Adverse reactions : תופעות לוואי

4.8     Undesirable effects
General (applies to all uses of iodinated contrast media)
Below are listed possible general side effects in relation with radiographic procedures, which include the use of non-ionic monomeric contrast media. For side effects specific to mode of administration, please refer to these specific sections.

Hypersensitivity reactions may occur irrespective of the dose and mode of administration and mild symptoms may represent the first signs of a serious anaphylactoid reaction/shock.
Administration of the contrast medium must be discontinued immediately and, if necessary, specific therapy instituted via the vascular access.

A transient increase in S-creatinine is common after iodinated contrast media, contrast induced nephropathy may occur.

Iodism or “iodide mumps” is a very rare complication of iodinated contrast media resulting in swelling and tenderness of the salivary glands for up to approximately 10 days after the examination.

The listed frequencies are based on internal clinical documentation and published large scale studies, comprising more than 200,000 patients.

The frequencies of undesirable effects are defined as follows:

OMNIPAQUE     Injection X-ray contrast medium
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) and not known (cannot be estimated from the available data)

Immune system disorders:
Rare: Hypersensitivity (may be life-threatening or fatal),including dyspnoea, rash, erythema, urticaria, pruritus, skin reaction, conjunctivitis, coughing, rhinitis, sneezing, vasculitis, angioedema, laryngeal oedema, laryngospasm, bronchospasm or non- cardiogenic pulmonary oedema. They may appear either immediately after the injection and may be indicative of the beginning of a state of shock. Hypersensitivity related skin reactions may appear up to a few days after the injection.
Very rare: Anaphylactic/anaphylactoid reaction (may be life-threatening or fatal) Not known: Anaphylactic/anaphylactoid shock (may be life-threatening or fatal) 
Nervous system disorders:
Uncommon: Headache
Very rare: Dysgeusia (transient metallic taste),syncope vasovagal

Cardiac disorders:
Rare: Bradycardia
Vascular disorders:
Very rare: Hypertension, hypotension

Gastrointestinal disorders:
Uncommon: Nausea
Rare: Vomiting, abdominal pain
Very rare: Diarrhoea
Not known: Salivary gland enlargement

General disorders and administration site conditions:
Common: Feeling hot
Uncommon: Hyperhidrosis, cold feeling, vasovagal reactions
Rare: Pyrexia
Very rare: Shivering (chills)
Injury, poisoning and procedural complications:
Not known: Iodism

Intravascular use (Intraarterial and Intravenous use)
Please first read the section labelled "General". Below, only undesirable events with frequency during intravascular use of nonionic monomeric contrast media are described.

The nature of the undesirable effects specifically seen during intra-arterial use depends on the site of injection and dose given. Selective arteriographies and other procedures in which the contrast medium reaches a particular organ in high concentrations may be accompanied by complications in that particular organ.

Blood and lymphatic system disorders:
Not known: Thrombocytopenia

Endocrine disorders:
OMNIPAQUE     Injection X-ray contrast medium
Not known: Thyrotoxicosis, transient hypothyroidism

Psychiatric disorders:
Not known: Confusion, agitation, restlessness, anxiety

Nervous system disorders:
Rare: Dizziness, paresis, paralysis, photophobia, somnolence
Very rare: Seizures, disturbance in consciousness, cerebrovascular accident, stupor, sensory abnormalities (including hypoaesthesia), paraesthesia, tremor.
Not known: Transient motor dysfunction (including speech disorder, aphasia, dysarthria), transient contrast induced encephalopathy (including transient memory loss, disorientation, coma, retrograde amnesia, hemiparesis, and brain oedema.)

Eye disorders:
Rare: Visual impairment (including diplopia, blurred vision)
Not known: Transient cortical blindness

Ear and labyrinth disorders:
Not known: Transient hearing loss
Cardiac disorders:
Rare: Arrhythmia (including bradycardia, tachycardia).
Very rare: myocardial infarction, chest pain
Not known: Severe cardiac complications (including cardiac arrest, cardio-respiratory arrest), cardiac failure, spasm of coronary arteries, cyanosis

Vascular disorders:
Very rare: Flushing
Not known: Shock, arterial spasm, thrombophlebitis and venous thrombosis 
Respiratory, thoracic and mediastinal disorders:
Common: Transient changes in respiratory rate, respiratory distress Rare: Cough, respiratory arrest
Very rare: Dyspnoea
Not known: Severe respiratory symptoms and signs, pulmonary oedema, acute respiratory distress syndrome, bronchospasm, laryngospasm, apnoea, aspiration asthma attack

Skin and subcutaneous tissue disorders:
Rare: Rash, pruritus, urticaria
Not known: Bullous dermatitis, Stevens-Johnson syndrome,, toxic epidermal necrolysis, acute generalised exanthematous pustulosis, drug rash with eosinophilia and systemic symptoms, psoriasis flare-up, erythema, drug eruption, skin exfoliation.

Gastrointestinal disorders:
Rare: Diarrhoea
Not known: Aggravation of pancreatitis

Musculoskeletal and connective tissue disorders:
Not known: Arthralgia, muscular weakness, musculoskeletal spasm, back pain 
Renal and urinary disorders:
Uncommon: Acute kidney injury
OMNIPAQUE     Injection X-ray contrast medium
Not known: Blood creatinine increased

General disorders and administration site conditions:
Uncommon: Pain and discomfort
Rare: Asthenic conditions (including malaise, fatigue).
Not known: Administration site reactions, including extravasation
Injury, poisoning and procedural complications:
Not known: Iodism

Intrathecal use
Please first read the section labelled "General". Below, only undesirable events with frequency during intrathecal use of nonionic monomer contrast media are described.

Undesirable effects following intrathecal use may be delayed and present some hours or even days after the procedure. The frequency is similar to lumbar puncture alone.
Headache, nausea, vomiting or dizziness may largely be attributed to pressure loss in the sub-arachnoid space resulting from leakage at the puncture site. Excessive removal of cerebrospinal fluid should be avoided in order to minimize pressure loss.

Psychiatric disorders:
Not known: Confusion, agitation, anxiety

Nervous system disorders:
Very common: Headache (may be severe and prolonged)
Uncommon: Aseptic meningitis (including chemical meningitis).
Rare: Seizures, dizziness
Not known: Electroencephalogram abnormal, meningism, status epilepticus, transient contrast-induced encephalopathy (including transient memory loss, coma, stupor, retrograde amnesia, hemiparesis), motor dysfunction (including speech disorder, aphasia, dysarthria), paraesthesia, hypoesthesia and sensory disturbance

Eye disorders:
Rare: Visual impairment (including diplopia and blurred vision)
Not known: Transient cortical blindness, photophobia

Ear and labyrinth disorders:
Not known: Transient hearing loss
Gastrointestinal disorders:
Common: Nausea, vomiting

Musculoskeletal and connective tissue disorders:
Rare: Neck pain, back pain
Not known: Muscle spasm

General disorders and administration site conditions:
Rare: Pain in extremity
Not known: Administration site conditions
Use in Body Cavities
Please first read the section labelled "General". Below, only undesirable events with frequency during use of non-ionic monomeric contrast media in body cavities are described.

OMNIPAQUE     Injection X-ray contrast medium

Endoscopic Retrograde Cholangiopancreatography (ERCP):
Gastrointestinal disorders:
Common: Pancreatitis, blood amylase increased
Oral use:
Gastrointestinal disorders:
Very common: Diarrhoea
Common: Nausea, vomiting
Uncommon: Abdominal pain

Hysterosalpingography (HSG):
Gastrointestinal disorders:
Very common: Lower abdominal pain

Arthrography:
Musculoskeletal and connective tissue disorders:
Not known: Arthritis
General disorders and administration site conditions:
Very common: Pain

Herniography:
General disorders and administration site conditions:
Not known: Post procedural pain

Description of selected adverse reactions
Thrombo-embolic complications have been reported in connection with contrast- enhanced angiography of coronary, cerebral, renal and peripheral arteries. The contrast agent may have contributed to the complications (see section 4.4).

Cardiac complications including acute myocardial infarction have been reported during or after contrast-enhanced coronary angiography. Elderly patients or patients with severe coronary artery disease, unstable angina pectoris and left ventricular dysfunction had a higher risk (see section 4.4).

In very rare occasions the contrast medium may cross the blood-brain barrier resulting in uptake of contrast medium in the cerebral cortex that may cause neurological reactions. They may include convulsions, transient motor or sensory disturbances, transient confusion, transient memory loss, and encephalopathy (see section 4.4).

Anaphylactoid reaction and anaphylactoid shock may lead to profound hypotension and related symptoms and signs like hypoxic encephalopathy, renal and hepatic failure (see section 4.4).
In several cases, extravasation of contrast media has caused local pain and oedema, which usually receded without sequelae. Inflammation, tissue necrosis and compartment syndrome have occurred (see section 4.4).

Paediatric patients:

Transient hypothyroidism has been reported in premature infants, neonates and in other children after administration of iodinated contrast media. Premature infants are OMNIPAQUE    Injection X-ray contrast medium particularly sensitive to the effect of iodine. Transient hypothyroidism in a premature breast fed infant has been reported. The nursing mother was repeatedly exposed to Omnipaque (see section 4.4).
Especially in infants and small children, adequate hydration should be assured before and after contrast media administration. Nephrotoxic medication should be suspended. The age dependent reduced glomerular filtration rate in infants can also result in delayed excretion of contrast agents.

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