Adverse reactions : תופעות לוואי

4.8 Undesirable effects
The list of the following undesirable effects comprises all undesirable effects that have become known under treatment with ibuprofen, also those under high-dose long-term therapy in rheumatism patients. The stated frequencies, which extend beyond very rare reports, refer to the short-term use of daily doses up to a maximum of 1200 mg ibuprofen for oral dosage forms and a maximum of 1800 mg for suppositories.

With the following adverse drug reactions, it must be accounted for that they are predominantly dose-dependent and vary inter-individually.

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: ≥ 1/1,000 to < 1/100          Rare: ≥ 1/10,000 to < 1/1,000 Very rare: < 1/10,000                   Not known: cannot be estimated from the available data

Within each frequency grouping, adverse events are presented in order of decreasing seriousness.

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 which is dependent on the dose range and duration of treatment. Peptic ulcers, perforation or GI bleeding, sometimes fatal, particularly in the elderly, may occur (see section 4.4). Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn’s disease (See section 4.4) have been reported following administration. Less frequently, gastritis has been observed.

Oedema, hypertension and cardiac failure have been reported in association with NSAID treatment.

Clinical studies suggest that use of ibuprofen, particularly at high dose (2400 mg daily), may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke) (see section 4.4).

Exacerbation of infection-related inflammations (e.g development of necrotizing fasciitis) coinciding with the use of nonsteroidal anti-inflammatory drugs has been described. This is possibly associated with the mechanism of action of the nonsteroidal anti-inflammatory drugs.

If signs of an infection occur or get worse during use of Nurofen Forte for Children Strawberry or Orange 40mg/1ml suspension, the patient is recommended to go to a doctor without delay. It is to be investigated whether there is an indication for an antimicrobial/antibiotic therapy.

The blood count should be checked regularly in long-term therapy.
The patient is to be instructed to inform a doctor at once and no longer to take Nurofen Forte for Children Strawberry or Orange 40mg/1ml suspension if one of the symptoms of hypersensitivity reactions occurs, which can happen even on first use, the immediate assistance of a doctor is required.

The patient is to be instructed to withdraw the medicinal product and to go to a doctor immediately if severe pain in the upper abdomen or melaena or haematemesis occurs.

System organ class            Frequency        Adverse Event

Exacerbation of infections related inflammation (e.g development of necrotizing fasciitis), in exceptional
Infections and infestations   Very rare cases, severe skin infections and soft-tissue complications may occur during a varicella infection

Haematopoietic disorders (anaemia,
leucopenia, thrombocytopenia,
pancytopenia, agranulocytosis).
First signs are: fever, sore throat,
superficial mouth ulcers, flu-like symptoms, severe exhaustion, nose
Blood and Lymphatic
Very rare        and skin bleeding and bruising. In system disorders such cases, the patient should be advised to discontinue this medicinal product, to avoid any self- medication with analgesics or antipyretics and to consult a physician.

Hypersensitivity reactions consisting
Uncommon         of 1:
Urticaria and pruritus


Severe hypersensitivity reactions.
Symptoms could be: facial, tongue
Immune System                                  and laryngeal swelling, dyspnoea, Very rare
Disorders                                      tachycardia, hypotension (anaphylaxis, angioedema or severe shock). Exacerbation of asthma.


Respiratory tract reactivity
Not known        comprising asthma, bronchospasm or dyspnoea.
Psychiatric disorders
Very rare        Psychotic reactions, depression
Uncommon
Central nervous disturbances such as headache, dizziness,
sleeplessness, agitation, irritability
Nervous System or tiredness
Disorders
Aseptic meningitis2
Very Rare

Eye disorders                Uncommoon   Visual disturbances

Ear and labyrinth
Rare        Tinnitus disorders
Cardiac failure, palpitations and
Cardiac Disorders            Very Rare oedema, myocardical infarction


Vascular Disorders           Very Rare   Hypertension, vasculitis 

Gastrointestinal complaints such as abdominal pain, nausea and dyspepsia, diarrhoea, flatulence,
Common      constipation, heartburn, vomiting and slight gastro-intestinal blood losses that may cause anaemia in exceptional cases.
Gastrointestinal Disorders
Gastrointestinal ulcers, perforation or GI bleeding, ulcerative stomatitis,
Uncommon exacerbation of colitis and Crohn’s disease (see section 4.4), gastritis.


Oesophagitis and formation of
Very Rare   intestinal diaphragm-like strictures,
pancreatitis.

Hepatic dysfunction, hepatic damage, particularly in long-term
Hepatobiliary Disorders      Very Rare theapy, hepatic failure, acute hepatitis.

Uncommon    Various skin rashes


Skin and Subcutaneous                    Severe forms of skin reactions such Tissue Disorders                         as bullous reactions including Very Rare   Stevens-johnson syndrome,
erythema multiforme and toxic epidermal necrolysis, alopecia
Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome)
Not known         Acute generalised exanthematous pustulosis (AGEP)

Photosensitivity reactions

Kidney-tissue damage (papillary
Renal and Urinary                           necrosis) and elevated urea Rare
Disorders                                   concentration in the blood may also occur rarely; elevated uric acid concentrations in the blood.
Formation of oedemas, particularly in patients with arterial hypertension or renal insufficiency, nephrotic
Very rare syndrome, interstitial nerphritis that may be accompanied by acute renal insufficiency.

Investigations            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 reaction and anaphlaxis, (b) respiratory tract activity comprising asthma, aggravated asthma, bronchospasm or dyspnoea, or (c) assorted skin disorders, including rashes of various types, pruritus, urticaria, purpura, angioedema and, more rarely, exfoliative and bullous dermatoses (including toxic epidermal necrolysis, Stevens Johnson Syndrome 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 an immune reaction (due to a temporal relationship with drug intake, and disappearance of symptoms after drug discontinuation). Single cases of symptoms of aseptic meningitis (such as stiff neck, headache, nausea, vomiting, fever or clouding of consciousness) have been observed during treatment with Ibuprofen in patients with existing autoimmune 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/