• last trimester of pregnancy

• history of asthma induced by administration of ketoprofen or similar acting substances, such as other non-steroidal anti-inflammatory agents (NSAIDs) or acetylsalicylic acid

• severe hepatic failure

• severe renal failure

• severe heart failure

• active peptic ulcer

• gastrointestinal bleeding, cerebrovascular bleeding or other active bleeding

• Concomitant use with St. John's wort or atazanavir sulphate

• Combination therapy with clarithromycin should not be used in patients with hepatic impairment

Special Precautions

Linked to Ketoprofen component

The use of Axorid with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided.

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms.

Elderly: the elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal.

Gastrointestinal bleeding, ulceration and perforation: GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at anytime during treatment, with or without warning symptoms or a previous history of serious GI events.

Some epidemiological evidence suggests that ketoprofen may be associated with a high risk of serious gastrointestinal toxicity, relative to some other NSAIDs, especially at high doses.

The risk of GI bleeding, ulceration or perforation is higher with increasing NSAID doses, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation, in patients with a platelet function disorder and in the elderly. These patients should commence treatment on the lowest dose available.

Patients with a history of GI toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.

Caution should be advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin-reuptake inhibitors or anti-platelet agents such as aspirin.

The association with omeprazole allows to decrease gastrointestinal toxicity. Nevertheless gastrointestinal haemorrhage or ulcers/perforations can occur at any time in the course of treatment. They are not necessarily preceded by premonitory signs and can occur in patients with no history of such manifestations. They have to be closely monitored.

When GI bleeding occurs in patients receiving Axorid, the treatment should be withdrawn.

NSAIDs should be given with care to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as these conditions may be exacerbated.

Patients with asthma associated with chronic rhinitis, chronic sinusitis and/or nasal polyposis are more likely to exhibit allergic reactions after taking acetylsalicylic acid and/or non-steroidal anti-inflammatory agents than the general population. Administration of this product may induce an attack of asthma.

Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with NSAID therapy.

Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). There are insufficient data to exclude such a risk for ketoprofen.

Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with ketoprofen after careful consideration. Similar consideration should be made before initiating longer-term treatment of the patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).

Urine output and renal function should be closely monitored in patients with renal or hepatic impairment, in patients on diuretic treatment, following major surgery which involved hypovolaemia, and particularly in the elderly.

In the elderly, as half-life of NSAIDs is longer, doses should be reduced.

During long-term treatment, monitoring of blood count and hepatic and renal function is recommended.

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs. Patients appear to be at highest risk for these reactions early in the course of the therapy: the onset of the reaction occurring in the majority of cases within the first month of treatment. Axorid should be discontinued at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity.

Patients with a previous history of photosensitivity or phototoxicity reactions should be carefully monitored.

Ketoprofen, as any other NSAID, may mask symptoms of an underlying infectious disease.

Ketoprofen component in Axorid is a prolonged-release formulation, therefore this treatment is not suitable when a quick onset of efficacy at the beginning of the treatment is required.

Linked to Omeprazole component

Decreased gastric acidity increases gastric counts of bacteria normally present in the gastro-intestinal tract. Treatment with acid-reducing medicinal products leads to a slightly increased risk of gastrointestinal infections, such as Salmonella and Campylobacter.

In patients with severe impaired hepatic function, liver enzyme values should be checked periodically during treatment with omeprazole.

During concomitant regimens with omeprazole and other medicinal products caution should be exercised when administering additional medicinal products as interactions might occur. This is particularly important with products with a narrow therapeutic index such as warfarin