Adverse reactions : תופעות לוואי

4.8.    Undesirable effects
Side effects in association with the use of gadoteric acid are usually mild to moderate in intensity and transient in nature. Injection site reactions, nausea and headache are the most frequently observed reactions.
During clinical trials, nausea, headache, injection site reactions, feeling cold, hypotension, somnolence, dizziness, feeling hot, burning sensation, rash, asthenia, dysgeusia and hypertension were the most frequent, uncommon (≥1/1000 to <1/100) adverse reactions.
Post-marketing the most commonly reported adverse reactions following administration of gadoteric acid have been nausea, vomiting, pruritus, and hypersensitivity reactions.
ln hypersensitivity reactions, the reactions most frequently observed are skin reactions, which can be localised, extended or generalised. These reactions occur most often immediately (during the injection or within one hour after start of the injection) or sometimes delayed (one hour to several days after injection), presenting as skin reactions skin in this case.
Immediate reactions include one or more effects, which appear simultaneously or sequentially, and are most often cutaneous, respiratory gastrointestinal, joint and/or cardiovascular reactions.
Each sign maybe a warning sign of shock and may very rarely lead to death.
Isolated cases of nephrogenic systemic fibrosis (NSF) have been reported with gadoteric acid, most of which were in patients co-administered other gadolinium-containing contrast agents (see section 4.4).

The adverse reactions are listed in the table below by SOC (system organ class) and by frequency according to the following categories: very common (≥1/10), common (≥1/100 to 1<1/10), uncommon (≥1/1 000 to 1<1/100), rare (≥1/10 000 to <1/1,000), very rare (<1/10,000), undetermined frequency (cannot be estimated on the basis of available data). The data presented are from clinical trials involving 2822 patients when available, or from a pool of observational studies involving 185,500 patients


System Organ Class                                  Frequency: adverse reaction Immune system disorders                             Uncommon: hypersensitivity Very rare: anaphylactic reaction, anaphylactoid reaction
Psychiatric disorders                               Rare: anxiety
Very rare: agitation
Nervous system disorders                            Uncommon: headache dysgeusia, dizziness drowsiness, paraesthesia (including burning sensation)
Rare: presyncope
Very rare: coma, convulsion, , syncope, , , parosmia,
tremor
Eye disorders                                       Rare: eyelid oedema Very rare: conjunctivitis, ocular hyperaemia, blurred vision, excess tears
Cardiac disorders                                   Rare: palpitations Very rare: cardiac arrest, bradycardia, tachycardia,
arrhythmia
Vascular disorders                                  Uncommon: hypotension, hypertension Very rare: vasodilatation, pallor
Respiratory, thoracic and mediastinal disorders     Rare: sneezing
Very rare: respiratory arrest, pulmonary oedema,
bronchospasm, laryngospasm, pharyngeal oedema,
dyspnoea, nasal congestion, cough, dry throat
Gastrointestinal disorders                           Uncommon: nausea, abdominal pain Very rare: vomiting diarrhoea, salivary hypersecretion
Skin and subcutaneous tissue disorders              Uncommon: rash
Rare: urticaria, pruritus, hyperhidrosis
Very rare: erythema, angioedema, eczema
Not known: nephrogenic systemic fibrosis
Musculoskeletal and connective tissue disorders     Very rare: muscle cramps, muscular weakness, back pain
General disorders and administration site            Uncommon: feeling hot, feeling cold, asthenia, injection conditions                                          site reactions (extravasation, pain, discomfort, oedema, inflammation, coldness)
Rare: chest pain, chills
Very rare: malaise, chest discomfort, pyrexia, face oedema , injection site necrosis (in case of extravasation), phlebitis superficial
Investigations                                      Very rare: decreased oxygen saturation 


The following adverse reactions have been reported with other intravenous contrast agents for MRI: 
System Organ Class                                  Adverse reaction
Blood and lymphatic system disorders                Haemolysis
Psychiatric disorders                               Confusion
Eye disorders                                       Blindness transient, eye pain Ear and labyrinth disorders                         Tinnitus, ear pain Respiratory, thoracic and mediastinal disorders     Asthma
Gastrointestinal disorders                          Dry mouth
Skin and subcutaneous tissue disorders              Dermatitis bullous Renal and urinary disorders                         Urinary incontinence, renal tubular necrosis, acute renal failure
Investigations                                      Electrocardiogram PR prolongation, blood iron increased, blood bilirubin increased, serum ferritin

increased, liver function test abnormal

Adverse reactions in children
Safety of paediatric patients was considered in clinical trials and post-marketing studies. As compared to adults, the safety profile of gadoteric acid did not show any specificity in children. The most common reactions are gastrointestinal symptoms or signs of hypersensitivity.


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/ And emailed to the Registration Holder’s Patient Safety Unit at: drugsafety@neopharmgroup.com