Adverse reactions : תופעות לוואי

4.8.   Undesirable effects

Adverse drug reactions (ADRs) that occurred after administration of Cernevit are presented with their relative frequencies; these include ADRs documented in clinical trials and those from post-marketing reports. Cernevit was administered during 3 clinical trials to 267 adult patients requiring a parenteral vitamin supplement.
Frequencies of ARs are reported, using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10000 to <1/1000); very rare (<1/10000); and unknown (cannot be estimated from the available data).

Clinical Trial and Post-Marketing Adverse Drug Reactions Reported for Cernevit:

System Organ Class                        Preferred MedDRA Term                                                    Frequency1 Immune system disorders                   Systemic hypersensitivity reactions with                                 Unknown manifestations such as respiratory distress,
chest discomfort, throat tightness, urticaria,
rash, erythema, epigastric discomfort, as well as cardiac arrest with fatal outcome
Metabolism and nutrition                  Vitamin A increased2,3,                                                  Unknown disorders                                 Retinol binding protein increased                                        Unknown Nervous system disorders                  Dysgeusia (metallic taste)                                               Unknown Cardiac disorders                         Tachycardia                                                              Unknown Respiratory, thoracic and                 Tachypnea                                                                Unknown mediastinal disorders
Gastrointestinal disorders                Nausea                                                                   Uncommon Vomiting                                                                 Uncommon Diarrhoea                                                                Unknown Hepatobiliary disorders                   Transaminases increased,                                                 Unknown Isolated alanine aminotransferase increased4,                            Unknown Glutamate dehydrogenase increased,                                       Unknown Blood alkaline phosphatase increased,                                    Unknown Bile acids increased5                                                    Unknown Gamma-glutamyltransferase increased                                      Unknown Skin and subcutaneous                     Pruritus                                                                 Unknown tissue disorders
General disorders and                     Injection/Infusion Site Pain                                             Common administration site                       Pyrexia,                                                                 Unknown conditions                                Generalized aching,                                                      Unknown infusion site reactions, i.e., burning                                   Unknown sensation, rash



1
The frequency either cannot be determined or the overall number of patients in the individual studies is too small to permit a valid estimation of frequency.
2
No symptoms of hypervitaminosis A were reported
3
Elevated plasma vitamin A levels have been reported in 8 of 20 patients receiving Cernevit in parenteral nutrition at day 45 of administration. From day 45 to day 90 of product administration the high values of vitamin A remained stable (maximum observed value of 3.6 µmol/L at day 90; normal values: 1 to 2.6 µmol/L). In addition, an average increase in retinol binding protein (RBP) was also identified.
A maximum observed RBP value of 60 mg/L at day 90 (normal values: 30 to 50 mg/L), was reported.
4
Isolated alanine aminotransferase increases was reported in the presence of inflammatory bowel disease. Cernevit was administered by intravenous injection in the absence of parenteral nutrition.
5
An increase in total and individual bile acids including glycocholic acid has been reported to develop early in the course of parenteral nutrition administration in patients receiving Cernevit.
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