Optiray

Optiray

Manufacturer:

Guerbet

Distributor:

Biogenetech
Full Prescribing Info
Contents
Ioversol.
Description
Chemical Name: N,N'-Bis(2,3-dihydroxypropyl)-5-[N-(2-hydroxyethyl)-glycolamido]-2,4,6-triiodoisophthalamide.
Molecular Formula: C18H24I3N3O9.
Molecular Weight: 807.12.
Appearance: Ioversol is a fine, white, non-crystalline powder.
Solubility: Ioversol is very soluble in water, freely soluble in dimethylformamide, sparingly soluble in ethanol, slightly soluble in acetone and very slightly soluble in acetonitrile.
Melting Point: No melting point is observed.
COMPOSITION: Characteristics: Optiray formulations are clear, colourless to pale yellow, sterile, non-pyrogenic aqeous solutions. Crystallization does not occur at room temperature.
The pH of the Optiray formulations is adjusted between 6.0 and 7.4 with hydrochloric acid or sodium hydroxide.
Concentrations/mL: Optiray 300: Each millilitre of Optiray 300 (ioversol injection 64%) provides 636 mg of ioversol with 3.6 mg of tromethamine as a buffer and 0.2 mg of edetate calcium disodium as a stabilizer. Optiray 300 provides 30% (300 mg/mL) organically bound iodine.
Optiray 320: Each millilitre of Optiray 320 (ioversol injection 68%) provides 678 mg of ioversol with 3.6 mg of tromethamine as a buffer and 0.2 mg of edetate calcium disodium as a stabilizer. Optiray 320 provides 32% (320 mg/mL) organically bound iodine.
Optiray 350: Each millilitre of Optiray 350 (ioversol injection 74%) provides 741 mg of ioversol with 3.6 mg of tromethamine as a buffer and 0.2 mg of edetate calcium disodium as a stabilizer. Optiray 350 provides 35% (350 mg/mL) organically bound iodine.
Physical and Chemical Properties: See Table 1.

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The product does not contain a preservative and is intended for single dose use only.
Action
Therapeutic or Pharmacological Classification: Non-ionic, low osmolality, water soluble radiopaque contrast medium for intravascular use.
Pharmacology: General: The pharmacokinetics of Optiray (ioversol) in normal subjects conform to an open two compartment model with first order elimination (a rapid alpha phase of 6.8 minutes for drug distribution and a slower beta phase of 92 minutes, for drug elimination). Based on the blood clearance curves for 12 healthy volunteers (6 receiving 50 mL and 6 receiving 150 mL of Optiray 320), the biological half-life was 1.5 hours for both dose levels and there was no evidence of any dose related difference in the rate of elimination. The mean half-life for urinary excretion following a 50 mL dose was 118 minutes (105-156) and following a 150 mL dose was 105 minutes.
Optiray is excreted mainly through the kidneys following intravascular administration. Fecal elimination is 3-9%. Approximately 50% of the injected dose is excreted at 1.5 hours and 86% at 48 hours; about 1.5% is retained, mostly by the thyroid and liver. In patients with impaired renal function and in infants with immature kidneys, the elimination half-life is prolonged. In patients with severe renal disease, excretion does not occur. Optiray does not notably bind to serum or plasma proteins to any marked extent and no significant metabolism, deiodination or biotransformation occurs.
Optiray, like all other contrast media, may induce changes in thyroid function in some patients, and elevation of thyroxine and/or TSH may be observed.
Optiray, like other non-ionic contrast media, has an insignificant effect on blood coagulation (as shown by slightly increased prothrombin time and partial thromboplastin time, and delayed platelet aggregation) and does not possess the anti-coagulant properties of ionic contrast media.
Optiray causes concentration-dependent hemolysis, aggregation and crenation of red blood cells.
Elevations of several laboratory parameters (AST, ALT, LDH, bilirubin, creatinine and BUN) following intravascular administration have been reported in several patients which were not considered clinically significant.
Intravascular: Intravascular injection of Optiray opacifies those vessels in the path of flow of the contrast bolus, permitting their radiographic visualization.
Following intravenous contrast medium administration, the increase in density in non-neural tissue is dependent on the presence of iodine in the vascular and extravascular (extra cellular) compartments. This is related to the rate and amount of contrast material administered, blood flow, vascularity, capillary permeability, extravascular effusion and renal filtration.
Peak iodine blood levels occur immediately following rapid intravenous administration, then fall rapidly as the contrast medium is diluted in the plasma volume and diffuses from the vascular into the extravascular spaces. Equilibration between plasma and extravascular iodine concentration occurs within a few minutes.
Contrast enhancement (increase in the difference in density between adjacent tissues) is the result of differential vascular and extravascular iodine concentration between normal and abnormal tissues, which may accentuate inherent differences in pre-existent tissue density. With contrast enhancement a pathological lesion may demonstrate increased or decreased density compared to the surrounding normal tissue. Some lesions, however, will remain or become isodense and thus undetectable by attempted contrast enhancement. Contrast enhancement in most cases is greatest immediately after bolus injection.
Optiray may be visualized in the renal parenchyma within 30-60 seconds following rapid intravenous injection. Opacification of the calyces and pelves in patients with normal renal function becomes apparent within 1-3 minutes, with optimum contrast occurring within 5-15 minutes.
In nephropathic conditions, particularly when excretory capacity has been altered, the rate of excretion varies unpredictably, and opacification may be delayed for up to several hours after injection. Severe renal impairment may result in a lack of diagnostic opacification of the urinary tract, and depending on the degree of renal impairment, prolonged plasma ioversol levels may be anticipated in these patients as well as in infants with immature kidneys.
Optiray (33% l) was compared in intra-carotid studies in 45 anesthetized rats to iopamidol (32% l) and iohexol (30% l). There was no detectable damage to the blood-brain barrier with any of these substances.
Generally, less warmth and pain are associated with the injection of Optiray than with conventional ionic media. Comparative studies using diatrizoate and iothalamate showed significantly less heat sensation and pain with Optiray. Other non-ionic agents, iohexol and iopamidol, gave results similar to Optiray.
Optiray had significantly less effect on cardiovascular and ECG parameters than did diatrizoate. For example, it produced significantly less bradycardia, tachycardia, T-wave changes, ST depression, ST elevation and hypotension than were seen with diatrizoate.
Computerized Tomography: CT Scanning of the Head: In brain scanning, the contrast medium does not accumulate in normal brain tissue due to the presence of the blood-brain barrier. The increase in X-ray absorption in the normal brain is due to the presence of the contrast agent within the blood pool. A break in the blood-brain barrier, such as occurs in malignant tumors of the brain allows accumulation of the contrast medium within the interstitial tumor tissue; adjacent normal brain tissue does not retain the contrast medium.
Rapid infusion of the dose yields peak blood iodine concentrations immediately following infusion (within 15 to 120 seconds), which fall rapidly over the next 5 to 10 minutes.
Diagnostic contrast enhancement images of the brain have been obtained up to 1 hour after intravenous bolus administration.
CT Scanning of the Body: During CT of the body, Optiray (ioversol) diffuses rapidly from the vascular to the extra-vascular space. Increase in X-ray absorption is related to blood flow, concentration of the contrast medium and extraction of the contrast medium by interstitial tissue. Contrast enhancement is thus due to the relative differences in extra-vascular diffusion between normal and abnormal tissue - a situation quite different from that in the brain.
Contrast enhancement appears to be greatest immediately after bolus infusion (15 to 120 seconds).
Utilization of a continuous scanning technique (dynamic CT scanning) may improve enhancement of tumor and other lesions, such as an abscess.
Indications/Uses
INTRAVASCULAR: Adults: Optiray 350 (ioversol 350 mgI/mL) is recommended in adults for coronary arteriography and ventriculography, peripheral and visceral arteriography, intravenous contrast enhancement in computed tomography of the head and body, excretory urography, intravenous digital subtraction angiography and venography.
Optiray 320 (ioversol 320 mgI/mL) is recommended for angiography throughout the cardiovascular system in adults. The uses include cerebral, coronary, peripheral, visceral and renal arteriography, aortography and left ventriculography. Optiray 320 is also recommended for contrast enhanced computed tomographic imaging of the head and body and in excretory urography.
Optiray 300 (ioversol 300 mgI/mL) is recommended for use in adults for cerebral angiography, aortography, peripheral and visceral arteriography, intravenous contrast enhancement of computed tomography of the brain and body, excretory urography, intravenous digital subtraction angiography and venography.
Pediatric: Optiray 300 (ioversol 300 mgI/mL) is recommended in children one year of age or over for intravenous excretory urography and intra-arterial digital subtraction angiography.
Optiray 320 is recommended in children one year of age or over for angiocardiography, contrast enhanced computed tomography of the head and body and for excretory urography.
Optiray 350 is indicated in children for angiocardiography.
Dosage/Direction for Use
GENERAL: Only the lowest dose necessary to obtain adequate visualization should be used.
Use only the recommended concentration for the particular procedure to be undertaken.
Patients should be well hydrated prior to and following administration of Optiray (ioversol).
Do not dehydrate patients for any procedure.
Optiray (ioversol) should be inspected visually for particulate matter and discoloration prior to administration.
If either is present the vial should be discarded.
Optiray should not be transferred into other delivery systems except immediately before use and should be used immediately once the seal has been punctured.
It is advisable that Optiray be at or close to body temperature when injected.
Under no circumstances should other drugs be administered concomitantly in the same syringe or i.v. administration set as Optiray because of a potential for chemical incompatibility.
Patency of the vessel and the position of the catheter tip or needle should be checked with a small pilot dose of Optiray before injecting the full dose. The catheter tip should be kept free of aspirated blood. Prolonged contact of Optiray with blood must be avoided because of potential thromboembolic complications.
The volume of each individual injection is a more important consideration than the total dose used. When large individual volumes are administered, sufficient time should be permitted to elapse between each injection to allow for subsidence of hemodynamic disturbances.
Any unused portion of one container should be discarded.
INTRAVASCULAR DOSAGE AND ADMINISTRATION: CEREBRAL ANGIOGRAPHY: Optiray 300 or Optiray 320 may be used to visualize the cerebral vasculature.
Patient Preparation: Suitable premedication may be given. Introduction of the catheter or needle is normally performed with local anaesthesia. General anaesthesia is rarely required. (See General under Precautions).
Precautions: In addition to the general precautions previously described, cerebral angiography with Optiray should be performed with special caution in elderly patients, patients in poor clinical condition, patients with advanced arteriosclerosis, severe hypertension, cardiac decompensation, senility, recent cerebral thrombosis, embolism or subarachnoid hemorrhage, following a recent attack of migraine, and in any condition compromising the integrity of the blood brain barrier, and only if the examination is considered to be necessary for the welfare of the patient. The patient should be watched carefully for possible adverse reactions.
Adverse Reactions: The major sources of cerebral arteriographic adverse reactions to Optiray appear to be related to repeated injections of the contrast material, administration of doses higher than those recommended, the presence of occlusive atherosclerotic vascular disease and the method and technique of injection.
Since non-ionic contrast media have no significant anticoagulant properties, meticulous technique is necessary to avoid thromboembolic complications (see Warnings).
A feeling of warmth in the face and neck is frequently experienced. Infrequently, a more severe burning discomfort is observed. Transient visual hallucinations have been reported.
Serious neurological reactions that have been associated with cerebral angiography include stroke, seizures, amnesia, hemiparesis, visual field loss, cortical blindness, aphasia, confusion, disorientation, hallucination, convulsions, coma and death.
Cardiovascular reactions that may occur with some frequency, but not necessarily with Optiray, are bradycardia, arrhythmia, either an increase or decrease in systemic blood pressure, and ECG changes.
Note: The EEG changes associated with the use of contrast media, including Optiray, for cerebral arteriography are not frequent: Optiray can be expected to have the same effect on the electrophysiology of the brain, but this has not been systematically assessed.
Usual Adult Dosage: Either Optiray 300 or Optiray 320 may be used for cerebral angiography. The usual adult dosage of Optiray employed varies with the site and method of injection and the age and condition of the patient. The usual adult dose range for common carotid arteriography is 5-10 mL; for vertebral arteriography 4-8 mL. For aortic arch injection (four vessel studies) the usual dose for Optiray 320 is 15-25 mL. Injections should be made at rates approximately equal to the flow rate of the vessel being injected.
These doses may be repeated if indicated. The total dose per procedure should be limited to the smallest volume necessary to achieve a diagnostic examination and should not exceed 200 mL.
INTRA-ARTERIAL DIGITAL SUBTRACTION ARTERIOGRAPHY: Optiray 300 is suitable agent for intra-arterial digital subtraction angiography (IA-DSA). With this technique lower iodine concentrations can yield diagnostic images. Other advantages of the procedure are the use of less contrast medium and a decreased need for selective arterial catheterization. However, with aortic injection, visualization of small vessels may be insufficient.
Patient Preparation: No special patient preparation is required for IA-DSA. However, patients should be normally hydrated prior to examination.
Precautions: In addition to the general precautions already described, the risks and adverse reactions associated with IA-DSA are those usually associated with the conventional procedure performed in the area of the specific vessel.
In IA-DSA of the distal aorta great care is necessary to avoid entry of a large aortic bolus into an aortic branch since this could cause deleterious effects on the organs supplied by the branch. Patient motion, including respiration and swallowing, can result in misregistration leading to image degradation and non-diagnostic studies.
Adverse Reactions: Adverse reactions seen with IA-DSA are similar to those observed during peripheral arteriography. They may sometimes occur due to trauma during the procedure.
Adverse reactions reported with the use of iodinated contrast media include hypotension, soreness in extremities, transient arterial spasm, gangrene, perforation of vessels, extravasation, hemorrhage, hematoma formation with tamponade, injury to nerves and other structures in close proximity to the artery, thrombosis, dissecting aneurysm, arteriovenous fistula, dislodgement of atheromatous plaques, subintimal injection and transient leg pain from contraction of calf muscles in femoral arteriography.
Usual Dose in Children 1 Year of Age and Over Using Optiray 300: The usual dose is 1 to 3 mL/kg, depending on the area to be examined.
PERIPHERAL ARTERIOGRAPHY: Optiray 300, Optiray 320 or Optiray 350 may be used for arteriograms of the lower extremities.
Patient Preparation: The procedure is normally performed with local anesthesia. General anesthesia usually is not required (see General under Precautions).
Precautions: In addition to the general precautions previously described, moderate decreases in blood pressure occur frequently with intra-arterial injections. This change is usually transient; however, the blood pressure should be monitored for approximately 10 minutes following injection.
Injection of Optiray in patients with severe arterial disease (e.g. thromboangiitis obliterans, severe atherosclerosis, ischemia, thrombosis, significant obstruction) should be undertaken with extreme caution and only when absolutely necessary.
When injections are being made in the distal aorta for aorto-iliac run-off studies, the possibility of inadvertent injection of a large dose into a branch of the aorta or intra-mural dissection should be considered.
To prevent extravasation or subintimal injection, the position of the catheter tip or needle should be carefully evaluated. Fluoroscopy is recommended. Pulsation must be present in the artery to be injected. A small dose of 1-2 mL should be administered to locate the exact site of the needle or catheter tip. Great care is necessary to avoid entry of a large bolus into an aortic branch.
Severe pain, paresthesia or peripheral muscle spasm during injection may require discontinuance of the procedure and a re-evaluation of the catheter tip or needle placement.
Following catheter procedures, gentle pressure hemostasis is advised, followed by observation and immobilization of the limb for several hours to prevent hemorrhage from the site of arterial puncture.
Adverse Reactions: Adverse reactions observed during peripheral arteriography may be due to trauma during the procedure or to the injection of the contrast material. Adverse reactions reported with the use of iodinated contrast media include hypotension, soreness in extremities, transient arterial spasm, contrast medium induced thrombosis, embolism, gangrene, perforation of vessels, extra-vasation, hemorrhage, hematoma formation with tamponade, injury to spinal cord and nerves and other structures in close proximity to the artery; transverse myelitis, thrombosis, dissecting aneurysm, arteriovenous fistula, dislodgement of atheromatous plaques, subintimal injection, leg pain, renal damage including infarction and tubular necrosis due to accidental filling of the renal arteries.
Usual Adult Dosage: The usual single adult dose for aorto-iliac run-off studies is 20-50 mL; for iliac and femoral arteries 10-30 mL. These doses may be repeated as indicated. The total procedural dose should be limited to the smallest volume required to obtain a diagnostic examination and should not usually exceed 250 mL.
SELECTIVE CORONARY ARTERIOGRAPHY WITH OR WITHOUT LEFT VENTRICULOGRAPHY: Either Optiray 320 or Optiray 350 is recommended for this procedure.
Precautions: Since the risk in coronary arteriography is increased if the procedure is performed shortly after acute myocardial infarction, some physicians recommend that this procedure should not be performed for approximately 4 weeks following the diagnosis of myocardial infarction. Mandatory pre-requisites to the procedure are experienced personnel, ECG monitoring apparatus and adequate facilities for immediate resuscitation and cardioversion.
Patients should be monitored continuously by ECG and vital signs throughout the procedure. The injection of relatively large volumes of hypertonic solutions (e.g. contrast media) into the heart chambers can cause significant hemodynamic disturbances. Caution is advised especially in 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.
Adverse Reactions: Most patients will have transient ECG changes during the procedure. The following adverse effects have occurred in conjunction with the administration of iodinated intravascular contrast agents for this purpose: hypotension, shock, anginal pain, coronary thrombosis, myocardial infarction, cardiac arrhythmias (bradycardia, ventricular tachycardia, heart block, ventricular fibrillation) cardiac arrest and death.
Severe adverse reactions, especially arrhythmias, are likely to occur with greater frequency following right coronary artery injection. Fatalities have been reported. Complications to the procedures include dissection of coronary arteries, dislodgement of atheromatous plaques, embolization from the catheter, perforation of heart chambers or coronary arteries with cardiac tamponade, hemorrhage and thrombosis.
Usual Adult Dosage: The usual adult dose range with Optiray 320 or Optiray 350 for left coronary arteriography is 2-10 mL and for right coronary arteriography is 2-6 mL. For left ventriculography, the usual single adult dose is 30-40 mL. These doses may be repeated if indicated; however, several minutes should be allowed to elapse between injections to allow for subsidence of hemodynamic disturbance, and the total procedural dose should be limited to the smallest volume necessary to obtain a diagnostic examination. The total procedural dose should not exceed 250 mL.
Pediatric Dosage and Administration: Optiray 320 and Optiray 350 are recommended for this procedure in children 1 year of age and over. The usual single injection dose of Optiray 320 and Optiray 350 is 1.25 mL/kg of body weight with a range of 1 mL/kg to 1.5 mL/kg. When multiple injections are given, the total administered dose should not exceed 5 mL/kg up to a total volume of 250 mL.
AORTOGRAPHY AND VISCERAL ARTERIOGRAPHY: Optiray 300, 320 or 350 is recommended for this procedure. Great care is necessary to avoid all entries of a large bolus into an aortic branch. Mesenteric necrosis, acute pancreatitis, renal infarction, acute tubular necrosis, renal shutdown and serious neurologic complications, including paraplegia and quadriplegia, have been reported and may be attributable to an excessive dose being injected into an aortic branch or arterial trunks supplying the spinal arteries or to prolonged contact time of the concentrated contrast medium with the CNS tissue. Conditions which can contribute to prolonged contact time include decreased circulation, aortic stenosis or partial occlusions distal to the site of injection, abdominal compression, hypotension, general anesthesia or the administration of vasopressors. When these conditions exist or occur, the necessity of performing or continuing the procedure should be carefully evaluated and the dose and number of repeat injections should be maintained at a minimum with appropriate intervals between injections.
Adverse Reactions: With aortic injection, depending on the technique employed, the risks of this procedure also include the following: injury to the aorta and neighbouring organs, pleural puncture, renal damage including infarction and acute tubular necrosis with oliguria and anuria due to accidental filling of the renal arteries, retroperitoneal hemorrhage from the translumbar approach and spinal cord injury and pathology associated with the syndrome of transverse myelitis. Occasional serious neurological complications including paraplegia have been reported in patients with aortoiliac or femoral artery obstruction, abdominal compression, hypotension, hypertension, spinal anesthesia and injection of vasopressor drugs to enhance contrast. In such patients, the concentration, volume and number of injections should be kept to a minimum.
Adult Dosage and Administration: Optiray 300, Optiray 320 or Optiray 350 is recommended for this procedure. The usual individual injection volumes are as follows: Abdominal aorta: 20-50 mL; superior mesenteric artery: 20-40 mL; renal artery: 4-10 mL.
Total procedural dose should not exceed 250 mL.
INTRAVENOUS CONTRAST ENHANCEMENT IN COMPUTED TOMOGRAPHY (CT):
Because unenhanced scanning may provide adequate information in the individual patient and the injection of contrast media may obscure certain lesions visible on the plain scan, contrast enhancement is usually performed only if the unenhanced scan has not provided sufficient information. The decision to employ contrast enhancement, which is associated with additional risk and increased radiation exposure, should be based upon a careful evaluation of the patient's clinical condition, renal and cardiac reserve, the status of the blood-brain barrier and other radiological and unenhanced CT findings.
Warnings: Patients with diabetes mellitus, impaired renal function and congestive heart failure are considered to be at greater risk of developing acute renal failure following injection of the large doses of contrast media required for contrast enhancement in CT scanning.
Convulsions and other serious neurologic complications including stroke have occurred in patients with primary or metastatic cerebral lesions or breached blood-brain barrier or slowed cerebral circulation following the administration of iodine-containing radiopaque media for enhancement of CT brain images.
Patient Preparation: No special patient preparation is required for contrast enhancement in computerized tomography. However, it has to be insured that patients are well hydrated prior to examination. In patients undergoing abdominal or pelvic examination, opacification of the bowel by dilute oral contrast medium may be valuable in scan interpretation.
Precautions: Patient motion, including respiration, can markedly affect image quality, therefore patient cooperation is essential.
The use of an intravascular contrast medium can obscure some tumors in patients undergoing CT evaluation, resulting in a false negative diagnosis.
Computed Tomography of the Head Neoplastic Conditions: Optiray 300, Optiray 320 or Optiray 350 may be used to enhance the demonstration of the presence and extent of certain primary or metastatic malignancies.
The usefulness of contrast enhancement for the investigation of the retrobulbar space and in cases of low grade or infiltrative glioma has not been demonstrated.
In cases where lesions have calcified, there is less likelihood of enhancement. Following therapy, tumors may show decreased or no enhancement. Maximum contrast enhancement of certain tumors may be delayed necessitating delayed scans.
Non-Neoplastic Conditions: The use of Optiray 300, 320 or 350 may be beneficial in the image enhancement of non-neoplastic lesions, such as cerebral infarctions of recent onset; however, some infarctions are obscured if contrast media are used.
Arteriovenous malformations and aneurysms will show contrast enhancement. In the case of these vascular lesions, the enhancement is probably dependent on the iodine content of the circulating blood pool.
Hematomas and intraparenchymal bleeders seldom demonstrate any contrast enhancement. However, in cases of intraparenchymal clot, for which there is no obvious clinical explanation, contrast medium administration may be helpful in ruling out the possibility of associated arteriovenous malformation. (Also see Precautions.)
The opacification of the inferior vermis following contrast medium administration has resulted in false positive diagnosis in a number of normal studies.
Usual Adult Dosage: For adults the usual dosage of Optiray 300, 320 or 350 is 50-100 mL. A maximum dose of 150 mL of Optiray 320 or 350 should not be exceeded. Scanning is usually performed immediately after injection.
Pediatric Dosage: The dose recommended for children one year of age and over is 1 mL/kg to 3 mL/kg of Optiray 320.
Body Computed Tomography: Optiray 300, 320 or 350 may be administered for contrast enhancement of the organs, tissues and larger blood vessels of the chest, abdomen and pelvis.
Continuous or multiple scans separated by intervals of 1-3 seconds during the first 30-90 seconds post-injection of the contrast medium (dynamic CT scanning) are required to demonstrate enhanceable lesions not seen with CT alone. Subsets of patients in whom delayed body CT scans might be helpful have not been identified.
Inconsistent results have been reported and abnormal and normal tissues are usually isodense during the time frame used for delayed CT scanning. At present, consistent results have been documented using dynamic CT techniques only.
Usual Adult Dosage: Optiray 300, 320 or 350 may be administered by bolus injection, rapid infusion or by a combination of both. Depending on the area to be examined, the usual dose range for infusion is 30-100 mL. When prolonged enhancement is required, 25-50 mL may be given as a rapid bolus and the remainder as an infusion. The total dose should not exceed 150 mL of Optiray 300, 320 or 350. Scanning is usually performed immediately after injection.
Pediatric Dosage: The dose recommended for use in children one year of age and over is 1 mL/kg to 3 mL/kg body weight of Optiray 320 with a usual dose of 2 mL/kg.
VENOGRAPHY: Optiray 300 or 350 may be used to visualize the peripheral venous circulation. Venograms are obtained by injection or infusion into an appropriate vein in the lower extremity.
Precautions: In addition to the general precautions previously described, specific caution is advised when venography is required in patients with suspected thrombosis, phlebitis, severe ischemic disease, local infection or a significantly obstructed venous system.
Extreme caution is necessary to avoid extravasation and fluoroscopy is recommended. This is especially important in patients with severe venous disease.
Adverse Reactions: Complications of the procedure include bleeding, thrombosis, embolism, contrast medium-induced thrombophlebitis, gangrene and major systemic adverse reactions.
Usual Adult Dosage: The usual adult dose of Optiray 300 or 350 will range from 20-100 mL for the lower extremity.
Following the procedure, the venous system should be flushed with normal or heparinized saline solution. Massage and elevation of the leg are also helpful for clearing the contrast medium from the extremity to prevent post-procedural thrombophlebitis. The maximum dose should not usually exceed 250 mL.
EXCRETORY UROGRAPHY: Optiray 300, 320 or 350 may be used for excretory urography. Following intravenous injection in patients with normal renal function. Optiray is excreted mostly by the kidneys. Maximum radiographic density in the calyces and pelves occurs in most instances within 5 to 15 minutes after injection.
In patients with severe renal impairment, contrast visualization may be substantially delayed, or may not occur at all.
Patient Preparation: A low residue diet the day preceding the examination, and a laxative the evening before the examination, may be given unless contraindicated. Partial dehydration is dangerous and may contribute to acute renal failure. Maintenance of normal hydration is desirable.
Precautions: Adequate renal function must be present. Dehydration will not improve contrast quality in patients with impaired renal function and will increase the risk of contrast induced renal damage. The examination should not be repeated for at least 72 hours because of the potential of additive renal damage. (Also see Warnings and Precautions.)
Adverse Reactions: All adverse reactions known to occur with the i.v. use of Optiray can also occur with excretory urography (see Adverse Reactions).
Usual Adult Dosage: The usual adult dose of Optiray 300, Optiray 320 or Optiray 350 is 50 mL in the average normal adult. In these patients, high dose urography may be preferred using Optiray 320 at a dose of 1.5-2 mL/kg. The dose is injected intravenously, usually within 1-3 minutes. Maximum doses of 150 mL of Optiray 300 or 320 and 140 mL of Optiray 350 should not be exceeded.
Pediatric Dosage: Optiray 300 and 320 at doses of 0.5 mL/kg to 3 mL/kg of body weight has produced diagnostic opacification of the urinary tract. The usual dose for children is 1 mL/kg. Dosage for children over 1 year of age should be administered in proportion to age and body weight. The total administered dose should not exceed 3 mL/kg. (See Table 2.)

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Dosage and Administration: It is advisable that sterile Optiray products in vials, bottles or in Ultraject syringes be at or close to body temperature when infused.
Overdosage
The adverse effects of overdosage are life-threatening and affect mainly the pulmonary, cardiovascular and central nervous systems. Treatment of an overdosage is directed toward the support of all vital functions, and prompt institution of specific therapy.
Optiray does not bind to plasma or serum proteins and is therefore dialysable.
Contraindications
Optiray (ioversol) should not be administered to patients with known or suspected hypersensitivity to ioversol or in cases of clinically significant impairment of both hepatic and renal function.
Warnings
USE THE RECOMMENDED OPTIRAY (IOVERSOL) CONCENTRATION FOR THE PARTICULAR PROCEDURE TO BE UNDERTAKEN.
GENERAL: Serious or fatal reactions have been associated with the administration of all iodine containing radiopaque media, including Optiray (ioversol). It is of utmost importance that a course of action be carefully planned in advance for immediate treatment of serious reactions, and that adequate facilities and appropriate personnel be readily available in case a severe reaction should occur.
A previous reaction to a contrast medium of different chemical structure or a history of iodine sensitivity is not an absolute contraindication to the use of Optiray. However, extreme caution should be exercised in injecting these patients and prophylactic therapy (as with corticosteroids for example) should be considered. (See General under Precautions.)
There must be a clear indication for performing procedures involving the administration of contrast agents in all patients.
Patients with a history of allergy, bronchial asthma or other allergic manifestations, combined renal and hepatic disease, the elderly, debilitated or severely ill patients, those with homocystinuria, endotoxemia, elevated body temperature, severe hypertension or congestive heart failure, other cardiovascular disease, hyperthyroidism and recent renal transplant recipients, as well as patients sensitive to iodine, present an additional risk and call for careful evaluation of the risks involved against the benefits expected.
Patients with a serum creatinine level above 3 mg/dL should not undergo excretory urography or other radiological procedures unless the benefits clearly outweigh the risks incurred.
In patients with advanced renal disease, iodinated contrast media should be used with caution and only when the examination is essential since excretion of the medium is impaired. Use of Optiray is not recommended in patients with anuria or severe oliguria.
Administration of radiopaque materials to patients known or suspected to have pheochromocytoma should be performed with extreme caution if, in the opinion of the physician, the possible benefits of such procedures outweigh the considered risks. The amount of radiopaque medium injected should be kept to an absolute minimum. The blood pressure should be assessed throughout the procedure and measures for treatment of a hypertensive crisis should be available.
General anaesthesia may be indicated in some procedures; however, one should be aware of possible increased incidence of adverse reactions in such circumstances.
The administration of Optiray should be terminated if rash, abdominal pain, vomiting and breathing difficulties occur and consult the physician for the further treatment.
VASCULAR USE: Intravascularly administered iodine containing contrast media are potentially hazardous.
Non-ionic iodinated contrast media, including Optiray (ioversol), inhibit blood coagulation less than ionic contrast media. Clotting has been reported when blood remains in contact with syringes, catheters or tubes containing non-ionic contrast media. Serious, rarely fatal, thromboembolic events causing myocardial infarction and stroke have been reported during angiographic procedures with non-ionic and also with ionic contrast media. Therefore, meticulous intravascular administration technique is necessary, particularly during angiographic procedures, to minimize thromboembolic events. Numerous factors, including length of procedure, number of injections, catheter and syringe material, underlying disease state and concomitant medications may contribute to the development of thromboembolic events. For these reasons, meticulous angiographic techniques are recommended including close attention to keeping guidewires, catheters and all angiographic equipment free of blood, use of manifold systems and/or three way stopcocks, frequent catheter flushing with heparinized saline solutions and minimizing the length of the procedure. Non-ionic iodinated contrast media are not recommended as flush solutions. The use of plastic syringes in place of glass syringes has been reported to decrease but not eliminate the likelihood of clotting.
In patients who are known to have multiple myeloma and other paraproteinemias, because of the risk of inducing transient to fatal renal failure, extreme caution should be used. In these instances, anuria has developed resulting in progressive uremia, renal failure and eventually death. A minimal diagnostic dose should be employed and renal function, as well as extent of urinary precipitation of the myelomatous protein, should be monitored for a few days subsequent to the procedure. The patients should be normally hydrated for the examination since dehydration may predispose to precipitation of myeloma protein in the renal tubules. No form of therapy, including dialysis, has been successful in reversing the effect.
Intravascular administration of contrast media may promote sickling in individuals who are homozygous for sickle cell disease. Fluid restriction is not advised in these patients.
As with any contrast medium, including Optiray, serious neurologic sequelae, including permanent paralysis, can occur following cerebral arteriography and injection into vessels supplying the spinal cord. The injection of a contrast medium should never be made following the administration of vasopressors since they strongly potentiate neurologic effects.
Special Precautions
GENERAL: All procedures utilizing contrast media carry a definite risk of producing severe, life threatening and fatal reactions. Therefore, the need for the examination should always be carefully assessed and the risk-benefit factor should always be carefully evaluated before such a procedure is undertaken.
At all times a fully equipped emergency cart, or equivalent supplies and equipment, and personnel competent in recognizing and treating adverse reactions of all severity, or situations which may arise as a result of the procedure, should be immediately available. If a serious reaction should occur, immediately discontinue administration and institute appropriate treatment. Since severe delayed reactions have been known to occur, emergency facilities and competent personnel should be available for at least 30 to 60 minutes after administration.
The reported incidences of adverse reactions to contrast media are twice as high in patients with a history of allergy than in the general population. Patients with a history of previous reactions to a contrast medium or iodine are three times more susceptible than other patients. Most adverse reactions to intravascularly injected contrast agents appear within one to 30 minutes after the start of injection, but delayed reactions may occur.
Before a contrast medium is injected, the patient should be questioned for a history of bronchial asthma or allergy.
Although a history of allergy may imply a greater than usual risk, it does not arbitrarily contraindicate the use of the medium. Premedication with corticosteroids to avoid or minimize possible allergic reactions may be considered.
The possibility of an idiosyncratic reaction in patients who have previously received a contrast medium without ill effect should always be considered. A positive history of bronchial asthma or allergy, a family history of allergy, or a previous reaction of hypersensitivity to another contrast agent warrant special attention. Such a history, by suggesting proneness to reactions, may be more accurate than pre-testing in predicting the potential for reaction, although not necessarily the severity or type of reaction in the individual case. A positive history of this type does not arbitrarily contraindicate the use of contrast agent, when a diagnostic procedure is thought essential, but calls for caution.
The sensitivity test most often performed is the slow injection of 0.5 to 1.0 mL of the radiopaque medium, administered intravenously, prior to injection of the full dose. It should be noted that the absence of a reaction to the test dose does not preclude the possibility of a reaction to the full dose. Severe reactions and fatalities have occurred with the full dose after a non-reactive test dose, and with or without a history of allergy.
Prophylactic therapy with corticosteroids should be considered for patients who present with a strong allergic history, a previous reaction to a contrast medium, or a positive pre-test (since in these patients the incidence of reaction is two to three times that of the general population). Adequate doses of corticosteroids should be started early enough prior to contrast medium injection to be effective and should continue through the time of injection and for 24 hours after injection. Corticosteroids should not be mixed in the same syringe with the contrast medium because of chemical incompatibility.
Renal failure has been reported in patients with liver dysfunction who were given an oral cholecystographic agent followed by an intravascular iodinated radiopaque agent and also in patients with occult renal disease, notably diabetics and hypertensives. Administration of Optiray should be postponed in patients with hepatic or biliary disorders who have recently taken a cholecystographic agent. An interval of at least 48 hours should be allowed between examinations, especially in patients with reduced renal reserve. Especially in these classes of patients there should be no fluid restriction and every attempt made to maintain normal hydration, prior to contrast medium administration, since dehydration is the single most important factor influencing further renal impairment.
Acute renal failure has been reported in patients with diabetic nephropathy and in susceptible non-diabetic patients (often elderly with pre-existing renal disease) following administration of iodinated contrast agents. Careful consideration of the potential risks should be given before performing radiographic procedures with Optiray (ioversol) in these patients.
INTRAVASCULAR: Diagnostic procedures which involve the use of iodinated intravascular contrast agents should be carried out under the direction of a physician skilled and experienced in the particular procedure to be performed.
Reports of thyroid storm occurring following intravascular use of iodinated radiopaque agents in patients with hyperthyroidism or with an autonomously functioning thyroid nodule, suggest that this additional risk be carefully evaluated in such patients before use of Optiray.
Special precaution is advised in patients with increased intra-cranial pressure, cerebral thrombosis or embolism, primary or metastatic cerebral lesions, subarachnoid hemorrhage, arterial spasm, transient ischemic attacks, and in any condition when the blood-brain barrier is breached or the transit time of the contrast agent material through the cerebral vasculature is prolonged, since clinical deterioration, convulsions, and serious temporary or permanent neurological complications (including stroke, aphasia, cortical blindness, etc.) may occur following intravenous or intra-arterial injection of relatively large doses of contrast media. Such patients, and patients in clinically unstable or critical condition should undergo examinations with intravascular contrast media only if in the opinion of the physician the expected benefits outweigh the potential risks, and the dose should be kept to the absolute minimum.
When considering the use of high doses of contrast media, caution should be exercised in patients with congestive heart failure because of the transitory increase in circulatory osmotic load, and such patients should be kept under surveillance for several hours in order to detect delayed hemodynamic disturbances.
There have been reports in the literature indicating that patients on adrenergic beta-blockers may be more prone to severe adverse reactions to contrast media. At the same time, treatment of allergic-anaphylactoid reactions in these patients is more difficult. Adrenaline should be administered with caution since it may not exert its usual effects. On the one hand larger doses of adrenaline may be needed to overcome the bronchospasm, while on the other, these doses can be associated with excessive alpha adrenergic stimulation with consequent hypertension, reflex bradycardia and heart-block and possible potentiation of bronchospasm. Alternatives to the use of large doses of adrenaline include vigorous supportive care such as fluids and the use of beta agonists including parenteral salbutamol or isoproterenol to overcome bronchospasm and norepinephrine to overcome hypotension.
In angiographic procedures, the presence of a vigorous pulsatile flow should be established before using a catheter or pressure injection technique. A small "pilot" dose of about 1-2 mL should be administered to locate the exact site of needle or catheter tip to help prevent injection of the main dose into a branch of the aorta or intramurally. Great care should be taken to avoid the entry of a large concentrated bolus into an aortic branch.
Mesenteric necrosis, acute pancreatitis, renal shutdown, serious neurologic complications including spinal cord damage and hemiplegia or quadriplegia have been reported following inadvertent injection of a large part of the aortic dose of contrast media into an aortic branch or arterial trunks providing spinal or cerebral artery branches.
Pulsation must be present in the artery to be injected. Extreme caution is advised in considering peripheral angiography in patients suspected of having thromboangiitis obliterans (Buerger's disease) since any procedure (even insertion of needle or catheter) may induce a severe arterial or venous spasm. Caution is also advisable in patients with severe ischemia associated with ascending infection. Special care is required in patients with suspected thrombosis, ischemic disease, local infection or a significantly obstructed vascular system. Occasional serious neurologic complications, including paraplegia, have been reported in patients with aorta-iliac or femoral artery bed obstruction, abdominal compression, hypotension, hypertension and following injection of vasopressors.
When large individual doses are administered an appropriate time interval should be permitted to elapse between injections to allow for subsidence of hemodynamic disturbances. Angiography should be avoided whenever possible in patients with homocystinuria because of the risk of inducing thrombosis and embolism. Following catheter procedures, gentle pressure hemostasis is advised followed by immobilization of the limb for several hours to prevent hemorrhage from the site of arterial puncture.
Intravenous Contrast Enhancement in Computed Tomography: Following injection of relatively large doses of contrast media used in the procedure, transient or permanent neurological changes have been reported.
Use in Pregnancy: No teratogenic effects attributable to Optiray (ioversol) have been observed to date in studies performed in animals. There are no studies on the use of Optiray in pregnant women. Many injectable contrast media cross the placental barrier in humans and appear to enter fetal tissue passively. Optiray probably crosses the placental barrier in humans by simple diffusion to reach fetal tissue. Optiray should be used during pregnancy only if the benefit to the mother clearly outweighs the risk to the fetus. It should be borne in mind that X-ray procedures involve a certain risk related to exposure of the fetus.
Use in Lactation: Because contrast media are secreted in human milk, if the administration of Optiray is considered to be essential, breast feeding should be discontinued for at least 48 hours following the procedure.
Use in Children: Some pediatric patients have a higher risk of adverse reactions to contrast media. Such patients may include those with sensitivity to allergens, including other drugs, those with asthma, congestive heart failure, a serum creatinine > 1.5 mg/dL, or ages under 12 months.
Use in the Elderly: The tolerance of elderly patients to drugs in general is diminished. These patients may have reduced renal reserve, impaired general health and may be taking medication (e.g. adrenergic B-blockers) which make them more susceptible to the potentially harmful effects of procedures involving the use of contrast media. The need for and the expected benefits of the procedure have to be carefully evaluated and dosage should be very conservative.
Use In Pregnancy & Lactation
Use in Pregnancy: No teratogenic effects attributable to Optiray (ioversol) have been observed to date in studies performed in animals. There are no studies on the use of Optiray in pregnant women. Many injectable contrast media cross the placental barrier in humans and appear to enter fetal tissue passively. Optiray probably crosses the placental barrier in humans by simple diffusion to reach fetal tissue. Optiray should be used during pregnancy only if the benefit to the mother clearly outweighs the risk to the fetus. It should be borne in mind that X-ray procedures involve a certain risk related to exposure of the fetus.
Use in Lactation: Because contrast media are secreted in human milk, if the administration of Optiray is considered to be essential, breast feeding should be discontinued for at least 48 hours following the procedure.
Adverse Reactions
Since Optiray (ioversol) is an iodinated contrast agent with an adverse reaction profile similar to other non-ionic contrast media, all known adverse effects associated with the use of any contrast agent can occur with Optiray.
Most adverse reactions following the use of Optiray are of mild or moderate intensity, however, serious, life-threatening and fatal adverse reactions, mostly of cardiovascular origin, have been reported.
It should be kept in mind that, although most adverse reactions occur soon after the administration of the contrast medium, some adverse reactions can be delayed and can be of long-lasting nature.
The reported incidence of adverse reactions to contrast media in patients with a history of allergy is twice that of the general population. Patients with a history of previous reactions to a contrast medium are three times more susceptible than other patients.
The incidence of serious adverse reactions is higher with coronary arteriography than with other procedures. In those patients only who had coronary arteriography with Optiray, the incidence of angina was 1.2%. Cardiac decompensation, serious arrhythmias, myocardial ischemia or myocardial infarction may occur during coronary arteriography and left ventriculography.
In a controlled clinical trial involving 30 pediatric patients undergoing angiocardiography, no adverse reactions were reported.
The following table of reactions is based upon clinical trials with Optiray formulations in 1506 patients, regardless of their direct attributability to the drug or the procedure.
Adverse reactions to specific procedures are also dealt with under Dosage & Administration. (See Table 3.)

Click on icon to see table/diagram/image

In addition to the previously reported reactions, the following may occur with any contrast agent, including Optiray: Cardiovascular System: Hypoxia, heart block, bundle branch block, coronary thrombosis, cyanosis, hypertensive crisis, peripheral vasodilation, acute vascular insufficiency, circulatory collapse, hypotensive shock, cardiogenic shock.
Central Nervous System: Photomas, persistent blindness, taste perversion, anxiety, tinnitus, motor dysfunction, convulsion, somnolence, confusion, psychotic reaction, stiff neck, hemiparesis, hemiplegia, nystagmus, restlessness, tremors, aphasia, paralysis, coma and death.
Allergic Type Reaction: Purpura, conjunctivitis, lacrimation, erythematous, bullous or pleomorphic rashes, laryngospasm, bronchospasm, apnea, cyanosis, edema of glottis, laryngeal edema, angioneurotic edema, peripheral edema, anaphylactic shock. These allergic type reactions can progress into anaphylaxis, coma and death.
Renal System: Transient proteinuria, hematuria and rarely oliguria, anuria and renal failure.
Other Reactions: Diarrhea, dry mouth, pallor, venous and arterial thrombosis and rarely thrombophlebitis, rare cases of disseminated intravascular coagulation, neutropenia.
Pediatrics: In controlled clinical trials involving 128 patients for pediatric angiocardiography, contrast enhanced computed tomography of the head and body, and intravenous excretory urography, adverse reactions following the use of Optiray 320 were generally less frequent than with adults. Adverse reactions reported were as follows: fever (1.6%), nausea (0.8%), muscle spasm (0.8%), LV pressure change (0.8%).
Related to Procedure: Extravasation, perforation, rupture, dissection of blood vessels, hemorrhage, hematoma, false aneurysm, muscle spasm, arterial spasm, vascular trauma, ecchymosis and tissue necrosis, dislodgement of atheromatous plaques, thrombophlebitis, thrombosis embolization, injury to nerves and neighbouring organs, brachial plexus palsy following axillary artery injections.
TREATMENT OF ADVERSE REACTIONS TO CONTRAST MEDIA: Contrast media should be administered only by physicians thoroughly familiar with the emergency treatment of all adverse reactions to contrast media. The assistance of other trained personnel such as cardiologists, internists and anesthetists is required in the management of severe reactions.
A guideline for the treatment of adverse reactions is presented as follows. This outline is not intended to be a complete manual on the treatment of adverse reactions to contrast media or on cardio-pulmonary resuscitation. The physician should refer to the appropriate texts on the subject.
It is also realized that institutions or individual practitioners will already have appropriate systems in effect and that circumstances may dictate the use of additional or different measures.
For Minor Allergic Reactions (if considered necessary): The intravenous or intramuscular administration of an antihistamine such as diphenhydramine HCl 25-50 mg is generally sufficient (contraindicated in epileptics). The resulting drowsiness makes it imperative to ensure that out-patients do not drive or go home unaccompanied.
Major or Life-threatening Reactions: A major reaction may be manifested by signs and symptoms of cardiovascular collapse, severe respiratory difficulty and nervous system dysfunction. Convulsions, coma and cardio-respiratory arrest may ensue. The following measures should be considered: 1. Start emergency therapy immediately - carefully monitoring vital signs.
2. Have emergency resuscitation team summoned - do not leave patient unattended.
3. Ensure patent airway - guard against aspiration.
4. Commence artificial respiration if patient is not breathing.
5. Administer oxygen, if necessary.
6. Start external cardiac massage in the event of cardiac arrest.
7. Establish route for i.v medication by starting infusion of appropriate solution (5% dextrose in water).
8. Judiciously administer specific drug therapy as indicated by the type and severity of the reaction.
Careful monitoring is mandatory to detect adverse reactions of all drugs administered: a) Soluble hydrocortisone 500-1000 mg i.v. for all acute allergic anaphylactic reactions.
b) Adrenaline 1:1000 solution (in the presence of anoxia it may cause ventricular fibrillation; CAUTION in patients on adrenergic beta blockers. See Precautions).
i) 0.2-0.4 mL subcutaneously for severe allergic reactions.
ii) in extreme emergency 0.1 mL per minute, appropriately diluted, may be given intravenously until desired effect is obtained. Do not exceed 0.4 mL.
iii) in case of cardiac arrest 0.1-0.2 mL, appropriately diluted, may be given intracardially.
c) In hypotension (carefully monitoring blood pressure): i) Phenylephrine HCl 0.1-0.5 mg appropriately diluted slowly i.v. or by slow infusion OR; ii) Noradrenalin 4 mL of 0.2% solution in 1000 mL of 5% dextrose by slow drip infusion.
d) Sodium bicarbonate 5%, 50 mL i.v. every 10 minutes as needed to combat post-arrest acidosis.
e) Atropine 0.4-0.6 mg i.v. to increase heart rate in sinus bradycardia. May reverse 2nd or 3rd degree block.
f) To control convulsions: i) Pentobarbital Sodium 50 mg in fractional doses slowly i.v. (contraindicated if cyanosis is present) OR; ii) Diazepam 5-10 mg slowly i.v. titrating the dose to the response of the patient.
9. Defibrillation, administration of antiarrhythmics and additional emergency measures and drugs may be required.
10. The patient should be transferred to the intensive care unit when feasible for further monitoring and treatment.
Drug Interactions
Drugs which lower seizure threshold, especially phenothiazine derivatives, including those used for their antihistaminic or antinauseant properties, should not be used with Optiray.
Renal toxicity has been reported in a few patients with liver dysfunction who were given oral cholecystographic agents followed by intravascular contrast agents. Therefore administration of a contrast agent should be postponed by at least 48 hours following use of an oral cholecystographic agent.
Repeat Procedures: If in the clinical judgment of the physician a repeat examination is required, an interval of 5 days between procedures is recommended.
Special precautions, to be observed when performing specific diagnostic procedures, are listed in Dosage & Administration, under individual paragraphs pertaining to said specific procedures.
Storage
Recommendations: Store at or below 25°C.
Discard unused portion.
Submersion of syringes in water is not recommended.
Do not re-autoclave plastic container because of possible damage to syringe. Protect from light.
Protect from freezing.
ATC Classification
V08AB07 - ioversol ; Belongs to the class of watersoluble, nephrotropic, low osmolar preparations used as X-ray contrast media.
Presentation/Packing
Inj 300 mg/mL x 50 mL x 10's, 100 mL x 10's. 350 mg/mL x 50 mL x 10's, 100 mL x 10's. Pre-filled syringe 320 mg/mL x 100 mL x 10's. 350 mg/mL x 100 mL x 10's.
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