects on organ development, ossification and neonatal mortality. Teratogenic effects were not observed. Tramadol crosses the placenta. There is inadequate evidence available on the safety of tramadol in human pregnancy.
Tramadol - administered before or during birth - does not affect uterine contractility. In neonates it may induce changes in the respiratory rate which are usually not clinically relevant. Chronic use during pregnancy may lead to neonatal withdrawal symptoms.
Considering the previously mentioned information Skudexa is contraindicated in pregnancy (see Contraindications).
Breastfeeding: No controlled trials have been conducted to study the excretion of Skudexa in human milk. Data reported for dexketoprofen and tramadol as single agents should be taken into account.
Dexketoprofen: It is not known whether dexketoprofen is excreted in human milk.
Tramadol: Tramadol and its metabolites are found in small amounts in human breast milk.
Approximately 0.1% of the maternal dose of tramadol is excreted in breast milk. In the immediate post partum period, for maternal oral dosage up to 400 mg, this corresponds to a mean amount of tramadol ingested by breast fed infants of 3% of the maternal weight-adjusted dosage, For this reason, tramadol should not be used during lactation or alternatively, breast-feeding should be discontinued during treatment with tramadol. Discontinuation of breast-feeding is generally not necessary following a single dose of tramadol.
Considering the previously mentioned information Skudexa is contraindicated during breastfeeding (see Contraindications).
Fertility: As with other NSAIDs, the use of dexketoprofen may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of dexketoprofen should be considered.