Special Warning : אזהרת שימוש

4.4       Special warnings and precautions for use

The use of Mesulid with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided. In addition, patients should be advised to refrain from other concomitant analgesics.

Undesirable effects may be minimised by using the minimum effective dose for the shortest duration necessary to control symptoms (see section 4.2).

Treatment should be discontinued if no benefit is seen.

Hepatic effects
Rarely Mesulid has been reported to be associated with serious hepatic reactions, including very rare fatal cases (see also section 4.8). Patients who experience symptoms compatible with hepatic injury during treatment with Mesulid (e.g. anorexia, nausea, vomiting, abdominal pain, fatigue, dark urine) or patients who develop abnormal liver function tests should have treatment discontinued. These patients should not be rechallenged with nimesulide. Liver damage, in most cases reversible, has been reported following short exposure to the drug.

Patients receiving nimesulide who develop fever and / or flu-like symptoms should discontinue treatment.

Gastrointestinal effects
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 GI events.

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 (see section 4.3), and in the elderly.
These patients should commence treatment on the lowest dose available. Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients, and also for patients requiring concomitant low dose acetylsalicylic acid, or other drugs likely to increase gastrointestinal risk (see below and 4.5). 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.

Gastrointestinal bleeding or ulceration / perforation can occur at any time during treatment with or without warning symptoms or a previous history of gastrointestinal events. If gastrointestinal bleeding or ulceration occurs, nimesulide should be discontinued. Nimesulide should be used with caution in patients with gastrointestinal disorders, including history of peptic ulceration, history of gastrointestinal haemorrhage, ulcerative colitis or Crohn’s disease.

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 antiplatelet agents such as acetylsalicylic acid (see section 4.5).
When GI bleeding or ulceration occurs in patients receiving Mesulid 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 their condition may be exacerbated (see section 4.8 – undesirable effects).

Elderly: the elderly have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation which may be fatal (see section 4.2). Therefore, appropriate clinical monitoring is advisable.
Cardiovascular and cerebrovascular effects

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.


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

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

As nimesulide can interfere with platelet function, it should be used with caution in patients with bleeding diathesis (see also section 4.3). However, Mesulid is not a substitute for acetylsalicylic acid for cardiovascular prophylaxis.

Renal effects
In patients with renal or cardiac impairment, caution is required since the use of Mesulid may result in deterioration of renal function. In the event of deterioration, the treatment should be discontinued (see also section 4.5).

Skin Reactions
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 (see section 4.8). Patients appear to be at highest risk of these reactions early in the course of therapy, the onset of the reaction occurring in the majority of cases within the first month of treatment. Mesulid should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Cases of fixed drug eruption (FDE) have been reported with nimesulide.
Nimesulide should not be reintroduced in patients with history of nimesulide-related FDE (see section 4.8).

Fertility effects
The use of Mesulid 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 Mesulid should be considered (see section 4.6).


Mesulid contain lactose, therefore patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Effects on Driving

4.7   Effects on ability to drive and use machines

No studies on the effect of Mesulid on the ability to drive or use machines have been performed. However, patients who experience dizziness, vertigo or somnolence after receiving Mesulid should refrain from driving or operating machines.