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 uncommon adverse reactions (≥ 1/1000 to < 1/100) were nausea, headache, injection site reactions, feeling cold, hypotension, somnolence, dizziness, feeling hot, burning sensation, rash, asthenia, dysgeusia and hypertension.
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 the start of injection) or sometimes delayed (one hour to several days after injection), presenting as skin reactions 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 may be 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, tremor, parosmia
Eye disorders                Rare: eyelid oedema
Very rare: conjunctivitis, ocular hyperaemia, blurred vision, excess tears Cardiac disorders            Rare: palpitations
Very rare: tachycardia, cardiac arrest, arrhythmia, bradycardia,
Vascular disorders           Uncommon: hypotension, hypertension
Very rare: pallor, vasodilatation
Respiratory, thoracic and    Rare: sneezing mediastinal disorders        Very rare: cough, dyspnoea, nasal congestion, respiratory arrest, bronchospasm, laryngospasm, pharyngeal oedema, dry throat, pulmonary oedema
Gastrointestinal disorders   Uncommon: nausea, abdominal pain
Rare: vomiting diarrhoea, salivary hypersecretion
Skin and subcutaneous        Uncommon: skin rash tissue disorders             Rare: urticaria, pruritus, hyperhidrosis Very rare: erythema, angioedema, eczema
Not known: nephrogenic systemic fibrosis
Musculoskeletal and          Very rare: muscle cramps, muscular weakness, back pain connective tissue disorders
General disorders and        Uncommon: feeling hot, feeling cold, asthenia, injection site reactions administration site          (extravasation, pain, discomfort, oedema, inflammation, coldness) conditions                   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