Adverse reactions : תופעות לוואי

4.8 Undesirable effects
The list of the following adverse effects relates to those experienced with ibuprofen at OTC doses (maximum 1200mg per day) in short-term use. In the treatment of chronic conditions, under long- term treatment, additional adverse effects may occur.

Adverse events which have been associated with Ibuprofen are given below, tabulated by system organ class and frequency.

Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10000 to <1/1000), very Rare (<1/10000) and not known (cannot be estimated from the available data). Within each frequency grouping, adverse events are presented in order of decreasing seriousness.
System Organ Class                  Frequency       Adverse Event
Blood and Lymphatic System          Very rare       Haematopoietic disorders 1 Disorders
Immune System Disorders             Uncommon        Hypersensitivity reactions consisting of urticaria and pruritus' Severe hypersensitivity reactions. Symptoms could be facial,
Very rare       tongue and throat swelling, dyspnoea, tachycardia,
2 hypotension (anaphylaxis, angioedema or severe shock)
Nervous System Disorders            Uncommon        Headache
Very rare       Aseptic meningitis3
4
Cardiac Disorders                   Very rare       Cardiac failure and oedema 4
Vascular Disorders                  Verv rare       Hypertension
Respiratory tract reactivity comprising of asthma, aggravated
Respiratory, Thoracic and           Very rare asthma, bronchospasm or dyspnoea'
Mediastinal Disorders
5
Gastrointestinal Disorders          Uncommon        Abdominal pain, nausea and dyspepsia Rare             Diarrhoea, flatulence, constipation and vomiting
Very rare        Peptic ulcers, perforation or gastrointestinal haemorrhage, melaena, haematemesis6 Mouth ulceration and qastritis
Not known        Exacerbation of colitis and Crohn's disease7
Hepatobiliary Disorders          Very rare        Liver disorders

Skin and Subcutaneous Tissue     Uncommon         Skin rash2
Disorders                                         Severe forms of skin reactions such as bullous reactions including Stevens-Johnson Syndrome, erythema multiforme and toxic epidermal necrolysis can occur'
Very rare
Drug reaction with eosinophilia and systemic symptoms
(DRESS syndrome)
Not known
Acute generalised exanthematous pustulosis (AGEP)

Photosensitivity reactions
Acute renal failure8
Very rare
Renal and Urinary Disorders

Investigations                   Very rare        Decreased haemoglobin levels, urea renal clearance decreased 
Exacerbation of infections related inflammation (e.g. development of necrotizing fasciitis), in exceptional cases severe skin infections and soft-tissue complications may occur
Very rare durinq a varicella infection.
Infections and infestations

Description of Selected Adverse Reactions
1
Examples include anaemia, leucopenia, thrombocytopenia, pancytopenia, and agranulocytosis. First signs are: fever, sore throat, superficial mouth ulcers and flu-like symptoms, severe exhaustion, unexplained bleeding and bruising.

2
Hypersensitivity reactions have been reported. These may consist of (a) non-specific allergic reactions and anaphylaxis, (b) respiratory tract activity, e.g. asthma, aggravated asthma, bronchospasm or dyspnea, or (c) various skin reactions, including rashes of various types, pruritus, urticarial, purpura, angioedema and more rarely, exfoliative and bullous dermatoses (including toxic epidermal necrolysis, Stevens-Johnson Syndrome and erythema multiforme).

3
The pathogenic mechanism of drug-induced aseptic meningitis is not fully understood. However, the available data on NSAID-related aseptic meningitis points to a hypersensitivity reaction (due to a temporal relationship with drug intake, and disappearance of symptoms after drug discontinuation).
Of note, single cases of symptoms of aseptic meningitis, (such as stiff neck, headache, nausea, vomiting, fever or disorientation) have been observed during treatment with ibuprofen in patients with existing auto-immune disorders (such as systemic lupus erythematosus, mixed connective tissue disease).

4
Clinical studies suggest that the 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) (see section 4.4).

5
The adverse events observed most often are gastrointestinal in nature.

6
Sometimes fatal, particularly in the elderly.
7
See Section 4.4.
8
Especially in long-term use, associated with increased serum urea and oedema. Also includes papillary necrosis.

Reporting of Suspected Adverse Reactions
Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form: https://sideeffects.health.gov.il