KETESE

Symptomatic treatment of mild to moderate intensity pain, such as musculoskeletal pain, dysmenorrhea and dental pain.

Dexkétoprofène is contraindicated during the 3rd trimester of pregnancy and during breastfeeding (see section 4.3).

Pregnancy

Inhibition of prostaglandin synthesis is likely to have deleterious effects on pregnancy and/or embryonic/fetal development. Data from epidemiological studies have raised concerns regarding an increased risk of miscarriage, cardiac malformations and laparoschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiovascular malformations has increased from less than 1 % to approximately 1,5 %.

It is assumed that this risk increases with the dose and the duration of treatment. In animals, it has been shown that the administration of a prostaglandin synthesis inhibitor leads to an increase in pre- and post-implantation loss and embryonic-fetal lethality. In addition, increased incidences of various malformations, notably cardiovascular, have been reported in animals to which a prostaglandin synthesis inhibitor was administered during organogenesis. Nevertheless, animal studies on dexkétoprofène have shown no reproductive toxicity (see section 5.3). From the 20th week of amenorrhea, the use of dexkétoprofène may cause oligohydramnios resulting from fetal renal dysfunction. This effect may occur shortly after the start of treatment and is generally reversible upon discontinuation. In addition, cases of constriction of the ductus arteriosus have been observed after treatment during the second trimester, most of which disappeared after discontinuation of treatment. For this reason, during the first two trimesters of pregnancy, dexkétoprofène should not be administered, except in cases of absolute necessity.

If dexkétoprofène is used in a woman attempting to conceive or during the first two trimesters of pregnancy, the dose should be maintained at the lowest possible level, and the treatment should be as short as possible. Prenatal monitoring for oligohydramnios and constriction of the ductus arteriosus should be considered after exposure to dexkétoprofène for several days from the 20th week of amenorrhea. Treatment with dexkétoprofène must be interrupted in case of oligohydramnios or constriction of the ductus arteriosus.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors are likely to expose the fetus to:

· cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);

· renal dysfunction (see above).

At the end of pregnancy, the mother and the newborn are likely to be exposed to:

· a possible prolongation of bleeding time, an antiplatelet effect that may occur even at very low doses;

· inhibition of uterine contractions which may delay or prolong labor.

Breastfeeding

It is unknown if dexkétoprofène is excreted in breast milk. Ketesse is contraindicated during breastfeeding (see section 4.3).

Fertility

Like other NSAIDs, the use of dexketoprofen may temporarily alter female fertility; it is not recommended in women trying to conceive. In women experiencing difficulties conceiving or undergoing fertility testing, discontinuation of dexketoprofen treatment should be considered.

Dexkétoprofène may have adverse effects such as dizziness, visual disturbances or drowsiness. If this occurs, the ability to drive vehicles and use machines may be impaired.

Adverse events reported as probably related to dexketoprofen intake reported during clinical trials and after marketing of dexketoprofen are presented below, classified by class-organ system and in order of frequency:

The most frequently observed adverse effects are of a gastrointestinal nature. Peptic ulcers, perforations or gastrointestinal hemorrhages, sometimes fatal, may occur, particularly in the elderly (see section 4.4). Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of ulcerative colitis or Crohn's disease (see section 4.4) have been reported. Less frequently, gastritis has been observed. Edemas, hypertension and heart failure have been reported in case of association with NSAIDs.

Just as with other NSAIDs, the following adverse effects may occur: aseptic meningitis, which appears mainly in patients with systemic lupus erythematosus or mixed connective tissue disease; hematological reactions (purpura, aplastic and hemolytic anemia, rarely agranulocytosis and bone marrow hypoplasia).

Bullous reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis may occur very rarely.

Clinical and epidemiological data suggest that the use of certain NSAIDs (particularly at high doses and long term) may be associated with a slight increase in the risk of arterial thrombotic events (for example myocardial infarction or stroke) (see section 4.4).

Reporting of suspected adverse effects

Reporting of suspected adverse effects after authorisation of the medicinal product is important. It allows continuous monitoring of the benefit/risk ratio of the medicinal product. Healthcare professionals report any suspected adverse effect via the national reporting system: French National Agency for Medicines and Health Products Safety (ANSM) and the network of Regional Pharmacovigilance Centres - Website: https://signalement.social-sante.gouv.fr .