Adverse reactions : תופעות לוואי

4.8   Undesirable effects

The most commonly observed adverse events are with ibuprofen are gastrointestinal in nature.

The following list of adverse effects relates to those experienced with ibuprofen at OTC doses (maximum 1200mg per day) and sympathomimetics including pseudoephedrine for 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 and sympathomimetics including pseudoephedrine are given below, listed by      system organ class and frequency. Frequencies are defined as: Very common (≥1/10), Common (≥1/100 and <1/10), Uncommon (≥1/1000 and <1/100), Rare (≥1/10,000 and <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.

System Organ Class           Frequency       Adverse Event
Blood and Lymphatic          Very rare       Haematopoietic disorders1 System Disorders
Immune System Disorders      Uncommon        Hypersensitivity with urticaria and pruritus2



Very rare      Severe hypersensitivity reactions including facial, tongue and throat swelling, dyspnoea, tachycardia,
hypotension (anaphylaxis, angioedema or severe shock)2
Psychiatric Disorders        Not known      Insomnia, anxiety, restlessness, agitation, hallucination.
Nervous System Disorders     Uncommon       Headache, tremor
Very rare      Aseptic meningitis3, muscular weakness
Not known      Posterior reversible encephalopathy syndrome (PRES) (see section 4.4)
Reversible cerebral vasoconstriction syndrome (RCVS) (see section 4.4)
Cardiac Disorders            Not known      Cardiac failure and oedema4, tachycardia, arrhythmia, palpitations.

Not known      Kounis Syndrome
Vascular Disorders           Not known      Hypertension4
Respiratory, Thoracic and    Not known      Respiratory tract reactivity including Mediastinal Disorders                       exacerbation of asthma, bronchospasm or dyspnoea2.
Gastrointestinal Disorders   Uncommon       Abdominal pain, nausea and dyspepsia5
Rare           Diarrhoea, flatulence, constipation and vomiting
Very rare      Peptic ulcers, gastrointestinal perforation or gastrointestinal haemorrhage, melaena,
haematemesis6. Mouth ulceration and gastritis.
Not known      Dry mouth, exacerbation of colitis and
Crohn's disease7, ischaemic colitis.
Hepatobiliary Disorders      Very rare      Liver disorders
Skin and Subcutaneous        Not known      Hyperhidrosis
Tissue Disorders                            Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome)
Severe skin reactions, including acute generalized exanthematous pustulosis
(AGEP)
Photosensitivity reactions
Uncommon       Skin rashes2



Very rare       Severe cutaneous adverse reactions
(SCARs), including Stevens-
Johnson syndrome, erythema multiforme, exfoliative dermatitis and toxic epidermal necrolysis2

Musculoskeletal and           Not known       Muscular weakness connective tissue disorders
Metabolism and Nutrition      Not known       Decreased Appetite Disorders                     Not known       Hypokalaemia9
Renal and Urinary             Very rare       Acute renal failure8 Disorders                     Not known       Urinary retention Not known       Ureteric colic, dysuria
Not known       Renal tubular acidosis9
General and                   Not known       Chest pain, irritability, thirst, Administration Site
Conditions


Investigations                Very rare       Haemoglobin decreased Eye disorders                 Not known       Ischaemic optic neuropathy 
Description of Selected Adverse Reactions:
1
Examples include anaemia, leucopenia, thrombocytopenia,
pancytopenia and agranulocytosis. First signs are fever, sore throat, superficial mouth ulcers, flu- like symptoms, severe exhaustion, unexplained bleeding and bruising.
2
Hypersensitivity reactions: These may consist of (a) non-specific allergic reaction and anaphylaxis, (b) respiratory tract reactivity including asthma, aggravated asthma, bronchospasm and dyspnoea, or (c) various skin reactions, including pruritis, urticaria, purpura, angioedema and, more rarely, severe forms of skin reactions such as exfoliative and bullous dermatoses (including toxic epidermal necrolysis can occur, Stevens-Johnson Syndrome and erythema multiforme).
3
The pathogenic mechanism of drug-induced aseptic meningitis is not fully understood. However, the available data suggest that NSAID- related meningitis develops in individuals rendered susceptible by an underlying autoimmune disorder who were previously sensitized or had a natural immunity to the drug. 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 and mixed connective tissue disease).

4
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 4.4).
5
The adverse events observed most often are gastrointestinal in nature.
6
Sometimes fatal, particularly in elderly.
7
See section 4.4.
8
Especially in long-term use, associated with increased serum urea and oedema. Also includes papillary necrosis.

9
Renal tubular acidosis and hypokalaemia have been reported in the post-marketing setting typically following prolonged use of the ibuprofen component at higher than recommended doses


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