Adverse reactions : תופעות לוואי

4.8 Undesirable effects

The following adverse events were seen during the clinical development of MultiHance.

System organ classes Clinical trials                                                          Post-marketing surveillance
Common             Uncommon               Rare                        Frequency (≥1/100, <1/10)    (≥1/1,000, <1/100)     (≥1/10,000, <1/1,000)       unknown** Immune system                                                     Anaphylactic                Anaphylactic disorders                                                         /anaphylactoid reaction,    shock Hypersensitivity reaction
Nervous system          Headache           Paraesthesia,          Convulsion, Syncope,        Loss of disorders                                  Hypoaesthesia,         Tremor, Parosmia            consciousness Dizziness, Taste perversion

Eye disorders                                                     Visual disturbance          Conjunctivitis 
Cardiac disorders                          Tachycardia, First-    Myocardial ischaemia,       Cardiac arrest, degree                 Bradycardia                 Cyanosis atrioventricular block
Vascular disorders                         Hypertension,
Hypotension,
Flushing
Respiratory, thoracic                                             Dyspnoea,                   Respiratory and mediastinal                                                   Laryngospasm,               failure, disorders                                                         Wheezing, Rhinitis,         Laryngeal Cough                       oedema,
Hypoxia,
Bronchospasm,
Pulmonary oedema
Gastrointestinal        Nausea           Diarrhoea, Vomiting, Faecal incontinence,         Oedema mouth disorders                                Abdominal pain       Salivary hypersecretion, Dry mouth
Skin & subcutaneous                      Pruritus, Rash       Face oedema                  Angioedema tissue disorders                         including erythematous rash,
macular, maculo- papular and papular rash, Urticaria,
Sweating increased

Musculoskeletal,                                                Myalgia connective tissue and bone disorders

Renal and urinary                        Proteinuria disorders
General disorders and Injection Site     Chest pain, Pyrexia,   Asthenia, Malaise, Chills Injection site administration site   Reaction           Feeling hot.                                     swelling conditions            including injection site pain,
inflammation,
burning, warmth,
coldness,
discomfort,
erythema,
paraesthesia and pruritus.
Investigations                           Electrocardiogram     Blood albumin abnormalities*,       decreased, Alkaline
Blood bilirubin       phosphatase increased increased, Blood iron increased, Increases in serum transaminases,
gamma-glutamyl- transferase, lactic dehydrogenase and creatinine
* Electrocardiogram abnormalities include electrocardiogram QT prolonged, electrocardiogram QT shortened, electrocardiogram T wave inversion, electrocardiogram PR prolongation, electrocardiogram QRS complex prolonged.
** Since the reactions were not observed during clinical trials with 4,956 subjects, best estimate is that their relative occurrence is rare (≥ 1/10,000 to <1/1000).
The most appropriate MedDRA (version 16.1) term is used to describe a certain reaction and its symptoms and related conditions.

Laboratory findings were mostly seen in patients with evidence of pre-existing impairment of hepatic function or pre-existing metabolic disease.

The majority of these events were non-serious, transient and spontaneously resolved without residual effects. There was no evidence of any correlation with age, gender or dose administered.

As with other gadolinium-chelates, there were reports of anaphylactic/ anaphylactoid/ hypersensitivity reactions. These reactions manifested with various degrees of severity up to anaphylactic shock and death, and involved one or more body system, mostly respiratory, cardiovascular, and/or mucocutaneous systems.

In patients with history of convulsion, brain tumours or metastasis, or other cerebral disorders, convulsions have been reported after MultiHance administration (see section 4.4 Special warnings and precautions for use).

Injection site reactions due to extravasation of the contrast medium leading to local pain or burning sensations, swelling, blistering and, in rare cases when localised swelling is severe, necrosis have been reported.

Localised thrombophlebitis has also been rarely reported (see section 4.4 Special warnings and precautions for use).
Isolated cases of nephrogenic systemic fibrosis (NSF) have been reported with MultiHance in patients co-administered other gadolinium-containing contrast agents (see Section 4.4).

Paediatric population

Adverse Reactions
Clinical Trials
System Organ Class
Common                              Uncommon
(≥1/100 to <1/10)                   (≥1/1000 to <1/100)
Nervous system disorders                                           Dizziness Eye disorders                                                      Eye pain, Eyelid oedema
Vascular disorders                                                 Flushing Gastrointestinal disorders     Vomiting                            Abdominal pain Skin and subcutaneous                                              Rash, tissue disorders                                                   Sweating increased                                Adverse Reactions
Clinical Trials
System Organ Class
Common                             Uncommon
(≥1/100 to <1/10)                  (≥1/1000 to <1/100)
General disorders and                                             Chest pain, administration site                                               Injection site pain, conditions                                                        Pyrexia The adverse reactions reported among paediatric patients treated with MultiHance during clinical trials and tabulated above were non-serious. The adverse reactions identified during post-marketing surveillance indicate that MultiHance safety profile is similar in children and adults.

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 http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic@moh.go v.il