Adverse reactions : תופעות לוואי

4.8     Undesirable effects
The most common observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation or GI bleeding, sometimes fatal in the elderly, may occur (see section 4.4). Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, abdominal distension, mouth ulcerations, 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

Hypersensitivity reactions have been reported following treatment with Ibuprofen. These may consist of;
a)     non-specific allergic reaction and anaphylaxis,
b)      Breathing: respiratory tract reactivity comprising of asthma, aggravated asthma, bronchospasm or dyspnoea,
Skin: assorted skin disorders, including rashes of various types, bruising pruritis, urticaria, purpura, angiodema and more rarely, exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).
c)      Very rarely, bullous reactions including Steven’s – Johnson syndrome and toxic epidermal necrolysis.

Clinical studies suggest that use of ibuprofen, particularly at a high dose (2400 mg/day) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke) (see section 4.4). Oedema, hypertension, angina pectoris and cardiac failure have been reported in association with NSAID treatment.

The following list of adverse effects relates to those experienced with ibuprofen and pseudoephedrine hydrochloride at OTC doses, for short-term use. In the treatment of chronic conditions, under long- term treatment, additional adverse effects may occur.
Patients should be informed that they should stop taking Advil Cold & Sinus immediately and consult a doctor if they experience a serious adverse drug reaction.








Infections and        Ibuprofen             Very rare     Exacerbation of infectious inflammations (e.g.
infestations                                              necrotizing fasciitis), Aseptic meningitis (stiffness of the neck, headache, nausea,
vomiting, fever or disorientation in patients with pre-existent autoimmune diseases (SLE, mixed connective tissue disease))


Blood and lymphatic   Ibuprofen             Very rare     Haematopoietic disorders (e.g. anaemia, system disorders                                          leucopenia, thrombocytopenia, pancytopenia, agranulocytosis)

Immune system         Ibuprofen             Uncommon      Hypersensitivity reactions with urticaria, disorders                                                 pruritus and asthma attacks (with drop in blood pressure)

Ibuprofen and         Very rare     Severe generalised hypersensitivity reactions, pseudoephedrine                     signs may be facial, oedema, angioedema, hydrochloride                       dyspnoea, tachycardia, drop in blood pressure, anaphylactic shock

Psychiatric           Ibuprofen             Very rare     Psychotic reactions, depression, nervousness.
disorders

Pseudoephedrine       Not known     Agitation, hallucination, anxiety, abnormal hydrochloride                       behaviour, insomnia, excitability, irritability, nervousness, restlessness
Nervous system       Ibuprofen         Uncommon    Central nervous system disturbances such as disorders                                          headache, dizziness, sleeplessness, agitation, irritability or tiredness


Ibuprofen         Not Known   Cerebrovascular accident (stroke)
Pseudoephedrine   Not known   Haemorhagic stroke, ischemic stroke,
hydrochloride                 convulsion, headache, insomnia, nervousness, anxiety, agitation, tremor, hallucinations,
dizziness, psychomotor hyperactivity.

Pseudoephedrine   Not known   Posterior reversible encephalopathy syndrome (PRES) (see section 4.4) Reversible cerebral vasoconstriction syndrome (RCVS) (see section
4.4)

Eye disorders        Ibuprofen         Uncommon    Visual disturbances 
Pseudoephedrine   Not known   Ischaemic optic neuropathy hydrochloride

Ear and labyrinth    Ibuprofen         Rare        Tinnitus disorders
Ibuprofen         Not known   Vertigo

Cardiac disorders    Ibuprofen         Very rare   Palpitations, heart failure, myocardial infarction, oedema, hypertention

Pseudoephedrine   Not known   Palpitations, tachycardia, chest pain, arrythmia hydrochloride

Vascular disorders   Ibuprofen         Very rare   Arterial hypertension 
Pseudoephedrine   Not known   Hypertension hydrochloride

Respiratory,         Pseudoephedrine   Rare        Exacerbation of asthma or hypersensitivity thoracic and         hydrochloride                 reaction with bronchospasm mediastinal disorders


Gastrointestinal     Ibuprofen         Common      Dyspepsia, abdominal pain, nausea, vomiting, disorders                                          flatulence, diarrhoea, constipation, anorexia, minor gastrointestinal blood loss in rare cases leading to anaemia

Ibuprofen         Uncommon    Gastric ulcer with bleeding and/or perforation, gastritis, ulcerous stomatitis, exacerbation of colitis and Crohn’s disease (see section 4.4)

Ibuprofen         Very rare   Oesophagitis, pancreatitis, intestinal diaphragm- like stricture

Pseudoephedrine   Not known   Dry mouth, thirst, nausea, vomiting, ischaemic hydrochloride                 colitis

Hepatobiliary        Ibuprofen         Very rare   Hepatic dysfunction, hepatic damage, disorders                                          particularly in long-term therapy, hepatic failure, acute hepatitis, jaundice
Skin and              Ibuprofen              Uncommon     Various skin rashes subcutaneous tissue disorders

Ibuprofen              Very rare    Bullous exanthema such as Stevens-Johnson syndrome, and toxic epidermal necrolysis
(Lyell syndrome), alopecia, severe skin infections, soft-tissue complications in a varicella infection


Ibuprofen              Not known    Angioedema, erythema multiforme, skin eruption, rash, purpura, pruritus, urticaria.
Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome).

Pseudoephedrine        Not known    Rash, urticaria, pruritus, hyperhidrosis.
hydrochloride

Pseudoephedrine                     Severe skin reactions, including acute hydrochloride          Not known    generalized exanthematous pustulosis (AGEP) 
Renal and Urinary     Ibuprofen              Rare         Kidney-tissue damage (papillary necrosis) and disorders                                                 elevated uric acid concentrations in the blood 
Ibuprofen              Very rare    Oedemas (particularly in patients with arterial hypertension or renal insufficiency), nephrotic syndrome, interstitial nephritis, acute renal insufficiency

Ibuprofen              Not known    Hematuria, renal failure, proteinuria, oliguria 
Pseudoephedrine        Not known    Difficulty in micturition (Urinary retention in hydrochloride                       men with urethra-prostatic disorders.) 
Investigations        Ibuprofen              Not Known    Haematocrit decreased and haemoglobin decreased

General disorders     Ibuprofen              Not known    Oedema, swelling, peripheral oedema and administration site conditions

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/
Healthcare professionals are asked to report any suspected adverse reactions to email: il.safety@gsk.com