MOBIC

· Short-term symptomatic treatment of acute osteoarthritis flares;

· Long-term symptomatic treatment of rheumatoid arthritis and ankylosing spondylitis.

MELOXICAM EG scored tablets is indicated in adults and children aged 16 years and older.

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies after the use of a prostaglandin synthesis inhibitor in early pregnancy suggest an increased risk of miscarriage, of cardiac malformation and of gastroschisis. The absolute risk for cardiac malformation is increased from less than 1 % to approximately 1,5 %. It 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.

From the 20th week of gestation onwards, meloxicam use may cause oligohydramnios resulting from foetal renal dysfunction. This effect may occur shortly after treatment initiation and is usually reversible upon discontinuation. In addition, there have been reports of ductus arteriosus constriction after treatment during the second trimester, most of which resolved after treatment cessation.

Consequently, unless clearly necessary, the use of meloxicam should be avoided during the first and second trimester of pregnancy. If meloxicam 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.

Antenatal monitoring for oligohydramnios and ductus arteriosus constriction should be considered after exposure to meloxicam for several days from the 20th gestational week onwards. Meloxicam treatment should be discontinued if oligohydramnios or ductus arteriosus constriction is found.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose:

· the foetus

o to cardiopulmonary toxicity (premature constriction/closure of the ductus arteriosus and pulmonary hypertension);

o to renal dysfunction (see above);

· the mother and the neonate, at the end of pregnancy

o to possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses;

o to inhibition of uterine contractions resulting in delayed or prolonged labour.

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

Breastfeeding

Although no specific information is available for meloxicam, NSAIDs are known to pass into mother's milk. Meloxicam has been found in the milk of lactating animals. Administration of meloxicam is therefore not recommended in women who are breastfeeding.

Fertility

Meloxicam, like any drug that inhibits cyclooxygenase and prostaglandin synthesis, may impair fertility. Its use is not recommended in women attempting to conceive. In women who have difficulties conceiving, or who are undergoing investigation of infertility, withdrawal of meloxicam should be considered.

No specific studies on the ability to drive and use machines have been carried out. However, given its pharmacodynamic profile and the reported adverse effects, it is unlikely that méloxicam affects the ability to drive or use machines. However, in the event of vision disturbances, notably blurred vision, dizziness, drowsiness, vertigo or other central nervous system disorders, it is recommended to refrain from driving or using machines.

a) General description

Clinical studies and epidemiological data suggest that the use of certain NSAIDs (especially when used at high doses and over a long duration) may be associated with a slight increase in the risk of an arterial thrombotic event (for example, myocardial infarction or stroke) (see section 4.4).

Edema, hypertension and heart failure have been reported in association with NSAID treatment.

The most frequently observed adverse effects are gastrointestinal in nature. Peptic ulcers, perforations or gastrointestinal haemorrhages, sometimes fatal, may occur, particularly in the elderly, (see section 4.4). Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melæna, haematemesis, ulcerative stomatitis, exacerbation of ulcerative colitis or Crohn's disease (see section 4.4) have been reported following the administration of NSAIDs. Less frequently, gastritis has been observed.

Severe cutaneous adverse effects: Stevens-Johnson syndrome and Lyell syndrome, have been reported (see section 4.4).

The frequencies of the events reported below are based on the incidence rates of adverse effects observed during 27 clinical trials, with a treatment duration of at least 14 days. The data are derived from clinical trials conducted on 15197 patients treated with daily oral doses of 7,5 or 15 mg of meloxicam in the form of tablets or capsules over periods of up to 1 year.

Adverse effects highlighted during spontaneous notifications after the product has been placed on the market are also mentioned. Adverse effects have been classified according to their incidence using the following classification:

Very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10 000, < 1/1000); very rare (< 1/10 000); unknown frequency (cannot be estimated on the basis of available data)

b) Table of adverse effects

Hematological and lymphatic system disorders

Uncommon: anaemia

Rare: blood count abnormalities (including differential white blood cell count), leucopenia, thrombocytopenia.

Very rare cases of agranulocytosis have been reported (see section c).

Immune system disorders

Uncommon: allergic reactions other than anaphylactic/anaphylactoid reactions.

Indeterminate: anaphylactic/anaphylactoid reactions.

Psychiatric disorders

Rare: altered mood, nightmares.

Unknown: confusion, disorientation.

Nervous system disorders

Common: headache.

Uncommon: dizziness, somnolence.

Eye disorders

Rare: vision disorders, notably blurred vision, conjunctivitis.

Ear and labyrinth disorders

Uncommon: vertigo

Rare: tinnitus

Cardiac disorders

Rare: palpitations.

Heart failure has been reported in association with NSAID treatment.

Vascular disorders

Uncommon: increased blood pressure (see section 4.4), flush.

Respiratory, thoracic and mediastinal disorders

Rare: asthma in subjects allergic to aspirin or other NSAIDs.

Gastro-intestinal disorders

Very common: gastro-intestinal disorders such as dyspepsia, nausea, vomiting, abdominal pain, constipation, flatulence, diarrhoea.

Uncommon: gastro-intestinal haemorrhages, occult or macroscopic, stomatitis, gastritis, eructation.

Rare: colitis, gastro-duodenal ulcers, oesophagitis.

Very rare: gastro-intestinal perforation

Undetermined: pancreatitis

Gastro-intestinal haemorrhages, ulcerations or perforations can sometimes be severe and potentially fatal, particularly in the elderly (see section 4.4).

Hepatobiliary disorders

Uncommon: abnormalities of hepatic function (for example increase in transaminases or bilirubin).

Very rare: hepatitis.

Skin and subcutaneous tissue disorders

Uncommon: angioedema, pruritus, skin rash.

Rare: Stevens-Johnson syndrome, Lyell syndrome, urticaria.

Very rare: bullous dermatosis, erythema multiforme.

Undetermined: photosensitivity reaction, fixed pigment erythema (see section 4.4).

Renal and urinary disorders

Uncommon: sodium and water retention, hyperkalaemia (see sections 4.4 and 4.5), abnormalities of renal function tests (increase in serum creatinine and/or serum urea).

Very rare: acute renal failure particularly in at-risk patients (see section 4.4).

Reproductive system and breast disorders

Undetermined: female infertility, delayed ovulation

General disorders and administration site conditions

Uncommon: oedema, including oedema of lower limbs.

c) Information concerning serious individual cases or particularly frequent reactions

Very rare cases of agranulocytosis have been reported in patients treated with meloxicam and other potentially myelotoxic drugs (see section 4.5).

d) Adverse effects not observed to date with the medicinal product, but generally known to be associated with the administration of other products of the same class

Organic renal lesions leading to acute renal failure: very rare cases of interstitial nephritis, acute tubular necrosis, nephrotic syndrome and renal papillary necrosis have been reported (see section 4.4).

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals report any suspected adverse reaction 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/ .