Adverse reactions : תופעות לוואי

4.8      Undesirable effects

Adverse events from historical clinical trial data are both infrequent and from small patient exposure. Accordingly, events reported from extensive post- marketing experience at therapeutic/labelled dose and considered attributable are tabulated below by system. The following convention has been utilised for the classification of undesirable effects: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1,000, <1/100), rare (≥1/10,000, 363 <1/1000), very rare (<1/10,000), not known (cannot be estimated from available data).

Paracetamol

Body System                      Undesirable effect                           Frequency Blood and lymphatic              Thrombocytopenia
Not known system disorders                 Agranulocytosis
Immune         system            Anaphylaxis                                  Not known disorders                        Allergies    (not           including Rare angioedema)
Respiratory, thoracic and
Bronchospasm*                                       Not known mediastinal disorders
Hepatobiliary disorders   Hepatic dysfunction                                 Not known Cutaneous         hypersensitivity reactions including skin rashes,
Very rare pruritus, sweating, purpura,
urticaria and angioedema


                                           Very rare cases of serious skin
Skin and subcutaneous            reactions have been reported.
tissue disorders                 Stevens Johnson syndrome(SJS),
toxic epidermal necrolysis(TEN),              Very rare drug-induced dermatitis, acute generalized exanthematous pustulosis (AGEP)
Renal     and        urinary disorders                        Sterile pyuria (cloudy urine)                 Very rare 

* There have been cases of bronchospasm with paracetamol, but these are more likely in asthmatics sensitive to aspirin or other NSAIDs.

Caffeine
Body System            Undesirable effect Frequency                          Frequency 
Central nervous           Nervousness                Not known                Not known system                    Dizziness

When the recommended paracetamol-caffeine-codeine dosing regimen is combined with dietary caffeine intake, the resulting higher dose of caffeine may increase the potential for caffeine-related adverse effects such as insomnia, restlessness, anxiety, irritability, headaches, gastrointestinal disturbances and palpitations.

Codeine
Adverse reactions identified during post-marketing use are listed below by MedDRA system organ class. The frequency of these reactions is not known.
Body System         Undesirable effect                          Frequency Drug dependency can occur
Psychiatric         after prolonged use of codeine (see         Not known disorders           section 4.4)
Constipation, nausea, vomiting,
Gastrointestinal    dyspepsia, dry mouth, acute                 Not known disorder            pancreatitis
Dizziness,
Nervous system      Hyperalgesia                                Not known disorder            Drowsiness.
General disorder Drug withdrawal syndrome                    Uncommon s          and administration
Renal     and urinary Difficulty with micturition                      Not disorders                                                        known Skin and subcutaneo Pruritus, sweating                               Not us                                                               known tissue disorder


          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.