Adverse reactions : תופעות לוואי

4.8 Undesirable Effects
General
The use of iodinated contrast media may cause untoward side effects. They are usually mild to moderate and transient in nature. However, severe and life-threatening reactions sometimes leading to death have been reported. In most cases, reactions occur within minutes of dosing but at times reactions may occur at later time.

Anaphylaxis (anaphylactoid/hypersensitivity reactions) may manifest with various symptoms, and rarely does any one patient develop all the symptoms. Typically, in 1 to 15 min (but rarely after as long as 2 h), the patient complains of feeling abnormal, agitation, flushing, feeling hot, sweating increased, dizziness, increased lacrimation, rhinitis, palpitations, paresthesia, pruritus, sore throat and throat tightness, dysphagia, cough, sneezing, urticaria, erythema, mild localised oedema, angioneurotic oedema and dyspnoea due to glottic/laryngeal/ pharyngeal oedema and/or spasm manifesting with wheezing and bronchospasm.
Nausea, vomiting, abdominal pain, and diarrhoea are also reported.
These reactions, which can occur independently of the dose administered or the route of administration, may represent the first signs of circulatory collapse.
Administration of the contrast medium must be discontinued immediately and, if needed, appropriate specific treatment urgently initiated via venous access.
Severe reactions involving the cardiovascular system, such as vasodilatation, with pronounced hypotension, tachycardia, dyspnoea, agitation, cyanosis and loss of consciousness progressing to respiratory and/or cardiac arrest may result in death. These events can occur rapidly and require full and aggressive cardio-pulmonary resuscitation.
Primary circulatory collapse can occur as the only and/or initial presentation without respiratory symptoms or without other signs or symptoms outlined above.

The adverse reactions reported in clinical trials among 4,903 adult patients and from post-marketing surveillance are represented in the tables below by frequency and classified by MedDRA system organ class.
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

4.8.1 Intravascular administration

Adult patients involved in clinical trials with intravascular administration of Iomeprol were 4,739.
Adults

System Organ Class      Adverse Reactions
Clinical Trials                                                  Post-marketing Surveillance
Common               Uncommon                 Rare               Frequency unknown* (≥1/100 to <1/10)    (≥1/1000 to <1/100)      (≥1/10,000 to
<1/1000)
Blood and lymphatic                                                                      Thrombocytopenia system disorders                                                                         Haemolytic anaemia Immune system                                                                            Anaphylactoid reaction disorders
Endocrine disorders                                                                      Hyperthyroidism Psychiatric disorders                                                                    Anxiety Confusional state
Nervous system                               Headache                 Presyncope         Coma disorders                                    Dizziness                                   Transient ischaemic attack Paralysis
Syncope
Convulsion
Loss of consciousness
Dysarthria
Paresthesia
Amnesia
Somnolence
Taste abnormality
Contrast induced encephalopathy***
Eye disorders                                                                            Blindness transient Visual disturbance
Conjunctivitis
Lacrimation increased
Photopsia
Cardiac disorders                                                     Bradycardia        Cardiac arrest Tachycardia        Myocardial infarction
Extrasystoles      Cardiac failure
Angina pectoris
Arrhythmia
Ventricular or atrial fibrillation
Atrioventricular block
Palpitations
System Organ Class      Adverse Reactions
Clinical Trials                                                Post-marketing Surveillance
Common              Uncommon                Rare               Frequency unknown* (≥1/100 to <1/10)   (≥1/1000 to <1/100)     (≥1/10,000 to
<1/1000)
Vascular disorders                          Hypertension            Hypotension        Circulatory collapse or shock
Hot flush
Flushing
Pallor
Cyanosis
Coronary artery thrombosis
Coronary artery embolism
Vasospasm****
Ischemia****
Respiratory, thoracic                       Dyspnoea                                   Respiratory arrest and mediastinal                                                                        Acute respiratory distress disorders                                                                              syndrome (ARDS) Pulmonary oedema
Laryngeal oedema
Pharyngeal oedema
Bronchospasm
Asthma
Cough
Hyperventilation
Pharynx discomfort
Laryngeal discomfort
Rhinitis
Dysphonia
Gastrointestinal                            Nausea                                     Diarrhoea disorders                                   Vomiting                                   Abdominal pain Salivary hypersecretion
Dysphagia
Salivary gland enlargement
Skin and                                    Erythema                Rash               Acute generalized subcutaneous tissue                         Urticaria                                  exanthematous pustulosis disorders                                   Pruritus                                   Angioedema Cold sweat
Sweating increased
Stevens-Johnson’s syndrome
Toxic epidermal necrolysis
Erythema multiforme
Drug Reaction with
Eosinophilia and
Systemic Symptoms
Musculoskeletal and                                                 Back pain          Arthralgia connective tissue disorder
Renal and urinary                                                                      Renal failure***** disorders
General disorders       Feeling hot         Chest pain              Asthenia           Injection site reaction** and administration                          Injection site warmth   Rigors             Coldness local site conditions                             and pain                Pyrexia            Fatigue Malaise
Thirst
Investigations                                                      Blood creatinine   Electrocardiogram ST increased          segment elevation
System Organ Class     Adverse Reactions
Clinical Trials                                                    Post-marketing Surveillance
Common                 Uncommon                 Rare               Frequency unknown* (≥1/100 to <1/10)      (≥1/1000 to <1/100)      (≥1/10,000 to
<1/1000)
Electrocardiogram abnormal
* Since the reactions were not observed during clinical trials with 4,739 patients, best estimate is that their relative occurrence is rare ( ≥1/10,000 to <1/1000).

The most appropriate MedDRA term is used to describe a certain reaction and its symptoms and related conditions.

** Injection site reactions comprise injection site pain and swelling. In the majority of cases they are due to extravasation of contrast medium. These reactions are usually transient and result in recovery without sequelae. Cases of extravasation with inflammation, skin necrosis and even development of compartment syndrome have been reported.

***Encephalopathy may manifest with symptoms and signs of neurological dysfunction such as headache, visual disturbance, cortical blindness, confusion, seizures, loss of coordination, hemiparesis, aphasia, unconsciousness, coma, brain oedema.

**** Vasospasm and consequent ischaemia have been observed during intra-arterial injections of contrast medium, in particular after coronary and cerebral angiography often procedurally related and possibly triggered by the tip of the catheter or excess catheter pressure.

*****Transient renal failure with oliguria, proteinuria and an increase in serum creatinine may develop, particularly in patients with impaired renal function. In case of extravasal injection a tissue reaction may develop in rare cases.

Paediatric patients
There is limited experience with paediatric patients. The clinical trial paediatric safety database comprises 184 patients. The Iomeprol safety profile is similar in children and adults.

Transient hypothyroidism may occur in neonates, especially in preterm or low birth weight neonates, and children (0-3 years), when exposed to iomeprol.

4.8.2 Administration to body cavities
After injection of an iodinated contrast media in body cavities, contrast media are slowly absorbed from the area of administration into the systemic circulation and subsequently cleared by renal elimination.
Blood amylase increased is common following ERCP. Very rare cases of pancreatitis have been described.
The reactions reported in cases of arthrography and fistulography usually represent irritative manifestations superimposed on pre-existing conditions of tissue inflammation.
Hypersensitivity reactions are rare, generally mild and in the form of skin reactions. However, the possibility of severe anaphylactoid reactions cannot be excluded.

As with other iodinated contrast media, pelvic pain and malaise may occur after hysterosalpingography.

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