Special Warning : אזהרת שימוש

4.4. Special warnings and precautions for use
Concomitant use of Profenid with other NSAIDs, including cyclooxygenase-2 (cox-2) selective inhibitors, should be avoided.

The occurrence of adverse effects can be minimized by using the lowest possible dose for the shortest possible duration to obtain relief of symptoms (see Section 4.2 and "Gastrointestinal effects" and "Cardiovascular and cerebrovascular effects" below).

Patients with asthma associated with chronic rhinitis, chronic sinusitis and/or nasal polyposis are at a higher risk of allergic reactions when taking aspirin and/or non-steroidal anti-inflammatory drugs than the general population. Administration of this proprietary medicinal product may induce asthma attacks or bronchospasm, particularly in subjects allergic to aspirin or an NSAID (see Section 4.3).

Elderly subjects

The elderly have an increased risk of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation that can be fatal (see Section 4.2 and below).

Gastrointestinal effects

Gastrointestinal bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs, at any time during treatment, even without warning signs or a patient history of serious gastrointestinal adverse reactions..

The relative risk increases with age, patients who presents with platelet dysfunction or in patients undergoing anticoagulant or antiplatelet treatment (see section Interactions with other drugs and other forms of interaction).

Some epidemiological evidence suggests that ketoprofen may be associated with a higher risk of serious gastrointestinal toxicity than other NSAIDs, especially at high doses (also see Sections 4.2 and 4.3).

The risk of gastrointestinal bleeding, ulceration or perforation increases with the dose used in patients with a history of ulcer, particularly if complicated with bleeding or perforation (see Section 4.3), in elderly subjects, as well as in patients with low body weight. In these patients, treatment should be initiated at the lowest possible dose. Treatment providing protection of the mucosa (e.g. misoprostol or proton pump inhibitors) should be considered for these patients, and also for patients requiring low-dose treatment with aspirin or treated with other medicinal products likely to increase the risk of gastrointestinal effects (see below and Section 4.5).

Patients with a history of gastrointestinal disorders, particularly elderly patients, should report any unusual abdominal symptoms (in particular gastrointestinal bleeding), especially at the start of treatment.

Special monitoring is required in patients receiving concomitant medication likely to increase the risk of ulceration or bleeding, such as glucocorticoids, oral anticoagulants such as warfarin, selective serotonin reuptake inhibitors (SSRIs) and antiplatelet agents such as aspirin (see Section 4.5).

If bleeding or ulceration occurs in patients receiving Profenid, treatment should be discontinued.

Caution should be exercised and close monitoring instituted when administering NSAIDs in patients with a history of gastrointestinal disease (ulcerative colitis, Crohn’s disease) as these conditions may be exacerbated (see Section 4.8).
Cardiovascular and cerebrovascular effects

Adequate monitoring and recommendations are required for patients with a history of hypertension and/or mild to moderate heart failure, since cases of water and sodium retention and edema have been reported in patients receiving treatment with NSAIDs.

Clinical studies and epidemiological data suggest that the use of certain NSAIDs (particularly when administered at high doses and over a long period) can be associated with a slight increase in the risk of arterial thrombotic events (e.g. myocardial infarction or stroke). Currently available data do not make it possible to rule out this increased risk with ketoprofen.

As is the case for all NSAIDs, patients with uncontrolled hypertension, congestive heart failure, ischemic heart disease, peripheral arterial disease, and/or a history of stroke (including transient ischemic attack) should only be treated with ketoprofen after careful assessment.

Similar caution is required before initiating long-term treatment in patients with risk factors for cardiovascular disease (such as hypertension, hyperlipidemia, diabetes or smoking).

Skin reactions
Serious skin reactions, some of which have been fatal, including exfoliative dermatitis, Stevens- Johnson syndrome and Lyell’s syndrome, have been reported in very rare cases during treatment with NSAIDs (see Section 4.8).

The incidence of these adverse effects appears to be higher at the start of treatment, occurring within the first month of treatment in most cases. Treatment with Profenid should be discontinued as soon as skin rash, mucosal damage or any other signs of hypersensitivity occur.

Functional renal failure

By inhibiting the vasodilatory effects of renal prostaglandins, NSAIDs are likely to cause functional kidney failure as a result of decreased glomerular filtration. This adverse effect is dose- dependent.
At the start of treatment or after an increase in dose, monitoring of urine output and kidney function is recommended in patients with the following risk factors:
• advanced age,
• concomitant medication such as ACE inhibitors, sartans, diuretics (see Section 4.5),
• hypovolemia regardless of the cause,
• heart failure,
• chronic kidney failure,
• nephrotic syndrome,
• lupus nephropathy,
• cirrhosis.

Water and sodium retention

Water and sodium retention with possible edema, hypertension or exacerbation of hypertension, exacerbation of heart failure. Clinical monitoring is required from the start of treatment in patients with hypertension or heart failure. The effect of antihypertensive agents may be reduced (see Section 4.5).

Hyperkalemia
Hyperkalemia promoted by diabetes or concomitant treatment with hyperkalemic agents (see Section 4.5).


Regular monitoring of blood potassium levels is required in these patients.
The use of NSAIDs may affect fertility in female patients, and is not recommended in female patients hoping to conceive. Discontinuation of NSAID therapy should be considered in women having difficulty conceiving or undergoing infertility tests.

Like other NSAIDs, ketoprofen can mask the signs of worsening infection such as fever.

Patients with a history of photosensitivity or phototoxicity reactions must be closely monitored.
Regular transaminase monitoring is recommended in patients with abnormal liver function tests or a history of liver disease particularly during long term treatment.

Rare cases of jaundice and hepatitis have been described with ketoprofen.

During long term treatment, the blood count, as well as kidney and liver function, should be monitored.

Treatment must be discontinued if visual disturbances, such as blurred vision, occur.

Administration of this medicinal product should be avoided during treatment with another non- steroidal anti-inflammatory drug, oral anticoagulant, lithium, aspirin at analgesic, antipyretic or anti-inflammatory doses, methotrexate at doses higher than 20 mg per week, with low-molecular- weight heparins and related products, and unfractionated heparins (at curative doses and/or in the elderly), pemetrexed, and in patients with low to moderate kidney function (see Section 4.5).

SLE and mixed connective tissue disease:
In patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders, there may be an increased risk of aseptic meningitis

In addition, for the capsules form:
This medicinal product contains lactose and is therefore not recommended in patients with galactose intolerance, Lapp lactase deficiency or glucose or galactose malabsorption syndrome (rare hereditary diseases).

Effects on Driving

4.7 Effects on ability to drive and use machines
Patients should be warned that dizziness, drowsiness, seizures or visual disturbances may occur.
Patients should be advised not to drive or use machines if any of these symptoms occur.