OMNIPAQUE Solution Ref.[9483] Active ingredients: Iohexol

Hydration: Adequate hydration should be assured before and after contrast media administration. This applies especially to patients with multiple myeloma, diabetes mellitus, renal dysfunction, as well as to infants, small children and elderly patients. Young infants (age<1 year) and especially neonates are susceptible to electrolyte disturbance and haemodynamic alterations.

Preventive measures include:

• Identification of high risk patients.
• Ensuring adequate hydration. If necessary by maintaining an i.v. infusion from before the procedure until the contrast medium has been cleared by the kidneys.
• Avoiding additional strain on the kidneys in the form of nephrotoxic drugs, oral cholecystographic agents, arterial clamping, renal arterial angioplasty, or major surgery, until the contrast medium has been cleared.
• Postponing a repeat contrast medium examination until renal function returns to preexamination levels.

Risk-benefit should be considered when the following medical problems exist:

Hypersensitivty to iohexol:

A positive history of allergy, asthma, or untoward reactions to iodinated contrast media indicates a need for special caution. Premedication with corticosteroids or histamine H₁ and H₂ antagonists might be considered in these cases.

The risk of serious reactions in connection with use of OMNIPAQUE is regarded as minor. However, iodinated contrast media may provoke anaphylactoid reactions or other manifestations of hypersensitivity. A course of action should therefore be planned in advance, with necessary drugs and equipment available for immediate treatment, should a serious reaction occur. It is advisable always to use an indwelling cannula or catheter for quick intravenous access throughout the entire X-ray procedure.

Contrast-medium induced nephrotoxicity:

Contrast medium induced nephrotoxicity is a condition in which impaired renal function (an increase in serum creatinine by more than 25% or 44 µmol/l) occurs within three days following the intravascular administration of a contrast medium in the absence of an alternative aetiology. Dialysis has been used in the prevention of contrast medium induced nephropathy.

Prevention of nephropathy – haemodialysis:

Patients on haemodialysis may receive contrast media for radiological procedures. If clinically indicated, haemodialysis is an effective method for eliminating iodinated contrast medium from the body. Correlation of the time of contrast media injection with the haemodialysis session is unnecessary, because there is no evidence that haemodialysis protects patients with impaired renal function from contrast medium induced nephropathy. The patient should not be re-exposed to contrast media before the kidney function has returned to its previous function. If contrast medium is to be given again, the patient must be adequately hydrated.

Pre-existing renal impairment and diabetes mellitus:

To prevent acute renal failure following contrast media administration, special care should be exercised in patients with pre-existing renal impairment and diabetes mellitus as they are at risk.

To prevent lactic acidosis, serum creatinine level should be measured in diabetic patients treated with metformin prior to intravascular administration of iodinated contrast medium.

Normal serum creatinine/renal function: Administration of metformin should be stopped at the time of administration of contrast medium and not resumed for 48 hours or until renal function/serum creatinine is normal.

Abnormal serum creatinine/renal function: Metformin should be stopped and the contrast medium examination delayed for 48 hours. Metformin should only be restarted if renal function/serum creatinine is unchanged. In emergency cases where renal function is abnormal or unknown, the physician should evaluate the risk/benefit of the contrast medium examination, and precautions should be implemented: Metformin should be stopped, patient hydrated, renal function monitored and patient observed for symptoms of lactic acidosis.

Severe renal or hepatic impairment:

A potential risk of transient hepatic dysfunction exists. Particular care is required in patients with severe disturbance of both renal and hepatic function, as they may have significantly delayed contrast medium clearance.

Severe cardiovascular disease or congestive heart failure: Care should also be taken in patients with serious cardiac disease and pulmonary hypertension as they may develop haemodynamic changes or arrhythmias.

History of seizures:

Patients with acute cerebral pathology, tumours or a history of epilepsy are predisposed for seizures and merit particular care. Also alcoholics and drug addicts have an increased risk for seizures and neurological reactions.

A few patients have experienced a temporary hearing loss or even deafness after myelography, which is believed to be due to a drop in spinal fluid pressure by the lumbar puncture per se. This also applies to elderly patients who are at increased risk of cerebral pathology. Discontinue medications that may lower the seizure threshold at least 48 hours before iohexol administration and do not resume for at least 24 hours post-procedure. Patients on anticonvulsant medication should be maintained on that therapy.

Severe thyrotoxicosis:

Iodinated contrast media should not be administered to patients with thyrotoxicosis (see section 4.3). Special care should be exercised in patients with hyperthyroidism. Patients with multinodular goitre may be at risk of developing hyperthyroidism following injection of iodinated contrast media. One should also be aware of the possibility of inducing transient hypothyroidism in premature infants receiving contrast media.

Multiple myeloma:

Patients with paraproteinemias (myelomatosis and Waldenström’s macroglobulinemia) are also at risk.

Known or suspected pheochromocytoma:

The administration of iodinated contrast media may aggravate the symptoms of myasthenia gravis. In patients with phaeochromocytoma undergoing interventional procedures, alpha blockers should be given as prophylaxis to avoid a hypertensive crisis.

Paediatric population:

Transient hypothyroidism has been reported in premature infants, neonates and in other children after administration of iodinated contrast media. Premature infants are particularly sensitive to the effect of iodine. It is advisable to monitor thyroid function. Thyroid function should be checked in neonates during the first week of life, following administration of iodinated contrast agents to the mother during pregnancy. Repeat testing of thyroid function is recommended at 2 to 6 weeks of age, particularly in low birth weight newborn or premature newborn.

Precautions related to administration technique:

Risk of procedure-related thrombosis and embolism:

Non-ionic contrast media have less effect on the coagulation system in vitro, compared to ionic contrast media. When performing vascular catheterisation procedures one should pay meticulous attention to the angiographic technique and flush the catheter frequently (e.g.: with heparinised saline) so as to minimise the risk of procedure-related thrombosis and embolism.

Extravasation:

Extravasation of contrast media may on rare occasions give rise to local pain, and oedema, which usually recedes without sequelae. However, inflammation and even tissue necrosis have been seen. Elevating and cooling the affected site is recommended as routine measures. Surgical decompression may be necessary in cases of compartment syndrome.

Observation-time:

After contrast medium administration the patient should be observed for at least 30 minutes, since the majority of serious side effects occurs within this time. However, delayed reactions may occur.

Following myelography the patient should rest with the head and thorax elevated by 20º for one hour. Thereafter he/she may ambulate carefully but bending down must be avoided. The head and thorax should be kept elevated for the first 6 hours if remaining in bed. Patients suspected of having a low seizure threshold should be observed during this period. Outpatients should not be completely alone for the first 24 hours.

Care is required in patient management to prevent inadvertent intracranial entry of a large bolus dose of the contrast medium. Prophylactic anti-convulsant treatment should be considered in patients with evidence of inadvertent intracranial entry of a large bolus of the medium, since there is an increased risk of seizure in such cases.

Other:

Other precautions which apply to the various radiographic contrast medium procedures are the same for OMNIPAQUE as they are for all other non-ionic contrast media. The risk of the procedure itself should be carefully evaluated in each patient. Such precautions include:

Cerebral angiography:

• Use with caution in patients with extreme senility, advanced atherosclerosis, or severe hypotension.
• The procedure may be hazardous in subarachnoid haemorrhage and in migraine (because of ischaemic complications).

Peripheral angiography:

• Pulsation should be present in the artery to be injected.
• In thromboangiitis obliterans (Buerger’s Disease) or ischaemia associated with ascending infection, angiography should be performed with extreme caution, if at all.

Cardioangiography:

• Caution is advised in the administration of large volumes to patients with incipient heart failure because of the possibility of aggravating the pre-existing condition. Hypotension should be corrected promptly since it may induce serious arrhythmias.
• Caution is advised with dosage in patients with right ventricular failure, pulmonary hypertension, or stenotic pulmonary vascular beds because of the haemodynamic changes which may occur after injection into the right heart outflow tract.

Urography:

• It is advisable to allow an interval of at least 48 hours before repeating excretory urography.
• Dehydration should be avoided in the elderly, particularly those with polyuria, oliguria, advanced vascular disease or pre-existing dehydration.
• Myelomatosis (see section 4.4).

Arthrography:

• Strict aseptic technique is required to prevent infection.
• Fluoroscopic control should be used to ensure proper needle placement, prevent extracapsular injection and prevent dilution of contrast medium.
• Undue pressure should not be exerted during injection.

Hysterosalpingography:

• In patients with carcinoma or in those in whom the condition is suspected, use caution to avoid possible spreading of the lesion by the procedure.

Use of contrast media may result in a transient impairment of renal function and this may precipitate lactic acidosis in diabetics who are taking metformin (see section 4.4).

Patients treated with interleukin-2 less than two weeks previously have been associated with an increased risk for delayed reactions (flu-like symptoms or skin reactions).

Patients using beta blockers may present with atypical symptoms of anaphylaxis which may be misinterpreted as a vagal reaction.

All iodinated contrast media may interfere with tests on thyroid function, thus the iodine binding capacity of the thyroid may be reduced for up to several weeks.

High concentrations of contrast media in serum and urine can interfere with laboratory tests for bilirubin, proteins or inorganic substances (e.g. iron, copper, calcium and phosphate). These substances should therefore not be assayed on the day of examination.

Pregnancy

The safety of OMNIPAQUE for use in human pregnancy has not been established. Teratogenicity studies have been performed in rats and rabbits at doses up to 4 g I/kg and 2.5 g I/kg, respectively. No evidence of harm to the embryo or foetus or of impaired fertility has been demonstrated due to OMNIPAQUE.

Since whenever possible, radiation exposure should be avoided during pregnancy, the benefits of an X-ray examination, with or without contrast media, should be carefully weighed against the possible risk. OMNIPAQUE should not be used in pregnancy unless the benefit outweighs the risk and it is considered essential by the physician.

Breast feeding

Approximately 0.5% of the weight adjusted maternal dose is excreted in breast milk during 24 hours after injection of iohexol. Nursing may be continued normally when iodinated contrast media are given to the mother.

It is not advisable to drive a car or use machines during the first 24 hours following intrathecal examination.

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.

Serious reactions as well as fatalities are only seen on very rare occasions.

Hypersensitivity reactions usually present as respiratory or cutaneous symptoms like dyspnoe, rash, erythema, urticaria, pruritus, skin disorder, angioneurotic oedema, laryngeal oedema, bronchospasm or pulmonary oedema. They may appear either immediately after the injection or up to a few days later.

Hypersensitivity reactions may occur irrespectively 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. Patients using beta-blockers may present with atypical symptoms of anaphylaxis, which may be misinterpreted as a vagal reaction.

An undesirable effect is said to be:

very frequent if its frequency is ≥10%
common if its frequency is between ≥1% and <10%
uncommon if its frequency is between ≥0.1% and <1%
rare if its frequency is between ≥0.01% and <0.1%
very rare if its frequency is <0.01%

Immune system disorders

Rare: Hypersensitivity

Not known: Anaphylactoid reaction/shock

Nervous system disorders

Rare: Headache

Very rare: Dysgeusia, Syncope vasovagal

Cardiac disorders

Rare: Bradycardia

Vascular disorders

Very rare: Hypertension, Hypotension

Gastrointestinal disorders

Uncommon: Nausea

Rare: Vomiting

Very rare: Diarrhoea, Abdominal pain/discomfort

Not known: Salivary gland enlargement

General disorders

Common: Feeling hot

Rare: Pyrexia

Very rare: Chills

Injury, poisoning and procedural complications

Not known: Iodism

Endocrine disorders

Not known: Transient hypothyroidism

Intravascular Use (Intra-arterial and Intravenous Use)

Please first read the section labelled “General”. Below, only undesirable events with frequency during intravascular use of OMNIPAQUE are described.

The nature of the undesirable effects specifically seen during intraarterial 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.

A transient increase in S-creatinine is common after iodinated contrast media, but usually is of no clinical relevance.

Endocrine disorders

Not known: Thyrotoxicosis

Psychiatric disorders

Not known: Confusional state

Nervous system disorders

Rare: Dizziness

Very rare: Convulsion, Disturbance in consciousness, Tremor

Not known: Motor dysfunction, Sensory disturbance, Transient contrast induced encephalopathy (including amnesia, hallucination, paralysis, paresis, disorientation, transient speech disorder, aphasia, dysarthria)

Eye disorders

Not known: Blindness transient

Ear disorders

Not known: Transient hearing loss

Cardiac disorders

Rare: Arrhythmia

Very rare: Myocardial infarction

Not known: Cardiac arrest, Myocardial ischaemia, Ventricular hypokinesia, Spasm of coronary arteries

Vascular disorders

Very rare: Flushing, Hypertension

Not known: Arterial spasm, Ischaemia, Thrombophlebitis, Thrombosis, Shock

Respiratory, thoracic and mediastinal disorders

Very rare: Cough, Dyspnoea, Non-cardiogenic pulmonary oedema

Not known: Bronchospasm, Laryngospasm, Asthma attack

Gastrointestinal disorders

Not known: Pancreatitis aggravated

Skin and subcutaneous tissue disorders

Not known: Bullous dermatitis, Stevens-Johnson syndrome, Erythema multiforme, Toxic epidermal necrolysis, Acute generalised exanthematous pustulosis, Drug rash with eosinophilia and systemic symptoms, Psoriasis flare-up

Musculoskeletal, connective tissue and bone disorders

Not known: Arthralgia

Renal and urinary disorders

Rare: Renal failure

General disorders

Common: Feeling hot

Uncommon: Pain

Rare: Asthenic conditions (eg. Malaise, fatigue)

Not known: Injection site reaction

Intrathecal use

Please first read the section labelled “General”. Below, only undesirable events with frequency during intrathecal use of non-ionic 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.

Psychiatric disorders

Not known: Confusional state

Nervous system disorders

Very frequent: Headache

Uncommon: Meningitis chemical

Rare: Convulsion, Dizziness

Not known: Electroencephalogram abnormal, Meningism, Motor dysfunction, Paraesthesia, Sensory disturbance

Eye disorders

Not known: Blindness transient, Photophobia

Gastrointestinal disorders

Common: Nausea, Vomiting

Rare: Diarrhoea

Musculoskeletal, connective tissue and bone disorders

Rare: Pain in extremity, Neck pain

Not known: Muscle spasms

General disorders

Not known: Injection site reaction

Headache, nausea, vomiting or dizziness may largely be attributed to pressure loss in the subarachnoid space resulting from leakage at the puncture site. Excessive removal of cerebrospinal fluid should be avoided in order to minimise pressure loss.

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.

Endoscopic Retrograde Cholangiopancreatography (ERCP):

Gastrointestinal disorders

Common: Pancreatitis, Blood amylase increased

Oral use:

Gastrointestinal disorders

Very frequent: Diarrhoea

Common: Nausea, Vomiting

Uncommon: Abdominal pain

Hysterosalpingography (HSG):

Gastrointestinal disorders

Very frequent: Abdominal pain

Arthrography:

Musculoskeletal, connective tissue and bone disorders

Not known: Arthritis

General disorders

Very frequent: Pain

Herniography:

General disorders

Not known: Pain

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions https://nzphvc.otago.ac.nz/reporting/.

Although no incompatibility has been found, OMNIPAQUE should not be directly mixed with other drugs. A separate syringe should be used.