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 1200mg per day), for short-term use. In the treatment of chronic conditions, under long-term treatment, additional adverse effects 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 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
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 Disorders                  Hypersensitivity reactions consisting of1:

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 Disorders     Uncommon Headache

Very rare   Aseptic meningitis2
Cardiac Disorders            Not known   Cardiac failure and oedema Vascular Disorders           Not known   Hypertension
Gastrointestinal Disorders   Uncommon    Abdominal pain, nausea, Dyspepsia 
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)
Acute generalised exanthematous pustulosis
(AGEP)

Photosensitivity reactions
Renal and Urinary Disorders   Very rare    Acute renal failure, papillary necrosis, 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 https://sideeffects.health.gov.il/