Adverse reactions : תופעות לוואי

4.8      Undesirable effects
Adverse events which have been associated with ibuprofen are given below, listed 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 (≥1/10,000 to <1/1000), very rare (<1/10,000) and not known (cannot be estimated from the available data). Within each frequency grouping, adverse events are presented in order of decreasing seriousness.
The list of the following adverse effects relates to those experienced with ibuprofen at OTC doses (maximum 1200 mg per day), for short-term use. In the treatment of chronic conditions, under long-term treatment, additional adverse effects may occur.

The most commonly observed adverse events are gastrointestinal in nature.
Adverse events are mostly dose-dependent; in particular the risk of occurrence of gastrointestinal bleeding is dependent on the dosage range and duration of treatment. Clinical studies suggest that use of ibuprofen, particularly at high dose (2400mg daily), may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke) (see section 4.4).



System Organ Class          Frequency            Adverse Event
Blood and Lymphatic         Very rare            Haematopoietic disorders (anaemia, System Disorders                                 leucopenia, thrombocytopenia, pancytopenia, agranulocytosis).
First signs are: fever, sore throat,
superficial mouth ulcers, flu-like symptoms, severe exhaustion,
unexplained bleeding and bruising.
Immune System                         Hypersensitivity reactions consisting of 1 : Disorders
Uncommon    Urticaria and pruritus

Very rare   Severe hypersensitivity reactions.
Symptoms could be facial, tongue and laryngeal swelling, dyspnoea,
tachycardia, hypotension (anaphylaxis,
angioedema or severe shock).

Not Known   Respiratory tract reactivity comprising asthma, aggravated asthma,
bronchospasm or dyspnoea.
Nervous System            Uncommon    Headache
Disorders
Very rare   Aseptic meningitis 2

Cardiac Disorders         Not Known   Cardiac failure and oedema 

Vascular Disorders        Not Known   Hypertension

Gastrointestinal          Uncommon    Abdominal pain, nausea, dyspepsia Disorders
Rare        Diarrhoea, flatulence, constipation and vomiting

Very rare   Peptic ulcer, perforation or gastrointestinal haemorrhage, melaena, haematemesis,
sometimes fatal, particularly in the elderly.
Ulcerative stomatitis, gastritis

Exacerbation of colitis and Crohn's
Not Known   disease (section 4.4).
Hepatobiliary Disorders   Very rare   Liver disorders
Skin and Subcutaneous     Uncommon    Various skin rashes
Tissue Disorders

Very rare   Severe forms of skin reactions such as bullous reactions including Stevens-
Johnson syndrome, erythema multiforme and toxic epidermal necrolysis can occur.

Not known   Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome)
Acute generalised exanthematous pustulosis (AGEP)

Photosensitivity reactions
Renal and Urinary             Very rare            Acute renal failure, papillary necrosis, Disorders                                          especially in long-term use, associated with increased serum urea and oedema.


Not Known            Renal insufficiency
Investigations                Very rare            Decreased haemoglobin levels 

Description of Selected Adverse Reactions

1
Hypersensitivity reactions have been reported following treatment with ibuprofen. These may consist of (a) non-specific allergic reactions and anaphylaxis, (b) respiratory tract activity comprising asthma, aggravated asthma, bronchospasm, dyspnoea or (c) assorted skin disorders, including rashes of various types pruritus, urticaria, purpura, angioedema and more rarely exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).
2The 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).

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation 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