Imiro IV Injection

37.75 gm Iohexol/50 ml equivalent to 350 mg Iodine/ml

Iohexol provides opacification of blood vessels and permits radiographic visualisation until sufficient haemodilution occurs or sufficient contrast medium has left the site of injection. Being a non-ionic compound, Iohexol yields solutions of lower osmolality than the conventional ionic contrast media. Intravenous or intra-arterial injection of Iohexol causes less pain and sensation of heat than conventional ionic media with similar iodine content. Iohexol solutions cause less cardiac and vascular disturbances on intravascular injection. The transit time of Iohexol through the coronary vascular system is slightly increased compared with conventional ionic contrast media, probably due to the increased viscosity of Iohexol at comparable iodine concentrations. The period of maximal opacification of the renal vessels may begin as early as 30 seconds after IV injection. Urograms become apparent in about 1 to 3 minutes with optimal contrast occurring between 5 to 15 minutes. In nephropathic conditions, particularly when excretory capacity has been altered, the rate of excretion may vary unpredictably, and opacification may be delayed after injection. Severe renal impairment may result in a lack of diagnostic opacification of the collecting system. The initial concentration and volume of the medium, in conjunction with appropriate patient manipulation and the volume of CSF into which the medium is placed, will determine the extent of diagnostic contrast that can be achieved. Following subarachnoid injection, Iohexol will continue to provide good diagnostic contrast by conventional radiography for at least 30 minutes. Slow diffusion of Iohexol takes place throughout the CSF as well as transfer into the circulation. At approximately 1 hour, contrast of diagnostic quality will not usually be available for conventional myelography. However, sufficient contrast for CT myelography will be available for several hours. If CT myelography is to follow, it should be deferred for several hours to allow the degree of contrast to decrease. Following lumbar subarachnoid placement, irrespective of the position in which the patient is later maintained, slow upward diffusion of Iohexol takes place throughout the CSF. CSF contrast enhancement for CT scanning may be expected in the thoracic region in about 1 hour, in the cervical region in about 2 hours and in the basal cisterns in 3 to 4 hours after administration into the lumbar subarachnoid space.

Injection As iohexol soln containing 6-350 mg iodine/mL: Dose and strength used depends on the procedure and route of administration.

Injection-

Angiocardiography:

• Adult: Ventriculography: 350 mg iodine/ml: 30-60 ml, usual: 40 ml, may be repeated as necessary. If with selective coronary arteriography: max 250 ml. Selective coronary arteriography: 350 mg iodine/ml: 3-14 ml per inj, usual: 5 ml. Aortic root and arch study when used alone: 350 mg iodine/ml: 20-75 ml, usual 50 ml. Multiple procedures: 350 mg iodine/ml: max 250 ml.
• Child: Ventriculography: 350 mg iodine/ml: 1-1.5 ml/kg, usual: 1.25 ml/kg; 300 mg iodine/ml: 1.5-2 ml/kg, usual 1.75 ml/kg. Max: 5 ml/kg; 350 mg iodine/ml: 250 ml; 300 mg iodine/ml: 291 ml. Pulmonary angiography: 350 mg iodine/ml: 1 ml/kg. Multiple procedures: Max: 5 ml/kg; 350 mg iodine/ml: 250 ml; 300 mg iodine/ml: 291 ml.

Aortography and selective visceral arteriography

• Adult: Use 300 or 350 mg iodine/ml solution, single inj. Aorta: 50-80 ml; major branches: 30-60 ml; renal arteries: 5-15 ml. Repeat as necessary. Max: 300 mg iodine/ml: 291 ml; 350 mg iodine/ml: 250 ml.
• Child: Use 350 mg iodine/ml solution: 1 ml/kg, single dose. Max: 5 ml/kg up to 250 ml.

Voiding cystourethrography:

• Adult: Use diluted solutions using sterile water for inj to concentrations of 50-100 mg iodine/ml. Usual volume: 50 mg iodine/ml solution: 50-600 ml; 100 mg iodine/ml: 50-300 ml.
• Child: Children: Use diluted solutions using sterile water for inj to concentrations of 50-100 mg iodine/ml: 50-300 ml.

Hysterosalpingography:

• Adult: 240 mg iodine/ml: 15-20 ml; 300 mg iodine/ml: 15-20 ml.

Arthrography:

• Adult: Knee: 240 mg iodine/ml: 5-15 ml; 300 mg iodine/ml: 5-15 ml; 350 mg iodine/ml: 5-10 ml. Shoulder: 240 mg iodine/ml: 3 ml; 300 mg iodine/ml: 10 ml. Temporomandibular: 300 mg iodine/ml: 0.5-1 ml. Lower volumes are recommended for double-contrast examinations; higher volumes are recommended fro single-contrast examinations.

Herniography:

• Adult: 240 mg iodine/ml: 50 ml.

Excretory urography:

• Adult: Use 300 or 350 mg iodine/ml solution: 200-350 mg iodine/kg.
• Child: Use 300 mg iodine/ml solution: 0.5-3 ml/kg, usual: 1-1.5 ml/kg; max: 3 ml/kg.

Endoscopic retrograde cholangiopancreatography (ERCP), Endoscopic retrograde pancreatography (ERP):

• Adult: Use 240 mg iodine/ml: 10-50 ml.

Intra-arterial-

Peripheral arteriography:

• Adult: Aortofemoral runoffs: 350 mg iodine/ml: 20-70 ml; 300 mg iodine/ml: 30-90 ml. Selective arteriograms (femoral/iliac): 350 mg iodine/ml: 10-30 ml; 300 mg iodine/ml: 10-60 ml. Venography (per leg): 240 mg iodine/ml: 20-150 ml; 300 mg iodine/ml: 40-100 ml.

Cerebral arteriography:

• Adult: Use 300 mg iodine/ml solution: Common carotid artery: 6-12 ml; internal carotid artery: 8-10 ml; external carotid artery: 6-9 ml; vertebral artery: 6-10 ml.

Digital subtraction angiography:

• Adult: Use 140 mg iodine/ml solution: Aorta: 20-45 ml at 8-20 ml/sec; carotid: 5-10 ml at 3-6 ml/sec; femoral: 9-20 ml at 3-6 ml/sec; vertebral: 4-10 ml at 2-8 ml/sec; renal: 6-12 ml at 3-6 ml/sec; other branches of the aorta (includes subclavian, axillary, innominate and iliac): 8-25 ml at 3-10 ml/sec.

Intrathecal-

Contrast-enhanced computerized tomography:

• Adult: Lumbar (via lumbar inj): 180 mg iodine/ml: 10-17 ml; 240 mg iodine/ml: 7-12.5 ml. Thoracic (via lumbar or cervical inj): 240 mg iodine/ml: 6-12.5 ml; 300 mg iodine/ml: 6-10 ml. Cervical (via lumbar inj): 240 mg iodine/ml: 6-12.5 ml; 300 mg iodine/ml solution: 6-10 ml. Cervical (via C1-2 inj): 180 mg iodine/ml: 7-10 ml; 240 mg iodine/ml: 6-12.5 ml; 300 mg iodine/ml: 4-10 ml. Total columnar (via lumbar inj): 240 mg iodine/ml: 6-12.5 ml; 300 mg iodine/ml: 6-10 ml.
• Child: Use 180 mg iodine/ml solution. 0-<3 mth: 240 ml; 3-<36 mth: 4-8 ml; 3-<7 yr: 5-10 ml; 7-<13 yr: 5-12 ml; 13-18 yr: 6-15 ml.

Intravenous-

Contrast-enhanced computerized tomography of the abdomen:

• Adult: In conjunction with dilute oral admin, use 300 mg iodine/ml solution: 100-150 ml. The oral dose is administered 20-40 min prior to IV dose and image acquisition.
• Child: In conjunction with dilute oral admin, use 240 or 300 mg iodine/ml solution: 1-2 ml/kg; max 3 ml/kg. The oral dose is administered 30-60 min prior to IV dose and image acquisition.

Digital subtraction angiography:

• Adult: 350 mg iodine/ml: 30-50 ml, as a bolus at 7.5-30 ml/second using a pressure injector, usually for 3 or more inj; max: 250 ml.

Contrast-enhanced computerized tomography:

• Adult: Head imaging by inj: 300 mg iodine/ml: 70-150 ml; 350 mg iodine/ml: 80 ml. Head imaging by infusion: 240 mg iodine/ml: 120-250 ml. Body imaging by inj: 300 mg iodine/ml: 50-200 ml; 350 mg iodine/ml: 60-100 ml.
• Child: Head imaging: 240 or 300 mg iodine/ml: 1-2 ml/kg. Max: 28 g iodine with 240 mg iodine/ml solution or 35 g iodine with 300 mg iodine/ml solution.

Dose and strength used depends on the procedure and route of administration.

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 Warnings and Precautions). 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). 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.

Manifest thyrotoxicosis. History of serious reaction to Iohexol.

Flushing or a sensation of heat; pain, extravasation, thrombophlebitis at the inj site; nausea, vomiting, headache, and dizziness; urticaria, pruritus, pallor, sweating, metallic taste, weakness, coughing, rhinitis, sneezing, lachrymation, visual disturbances; hypotension, tachycardia, bradycardia, transient ECG abnormalities, haemodynamic disturbances; dyspnoea, bronchospasm, angioedema, severe urticaria; convulsions, paraesthesia, paralysis; acute renal failure; thromboembolism, disseminated intravascular coagulation, thrombocytopenia; hyperthyroidism, thyroid storm thyrotoxicosis.

Use in Pregnancy: The safety of Iohexol for use in human pregnancy has not been established. An evaluation of experimental animal studies does not indicate direct or indirect harmful effects with respect to reproduction, development of the embryo or foetus, the course of gestation and peri- and postnatal development. 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. Iohexol should not be used in pregnancy unless the benefit outweighs the risk and it is considered essential by the physician.

Use during Lactation: Breast feeding may be continued normally when iodinated contrast media are given to the mother.

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 Imiro 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. 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. 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. Care should also be taken in patients with serious cardiac disease and pulmonary hypertension as they may develop haemodynamic changes or arrhythmias. 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. 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. Patients with paraproteinemias (myelomatosis and Waldenström's macroglobulinemia) are also at risk

Preclinical data indicate a high safety margin for Imiro and no fixed upper dose level has been established for routine intravascular use. Symptomatic overdosing is unlikely in patients with normal renal function unless the patient has received an excess of 2000 mg I/kg body-weight over a limited period of time. The duration of the procedure is important for the renal tolerability of high doses of contrast media (t½ ~ 2 hours). Accidental overdosing is most likely following complex angiographic procedures in children, particularly when multiple injections of contrast medium with high-concentration are given. In cases of overdose, any resulting water or electrolyte imbalance must be corrected. Renal function should be monitored for the next 3 days. If needed, haemodialysis may be used for clearance of excessive contrast medium. There is no specific antidote.

Contrast medium for diagnostic procedures

Like all parenteral products, Imiro should be inspected visually for particulate matter, discoloration and the integrity of the container prior to use. The product should be drawn into the syringe immediately before use. Vials are intended for single use only, any unused portions must be discarded. The 500 ml contrast medium bottles should only be used in connection with auto injectors/pumps approved for this volume. A single piercing procedure should be used. The line running from the auto injector/pump to the patient must be exchanged after each patient. Any unused portions of the contrast medium remaining in the bottle and all connecting tubes must be discarded at the end of the day. When convenient, smaller bottles can also be used. Instructions from the manufacturer of the auto injector/pump must be followed.

Store at room temperature below 30° C and protect from light and secondary X-rays. The product in glass vials and bottles may be stored at 37° C for up to 3 months prior to use.Do not freeze.