Adverse reactions : תופעות לוואי

4.8. Undesirable effects

Hypersensitivity reactions have been reported and these may consist of : a. non-specific allergic reactions and anaphylaxis b. respiratory tract reactivity e.g. asthma, aggravated asthma, bronchospasm, dyspnoea c. various skin reactions e.g. pruritus, urticaria, angioedema and more rarely exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme) 
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, 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 trial and epidemiological data suggest that use of ibuprofen (particularly at high doses 2400mg daily) and in long-term treatment may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke (see section "special warnings and precautions for use").

Gastrointestinal disorders
Uncommon: abdominal pain, dyspepsia and nausea.

Rare: diarrhea, 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 ulcerative colitis and Crohn's disease (see section "special warnings and precautions for use").

Nervous System
Uncommon:
Very rare: Aseptic meningitis

NUROFEN® LIQUID CAPSULES 200mg                                                    April 2015 Renal and Urinary Disorders
Very rare: Decrease of urea excretion and oedema can occur., acute renal failure. Papillary necrosis, especially in long-term use, associated with increased serum urea and oedema 
Not Known : Renal insufficiency

Liver/Hepatobiliary Disorders
Very rare: Liver disorders
Blood and Lymphatic System Disorders
Very rare: Haematopoietic disorders (anaemia, leucopenia, thrombocytopenia, pancytopenia, agranulocytosis). First signs are: fever, sore throat, superficial mouth ulcers, flu-like symptoms, severe exhaustion, unexplained bleeding and bruising.

Skin and Subcutaneous Tissue Disorders
Uncommon: Various skin rashes.
Very rare: Severe forms of skin reactions such as bullous reactions, including Stevens- Johnson Syndrome, erythema multiforme and toxic epidermal necrolysis can occur.

Immune system disorder:
1
Hypersensitivity reactions consisting of :
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).

In patients with existing auto-immune disorders (systemic lupus erythematosus, mixed connective tissue disease) during treatment with ibuprofen, single cases of symptoms of aseptic meningitis such as stiff neck, headache, nausea, vomiting, fever or disorientation have been observed (see section "special warnings and precautions for use").

Not Known: Respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea.

Hypersensitivity Reactions:
Exacerbation of asthma and bronchospasm.

Cardiac disorder:
Not Known : Cardiac failure and oedema
Vascular Disorder
Not Known : Hypertension

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 NUROFEN® LIQUID CAPSULES 200mg                                                       April 2015 disorientation) have been observed during treatment with ibuprofen, in patients with existing auto-immune disorders (such as systemic lupus erythematosus, mixed connective tissue disease).