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CONRAY® 30 CONRAY® 43 CONRAY® 60
Mallinckrodt
Iothalamate Meglumine
Radiopaque Medium
 
Action And Clinical Pharmacology: Following intravascular injection, Conray is rapidly transported through the circulatory system to the kidneys and is excreted unchanged in the urine by glomerular filtration. Renal accumulation is sufficiently rapid that maximum radiographic density in the calyces and pelves occurs in most instances about 3 to 8 minutes after injection. In patients with impaired renal function, diagnostic opacification frequently is achieved only after prolonged periods.

Angiography may be performed following intravascular injection of Conray which will permit visualization until significant hemodilution occurs.

The biliary system, pancreatic duct or joint spaces may be visualized by injecting the contrast medium directly into the region to be studied.

Injectable iodinated contrast agents are excreted either through the kidneys or through the liver. These 2 excretory pathways are not mutually exclusive, but the main route of excretion seems to be related to the affinity of the contrast medium for serum albumin. Iothalamate salts are poorly bound to serum albumin, and are excreted mainly through the kidneys.

The liver and small intestine provide the major alternate route of excretion. In patients with severe renal impairment, the excretion of this contrast medium through the gallbladder and into the small intestine sharply increases.

Pregnancy and Lactation: Iothalamate salts cross the placental barrier in humans; and are excreted unchanged in human milk.

Computerized Tomography of the Head: When Conray 30, Conray 43 or Conray 60 is used for contrast enhancement in computed tomographic brain scanning, the degree of enhancement is directly related to the amount of iodine administered. Rapid infusion of the entire dose amount yields peak blood iodine concentrations immediately following the infusion, which fall rapidly over the next 5 to 10 minutes. This can be accounted for by the dilution in the vascular and extracellular fluid compartments which causes an initial sharp fall in plasma concentration. Equilibration with the extracellular compartments is reached by about 10 minutes; thereafter, the fall becomes exponential. With respect to tumors, maximum contrast enhancement frequently occurs at a time following peak blood iodine concentration. This delay in maximum contrast enhancement can range from 5 to 40 minutes, depending on the peak iodine levels achieved and the cell type and vascularity of the tumor. This lag suggests that the contrast enhancement of the image is at least in part dependent on the passage of iodine through the defective blood-brain barrier and on its accumulation within the lesion and outside the blood pool. The image enhancement of nontumoral lesions, such as arteriovenous malformations and aneurysms, is probably dependent on the iodine content of the circulating blood pool. Studies indicate that equilibrated blood iodine levels of 100 mg% are required in most cases to achieve adequate contrast enhancement. This can be accomplished by the infusion of approximately 30 to 40 g of iodine (100 to 150 mL of Conray 60 or 200 to 300 mL of Conray 30).

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 contain the contrast medium. When used for cranial computerized angiotomography, rapid bolus injection and/or infusion combined with rapid CT scanning will provide clear delineation of the cerebral vessels.

Computerized Tomography of the Body: In non-neural tissues (during CT of the body), Conray 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 since no barrier exists; contrast enhancement is thus due to the relative differences in extravascular diffusion between normal and abnormal tissue, quite different from that in the brain.

Enhancement of CT with Conray 60 may be of benefit in establishing diagnoses of certain lesions in some sites with greater assurance than is possible with unenhanced CT and in supplying additional features of the lesions. In other cases, the contrast medium may allow visualization of lesions not seen with CT alone or may help to define suspicious lesions seen with unenhanced CT.

The pharmacokinetics of Conray in normal and abnormal tissue has been shown to be variable. Contrast enhancement appears to be greatest within 30 to 90 seconds after bolus administration, thus greatest enhancement can be detected by a series of consecutive 2- to 3-second scans ("Dynamic CT Scanning") during this time period. Dynamic scanning may improve enhancement and diagnostic assessment of tumors and other lesions such as an abscess, occasionally revealing more extensive disease. A cyst, or similar nonvascularized lesions may be distinguished from vascularized solid lesions by comparing enhanced and unenhanced scans; the vascularized lesions would show an increase. The latter might be benign, malignant or normal, but it is unlikely that it would be a cyst, hematoma or other nonvascularized lesion.

Venography: Venography may be performed with Conray 43 or Conray 60 following injection into an appropriate vein and will permit visualization until sufficient hemodilution occurs.

Indications And Clinical Uses: Conray 30: For use in i.v. infusion urography and for contrast enhancement in computerized tomography of the brain.

Conray 43: For use in lower extremity venography, i.v. infusion urography and for the i.v. contrast enhancement in computerized tomography of the brain.

Conray 60: For use in excretory urography, cerebral angiography, peripheral arteriography, venography, arthrography, direct cholangiography, endoscopic retrograde cholangiopancreatography, i.v. contrast enhancement in computed tomography and digital subtraction angiography.

Contra-Indications: Known hypersensitivity to salts of iothalamic acid and in patients with anuria or severe oliguria. Arthrography should not be performed if infection is present in or near the joint.

Percutaneous transhepatic cholangiography is contraindicated in patients with coagulation defects and prolonged prothrombin times until normal, or near normal, coagulation is achieved.

Endoscopic retrograde cholangiography is contraindicated during an acute attack of pancreatitis or during clinically evident cholangitis. The procedure is also contraindicated in patients in whom endoscopic examination is prohibited.

Conray must not be used for myelography or for injection into cysts and sinuses that might communicate with the subarachnoid space.

Conray should not be used for the enhancement of CT brain images in patients suspected of having cranial subarachnoid hemorrhage.

Manufacturers' Warnings In Clinical States: Ionic iodinated contrast media inhibit blood coagulation more than nonionic contrast media. Nonetheless, it is necessary to avoid prolonged contact of blood with syringes containing all contrast media.

Serious, rarely fatal, thromboembolic events causing myocardial infarction and stroke have been reported during angiographic procedures with both ionic and nonionic 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 3-way stopcocks, frequent catheter flushing and heparinized saline solutions, and minimizing the length of the procedure. The use of plastic syringes in place of glass syringes has been reported to decrease but not eliminate the likelihood of in vitro clotting.

Serious or fatal reactions have been associated with the administration of iodine containing radiopaque media. It is of utmost importance to be completely prepared to treat any contrast medium reaction.

A definite risk exists in the use of intravascular contrast agents in patients who are known to have multiple myeloma. In some instances anuria has developed resulting in progressive uremia, renal failure and eventually death. Although neither the contrast agent nor dehydration has separately proved to be the cause of anuria in myeloma, it has been speculated that the combination of both may be causative factors. The risk in myelomatous patients is not an absolute contraindication to the procedure; however, partial dehydration in the preparation of these patients for the examination is not recommended since this may predispose to precipitation of myeloma protein in the renal tubules. No form of therapy, including dialysis, has been successful in reversing the effect. Myeloma, which occurs most commonly in persons over 40, should be considered before instituting intravascular administration of contrast agents.

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 procedures may be performed; however, 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.

Contrast media have been shown to promote the phenomenon of sickling in individuals who are homozygous for sickle cell disease when the material is injected i.v. or intra-arterially.

Conray must not be used for myelography or for injection into cysts and sinuses that might communicate with the subarachnoid space.

In computed tomography of the brain, it has been reported that in low density lesions false negative results may be produced following contrast media administration, i.e., contrast media may obscure low density lesions. Steps should be taken to insure that patients undergoing computed tomography have received no injections of water-soluble contrast media at least 24 hours prior to examination. It is recommended that a computed tomographic brain scan always be obtained prior to the administration of Conray.

Precautions: General: All procedures utilizing contrast media carry a definite risk of producing adverse reactions. While most reactions may be minor, life-threatening and fatal reactions may occur without warning. 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. 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.

Diagnostic procedures which involve the use of iodinated intravascular contrast agents should be carried out under the direction of personnel skilled and experienced in the particular procedure to be performed.

The possibility of an idiosyncratic reaction in patients who have previously received a contrast medium without ill effect should always be considered. Prior to the injection of any contrast medium, the patient should be questioned to obtain a medical history with emphasis on allergy and hypersensitivity. A positive history of bronchial asthma or allergy, a family history of allergy, or a previous reaction or hypersensitivity to a contrast agent may imply a greater than usual risk. Such a history, by suggesting histamine sensitivity and consequently 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 does call for caution. Premedication with antihistamines or corticosteroids to avoid or minimize the possible allergic reactions in such patients should be considered. Under no circumstance should the antihistamine or the corticosteroid be mixed in the same syringe with the contrast medium because of chemical incompatibility.

In order to screen patients for allergy potential, various pretesting procedures have been developed; however, specific literature reports indicate that none of these provocative test procedures can be relied upon to predict severe or fatal reactions. The pretest most often performed is the slow i.v. injection of 0.5 to 1.0 mL of the radiopaque medium prior to the injection of the full dose. The absence of a reaction to the test dose does not preclude the possibility of a reaction to the full dose. In some instances, reactions to the test dose itself may be extremely severe; therefore, close observation of the patient and facilities for emergency treatment are indicated.

Partial dehydration prior to the examination should be avoided in patients with chronic renal disease, multiple myeloma, diabetes and in infants and small children.

In patients with advanced renal disease, iodinated contrast media should be used with caution, and only when the need for the examination dictates, since excretion of the medium may be impaired. Patients with combined renal and hepatic disease and those with severe hypertension or congestive heart failure may present an additional risk. 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 Conray should, therefore, be postponed in any patient with a known or suspected hepatic or biliary disorder who has recently taken cholecystographic contrast agent.

Caution should be exercised in performing contrast medium studies in patients with endotoxemia and/or those with elevated body temperatures.

Reports of thyroid storm occurring following the intravascular use of iodinated radiopaque agents in patients with hyperthyroidism or with an autonomously functioning thyroid nodule, suggest that this additional risk be evaluated in such patients before use of this drug.

Iodine-containing contrast agents may alter the results of thyroid function tests which depend on iodine estimation, e.g., PBI and radioactive iodine uptake studies. Such tests, if indicated, should be performed prior to the administration of this preparation.

Pregnancy: Reproduction studies with various concentrations of iothalamate sodium, iothalamate meglumine or a combination of both have been performed in mice, rats, and rabbits, and have revealed no evidence of impaired fertility or harm to the fetus.

There are no well controlled studies in pregnant women, but marketing experience does not include any positive evidence of adverse effects on the fetus. Although there is no clearly defined risk, such experience cannot exclude the possibility of infrequent or subtle damage to the fetus. Conray should be used in pregnant women only when clearly needed.

Lactation: It is not known whether this drug is excreted in human milk. As a general rule, nursing should not be undertaken or continued following administration of this drug since many drugs are excreted in human milk.

Precautions for specific procedures receive comment under that procedure in the Dosage section.

Adverse Reactions: General: Adverse reactions accompanying the use of iodine-containing intravascular contrast agents are usually mild and transient, although severe and life-threatening reactions, including fatalities, have occurred. Because of the possibility of severe reactions to both the procedure and radiopaque medium, appropriate emergency facilities and well trained personnel should be available to treat both types. These emergency facilities and personnel should remain available for 30 to 60 minutes following the procedure since severe delayed reactions have been reported.

The following adverse reactions have been observed in conjunction with the use of iodine-containing intravascular contrast agents.

The most frequent reactions are nausea, vomiting, facial flush and a feeling of body warmth. These are usually of brief duration. Other reactions include the following:

Allergic-type: dermal manifestations of urticaria with or without pruritus, erythema and maculopapular rash, dry mouth, sweating, conjunctival symptoms, facial, peripheral and angioneurotic edema. Symptoms relating to the respiratory system include sneezing, nasal stuffiness, coughing, choking, dyspnea, chest tightness and wheezing, which may be initial manifestations of more severe and infrequent reactions including asthmatic attack, laryngospasm and bronchospasm with or without edema, pulmonary edema, apnea and cyanosis. Rarely, these allergic type reactions can progress into anaphylactic shock with loss of consciousness and coma and severe cardiovascular disturbances.

Cardiovascular: generalized vasodilatation, flushing and venospasm. Occasionally, thrombosis or, rarely, thrombophlebitis. Red blood cell clumping and agglutination, crenation and interference in clot formation. Extremely rare cases of disseminated intravascular coagulation resulting in death have been reported. Severe cardiovascular responses include rare cases of hypotensive shock, coronary insufficiency, cardiac arrhythmia, fibrillation and arrest. These severe reactions are usually reversible with prompt and appropriate management; however, fatalities have occurred.

Technique: extravasation with burning pain, hematomas, ecchymosis and tissue necrosis, paresthesia or numbness, vascular constriction due to injection rate, thrombosis and thrombophlebitis, perforation and dissection of blood vessels, dislodgement of atheromatous plaques, injury to neighboring organs.

Neurological: spasm, convulsions, aphasia, syncope, paresis, paralysis resulting from spinal cord injury and pathology associated with the syndrome of transverse myelitis, visual field losses which are usually transient, but may be permanent, coma and death.

Other: headache, trembling, shaking, chills without fever and lightheadedness. Temporary renal shutdown or other nephropathy. (Adverse reactions to specific procedures receive comment under that procedure in the Dosage section.)

Treatment of Adverse Effects 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 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 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 cardiorespiratory arrest may ensue.

The following measures should be considered: Start emergency therapy immediately - carefully monitoring vital signs. Have emergency resuscitation team summoned - do not leave patient unattended. Ensure patent airway - guard against aspiration. Commence artificial respiration if patient is not breathing. Administer oxygen if necessary. Start external cardiac massage in the event of cardiac arrest. Establish route for i.v. medication by starting infusion of appropriate solution (5% dextrose in water). 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): i) 0.2 to 0.4 mL s.c. for severe allergic reactions. ii) in extreme emergency 0.1 mL/min, appropriately diluted, may be given i.v. until desired effect is obtained. Do not exceed 0.4 mL. iii) in case of cardiac arrest 0.1 to 0.2 mL appropriately diluted may be given intracardially. c) in hypotension (carefully monitoring blood pressure): i) phenylephrine HCl 0.1 to 0.5 mg appropriately diluted slowly i.v. or by slow infusion or ii) levarterenol bitartrate 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: i) pentobarbital sodium 50 mg in fractional doses slowly i.v. (contraindicated if cyanosis is present) or ii) Diazepam 5 to 10 mg slowly i.v. titrating the dose to the response of the patient. Defibrillation, administration of antiarrhythmics and additional emergency measures and drugs may be required. Transfer patient to intensive care unit when feasible for further monitoring and treatment.

Symptoms And Treatment Of Overdose: Symptoms: Overdosage may occur. The adverse effects of overdosage are life-threatening and affect mainly the pulmonary and cardiovascular system. The symptoms may include cyanosis, bradycardia, acidosis, pulmonary hemorrhage, convulsions, coma and cardiac arrest. tag_Treatment

Treatment: Treatment of an overdose is directed toward the support of all vital functions and prompt institution of specific therapy. Iothalamate salts are dialyzable.

Dosage And Administration: I.V. Infusion Urography: (Conray 30, Conray 43): I.V. infusion urography enhances the potential for more diagnostic information in those patients in whom the usual i.v. pyelography technique has not provided satisfactory visualization, or in those patients in whom there is reason to believe the usual i.v. pyelography technique will not provide satisfactory visualization. If renal function is not seriously impaired, the infusion urography technique usually provides satisfactory visualization of an unobstructed urinary tract, including nephrogram and cystogram. Additional advantages are the lack of necessity for dehydration of the patients and compression techniques.

Patient Preparation: For urography study, appropriate preparation of the patient is important for optimal visualization. A low residue diet is recommended on the day preceding the examination. Dehydration is not indicated for the performance of infusion urography. Patients should be maintained in an optimal state of hydration prior to the procedure. Unless contraindicated, a laxative may be given the evening before examination.

A preliminary radiograph usually is made prior to infusion of the contrast agent.

Precautions: A definite risk is involved in i.v. infusion urography in patients known to have chronic renal disease or multiple myeloma. This risk is not a contraindication to the procedure. However, partial dehydration in preparation of these patients is not recommended.

In addition to the general precautions previously described, infants and small children should not have any fluid restrictions prior to i.v. infusion urography. Injections of Conray represent an osmotic load which, if superimposed on increased serum osmolality due to partial dehydration, may magnify hypertonic dehydration. I.V. infusion urography in diabetic patients may involve increased risks and partial dehydration in these patients is not recommended (see also Precaution, General).

Patients with severely impaired renal function should be maintained in an appropriate state of hydration before the procedure. The increased osmotic load associated with i.v. infusion urography should be considered in patients with congestive heart failure.

Adverse Reactions: (see Adverse Effects, General).

Dosage And Administration: It is advisable that Conray be at or close to body temperature when infused.

Conray 30: The recommended dose for adults, older children and infants is 2 to 4 mL/kg with a maximum not exceeding 300 mL in adults and a proportionally smaller amount in children according to age and weight.

The solution is injected through an appropriate i.v. needle at a rate of approximately 50 mL/min. Any appropriate i.v. administration set may be used observing the usual precautions for maintaining sterility and safety in administration. Films are usually taken at 5-minute intervals following the initiation of the infusion for a total of 20 minutes.

In patients with impaired renal function, diagnostic opacification frequently is achieved only after prolonged periods. In these individuals, periodic film obtained up to 24 hours after infusion might yield useful information.

Special procedures such as nephrotomography and cystography are best accomplished within 30 minutes of the conclusion of the infusion.

Conray 43: The usual dose in adults and children is 2 to 3 mL/kg by i.v. administration, not to exceed a total dose of 200 mL in adults and a proportionally smaller amount in children according to age and weight.

The solution is infused at a rate of approximately 40 to 50 mL/min. Other infusion details are as for Conray 30.

Contrast Enhancement of Computed Tomographic (CT) Brain Imaging: Tumors: Conray may be useful to enhance the demonstration of the presence and extent of certain malignancies such as: gliomas including malignant gliomas, glioblastomas, astrocytomas, oligodendrogliomas and gangliomas; ependymomas, medulloblastomas; meningiomas; neuromas, pinealomas; pituitary adenomas; craniopharyngiomas; germinomas; and metastatic lesions.

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.

Maximum contrast enhancement frequently occurs at a time following peak blood iodine concentration. This delay in maximum contrast enhancement can range from 5 to 40 minutes, depending on the peak blood iodine concentration achieved (total dose and rate of administration) and the cell type of the tumor.

In cases where lesions have calcified, there is less likelihood of enhancement. Following therapy, tumors may show decreased or no enhancement.

Non-neoplastic Conditions: The use of Conray may be beneficial in the image enhancement of non-neoplastic lesions. Cerebral infarctions of recent onset may be better visualized with the contrast enhancement while some infarctions are obscured if contrast media are used. The use of Conray resulted in contrast enhancement in 60% of cerebral infarctions studied from 1 to 4 weeks from the onset of symptoms.

Sites of active infection may also be enhanced following contrast medium administration.

Arteriovenous malformations and aneurysms usually 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 case 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.

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

Patient Preparation: No special patient preparation is required for contrast enhancement of CT brain scanning. However, it is advisable to ensure that patients are well hydrated prior to examination.

Warning: Convulsions have occurred in patients with primary or metastatic cerebral lesions following the administration of iodine containing radiopaque media for the contrast enhancement of CT brain images.

Dosage And Administration: Conray 60: Usual Dose: Computed Tomography of the Brain: The recommended dose of Conray 60 for adults and children is 1 to 2 mL/kg of body weight, not exceeding 150 mL in adults and proportionally smaller amount in children according to age and weight. In most cases, scanning may be performed immediately after completion of administration; however when fast scanning equipment (less than 1 minute) is used consideration should be given to waiting approximately 5 minutes to allow for maximum contrast enhancement of the neoplasm (tumor).

Conray 43: Usual Dose: The usual dose in adults and children is 2 to 3 mL/kg by i.v. administration, not to exceed a total dose of 200 mL in adults and a proportionally smaller amount in children according to age and weight. In most cases, scanning may be performed immediately after completion of administration; however when fast scanning equipment (less than 1 minute) is used consideration should be given to waiting approximately 5 minutes to allow for maximum contrast enhancement.

Conray 30: Usual Dose: The recommended dose for adults and children is 2 to 4 mL/kg, not exceeding 300 mL in adults and proportionately smaller amount in children according to age and weight. The dose should be infused as rapidly as possible through any well vented i.v. administration set and needle, observing the usual precautions for maintaining sterility.

Cranial Computed Angiotomography: Conray 60 may be administered by i.v. bolus injection, or by bolus injection followed by rapid infusion.

For bolus injection, the usual dose in adults and children is 1 mL/kg at an injection rate of 2 mL/s with scanning begun immediately after administration.

This dose may be repeated as necessary. The total dose per procedure should not exceed 200 mL in adults and in children the total dose is reduced in approximate proportion to age and body weight.

In adults, when the rapid, high dose combination bolus and infusion technique is used, a 50 mL bolus injection followed by a rapid infusion of 150 mL may be given or a 100 mL bolus injection followed by a rapid infusion of 100 mL may be used. Scanning is begun immediately after the bolus administration. In children, the dose is reduced in approximate proportion to age and body weight.

Computed Tomography of the Body: Conray 60 may be administered when necessary to visualize vessels and organs in patients undergoing CT of the chest, abdomen and pelvis.

Because unenhanced scanning may provide adequate information in the individual patient, the decision to employ contrast enhancement, which may be associated with additional risk and increased radiation exposure, should be based upon a careful evaluation of clinical, other radiological and unenhanced CT findings.

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) provide enhancement of diagnostic significance. 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. The risks of such indiscriminate use of contrast media are well known and such use is not recommended. At present, consistent results have been documented using dynamic CT techniques only.

Precautions: In addition to the general precautions previously described, it should be noted that patient motion, including respiration, can markedly effect image quality, therefore, patient cooperation is essential. The use of an intravascular contrast medium can obscure tumors in patients undergoing CT evaluation of the liver resulting in a false negative diagnosis (see Pharmacology).

Patient Preparation: No special patient preparation is required for contrast enhancement in computerized tomography. However, it is advisable to insure that patients are well hydrated prior to examination.

In patients undergoing abdominal or pelvic examination, opacification of the bowel may be valuable in scan interpretation.

Usual Dosage: Conray 60 may be administered by bolus injection, by rapid infusion or by a combination of both.

For vascular opacification, a bolus injection of 25 to 50 mL may be used, repeated as necessary. When prolonged arterial or venous phase enhancement is required and for the enhancement of specific lesions, a rapid infusion of 150 mL may be used. In some instances, a 100 to 150 mL infusion may be employed to define the area of interest followed by bolus injections of 20 to 50 mL to clarify selected scans.

Excretory Urography: (Conray 60): Following i.v. injection, Conray is rapidly excreted by the kidneys. Conray may be visualized in the renal parenchyma 30 seconds following bolus injection. Maximum radiographic density of the calyces and pelves occurs in most instances about 3 to 8 minutes after injection. In patients with severe renal impairment, contrast visualization may be substantially delayed, or opacification may not occur at all.

Patient Preparation: Appropriate preparation of the patient is important for optimal visualization. A low residue diet is recommended for the day preceding the examination and a laxative is given the evening before the examination, unless contraindicated. A preliminary radiograph is usually made prior to the injection of the contrast agent.

Precautions: In addition to the general precautions previously described, infants and small children should not have any fluid restrictions prior to excretory urography. Injections of Conray represent an osmotic load which, if superimposed on increased serum osmolality due to partial dehydration, may magnify hypertonic dehydration. Therefore, patients' state of dehydration should be evaluated prior to and following this procedure and adjusted if necessary.

A definite risk is involved in excretory urography in patients known to have chronic renal disease, multiple myeloma or diabetes. This risk is not a contraindication to the procedure (see Warnings and Precautions, General Concerning Preparatory Dehydration).

Adverse Reactions: see Adverse Effects, General.

Usual Dosage: (Conray 60): Adults: The usual dose is 30 to 60 mL. Children 14 years of age and over, of average weight, may receive the adult dose.

The total dose is normally injected within 30 to 90 seconds. The higher dosage may be indicated to achieve optimum results in instances where poor visualization may be anticipated. When nephrograms and/or sequential urograms are desired, the total dose should be rapidly injected, normally within 15 to 30 seconds. The dosage for children is reduced in proportion to age and body weight. The following approximate schedule is recommended for infants and children based on a dosage of about 0.5 mL/kg of body weight: Under 6 months of age: 5 mL, 6 to 12 months: 8 mL, 1 to 2 years: 10 mL, 2 to 5 years: 12 mL, 5 to 8 years: 15 mL, 8 to 12 years: 18 mL, 12 to 14 years: 20 to 30 mL.

Cerebral Angiography: Conray 60 may be used to visualize the cerebral vasculature by any of the accepted techniques, including digital subtraction angiography.

Patient Preparation: Cerebral angiography is normally performed with local or general anesthesia (see Precautions, General). Premedication may be employed as indicated.

A preliminary radiograph is usually made prior to injection of the contrast agent.

Precautions: In addition to the general precautions previously described, cerebral angiography should be performed with special caution in patients with advanced arteriosclerosis, severe hypertension, cardiac decompensation, senility, recent cerebral thrombosis or embolism and migraine.

Adverse Reactions: In addition to the general adverse reactions previously described, the major sources of cerebral arteriographic adverse reactions 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.

Adverse reactions are normally mild and transient. A feeling of warmth in the face and neck is frequently experienced. Infrequently, a more severe burning discomfort is observed.

Serious neurological reactions that have been associated with cerebral angiography include stroke, amnesia, respiratory difficulties, hemiparesis, visual field loss, aphasia, convulsions, hypotension, bradycardia, coma and death.

Usual Dosage: The usual dosage employed varies with the site and method of injection and the age, condition and weight of the patient. In adults carotid and vertebral angiography, by either the percutaneous needle or catheter methods, is usually performed with a single rapid injection of 6 to 10 mL. Additional injections are made as indicated. Retrograde brachial cerebral angiography, in adults, is usually performed with a single rapid injection of 35 to 50 mL into the right brachial artery. Other dosages may be employed depending upon the vessel injected and the procedure followed. The dose for children is reduced in approximate proportion to age and body weight.

The use of an arterial digital subtraction technique allows the dose (concentration and/or volume) of the contrast material to be reduced by approximately 50% and permits less selective arterial catheterization.

Peripheral Arteriography and Venography: (Conray 60): Conray may be injected to visualize the arterial and venous peripheral circulation. Arteriograms of the upper and lower extremities may be obtained by any of the established techniques. Most frequently a percutaneous injection is made into the brachial artery in the arm or the femoral artery in the leg. Venograms are obtained by injection into an appropriate vein in the upper and lower extremity.

Patient Preparation: The procedure is normally performed with local or general anesthesia (see Precautions, General). Premedication may be employed as indicated. A preliminary radiograph is usually made prior to the injection of the contrast agent.

Precautions: In addition to the general precautions previously described, moderate decreases in blood pressure occur frequently with intra-arterial (brachial) injections. This change is usually transient and requires no treatment; however, the blood pressure should be monitored for approximately 10 minutes following injection. Special care is required when venography is performed in patients with suspected thrombosis, phlebitis, severe ischemic disease, local infection or a totally obstructed venous system. In the presence of venous stasis, vein irrigation with normal saline should be considered following the procedure.

Adverse Reactions: In addition to the general adverse reactions previously described, hemorrhage and thrombosis have occurred at the puncture site of the percutaneous injection.

Brachial plexus injury has been reported following axillary artery injection. Thrombophlebitis, syncope and very rare cases of gangrene have been reported following venography.

Usual Dosage: Peripheral Arteriography: In adults a single rapid injection of 20 to 40 mL is normally sufficient to visualize the entire extremity. The dose for children is reduced in proportion to body weight.

The use of an arterial digital subtraction technique allows the dose (concentration and/or volume) of the contrast material to be reduced by approximately 50% and permits less selective arterial catheterization.

Venography: The usual dose of Conray 60 for adults is a single rapid injection of 20 to 40 mL. The dose for children is reduced in proportion to body weight.

The usual dose of Conray 43 is 30 mL single dose up to a cumulative total dose of 125 mL per lower extremity, depending on the technique used. The dose for children is reduced in proportion to body weight. Following the procedure the venous system should be flushed with either 5% dextrose in water (D5W) or normal saline (Sodium Chloride Injection U.S.P.), or the contrast medium should be removed by leg massage and/or leg elevation.

Arthrography: (Conray 60): Precautions: In addition to the general precautions previously described, strict aseptic technique is required to prevent the introduction of infection. Fluoroscopic control should be used to ensure proper introduction of the needle into the synovial space and prevent extracapsular injection. Aspiration of excessive synovial fluid will reduce the pain on injection and prevent the rapid dilution of the contrast agent. It is important that undue pressures not be exerted during the injection.

Adverse Reactions: In addition to the general adverse reactions previously described, arthrography may induce joint pain or discomfort which is usually mild and transient but occasionally may be severe and persist for 24 to 48 hours following the procedure. Effusion requiring aspiration may occur in patients with rheumatoid arthritis.

Usual Dosage: Arthrography is usually performed under local anesthesia. The amount of contrast agent required is solely dependent on the size of the joint to be injected and the technique employed.

The following dosage schedule for normal adult joints should serve only as a guide since joints may require more or less contrast medium for optimal visualization. Dosage should be reduced for children in proportion to body weight. Knee, hip: 5 to 15 mL. Shoulder, ankle: 5 to 10 mL. Other: 1 to 4 mL.

Passive or active manipulation is used to disperse the medium throughout the joint space.

The lower volumes of contrast medium are usually employed for double contrast examinations. Following the injection of the contrast medium 50 to 100 mL of either filtered room air or carbon dioxide is introduced for examination of the knee and lesser volumes for other joints.

Direct Cholangiography: (Conray 60): Precautions: In addition to the general precautions previously described, percutaneous transhepatic cholangiography should only be attempted when compatible blood for potential transfusions is in readiness and emergency surgical facilities are available.

The patient should be carefully monitored for at least 24 hours to ensure prompt detection of bile leakage and hemorrhage. Appropriate premedication of the patient is recommended and drugs which are cholespastic, such as morphine, should be avoided. Respiratory movements should be controlled during introduction of the needle.

Adverse Reactions: In addition to the general adverse reactions previously described, adverse reactions may often be attributed to injection pressure or excessive volume of the medium resulting in overdistention of the ducts and producing local pain.

Some of the medium may enter the pancreatic duct which may result in pancreatic irritation. Occasionally, nausea, vomiting, fever, and tachycardia have been observed. Pancholangitis resulting in liver abscess or septicemia has been reported.

In percutaneous transhepatic cholangiography, some discomfort is common, but severe pain is unusual. Complications of the procedure are often serious and have been reported in 4 to 5% of patients. These reactions have included bile leakage and biliary peritonitis, gallbladder perforation, internal bleeding (sometimes massive), blood-bile fistula resulting in septicemia involving gram-negative organisms, and tension pneumothorax from inadvertent puncture of the diaphragm or lung. Bile leakage is more likely to occur in patients with obstructions that cause unrelieved high biliary pressure.

Dosage And Administration: It is advisable that Conray 60 be at or close to body temperature when injected. The injection is made slowly without undue pressure, taking the necessary precautions to avoid the introduction of bubbles.

Operative Cholangiography: The usual dose is 10 mL but as much as 25 mL may be needed depending upon the caliber of the ducts. If desired, the contrast agent may be diluted 1:1 with Sodium Chloride Injection U.S.P. using strict aseptic procedures. Following surgical exploration of the ductal system, repeat studies may be performed before closure of the abdomen, using the same dose as before.

Postoperative Cholangiography: Postoperatively, under fluoroscopic control, the ductal system may be examined by injection of the contrast agent through an in-place T-tube. These delayed cholangiograms are usually made from the fifth to the tenth postoperative day prior to removal of the T-tube. The usual dose is the same as for operative cholangiography.

Percutaneous Transhepatic Cholangiography: This procedure is recommended for carefully selected patients only for the diagnosis of jaundice in suspected extrahepatic biliary obstruction. The procedure is only employed where oral or i.v. cholangiography and other procedures have failed to provide the necessary information. In obstructed cases, percutaneous transhepatic cholangiography is used to determine the cause and site of obstruction to help plan surgery. The technique may also be of value in avoiding laparotomy in poor risk jaundice patients since failure to enter a duct by an experienced physician is considered to be suggestive evidence against obstructive jaundice. Careful attention to technique is essential for the success and safety of the procedure. The procedure is performed under fluoroscopic control; local anesthesia following analgesic premedication is usually employed.

Depending upon the caliber of the biliary tree, a dose of 10 to 40 mL is generally sufficient to opacify the entire ductal system. If desired, the contrast agent may be diluted 1:1 with Sodium Chloride Injection U.S.P. using strict aseptic procedures.

As the needle is advanced or withdrawn, a bile duct may be located by frequent aspiration for bile or mucus. Before the dose is administered, as much bile as possible is aspirated. The injection may be repeated for exposures in different planes and repositioning of the patient, if necessary, should be done with care. If a duct is not readily located by aspiration, successive small doses of 1 to 2 mL of the medium are injected into the liver as the needle is gradually withdrawn, until a duct is visualized by X-ray. If no duct can be located after 3 or 4 attempts, the procedure should be terminated. Inability to enter a duct by a person experienced in the technique is generally considered to be suggestive evidence against obstructive disease.

Endoscopic Retrograde Cholangiopancreatography: (Conray 60): Endoscopic retrograde cholangiopancreatography (ERCP) is indicated in carefully selected patients with known or suspected pancreatic or biliary tract disease when other diagnostic procedures have failed to provide the necessary diagnostic information. Prior to the development of ERCP, X-ray examination of the pancreatic ducts could only be obtained at laparotomy.

Precautions: In addition to the general precautions previously described, endoscopic retrograde cholangiopancreatography should only be performed by personnel skilled and experienced with the procedure, and careful attention to technique is essential for the success and safety of the procedure. Fluoroscopy is mandatory during injection to prevent over distention of the duct systems.

Filling of the pancreatic parenchyma must be avoided. Retrograde injection of contrast media beyond a significant stenosis or obstruction is not recommended, since this is considered to increase the risk of ascending infection. ERCP should not be performed in patients with a positive test for Hepatitis Associated Antigen, since fiberscopes cannot be sterilized and there is a real possibility of transmitting viral hepatitis to successive patients.

Adverse Reactions: In addition to the general adverse reactions previously described, adverse reactions that have occurred and attributable to either the procedure or contrast agent include nausea, vomiting, fever, severe abdominal pain, duodenal wall intravasation, septicemia, pancreatitis, and perforation of the common bile duct associated with pathology. Frequently, elevation of serum amylase is observed following an ERCP procedure.

Dosage And Administration: The procedure is usually performed following pharyngeal anesthesia and analgesic or sedative premedication. Duodenal motility may be controlled in patients with active duodenal peristalsis with an appropriate antiperistaltic agent.

The contrast medium should be injected slowly without undue pressure under fluoroscopic control employing the minimal dose that is adequate to visualize the common bile duct, the pancreatic duct, or both duct systems. When both systems are filled simultaneously, overfilling of the pancreas is a potential risk. The dosage will vary greatly depending on the pathological findings and can range from 10 to 40 mL for visualization of the common bile duct, and from 2 to 10 mL for visualization of the pancreatic duct. Following the procedure, the patient should be kept under close observation for 24 hours.

Intravenous Digital Subtraction Angiography: (Conray 60): I.V. digital subtraction angiography (IV DSA) is a radiographic modality which allows dynamic imaging of the arterial system following i.v. injection of iodinated X-ray contrast media through the use of image intensification, enhancement of the iodine signal and digital processing of the image data. Temporal subtraction of the images obtained during the "first arterial pass" of the injected contrast medium injection yield images which are devoid of bone and soft tissue.

Areas that have been examined by i.v. DSA are the heart, including coronary by-pass grafts; the pulmonary arteries; the arteries of the brachiophalic circulation; the aortic arch; the abdominal aorta and its major branches including the celiac, mesenterics and renal arteries; the iliac arteries; and the arteries of the extremities.

Patient Preparation: No special patient preparation is required for i.v. digital subtraction angiography. However, it is advisable to ensure that patients are well hydrated prior to examination.

Manufacturers' Warnings In Clinical States: Convulsions have occurred in patients with primary or metastatic cerebral lesions following the administration of iodine containing radiopaque media for the contrast enhancement of CT brain images.

Patients with diabetes mellitus and impaired renal function are considered to be at greater risk to develop acute renal failure following the injection of large doses of contrast media for contrast enhancement in CT scanning.

Precautions: In addition to the general precautions previously described, the risks associated with IV DSA are those usually attendant with catheter procedures and include intramural injections, vessel dissection or rupture and tissue extravasation. Small test injections of contrast medium made under fluoroscopic observation to ensure the catheter tip is properly positioned, and in the case of peripheral placement that the vein is of adequate size, will reduce the potential for intramural injections, vessel dissection or tissue extravasation occurring.

Patient motion, including respiration and swallowing, can result in marked image degradation yielding nondiagnostic studies. Therefore, patient cooperation is essential.

Adverse Reactions: see section on Adverse Effects, General.

Usual Dosage: Conray 60 may be injected either centrally, into the superior or inferior vena cava, or peripherally into an appropriate arm vein. For central injections, catheters may be introduced at the antecubital fossa into either the basilic or cephalic vein or at the leg into the femoral vein and advanced to the distal segment of the corresponding vena cava. For peripheral injections, the catheter is introduced at the antecubital fossa into an appropriate size arm vein. In order to reduce the potential for extravasation during peripheral injection, a catheter of approximately 20 cm in length should be employed.

Depending on the area to be imaged, the usual adult dose range is 20 to 60 mL. Injections may be repeated as necessary.

Central catheter injections are usually made with a power injection rate of between 10 and 30 mL/s. When making peripheral injections, rates of 12 to 20 mL/s should be used, depending on the size of the vein. Also, since contrast medium may remain in the arm vein for an extended period following injection, it may be advisable to flush the vein, immediately following injection, with an appropriate volume (20 to 25 mL) or 5% Dextrose in water or normal saline.

Administration: It is advisable that sterile Conray product in vials, bottles or in Ultraject syringes be at or close to body temperature when infused.

Availability And Storage: Conray 30: Each mL of sterile aqueous solution contains: iothalamate meglumine 300 mg (organically bound iodine 14.15%-141 mg/mL). Nonmedicinal ingredients: edetate calcium disodium and monobasic sodium phosphate. Conray 30 has an osmolarity of approximately 750 mOsm/L (0.75 mOsm/mL) and is, therefore, hypertonic under conditions of use and is supplied in containers from which the air has been displaced by nitrogen. Bottles of 150 mL containing 100 mL (partial fill), boxes of 12. Bottles of 150 mL, boxes of 12. Infusion bottles of 300 mL, packages of 12.

Conray 43: Each mL of sterile aqueous solution contains: iothalamate meglumine 430 mg (organically bound iodine 20.2%-202 mg/mL). Nonmedicinal ingredients: edetate calcium disodium and monobasic sodium phosphate. Conray 43 has an osmolarity of approximately 800 mOsm/L (0.80 mOsm/mL) and is, therefore, hypertonic under conditions of use and is supplied in containers from which the air has been displaced by nitrogen. Conray 43 has a specific gravity of 1,22 at 25°C and a viscosity of 3 cps at 25°C and 2 cps at 37°C. Vials of 50 mL, packages of 50. Bottles of 150 mL containing 100 mL (partial fill), boxes of 12. Bottles of 200 mL and 250 mL, packages of 12.

Conray 60: Each mL of sterile aqueous solution contains: iothalamate meglumine 600 mg (organically bound iodine 28.2%-282 mg/mL). Nonmedicinal ingredients: edetate calcium disodium and monobasic sodium phosphate. Conray 60 has an osmolarity of approximately 1 000 mOsm/L (1.0 mOsm/mL) and is, therefore, hypertonic under conditions of use and is supplied in containers from which the air has been displaced by nitrogen. Conray 60 has a specific gravity of 1,32 at 25°C and a viscosity of 6 cps at 25°C and 4 cps at 37°C. Vials of 20, 30 and 50 mL, packages of 50. Bottles of 150 and 200 mL, packages of 12. Bottles of 150 mL containing 100 mL (partial fill), packages of 12. Ultraject prefilled syringes of 50 mL (hand held), boxes of 20.

Store between 15 and 30°C. Protect from light. Protect from freezing. Crystallization does not occur at normal room temperatures. Discard unused portion.