Source: Medicines and Medical Devices Safety Authority (NZ) Revision Year: 2017 Publisher: GE Healthcare, 8 Tangihua Street, PO Box 106911, Auckland 1010, Ph 0800 659465, Fax (09) 353-6701
Hypersensitivity to the active substance or iodine or hypersensitivity to any of the excipients.
Manifest thyrotoxicosis.
History of serious hypersensitivity reaction to VISIPAQUE.
Precautions for use of non-ionic contrast media in general: The risk of serious reactions in connection with use of VISIPAQUE 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.
As with other iodinated contrast agents, the use of VISIPAQUE injection contrast enhancement may obscure some lesions which are seen on previously unenhanced CT scans.
In patients with normal blood-brain barriers and renal failure, iodinated contrast agents have been associated with blood-brain barrier disruption and accumulation of contrast in the brain.
Enhancement of the inferior vermis following contrast agent administration has resulted in falsepositive diagnosis.
Patients should be well hydrated prior to, and following, administration of any contrast medium, including VISIPAQUE, in order to prevent from acute renal failure. This applies especially to patients with multiple myeloma, diabetes mellitus, renal dysfunction and elderly patients. Preparatory dehydration is dangerous and may contribute to acute renal failure in patients with pre-existing renal insufficiency, diabetes or advanced vascular disease. It is believed that overnight fluid restriction prior to excretory urography generally does not provide better visualisation in normal patients.
To avoid contrast induced nephropathy, the following should be considered:
In the paediatric population, prolonged fasting and the administration of a laxative before VISIPAQUE injection are to be avoided.
Adequate hydration should be ensured; infants and especially neonates are susceptible to electrolyte disturbance and haemodynamic changes.
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.
Risk-benefit should be considered when the following medical problems exist:
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 goiter may be at risk of developing hyperthyroidism following injection of iodinated contrast media.
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. Recent reports of the use of iodinated contrast agents indicate that such pretreatment does not prevent serious life-threatening reactions but may reduce both their incidence and severity.
Radiopaque contrast agents are potentially hazardous in patients with multiple myeloma or other paraproteinemias, particularly in those with the therapeutically resistant anuria. Although neither the contrast agent nor dehydration have been proved separately to be the cause of anuria in myelomatous patients, it has been speculated that the combination of both may be causative. The risk in myelomatous patients is not a contraindication; however, they require special precautions. Preparatory dehydration of these patients is not recommended since it may predispose the patient to precipitation of the myeloma protein in the renal tubules. The presence of myeloma should be considered before instituting intravascular administration of contrast agents.
Administration of radiopaque materials to patients known to have, or suspected of having, phaeochromocytoma should be performed with extreme caution. If, in the opinion of the physician, the possible benefits of such procedures outweigh the considered risks, the procedures may be performed; however, the amount of radiopaque medium injected should be kept to an absolute minimum. The patient’s blood pressure should be assessed throughout the procedure, and measures for the treatment of hypertensive crisis should be readily available.
Angiography should be avoided whenever possible in patients with homocystinuria because of the risk of inducing embolism.
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.
Care should also be taken in patients with serious cardiac disease and pulmonary hypertension as they may develop haemodynamic changes or arrhythmias.
To prevent lactic acidosis, serum creatinine level should be measured in diabetic patients treated with metformin prior to intravascular administration of iodinated contrast medium.
A benefit to risk assessment should be made before use of an iodinated contrast medium in patients with pre-existing renal impairment (serum creatinine >1.5 mg/dL).
Iso-osmolar or low-osmolar contrast media should always be used in these patients.
Contrast medium induced nephrotoxicity is a condition in which impaired renal function (an increase in serum creatinine by more than 25% or 44 Dmol/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 media induced nephrotoxicity. If clinically indicated, haemodialysis is an effective method for eliminating iodinated contrast medium from the body. Correlating the time of contrast medium to the dialysis schedule is unnecessary, because there is no evidence that haemodialysis protects patients with impaired renal function from contrast media 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.
Patients on haemodialysis may receive contrast media for radiological procedures.
In angiographic procedures, the possibility of dislodging plaques, rupturing aneurisms, or damaging or perforating the vessel wall should be borne in mind during catheter manipulations and contrast medium injection. Test injections to ensure proper catheter placement are recommended.
Serious, rarely fatal, thromboembolic events causing myocardial infarction and stroke have been reported during angiographic procedures with both ionic and nonionic contrast media. Non-ionic contrast media have less effect on the coagulation system in vitro, compared to ionic contrast media. For these reasons, meticulous intravascular administration technique is necessary, particularly during angiographic procedures. Close attention to guidewire and catheter manipulation, use of manifold systems and/or three-way stopcocks, frequent catheter flushing with heparinised saline solutions, and minimising the length of the procedure may minimise thromboembolic events. Numerous factors, including catheter and syringe material, underlying disease state, and concomitant medications may contribute to the development of thromboembolic events. The use of plastic syringes in place of glass syringes has been reported to decrease but not eliminate the likelihood of in vitro clotting.
No safety data have been submitted regarding the following:
Extravasation: It is likely that VISIPAQUE due to its isotonicity gives rise to less local pain and extravascular oedema than hyperosmolar contrast media. In case of extravasation, 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 occur within this time. However, experience shows that hypersensitivity reactions may appear up to several hours or days post injection.
Selective coronary arteriography should be performed only in those patients in whom the expected benefits outweigh the risk. The inherent risks of angiocardiography in patients with chronic obstructive pulmonary disease must be weighed against the necessity for performing this procedure.
During left ventriculography and coronary arteriography, vital signs and the ECG should be monitored routinely throughout the procedure. Caution is advised in the administration of large volumes to patients with incipient heart failure because of the possibility of aggravating the preexisting condition. Hypotension should be corrected promptly.
Special care regarding dosage should be observed in patients with right ventricular failure, pulmonary hypertension, or stenotic pulmonary vascular beds, because of the haemodynamic changes that may occur after injection into the right heart outflow tract.
Pulsation should be present in the artery to be injected. In thromboangiitis obliterans or ascending infection associated with severe ischaemia, arteriography should be performed only if the benefits clearly outweigh the risks.
In thromboangiitis obliterans or ascending infection associated with severe ischaemia, arteriography should be performed only if the benefits clearly outweigh the risks.
Cerebral arteriography should be undertaken with extreme care, especially in elderly patients, patients in poor clinical condition, or patients with advanced arteriosclerosis, severe arterial hypertension, cardiac decompensation or recent cerebral embolism or thrombosis.
Since VISIPAQUE is given by rapid injection, the patient should be monitored for possible untoward reactions. In cerebral arteriography, patients should be appropriately prepared consistent with existing or suspected disease states.
In patients with cerebral haemorrhage, a rare association between contrast administration and clinical deterioration, including severe headache and death, has been reported. Therefore, administration of intra-arterial iodinated contrast media in these patients should be undertaken with caution.
In thromboangiitis obliterans or ascending infection associated with severe ischaemia, venography should be performed only if the benefits clearly outweigh the risks.
Urography should be performed with caution in patients with impaired renal function, patients with combined renal and hepatic disease, and patients with diabetic nephropathy.
Use of iodinated contrast media may result in a transient impairment of renal function and this may precipitate lactic acidosis in diabetics who are taking biguanides/metformin (see section 4.4).
Patients treated with interleukin-2 less than two weeks previous to an iodinated contrast medium injection have been associated with an increased risk for delayed reactions (flu-like symptoms or skin reactions).
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.
General anaesthesia may be indicated in the performance of some procedures in selected patients. However, a higher incidence of adverse reactions following administration of contrast agents has been reported in anaesthetised patients. This may be attributable either to the inability of the patient to identify untoward symptoms or to the hypotensive effect of anaesthesia, which can reduce cardiac output and increase the duration of exposure to a contrast agent.
Patients using beta blockers may present with atypical symptoms of anaphylaxis which may be misinterpreted as a vagal reaction (see section 4.8).
Addition of an inotropic agent to contrast agents may produce a paradoxical depressant response, which can be deleterious to the ischaemic myocardium.
Many radiopaque contrast agents are incompatible in vitro with some antihistamines and many other drugs. Therefore, other pharmaceuticals should not be mixed with contrast agents, including VISIPAQUE, in the same syringe.
Protein-bound iodine (PBI) and total serum organic iodine: transient increases of both tests following urography have been noticed. The results of PBI and radioactive iodine uptake studies which depend on iodine estimations will not accurately reflect thyroid function for up to 16 days following administration of iodinated urographic media. However, thyroid function tests not depending on iodine estimations, such as T3, resin uptake or free thyroxine assays, are not affected.
VISIPAQUE interferes with Multistix measurements of specific gravity and produces a falsepositive result for protein in the urine via Multistix. However, the Coomassie blue method has been shown to give accurate results for the measurement of urine protein in the presence of VISIPAQUE.
Category B1.
Since, wherever possible, radiation exposure should be avoided during pregnancy, the benefits of any X-ray examination, with or without contrast media, should be carefully weighed against the possible risk. The product should not be used in pregnancy unless benefit outweighs risk and it is considered essential by the physician.
Reproduction studies have been performed in rats and rabbits at doses up to 2 gI/kg/day and have revealed no evidence of harm to the foetus due to VISIPAQUE. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, the drug should be used during pregnancy only if clearly needed.
It is not known whether the use of contrast agents during labour or delivery has immediate or delayed effects on the foetus, prolongs the duration of labour or increases the likelihood that forceps delivery or other obstetrical intervention or resuscitation of the newborn will be necessary.
Occurrence of serious adverse reactions has not been established in nursing infants.
The amount of contrast medium excreted in human milk appears to be low. Breast feeding may be continued normally when iodinated contrast media are given to the mother.
VISIPAQUE did not affect male or female fertility in rats at IV doses up to 2 gI/kg/day.
None known.
None known.Below are listed possible side effects in relation with radiographic procedures which include the use of VISIPAQUE.
Serious reactions as well as fatalities are only seen on very rare occasions.
Hypersensitivity reactions usually present as respiratory or cutaneous symptoms like dyspnoea, rash, erythema, urticaria, pruritus, skin reaction, angioneurotic oedema, hypotension, fever, 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 hypersensitivity which may be misinterpreted as a vagal reaction.
A minor transient increase in serum creatinine is common after iodinated contrast media, but is usually of no clinical relevance.
An undesirable effect is said to be:
Reactions, for which no frequency rate can be provided due to lack of clinical data, have been entered with ‘not known’.
The listed frequencies are based on internal clinical documentation and published studies, comprising more than 48,000 patients.
Adults Intravascular use (Intra-arterial and Intravenous use):
| MedDRA System Organ Class | Adverse Drug Reaction (ADR) | Frequency |
|---|---|---|
| Immune system disorders | Hypersensitivity Anaphylactoid reaction Anaphylactoid shock severe pustular or bullous skin reactions | Uncommon Not known Not known Not known |
| Psychiatric disorders | Confusional state | Not known |
| Nervous system disorders | Headache Dizziness Sensory disturbance Motor dysfunction Convulsion Disturbance in consciousness | Uncommon Rare Very rare Not known Not known Not known |
| Eye disorders | Blindness transient | Very rare |
| Cardiac disorders | Arrhythmia Ventricular hypokinesia Myocardial ischaemia | Rare Not known Not known |
| Vascular disorders | Hypotension Hypertension Ischaemia Arterial spasm Thrombosis Thrombophlebitis | Rare Very rare Very rare Not known Not known Not known |
| Respiratory, thoracic and mediastineal disorders | Cough Dyspnoea Non-cardiogenic pulmonary oedema | Rare Very rare Not known |
| Gastrointestinal disorders | Nausea Vomiting Abdominal pain/discomfort | Uncommon Uncommon Very rare |
| Musculoskeletal, connective tissue and bone disorders | Arthralgia | Not known |
| Renal and urinary disorders | Acute renal failure | Very rare |
| General disorders and administration site conditions | Feeling hot Pain Pyrexia Feeling cold Asthenic conditions (e.g., malaise, fatigue) | Uncommon Rare Rare Very rare Very rare |
| Injury and poisoning | Iodism | Not known |
Paediatrics:
| MedDRA System Organ | Class Adverse Drug Reaction (ADR) | Frequency |
|---|---|---|
| Endocrine disorders | Transient hypothyroidism | Not known |
In general the type of adverse events reported are similar to those of adults. Although the frequency of events appears to be comparable, the frequency cannot be confirmed because of the different ability of paediatric and adult patients to report adverse events.
The overall character, quality, and severity of adverse reactions in paediatric patients is similar to that reported in adult populations from domestic and foreign postmarketing surveillance and other information. Selected commonly reported adverse events in paediatrics include: vomiting, nausea, fever, rash, pruritus and injection associated discomfort and distress. Diarrhoea and taste perversion were reported in gastrointestinal studies.
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/.
No incompatibility has been found. However, VISIPAQUE should not be directly mixed with other drugs. A separate syringe should be used.
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