Special Warning : אזהרת שימוש

4.4. Special warnings and precautions for use
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see gastrointestinal and cardiovascular risks below).

Older people:
Older people have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation which may be fatal.

Respiratory:
Bronchospasm may be precipitated in patients suffering from or with a previous history of bronchial asthma or allergic disease and Advil Liqui-Gels 200 and Advil Forte 400 mg should not be used where other NSAIDs have produced reactions.

Other NSAIDs:
The use of Advil Liqui-Gels 200 and Advil Forte 400 mg with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided (see section 4.5).

Systemic Lupus Erythematosus (SLE) and mixed connective tissue disease: Caution should be taken when ibuprofen is given to patients with SLE and autoimmune diseases – increased risk of aseptic meningitis has been reported. (see section 4.8).

Renal, Cardiac and Hepatic:
Caution is required in patients with renal, cardiac or hepatic impairment since renal function may deteriorate (see sections 4.3 and 4.8). The dose should be as low as possible and renal function should be monitored.

There is a risk of renal impairment in dehydrated children or adolescents between 12 -18 years of age.

Cardiovascular and cerebrovascular effects:
Caution (discussion with doctor or pharmacist) is required prior to starting treatment in patients with a history of hypertension and/or heart failure as fluid retention, hypertension and oedema have been reported in association with NSAID therapy.

Clinical studies suggest that use of ibuprofen, particularly at high doses (2400mg/day) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). Overall, epidemiological studies do not suggest that low dose ibuprofen (e.g. ≤ 1200mg/day) is associated with an increased risk of arterial thrombotic events.

Patients with uncontrolled hypertension, congestive heart failure (NYHA II-III), established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with ibuprofen after careful consideration and high doses (2400 mg/day) should be avoided.
Careful consideration should also be exercised before initiating long-term treatment of patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus and smoking), particularly if high doses of ibuprofen (2400 mg/day) are required.

Cases of Kounis syndrome have been reported in patients treated with Advil Liqui-Gels 200 and Advil Forte 400 mg. Kounis syndrome has been defined as cardiovascular symptoms secondary to an allergic or hypersensitive reaction associated with constriction of coronary arteries and potentially leading to myocardial infarction.
Impaired female fertility:
There is limited evidence that drugs which inhibit cyclo-oxygenase/prostaglandin synthesis may cause impairment of female fertility by an effect on ovulation. This is reversible upon withdrawal of treatment.

Gastrointestinal:
NSAIDs should be given with care to patients with a history of gastrointestinal disease (e.g.
ulcerative colitis, Crohn’s disease) as these conditions may be exacerbated (see section 4.8).

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

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 (SSRIs) or anti-platelet agents such as aspirin (see section 4.5).

When GI bleeding or ulceration occurs in patients receiving ibuprofen, the treatment should be withdrawn.

Dermatological:
Severe skin reactions
Severe cutaneous reactions (SCARs):
Severe cutaneous reactions (SCARs), including exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome (SJS), Toxic Epidermal Necrolysis (TEN), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS syndrome) and acute generalized exanthematous pustulosis (AGEP), which can be life-threatening or fatal, have been reported in association with the use of ibuprofen (see section 4.8). Most of these reactions occurred within the first month.
If signs and symptoms suggestive of these reactions appear. Advil Liqui-Gels 200 and Advil Forte 400 should be withdrawn immediately and an alternative treatment considered (as appropriate)

Exceptionally, varicella can be at the origin of serious cutaneous and soft tissue infectious complications. To date, the contributing role of NSAIDs in the worsening of these infections cannot be ruled out. Thus, it is advisable to avoid use of Advil Liqui-Gels 200 mg and Advil Forte 400 mg in case of varicella.

Masking of symptoms of underlying infections
Advil Liqui-gels 200 and Advil Forte 400 can mask symptoms of infection, which may lead to delayed initiation of appropriate treatment and thereby worsening the outcome of the infection. This has been observed in bacterial community acquired pneumonia and bacterial complications to varicella. When Advil Liqui-gels 200 and Advil Forte 400 are administered for fever or pain relief in relation to infection, monitoring of infection is advised. In non-hospital settings, the patient should consult a doctor if symptoms persist or worsen.
The pharmacological activity of ibuprofen may reduce fever and inflammation, thus diminishing their utility as diagnostic signs in detecting underlying conditions.

Advil Liqui-gel 200 and Advil Forte 400 contain sorbitol.
Patients with rare hereditary problems of fructose intolerance should not take this medicine.
Advil Liqui-gels 200 and Advil Forte 400 Capsules contain soya lecithin. If you are allergic to peanut or soya, do not use this medicinal product.

Effects on Driving

4.7 Effects on ability to drive and use machines
No studies on the effect of ability to drive or use machines have been performed.
None expected at recommended doses and duration of therapy.