Adverse reactions : תופעות לוואי

4.8.    Undesirable effects
During clinical studies on 905 patients, 11% of patients experienced an adverse reaction related to administration of XENETIX (apart from feeling of warmth), the most common being pain, injection site pain, bad taste in the mouth and nausea.
Adverse reactions related to the use of XENETIX are generally mild to moderate, and transient.
The adverse reactions most commonly reported during administration of XENETIX since marketing are a feeling of warmth, and pain and oedema at the injection site.
Hypersensitivity reactions are usually immediate (during the injection or over the hour following the start of the injection) or sometimes delayed (one hour to several days after the injection), and then appear in the form of adverse skin reactions.
Immediate reactions comprise one or several, successive or concomitant effects, usually including skin reactions, respiratory and/or cardiovascular disorders, which may be the first signs of shock, and can be fatal in rare cases.
Severe heart rhythm disorders including ventricular fibrillation have been very rarely reported in heart disease patients, and outside the context of hypersensitivity (see Section 4.4 Precaution for use).
The adverse reactions are listed in the table below by SOC (System Organ Class) and by frequency with the following guidelines: very common (1/10), common (1/100 to <1/10), uncommon (1/1,000 to <1/100), rare (1/10 000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data). The frequencies presented are from the data of an observational study on 352,255 patients.


System Organ Class               Frequency: adverse reaction
Immune system disorders          Rare: hypersensitivity
Very rare: anaphylactic shock, anaphylactoid reaction, anaphylactic reaction
Endocrine disorders              Very rare: thyroid disorders
Not known: transient neonatal hypothyroidism,
hypothyroidism***
Nervous system disorders         Rare: presyncope (vasovagal reaction), tremor*, paresthesia*
Very rare: coma*, convulsions*, confusion*, visual disorders*, amnesia*, photophobia*, transient blindness*, drowsiness *, agitation*, headache
Not known: dizziness**
Ear and labyrinth disorders      Rare: dizziness
Very rare: hearing impaired

Cardiac disorders                Rare: tachycardia, bradycardia
Very rare: cardiac arrest, myocardial infarction (more frequent after intracoronary injection), arrhythmia,
ventricular fibrillation, angina pectoris, Torsades de
Pointes, coronary arteriospasm
Vascular disorders               Rare: arterial hypotension (low blood pressure), high blood pressure
Very rare: circulatory collapse
Not known: cyanosis**
Respiratory, thoracic and        Rare: dyspnoea, cough, tightness in the throat, mediastinal disorders            sneezing
Very rare: respiratory arrest, pulmonary oedema,
bronchospasm, laryngospasm, laryngeal oedema
Gastrointestinal disorders       Uncommon: nausea
Rare: vomiting
Very rare: abdominal pain
Skin and subcutaneous tissue     Rare: angioedema, urticaria (localised or extensive), disorders                        erythema, pruritus
Very rare: Acute Generalized Exanthematous
Pustulosis, Stevens-Johnson syndrome, Lyell's syndrome, eczema, maculopapulous exanthema (all as delayed hypersensitivity reactions) (see Section
4.4)
Undetermined frequency: systemic drug hypersensitivity syndrome with eosinophilia (DRESS) and systemic symptoms (see Section 4.4).

Renal and urinary disorders      Very rare: acute renal insufficiency, anuria 
General disorders and            Uncommon: feeling of warmth administration site conditions   Rare: facial oedema, malaise, chills, injection site pain

Very rare: injection site necrosis following extravasation, injection site inflammation following extravasation, injection site oedema
Investigations                    Very rare: blood creatinine increased 
*Examinations during which the iodinated contrast agent concentration in cerebral arterial blood is high.
**Effect most often reported in the context of a hypersensitivity reaction.
***Transient hypothyroidism has been reported in younger children after exposure to iodine-based contrast agents (see Section 4.4)

As described in Section 4.4, compartment syndrome may be observed after extravasation.

The following adverse reactions were reported for other water-soluble iodinated contrast agents:

System Organ Class                 Frequency: adverse reaction
Nervous system disorders
Paralysis, paresis, speech disorders

Psychiatric disorders
Hallucinations
Gastrointestinal disorders
Acute pancreatitis (after ERP), abdominal pain,
diarrhoea, parotid gland enlargement, salivary hypersecretion, dysgeusia
Skin and subcutaneous tissue       Erythema multiforme disorders
Vascular disorders                 Thrombophlebitis
Investigations                    abnormal electroencephalogram, blood amylase increased
Cardiovascular collapse of variable severity may occur immediately with no warning signs or may complicate the cardiovascular symptoms mentioned in the above table.
Abdominal pain and diarrhoea, not reported for XENETIX, are linked mainly to administration via the oral or rectal route.
Local pain and oedema may occur at the injection site without extravasation of the injected product and are benign and transient.
During intra-arterial administration, the sensation of pain at the injection site depends on the osmolality of the product injected.

Paediatric population

The expected nature of the undesirable effects related to Xenetix is the same as that of the effects reported in adults. Their frequency cannot be estimated from the available data.


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