Iodixanol

Excretory Urography

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.

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

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.

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.

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.

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.

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 the 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 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.

Patients should be well hydrated prior to, and following, administration of any contrast medium, including iodixanol, 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:

• Identification of high risk patients
• Ensuring adequate hydration. The patient should be hydrated (e.g. at least 100 mL per hour of soft drinks or intravenous saline up to 24 hours after contrast medium administration. In warm areas more fluid should be given).
• 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.
• Monitor renal function (serum creatinine), serum lactic acid and pH of blood.
• Look for symptoms of lactic acidosis (vomiting, somnolence, nausea, epigastric pain, anorexia, hyperpnea, lethargy, diarrhoea and thirst). Blood test results indicative of lactic acidosis: pH <7.25 and lactic acid >5 mmol.

The administration of iodinated contrast media may exacerbate the symptoms of myasthenia gravis.

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).

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 iodixanol. 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.

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.

Labour and delivery

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.

Effects on Fertility

Iodixanol 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 iodixanol.

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:

• very common 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%

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):

Paediatrics:

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.