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 events relates to those experienced with ibuprofen at OTC doses, for short-term use. In the treatment of chronic conditions, under long-term treatment, additional adverse events may occur.

The adverse events observed most often 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 and epidemiological data suggest that use of ibuprofen particularly at a high dose 2400mg /day 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
Very rare:            Haematopoietic disorders (anaemia,
Blood and Lymphatic                         leucopenia,            thrombocytopenia, System Disorders                            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 of1: 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 meningitis2
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
Not Known
Exacerbation of colitis and Crohn's 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)
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).
2
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).

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 http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffe ctMedic@moh.gov.il