Optiray (Ioversol)

OPTIRAY®

Mallinckrodt

Ioversol

Radiopaque Medium

Action And Clinical Pharmacology: General: The pharmacokinetics of ioversol in normal subjects conform to an open 2 compartment model with first order elimination (a rapid alpha phase 6.8 minutes, for drug distribution and a slower beta phase 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 to 156) and following a 150 mL dose was 105 minutes.

Ioversol is excreted mainly through the kidneys following intravascular administration. Fecal elimination is 3 to 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.

Ioversol does not notably bind to serum or plasma proteins to any marked extent and no significant metabolism, deionization or biotransformation occurs.

Ioversol, like all other contrast media, may induce changes in thyroid function in some patients, and elevation of thyroxine and/or TSH may be observed.

Ioversol, like other nonionic 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 anticoagulant properties of ionic contrast media.

Ioversol causes concentration-dependent hemolysis, aggregation and crenation of red blood cells.

Elevations of several laboratory parameters (AST, ALT, LDH, bilirubin, creatinine, BUN) following intravascular administration have been reported in several patients which were not considered clinically significant.

Intravascular: Intravascular injection of ioversol opacifies those vessels in the path of flow of the contract bolus, permitting their radiographic visualization.

Following i.v. 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 i.v. 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.

Ioversol may be visualized in the renal parenchyma within 30 to 60 seconds following rapid i.v. injection. Opacification of the calyces and pelves in patients with normal renal function becomes apparent within 1 to 3 minutes, with optimum contrast occurring within 5 to 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.

Ioversol (33%I) was compared in intra-carotid studies in 45 anesthetized rats to iopamidol (32%I) and iohexol (30%I). 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 ioversol than with conventional ionic media. Comparative studies using diatrizoate and iothalamate showed significantly less heat sensation and pain with ioversol. Other non-ionic agents, iohexol and iopamidol, gave results similar to ioversol.

Ioversol 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.

Subarachnoid: Following its injection into the subarachnoid space, ioversol mixes readily with the cerebrospinal fluid (CSF) and diffuses into root sleeves and upward in the spinal and intracranial subarachnoid spaces. The time it takes ioversol to reach the cervical and intracranial subarachnoid spaces will depend to a large degree on the patient’s position and movements. As it diffuses upward, its concentration decreases.

Following lumbar subarachnoid injection, conventional radiography will continue to provide good diagnostic degree of contrast for at least 30 minutes. At about 1 hour, a diagnostic degree of contrast will usually not be available due to diffusion through the CSF and transfer to the general circulation.

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 i.v. bolus administration.

CT Scanning of the Body: During CT of the body, ioversol diffuses rapidly from the vascular to the extravascular 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 extravascular 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 And Clinical Uses: Intravascular: Optiray 160: Adults: For use in adults for intra-arterial digital subtraction angiography.

Optiray 240: Adults: For use in adults for cerebral angiography, venography, excretory urography and for contrast enhanced computed tomographic imaging of the head and body. Optiray 240 may be used in myelography.

Optiray 300: Adults: For use in adults for cerebral angiography, aortography, peripheral and visceral arteriography, i.v. contrast enhancement of computed tomography of the brain and body, excretory urography, i.v. digital subtraction angiography and venography.

Children: In children 1 year of age or over for i.v. excretory urography and intra-arterial digital subtraction angiography.

Optiray 320: Adults: 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 in excretory urography.

Children: For angiocardiography, contrast enhanced computed tomography of the head and body, excretory urography.

Optiray 350: Adults: For coronary arteriography and ventriculography, peripheral and visceral arteriography, i.v. contrast enhancement in computed tomography of the head and body, excretory urography, i.v. digital subtraction angiography and venography.

Children: For angiocardiography.

Subarachnoid: Optiray 240: Adults: For subarachnoid administration in adults for lumbar, thoracic and cervical myelography.

Contra-Indications: 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.

Manufacturers’ Warnings In Clinical States: General: Serious or fatal reactions have been associated with the administration of all iodine-containing radiopaque media, including 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 ioversol. However, extreme caution should be exercised in injecting these patients and prophylactic therapy (as with corticosteroids, for example) should be considered (see Precautions, General).

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 ioversol 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 anesthesia may be indicated in some procedures; however, one should be aware of possible increased incidence of adverse reactions in such circumstances.

Intravascular: Intravascularly administered iodine-containing contrast media are potentially hazardous.

Non-ionic iodinated contrast media, including 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.

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 ioversol, 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.

Subarachnoid: Myelography should not be performed when lumbar puncture is contraindicated as in the presence of local or systemic infection where bacteremia is likely.

Myelography should be performed only in hospitalized patients under close medical supervision, which is to be continued for 24 hours following the procedure.

Patients receiving anticonvulsants should be maintained on this therapy. Should a seizure occur, i.v. diazepam or phenobarbital is recommended. In patients with a history of seizure activity who are not on anticonvulsant therapy, premedication with barbiturates should be considered. Ioversol should be used in epileptics only if a water soluble contrast medium is considered essential.

Prophylactic anticonvulsant treatment with barbiturates should be considered in patients with evidence of inadvertent intracranial entry of a large bolus of contrast medium, since there may be increased risk of seizure in such cases.

Gravitational displacement of a concentrated bolus of ioversol above the level of C1 and especially into the intracranial subarachnoid spaces is to be avoided.

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 3 times more susceptible than other patients. Most adverse reactions to intravascularly injected contrast agents appear within 1 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 warrants special attention. Such a history, by suggesting proneness to reactions, may be more accurate than pretesting 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 a 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 mL of the radiopaque medium, administered i.v., 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 pretest (since in these patients the incidence of reaction is 2 to 3 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 ioversol should be postponed in patients with hepatic or biliary disorder 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 nondiabetic 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 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 ioversol.

Special precaution is advised in patients with increased intracranial 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 i.v. 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. Epinephrine should be administered with caution since it may not exert its usual effects. On the one hand larger doses of epinephrine 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 epinephrine 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 angiography 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 to 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, and 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 aorto-iliac or femoral artery bed obstruction, abdominal compression, hypotension, and 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.

I.V. 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.

Pregnancy: No teratogenic effects attributable to ioversol have been observed to date in studies performed in animals. There are no studies on the use of ioversol in pregnant women. Many injectable contrast media cross the placental barrier in humans and appear to enter fetal tissue passively. Ioversol probably crosses the placental barrier in humans by simple diffusion to reach fetal tissue. Ioversol 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.

Lactation: Because contrast media are secreted in human milk, if the administration of ioversol is considered to be essential, breast-feeding should be discontinued for at least 48 hours following the procedure.

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.

Geriatrics: The tolerance of elderly patients to drugs in general is diminished. These patients may have reduced renal reserve and 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.

Drug Interactions: Drugs which lower seizure threshold, especially phenothiazine derivatives, including those used for their antihistaminic or antinauseant properties, should not be used with ioversol.

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.

Subarachnoid: Elderly patients may present a greater risk following myelography. The need for the procedure in these patients should be evaluated carefully. Special attention must be given not to exceed the recommended dose of the contrast medium, to see that the patient is sufficiently hydrated and to ensure proper and sterile radiographic technique.

If grossly bloody CFS is encountered, the possible benefits of a myelographic procedure should be considered in terms of the risk to the patient.

Any intrathecally administered medication including non-ionic contrast media such as ioversol can enter the brain substance which may increase the risk of adverse effects associated with the procedure. Such adverse reactions may be delayed and, in extremely rare cases, may be life-threatening. Careful patient and dose selection and proper patient management before, during and after the procedure are therefore imperative. Care is required in patient management to prevent inadvertent intracranial entry of a large bolus of contrast medium. Also, effort should be directed to avoid rapid dispersion of the medium (i.e., by active patient movement).

Experience with the use of water-soluble contrast media in myelography indicates that in most cases of major motor seizure one or more of the following factors were present, and should therefore, be avoided: deviations from recommended procedure on myelographic management; use in patients with a history of epilepsy; inadvertent overdosage; intracranial entry of a bolus or premature diffusion of a high concentration of the medium; medication with neuroleptic drugs or phenothiazine antinauseants; failure to maintain elevation of the head during and after the procedure; active patient movement or straining.

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 with performing specific diagnostic procedures are listed in the Dosage section, under individual paragraphs pertaining to said specific procedures.

Adverse Reactions: Since 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 ioversol.

Most adverse reactions following the use of ioversol 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 3 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 ioversol, the incidence of angina was 1.2%. Cardiac decompensation, serious arrhythmias, myocardial ischemia or myocardial infarction may occur during coronary arteriography and left ventriculography.

Adverse Reactions seen with Optiray

Cardiovascular – none angina pectoris, hypotension, blood pressure fluctuation, arterial spasm, bradycardia, conduction defect, false aneurysm, hypertension, transient arrhythmia, vascular trauma

Digestive – none nausea, vomiting

Nervous – none cerebral infarct, headache, blurred vision, vertigo, lightheadedness, vasovagal reaction, disorientation, paresthesia, dysphasia, muscle spasm, syncope, visual hallucination

Respiratory – none laryngeal edema, pulmonary edema, sneezing, nasal congestion, coughing, shortness of breath, hypoxia

Skin – none periorbital edema, urticaria, facial edema, flush, pruritus

Miscellaneous – none extravasation, hematoma, shaking chills, bad taste, general pain

The following may occur with any contrast agent including ioversol: Cardiovascular: hypoxia, heart block, bundle branch block, coronary thrombosis, cyanosis, hypertensive crisis, peripheral vasodilation, acute vascular insufficiency, circulatory collapse, hypotensive shock and cardiogenic shock.

CNS: 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: 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.

Children: In controlled clinical trials involving 128 patients for pediatric angiocardiography, contrast enhanced computed tomography of the head and body and i.v. excretory urography, adverse reactions following the use of Optiray 320 were generally less 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, dislodgment of atheromatous plaques, thrombophlebitis, thrombosis embolization, injury to nerves and neighboring organs, brachial plexus palsy following axillary artery injections.

Treatment of Adverse Effects: 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 below. This outline is not intended to be a complete manual on the treatment of adverse reactions to contrast media or on cardiopulmonary 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.

Minor Allergic Reactions: (if considered necessary). The i.v or i.m. administration of an antihistamine such as diphenhydramine HCl 25 to 50 mg is generally sufficient (contraindicated in epileptics). The resulting drowsiness makes it imperative to ensure that outpatients 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 cardiorespiratory 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 to 1 000 mg i.v. for all acute allergic-anaphylactic reactions. (b) Epinephrine 1:1 000 solution (in the presence of anoxia it may cause ventricular fibrillation, caution in patients on adrenergic beta blockers. See Precautions.) 0.2 to 0.4 mL s.c. for severe allergic reactions; in extreme emergency 0.1 mL/minute, appropriately diluted, may be given i.v. until desired effect is obtained. Do not exceed 0.4 mL; in case of cardiac arrest 0.1 to 0.2 mL, appropriately diluted, may be given intracardially. (c) In hypotension (carefully monitoring blood pressure): phenylephrine HCl 0.1 to 0.5 mg appropriately diluted slowly i.v. or by slow infusion or norepinephrine 4 mL of 0.2% solution in 1 000 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 to 0.6 mg i.v. to increase heart rate in sinus bradycardia. May reverse 2nd or 3rd degree block. (f) To control convulsions: pentobarbital sodium 50 mg in fractional doses slowly i.v. (contraindicated if cyanosis is present) or diazepam 5 to 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.

Symptoms And Treatment Of Overdose: Symptoms and Treatment: 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.

Ioversol does not bind to plasma or serum proteins and is t herefore dialyzable.

Dosage And Administration: Intravascular: 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 ioversol.

Do not dehydrate patients for any procedure.

Ioversol should be inspected visually for particulate matter and discoloration prior to administration. If either is present the vial should be discarded.

Ioversol 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 ioversol 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 ioversol 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 ioversol before injecting the full dose. The catheter tip should be kept free of aspirated blood. Prolonged contact of the contrast medium 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.

Cerebral Angiography: Optiray 320, 300 or 240 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 anesthesia. General anesthesia is rarely required (see Precautions, General).

Precautions: In addition to the general precautions previously described, cerebral angiography with ioversol 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 ioversol 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 nonionic 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 ioversol, 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 ioversol, for cerebral arteriography are not infrequent: ioversol 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 240, Optiray 300 or Optiray 320 may be used for cerebral angiography. The usual adult dosage of ioversol 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 to 10 mL; for vertebral arteriography 4 to 8 mL. For aortic arch injection (4 vessel studies) the usual dose for Optiray 320 is 15 to 25 mL, and for Optiray 240 is 15 to 40 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 160 and Optiray 300 are suitable agents 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 nondiagnostic 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, dislodgment of atheromatous plaques, subintimal injection and transient leg pain from contraction of calf muscles in femoral arteriography.

Usual Adult Dosage Using Optiray 160: As a general rule, the volume and concentration used for IA-DSA are about 50%, or less, of that used for conventional procedures. The actual dosage and flow rate will vary depending on the selectivity of the injection site and the area being examined. The following suggested volumes per injection are intended as a guide (see Table II). Injections may be repeated if necessary. It is advisable to inject at rates approximately equal to the flow rate of the vessel being injected.

Dosage should not usually exceed 250 mL.

Usual Dose in Children 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 Precautions, General).

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 ioversol 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 intramural 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 to 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, extravasation, 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, dislodgment 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 to 50 mL; for iliac and femoral arteries 10 to 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 prerequisites 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, dislodgment 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 to 10 mL and for right coronary arteriography is 2 to 6 mL. For left ventriculography, the usual single adult dose is 30 to 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.

Children: Optiray 320 or 350 is recommended for this procedure. The usual single dose of Optiray 320 is 1.25 mL/kg body weight with a range of 1 to 1.5 mL/kg. When multiple injections are given, the total administered dose should not exceed 5 mL/kg up to a total of 250 mL.

Aortography and Visceral Arteriography: Optiray 300, 320 or 350 is recommended for this procedure. Great care is necessary to avoid all entry 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 on 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 neighboring 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 aorto-iliac 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: Optiray 300, Optiray 320 or Optiray 350 is recommended for this procedure. The usual individual injection volumes are as follows: abdominal aorta 20 to 50 mL, superior mesenteric artery 20 to 40 mL and renal artery 4 to 10 mL.

Total procedural dose should not exceed 250 mL.

I.V. 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.

Manufacturers’ Warnings In Clinical States: 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 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 240, 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 240, Optiray 300, Optiray 320 or Optiray 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 (see Precautions).

The opacification of the inferior vermis following contrast medium administration has resulted in false positive diagnoses in a number of normal studies.

Usual Adult Dosage: For adults the usual dosage of Optiray 300, 320 or 350 is 50 to 100 mL; of Optiray 240, 100 to 250 mL. A maximum dose of 150 mL of Optiray 320 or 350 should not be exceeded. For Optiray 240 the maximum dose is 250 mL. Scanning is usually performed immediately after injection.

Children: The dose recommended for use in children 1 year of age and over is 1 to 3 mL/kg of Optiray 320.

Body Computed Tomography: Optiray 240, 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 to 3 seconds during the first 30 to 90 seconds postinjection 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 240, 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 is 30 to 100 mL. When prolonged enhancement is required, 25 to 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 or 200 mL of Optiray 240. Scanning is usually performed immediately after injection.

Children: The dose recommended for use in children 1 year of age and over is 1 to 3 mL/kg of Optiray 320.

Venography: Optiray 240, 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 240, 300 or 350 will range from 20 to 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 240, 300, 320 or 350 may be used for excretory urography. Following i.v. 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 (see Warnings and Precautions).

Adverse Reactions: All adverse reactions known to occur with the i.v. use of ioversol can also occur with excretory urography (see Adverse Effects).

Usual Adult Dosage: The usual adult dose of Optiray 300, 320 or 350 is 50 mL in the average normal adult. With Optiray 240 the equivalent dose range is 65 mL in the average normal adult. The dose is injected i.v., usually within 1 to 3 minutes. Maximum doses of 200 mL of Optiray 240, 150 mL of Optiray 300 or 320 and 140 mL of Optiray 350 should not be exceeded.

Children: Optiray 300 and 320 at doses of 0.5 to 3 mL/kg body weight have produced diagnostic opacification of the urinary tract. The usual dose for children is 1 mL/kg.

The total dosage in children should not normally exceed 3 mL/kg.

Subarachnoid: Precautions: Optiray 240 is recommended for the examination of lumbar, thoracic and cervical regions in adults by lumbar injection. Myelography should not be performed in the presence of significant local or systemic infection where bacteremia is likely or when lumbar or cervical puncture is contraindicated.

The volume and concentration of Optiray 240 to be administered will depend on the degree and extent of contrast required within the recommended dose range in the area under examination, and on the equipment and technique employed. Optiray 240 is slightly hypertonic to CSF.

A total dose of 3 600 mg (15 mL) iodine should not be exceeded in adults. As in all diagnostic procedures, the minimum volume and dose to produce adequate visualization should be used. Most procedures do not require the total maximum dose.

Anesthesia is not necessary. Patients should be well hydrated. Seizure-prone patients should be maintained on anticonvulsant medication.

Adverse Reactions: Any adverse reactions known to occur with the i.v. use of ioversol can also occur during myelography, especially those which originate in the CNS. The most commonly observed adverse reaction was headache, which had an incidence of 8.6%.

Rate of injection: To avoid excessive mixing with CSF and consequent dilution of contrast, injection should be made slowly, over 1 to 2 minutes.

Depending on the estimated volume of ioversol which may be required for the procedure, a small amount of CSF may be removed to minimize distension of the subarachnoid spaces, unless contraindicated.

The spinal puncture needle may be removed immediately following injection because it is not usually necessary to remove ioversol after injection into the subarachnoid space.

If, in the clinical judgment of the physician, a repeat examination is required, an interval of 5 days between procedures is recommended.

Adults: Usual Dose: The usual recommended total dose of Optiray 240 for use in lumbar myelography is 10 mL and for thoracic and cervical myelography 15 mL. The following table (see Table III) indicates these dosages.

If computerized tomography is to follow, it should be deferred for 2 to 6 hours to allow the amount of contrast to decrease. Computerized tomography shows CSF contrast enhancement in the thoracic region in about one hour.

Patient Management – Subarachnoid Administration: Good patient management should be exercised at all times to minimize the potential for complications.

Pre-procedure: Discontinue neuroleptic drugs (including phenothiazines, e.g., chlorpromazine, prochlorperazine and promethazine) at least 48 hours beforehand. Maintain normal diet up to 2 hours before procedure. Premedication is not usually considered necessary. Should myelography be necessary in patients with a history of seizures, such patients should be maintained on their anticonvulsant medication.

During Procedure: Use minimum dose required for satisfactory contrast (see Dosage). In all positioning techniques keep the patient’s head elevated above highest level of spine. Do not lower head of table more than 15° during examination. In patients with excessive lordosis consider lateral position for injection. Inject slowly (over 1 to 2 minutes) to avoid excessive mixing. Move medium within the spinal subarachnoid space under fluoroscopic monitoring. Avoid intracranial entry of a bolus. Avoid early and high cephalad dispersion of the medium. Avoid abrupt or active patient movement to minimize excessive mixing with CSF. Instruct patient to remain passive . Move patient slowly and only as necessary.

Post-procedure: Following myelography move contrast medium to low lumbosacral area by upright positioning of the patient, for a few minutes. Raise head of stretcher to at least 30° before moving patient onto it. Movement onto and off the stretcher should be done slowly with patient completely passive, maintaining head-up position.

Before moving patient onto bed, raise head of bed 30 to 45°. Some clinicians advise patients to remain still in bed, in head-up position or in the semi-sitting position, especially in the first few hours. Others have encouraged their patients to be fully ambulatory and have noted a reduction in the incidence of headache, nausea and vomiting. Maintain close observation and head-up position for at least 24 hours after myelogram. Obtain visitors’ cooperation in keeping the patient quiet and in head-up position, especially in first few hours. Encourage oral fluids. Diet as tolerated. If nausea or vomiting occur do not use phenothiazine antinauseants. Persistent nausea and vomiting will result in dehydration. Therefore prompt consideration of replacement by i.v. fluids is recommended.

Availability And Storage: Optiray 160: Each mL of clear, colorless to pale yellow, sterile, nonpyrogenic aqueous solution (ioversol injection 34%) contains: ioversol 339 mg with tromethamine 3.6 mg as a buffer and edetate calcium disodium 0.2 mg as a stabilizer. Optiray 160 provides 16% (160 mg/mL) of organically bound iodine. Osmolality (mOsm/kg water): 355. Viscosity (cps): 2.7 (25°C) and 1.9 (37°C). Vials of 50 mL, boxes of 10 and 25. Bottles of 100 mL fill/150 mL, boxes of 6 and 12.

Optiray 240: Each mL of clear, colorless to pale yellow, sterile, nonpyrogenic aqueous solution (ioversol injection 51%) contains: ioversol 509 mg with tromethamine 3.6 mg as a buffer and edetate calcium disodium 0.2 mg as a stabilizer. Optiray 240 provides 24% (240 mg/mL) organically bound iodine. Osmolality (mOsm/kg water): 502. Viscosity (cps): 4.0 (25°C) and 3.0 (37°C). Vials of 15 mL fill/20 mL, boxes of 10, vials of 50 mL, boxes of 10 and 25. Bottles of 100 mL fill/150 mL, boxes of 6 and 12. Bottles of 200 mL fill/250 mL, boxes of 6 and 12.

Optiray 300: Each mL of clear, colorless to pale yellow, sterile nonpyrogenic aqueous solution (ioversol injection 64%) contains: ioversol 636 mg with tromethamine 3.6 mg as a buffer and edetate calcium disodium 0.2 mg as a stabilizer. Optiray 300 provides 30% (300 mg/mL) organically bound iodine. Osmolality (mOsm/kg water): 651. Viscosity (cps): 8.2 (25°C) and 5.5 (37°C). Vials of 30 mL, boxes of 25. Vials of 50 mL, boxes of 25. Bottles of 100 mL fill/150 mL, boxes of 12. Bottles of 150 mL, boxes of 12. Ultraject prefilled syringes 30 and 50 mL, hand-held 50 mL fill/125 mL power injector, 100 mL fill/125 mL power injector; 125 mL power injector, boxes of 20.

Optiray 320: Each mL of clear, colorless to pale yellow, sterile, nonpyrogenic aqueous solution (ioversol injection 68%) contains: ioversol 678 mg with tromethamine 3.6 mg as a buffer and edetate calcium disodium 0.2 mg as a stabilizer. Optiray 320 provides 32% (320 mg/mL) organically bound iodine. Osmolality (mOsm/kg water): 702. Viscosity (cps): 9.9 (25°C) and 5.8 (37°C). Vials of 20 mL, boxes of 10 and 25. Vials of 30 mL, boxes of 10 and 25. Vials of 50 mL, boxes of 10 and 25. Bottles of 100 mL fill/150 mL, boxes of 6 and 12. Bottles of 150 mL, boxes of 6 and 12. Bottles of 200 mL fill/250 mL, boxes of 6 and 12. Ultraject prefilled syringes 30 mL and 50 mL hand-held, 50 mL fill/125 mL power injector, 75 mL fill/125 mL power injector; 100/125 mL power injector; 125 mL power injector, boxes of 20. Pharmacy Bulk Vial: Multi-dispensing bottles of 500 mL, boxes of 12.

Optiray 350: Each mL of clear, colorless to pale yellow, sterile nonpyrogenic aqueous solution (ioversol injection 74%) contains: ioversol 741 mg with tromethamine 3.6 mg as a buffer and edetate calcium disodium 0.2 mg as a stabilizer. Optiray 350 provides 35% (350 mg/mL) organically bound iodine. Osmolality (mOsm/kg water): 792. Viscosity (cps): 14.3 (25°C) and 9.0 (37°C). Vials of 30 mL, boxes of 25. Vials of 50 mL, boxes of 25. Bottles of 75 mL fill/150 mL, boxes of 12. Bottles of 100 mL fill/150 mL, boxes of 12. Bottles of 150 mL, boxes of 12. Bottles of 200 mL fill 250/mL, boxes of 12. Ultraject prefilled syringes 30 and 50 mL hand-held; 50 mL fill/125 mL power injector, 75 mL fill/125 mL power injector; 100 mL fill/125 mL power injector; 125 mL power injector, boxes of 20.

The pH of the formulations is adjusted between 6.0 and 7.4 with hydrochloric acid or sodium hydroxide. The products do not contain a preservative and are intended for single dose use only. Store between 15 and 30°C. Protect from light. Protect from freezing. Discard unused portion.

OPTIRAY® Mallinckrodt Ioversol Radiopaque Medium

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Clinical Medicine

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