August 2017

Conray®
(Iothalamate Meglumine Injection USP 60%)

NOT FOR INTRATHECAL USE
DESCRIPTION
Conray is a sterile aqueous solution intended for use as a diagnostic radiopaque medium.
Conray contains 60% w/v iothalamate meglumine, which is 1-deoxy-1-(methylamino)-Dglucitol 5-acetamido-2,4,6 triiodo-N-methyliso­phthalamate (salt), and has the following
structural formula:

Conray®
(Iothalamate Meglumine Injection USP 60%)

Each milliliter contains 600 mg of iothalamate meglumine, 0.09 mg edetate calcium
disodium as a stabilizer and 0.125 mg of monobasic sodium phosphate as a buffer. The
solution provides 28.2% (282 mg/mL) organically bound iodine. Conray has an osmolarityof approximately 1000 mOsmol per liter, an osmolality of approximately 1400 mOsmol
per kilogram and is, therefore, hypertonic under conditions of use. The viscosity (cps) isapproximately 6 at 25˚C and 4 at 37˚C. The pH is 6.5 to 7.7.
Conray is a clear solution containing no undissolved solids. Crystalliza­tion does not occur
at normal room temperatures. It is supplied in containers from which the air has been
displaced by nitrogen.
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.
The pharmacokinetics of intravascularly administered radiopaque contrast media areusually best described by a two compartment model with a rapid alpha phase for drug
distribution and a slower beta phase for drug elimination. In patients with normal renal
function, the alpha and beta half-lives of Conray were approximately 10 and 90 minutes,
respectively.
Angiography may be performed following intravascular injection which will permit
visualization until significant hemodilution occurs.
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 patientswith impaired renal function, diagnostic opacification frequently is achieved only after
prolonged periods.
Injectable iodinated contrast agents are excreted either through the kidneys or
through the liver. These two excretory pathways are not mutually exclusive, but the mainroute 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 patientswith severe renal impairment, the excretion of this contrast medium through the
gallbladder and into the small intestine sharply increases.
Iothalamate salts cross the placental barrier in humans and are excreted unchanged inhuman milk.
The biliary system, pancreatic duct or joint spaces may be visualized by the direct injectionof contrast medium into the region to be studied.

0953ax-in0000-us0817.indd 1

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.
CT Scanning of the Body1
In non-neural tissues (during CT of the body), Conray diffuses rapidly fromthe vascular to the extra-vascular space. Increase in x-ray absorption is related
to blood flow, concentration of the contrast medium and extraction of the contrast
medium by interstitial tissue, since no barrier exists; contrast enhancement is thus
due to the relative differences in extra-vascular diffusion between normal andabnormal tissue, a situation quite different than that in the brain.
The pharmacokinetics of Conray in normal and abnormal tissues has been shown to
be variable.
Enhancement of CT with Conray may be of benefit in establishing diagnoses ofcertain 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 todefine suspicious lesions seen with unenhanced CT.
Contrast enhancement appears to be greatest within the 30 to 90 seconds
after bolus administration of the contrast agent, and after intra-arterial, rather
than intravenous, administration. Therefore, the use of a continuous scanningtechnique (a series of 2 to 3 second scans beginning at the injection – dynamic
CT scanning) may improve enhancement and diagnostic assessment oftumors and other lesions, such as an abscess, occasionally revealing
more extensive disease. A cyst, or similar non-vascularized lesion, may
be distinguished from vascularized solid lesions by comparing enhanced andunenhanced scans; non-vascularized lesions show no change in CT number,whereas vascularized lesions would show an increase. The latter might bebenign, malignant or normal, but it is unlikely that it would be a cyst, hematoma, orother non-vascularized lesion.
Because unenhanced scanning may provide adequate information in the individual
patient, the decision to em­ploy contrast enhancement, which is associated withadditional risk and in­creased exposure, should be based upon a careful evaluation ofclinical, other radiological, and unenhanced CT findings.
INDICATIONS AND USAGE
Conray is indicated for use in excretory urography, cerebral angiography, peripheralarteriography, venography, arthrography, direct cholangiography, endoscopic
retrograde cholangiopancreatography, contrast enhancement of computed­tomographic brain images, cranial ­computerized angiotomography, in­travenous
digital subtraction angiography and arterial digital subtraction angiography.
Conray may also be used for enhancement of computed tomographic scans
performed for detection and evaluation of lesions in the liver, pancreas, kidneys,
abdominal aorta, mediastinum, abdominal cavity and retroperitoneal space.
Continuous or multiple scans separated by intervals of 1 to 3 seconds during thefirst 30 to 90 seconds post-injection of the contrast medium (dynamic CT scanning)
may provide enhancement of diagnostic significance, and may be of benefit inestablishing diagnoses of certain lesions in these sites with greater assurance thanis possible with CT alone, and in supplying additional features of the lesions. In
other cases, the contrast agent may allow visualization of lesions not seen withCT alone, or may help to define suspicious lesions seen with unenhanced CT (seeCLINICAL PHARMACOLOGY). Subsets of pa­tients in whom delayed body CT scansmight be helpful have not been identified. Inconsistent results have been reported
and abnormal and normal tissues may be isodense during the time frame used fordelayed CT scanning. The risks of such indiscriminate use of contrast media are wellknown and such use is not recommended. At present, consistent results have been
documented using dynamic CT techniques only.
CONTRAINDICATIONS
Refer to PRECAUTIONS, General, concerning hypersensitivity. Conray should not be
used for myelography. Arthrography should not be performed if infection is present
in or near the joint. Percutaneous transhepatic cholangiography is contraindicatedin patients with coagulation defects and prolonged prothrombin times. Endoscopic
retrograde cholangiopancreatography is contraindicated during an acute attack ofpancreatitis or during severe clinically evident cholangitis and in patients in whom
endoscopy is prohibited.
WARNINGSCT Scanning of the Head
When used for contrast enhancement in computed tomographic brain scanning, thedegree of enhancement is directly related to the amount of iodine administered. Rapid
injection of the entire dose yields peak blood iodine concentrations immediately following
the injection, which fall rapidly over the next five to ten minutes. This can be accounted forby 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 ten minutes; thereafter, the fall becomes exponential. Maximum
contrast enhancement frequently occurs after peak blood iodine levels are reached. The
delay in maximum contrast enhancement can range from five to forty minutes, dependingon the peak iodine levels achieved and the cell type of the lesion. This lag suggests thatthe contrast enhancement of the image is at least in part dependent on the accumulationof iodine within the lesion and outside the blood pool.
In brain scanning, the contrast medium (Conray) 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 contrast medium within the interstitial tumor tissue; adjacent normal
brain tissue does not contain the contrast medium.
The image enhancement of non-tumoral lesions, such as arteriovenous malformations andaneurysms, is dependent on the iodine content of the circulating blood pool.

SEVERE ADVERSE EVENTS – INADVERTENT INTRATHECAL ADMINISTRATION:
Serious adverse reactions have been reported due to the inadvertent intrathecal
administration of iodinated contrast media that are not indi­cated for intrathecal use.
These serious adverse reactions include: death, convulsions, cerebral hemorrhage,coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, seizures,
rhabdomyolysis, hyperthermia, and brain edema. Special attention must be given to
ensure that this drug product is not administered intrathecally.
Ionic iodinated contrast media inhibit blood coagulation, in vitro, more thannonionic contrast media. Nonetheless, it is prudent to avoid prolonged contact ofblood with syringes containing ionic contrast media.
Serious, rarely fatal, thromboembolic events causing myocardial infarction andstroke have been reported during angiographic procedures with both ionicand nonionic contrast media. Therefore, meticulous intravascular administration
technique is necessary, particularly during angiographic procedures, tominimize thromboembolic events. Numerous factors, including lengthof procedure, catheter and syringe material, underlying disease stateand concomitant medications may contribute to the development ofthromboembolic events. For these reasons, meticulous angiographic techniques arerecommended, including close attention to guidewire and catheter manipulation,use of manifold systems and/or three-way stopcocks, frequent catheter flushing withheparinized saline solutions and minimizing the length of the procedure. The useof plastic syringes in place of glass syringes has been reported to decrease, but noteliminate, the likelihood of in vitro clotting.

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Serious or fatal reactions have been associated with the administration ofiodine-containing radiopaque media. It is of utmost importance to be completely
prepared to treat any contrast medium reaction.
Serious neurologic sequelae, including permanent paralysis, have been reported
following cerebral arteriography, selective spinal arteriography and arteriography ofvessels supplying the spinal cord. The intravascular injection of a contrast medium
should never be made following the administration of vasopressors since theystrongly potentiate neurologic effects.
In patients with subarachnoid hemorrhage, a rare association between contrast
administration and clinical deterioration, including convulsions and death, has beenreported. Therefore, administration of intravascular iodinated ionic contrast media inthese patients should be undertaken with caution.
A definite risk exists in the use of intravascular contrast agents in patients
who are known to have multiple myeloma. In such instances, anuria hasdeveloped, resulting in progressive uremia, renal failure and eventually death.
Although neither the contrast agent nor dehydration has separately proved tobe the cause of anuria in myeloma, it has been speculated that the combinationof both may be causative factors. The risk in myelomatous patients is not acontraindication to the procedure; however, partial dehydration in the preparation ofthese 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 mostcommonly in persons over 40, should be considered before instituting intravascularadministration of contrast agents.
Administration of radiopaque materials to patients known or suspected to havepheochromocytoma should be performed with extreme caution. If, in the opinionof the physician, the possible benefits of such procedures outweigh theconsidered risks, the procedures may be performed; however, the amount ofradiopaque medium injected should be kept to an absolute minimum. The bloodpressure should be assessed throughout the procedure, and measures for treatmentof 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 intravenously or
intra-arterially.
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.
In patients with advanced renal disease, iodinated contrast media should be usedwith caution, and only when the need for the examination dictates, since excretionof the medium may be impaired. Patients with combined renal and hepatic disease,those with severe hypertension or congestive heart failure, and recent renaltransplant recipients 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 iodinatedradiopaque agent, and also in patients with occult renal disease, notably diabetics
and hypertensives. In these classes of patients, there should be no fluid restrictionand 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 diabetic patients with diabetic
nephropathy and in susceptible non-diabetic patients (often elderly with preexisting renal disease) following the administration of iodinated contrast agents.
There­fore, careful consideration of the potential risks should be given before
performing this radiographic procedure in these patients.
Caution should be exercised in performing contrast medium studies in patients withendotoxemia and/or those with elevated body temperatures.
Reports of thyroid storm occurring following the intravascular use of iodinatedradiopaque agents in patients with hyperthyroidism or with an auton­o­mously functioning thyroid nodule, suggest that this additional risk be evaluatedin 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 andradioactive iodine uptake studies. Such tests, if indicated, should be performed prior
to the administration of this preparation.
Severe Cutaneous Adverse Reactions: Severe cutaneous adverse reactions (SCAR)
may develop from 1 hour to several weeks after intravascular contrast agent
administration. These reactions include Stevens-Johnson syndrome and toxic
epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis (AGEP)
and drug reaction with eosinophilia and systemic symptoms (DRESS). Reaction
severity may increase and time to onset may decrease with repeat administrationof contrast agent; prophylactic medications may not prevent or mitigate severe
cutaneous adverse reactions. Avoid administering Conray to patients with a historyof a severe cutaneous adverse reaction to Conray.
PRECAUTIONSGeneralDiagnostic procedures which involve the use of iodinated intra-vascular
contrast agents should be carried out under the direction of personnel skilled
and experienced in the particular procedure to be performed. 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. A fully equipped emergency
cart, or equivalent supplies and equipment, and personnel competent inrecognizing and treating adverse reactions of all severity, or situations which
may arise as a result of the procedure, should be immediately available at all
times. If a serious reaction should occur, immediately discontinue administration.
Since severe delayed reactions have been known to occur, emergency facilities
and competent personnel should be available for at least 30 to 60 minutes afteradministration (see ADVERSE REACTIONS).
Preparatory dehydration is dangerous and may contribute to acute renal failure in
infants, young children, the elderly, patients with pre-existing renal insufficiency,
patients with advanced vascular disease and diabetic patients.
Severe reactions to contrast media often resemble allergic responses. Thishas prompted the use of several provocative pretesting methods, none of3

which can be relied on to predict severe reactions. No conclusive relationshipbetween severe reactions and antigen-antibody reactions or othermanifestations of allergy has been established. 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 historyof bronchial asthma or allergy, including food, a family history of allergy, or aprevious reaction or hypersensitivity to a contrast agent, may imply a greaterthan usual risk. Such a history, by suggesting histamine sensitivity andconsequently proneness to reactions, may be more accurate than pre-testingin predicting the potential for reaction, although not necessarily the severity ortype of reaction in the individual case. A positive history of this type does notarbitrarily contraindicate the use of a contrast agent, when a diagnostic procedure isthought essential, but does call for caution (see ADVERSE REACTIONS).
Prophylactic therapy including corticosteroids and antihistamines should beconsidered for patients who present with a strong allergic history, a previous
reaction to a contrast medium, or a positive pretest, since the incidence ofreaction in these patients is two to three times that of the general population.
Adequate doses of corticosteroids should be started early enough prior tocontrast medium injection to be effective and should continue through the timeof injection and for 24 hours after injection. Antihistamines should be administered
within 30 minutes of the contrast medium injection. Recent reports indicate thatsuch pre-treatment does not prevent serious life-threatening reactions, but may
reduce both their incidence and severity. A separate syringe should be used for these
injections.
General anesthesia may be indicated in the performance of some procedures inyoung or uncooperative children and in selected adult patients; however, a higher
incidence of adverse reactions has been reported in these patients. This may be
attributable to the inability of the patient to identify untoward symptoms, or to the
hypotensive effect of anesthesia, which can prolong the circulation time and increase
the duration of contact of the contrast agent.
Angiography should be avoided whenever possible in patients with homocystinuria
because of the risk of inducing thrombosis and embolism.
Information for Patients
Patients receiving iodinated intravascular contrast agents should be instructed to:1.
Inform your physician if you are pregnant.
2.	Inform your physician if you are diabetic or if you have multiple
myeloma, pheochromocytoma, homozygous sickle cell disease or known
thyroid disease (see WARNINGS).
3.	Inform your physician if you are allergic to any drugs, food or if you had
any reactions to previous injections of dyes used for x-ray procedures (seePRECAUTIONS, General).
4.	Inform your physician about any other medications you are currently
taking, including non-prescription drugs.
5.	Consult with your physician if, at some future date, any thyroid tests areplanned. The iodine in this agent may interfere with later thyroid tests.
6.	Advise patients to inform their physician if they develop a rash after
receiving Conray.
Carcinogenesis, Mutagenesis, Impair­ment of Fertility
No long-term animal studies have been performed to evaluate carcinogenic
potential. However, animal studies suggest that this drug is not mutagenic and does
not affect fertility in males or females.
Pregnancy Category B
Reproduction studies have been performed in mice, rats, and rabbits at doses up
to 6.6 times the human dose and have revealed no evidence of impaired fertilityor harm to the fetus due to Conray. There are, however, no adequate and wellcontrolled studies in pregnant women. Because animal reproduction studies are notalways predictive of human response, this drug should be used during pregnancy
only if clearly needed.
Nursing Mothers
Iothalamate salts are excreted unchanged in human milk. Because of the potential
for adverse effects in nursing infants, bottle feedings should be substituted for breast
feedings for 24 hours following the administration of this drug.
(Precautions for specific procedures receive comment under that procedure.)
ADVERSE REACTIONSAdverse reactions to injectable contrast media fall into two categories: chemotoxic
reactions and idiosyncratic reactions.
Chemotoxic reactions result from the physio-chemical properties of thecontrast media, the dose and speed of injection. All hemodynamic disturbances andinjuries to organs or vessels perfused by the contrast medium are included in thiscategory.
Idiosyncratic reactions include all other reactions. They occur more frequently
in patients 20 to 40 years old. Idiosyncratic reactions may or may not be
dependent on the amount of dose injected, the speed of injection, the modeof injection and the radiographic procedure. Idiosyncratic reactions are
subdivided into minor, intermediate and severe. The minor reactions are self-limited
and of short duration; the severe reactions are life-threatening and treatment isurgent and mandatory.
Fatalities have been reported following the administration of iodine-containing
contrast agents. Based upon clinical literature, the incidence of death is reported torange from one in 10,000 (0.01 percent) to less than one in 100,000 (0.001 percent).
The following adverse reactions have been observed in conjunction with the use ofiodine-containing contrast agents.
The most frequent adverse reactions are nausea, vomiting, facial flush and afeeling of body warmth. These are usually of brief duration. Other reactions include
the following:
Hypersensitivity reactions: Dermal manifestations of urticaria with or without
pruritus, erythema and maculopapular rash. Dry mouth. Sweating. Con­junctival

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symptoms. Facial, peripheral and angioneurotic edema. Symptoms related to
the respiratory system include sneezing, nasal stuffiness, coughing, choking,dyspnea, chest tightness and wheezing, which may be initial manifestations ofmore 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 anaphylaxis with loss of
consciousness and coma and severe cardiovascular disturbances.
Cardiovascular reactions: Gen­e ral­ized vasodilation, flushing and veno­s pasm.
Occasionally, thrombosis or rarely, thrombophlebitis. Red blood cell clumping
and agglutination, crenation and interference in clot formation. Extremely rarecases of disseminated intravascular coagulation resulting in death havebeen reported. Severe cardiovascular responses include rare cases ofhypotensive shock, coronary insufficiency, cardiac arrhythmia, fibrillation andarrest. These severe reactions are usually reversible with prompt and appropriate
management; however, fatalities have occurred.
Endocrine reactions: Thyroid function tests indicative of hypothyroidism or transient
thyroid suppression have been uncommonly reported following iodinated contrast
media administration to adult and pediatric patients, including infants. Somepatients were treated for hypothyroidism.
Skin and Subcutaneous Tissue Disorders: Reactions range from mild (e.g. rash,erythema, pruritus, urticaria and skin discoloration) to severe: [e.g. StevensJohnson syndrome and toxic epidermal necrolysis (SJS/TEN), acute generalized
exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic
symptoms (DRESS)].
Technique reactions: Extravasation with burning pain, hematomas, ecchymosis andtissue necrosis, paresthesia or numbness, vascular constriction due to injection rate,
thrombosis and thrombophlebitis.
Neurological reactions: Spasm, convulsions, aphasia, syncope, paresis, paralysis
resulting from spinal cord injury and pathology associated with syndrome oftransverse myelitis, visual field losses which are usually transient but may bepermanent, coma and death.
Other reactions: Headache, trembling, shaking, chills without fever andlightheadedness. Temporary renal shutdown or other nephropathy.
(Adverse reactions to specific procedures receive comment under that procedure.)
OVERDOSAGE
Overdosage may occur. The ad­v erse effects of overdosage are lifethreat­­ening and affect mainly the pulmonary and cardiovascular system. The
symptoms may include cyanosis, bradycardia, acidosis, pulmonary hemorrhage,
convulsions, coma and cardiac arrest. Treatment of an overdose is directed toward
the support of all vital functions and prompt institution of symptomatic therapy.
Iothalamate salts are dialyzable.
The intravenous LD 50 value of various concentrations of Iothalamate
Meglumine (in grams of iodine/kilogram body weight) varied from 5.7 to
8.9 g/kg in mice and 9.8 to 11.2 g/kg in rats. The LD50 values decrease as the rate of
injection increases.
DOSAGE AND ADMINISTRATION
It is advisable that Conray be at or close to body temperature when injected.
The patient should be instructed to omit the meal that precedes the examination.
Appropriate premedication, which may include a barbiturate, tranquilizer or
analgesic drug, may be ad­ministered prior to the examination.
A preliminary film is recommended to check the position of the patient and the x-ray
exposure factors.
If a minor reaction occurs during administration, the injection should be slowed
or stopped until the reaction has subsided. If a major reaction occurs, the injection
should be discontinued immediately.
Under no circumstances should either corticosteroids or antihistamines be mixed
in the same syringe with the contrast medium because of a potential for chemical
incompatibility.
Parenteral drug products should be inspected visually for particulate matter anddiscoloration prior to administration.
EXCRETORY UROGRAPHY
Following intravenous injection, Conray is rapidly excreted by the kidneys. Conray
may be visualized in the renal parenchyma 30 seconds following bolus injection.
Maximum radiographic density in the calyces and pelves occurs in most instances
within 3 to 8 minutes after injection. In patients with severe renal impairment
contrast visualization may be substantially delayed.
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.
Precautions
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 (see WARNINGS and PRECAUTIONS, General
concerning preparatory dehydration).
Adverse Reactions
See section on general Adverse Reactions.
Usual Dosage
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. Higher dosage may be indicated to achieve optimum
results in instances where poor visualization may be anticipated (e.g., elderly
patients or patients with impaired renal function). When nephrograms and/or
sequential urograms are desired, the total dose should be rapidly injected, normallywithin 15 to 30 seconds.

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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 adosage of about 0.5 mL/kg of body weight:
Under 6 months of age
6-12 months
1-2 years
2-5 years
5-8 years
8-12 years
12-14 years

5 mL
8 mL
10 mL
12 mL
15 mL
18 mL
20-30 mL
CEREBRAL ANGIOGRAPHY

Conray may be used to visualize the cerebral vasculature by any of the accepted
techniques.
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 orembolism, and migraine.
Adverse Reactions
The major sources of cerebral arteriographic adverse reactions appear to be related torepeated injections of the contrast material, administration of doses higher than thoserecommended, the presence of occlusive atherosclerotic vascular disease and themethod and technique of injection.
Adverse reactions are normally mild and transient. A feeling of warmth in the faceand neck is frequently experienced. Infrequently, a more severe burning discomfort isobserved.
Serious neurological reactions that have been associated with cerebral angiography
and not listed under the general Adverse Reactions include stroke, amnesia andrespiratory difficulties.
Cardiovascular reactions that may occur with some frequency are bradycardia
and decrease in systemic blood pressure. The blood pressure change is transientand usually requires no treatment.
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, byeither 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. Retrogradebrachial 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 employeddepending upon the vessel injected and the procedure followed. The dose for children
is reduced in approximate proportion to age and body weight.
PERIPHERAL ARTERIOGRAPHY AND VENOGRAPHY
Conray may be injected to visualize the arterial and venous peripheral
circulation. Arteriograms of the upper and lower extremities may be obtained byany of the established techniques. Most frequently, a percutaneous injection ismade 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 inblood pressure occur frequently with intra-arterial (brachial) injections. This change isusually transient and requires no treatment; however, the blood pressure should bemonitored for approximately ten 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 thepresence of venous stasis, vein irrigation with normal saline should be consideredfollowing the procedure. Venog­raphy is optimally performed with a more dilute
solution such as Conray 43 (Iothalamate Meglumine Injection USP 43%).
Extreme caution during injection of the contrast agent is necessary to avoid
extravasation and fluoroscopy is recommended. This is especially important in patientswith severe arterial or venous disease.
Adverse Reactions
In addition to the general adverse reactions previously described, hemorrhage andthrombosis 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 normallysufficient to visualize the en­t ire extremity. The dose for children is reduced inproportion to body weight. Venography: The usual dose for adults is a single rapid
injection of 20 to 40 mL. The dose for children is reduced in proportion to body weight.
Following the procedure, the venous system should be flushed with either 5% dextrosein water (D5W) or normal saline (Sodium Chloride Injection USP) or the contrast
medium should be removed by leg massage and/or leg elevation.

60953ax-in0000-us0817.indd 2

ARTHROGRAPHY
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 pressure 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 thetechnique 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
5-15 mL
Shoulder, ankle
5-10 mL
Other
1-4 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 cc ofeither filtered room air or carbon dioxide is introduced for examination of the knee andlesser volumes for other joints. The concomitant use of epinephrine 1:1000 will reduce
the rate of contrast medium absorption as well as the production of synovial fluids andconsequent dilution of the medium.
DIRECT CHOLANGIOGRAPHY
Precautions
In addition to the general precautions previously described, in the presence ofacute pancreatitis, direct cholangiography, if necessary, should be employed withcaution, injecting no more than 5 to 10 mL without undue pressure.
Percutaneous transhepatic cholangiography should only be attempted whencompatible blood for potential transfusions is in readiness and emergency
surgical facilities are available. The patient should be carefully monitored for atleast 24 hours to ensure prompt detection of bile leakage and hemorrhage.
Appropriate premedication of the patient is recommended and drugs which arecholespastic, such as morphine, should be avoided. Respiratory movements should becontrolled during introduction of the needle.
Adverse Reactions
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 andhave been reported in 4 to 6 percent of patients. These reactions have included
bile leakage and biliary peritonitis, gall bladder perforation, internal bleeding(sometimes massive), blood-bile fistula resulting in septicemia involving gramnegative organisms, and tension pneumothorax from inadvertent puncture of thediaphragm 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 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 – 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 USP 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 – Postoperatively, the ductal system may be examined byinjection 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 Cholan­g iography – This procedure is recommended
for carefully selected patients for the differential diagnosis of jaundice
due to extrahepatic biliary obstruction or parenchymal disease. The procedureis only employed where oral or intravenous cholangiography and otherprocedures have failed to provide the necessary information. In obstructed cases,
percutaneous transhepatic cholangiography is used to determine the cause and siteof 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 suggests
hepatocellular disease. Careful attention to technique is essential for the success andsafety of the procedure. The procedure is usually performed under local anesthesia
following analgesic premedication.
Depending upon the caliber of the biliary tree, a dose of 20 to 40 mL is generally
sufficient to opacify the entire ductal system. If desired, the contrast agent may bediluted 1:1 with Sodium Chloride injection USP using strict aseptic procedures.
As the needle is advanced or withdrawn, a bile duct may be located byfrequent aspiration for bile or mucus. Before the dose is administered, as much
bile as possible is aspirated. The injection may be repeated for exposuresin different planes and repositioning of the patient, if necessary, should be done7

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 strongly sug­­gestive of hepatocellular disease.

In adults, when the combination bolus and infusion technique is used, a 50 mLbolus injection followed by a rapid infusion of 150 mL may be given or a 100 mLbolus 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 inapproximate proportion to age and body weight.

ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY

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

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
Endoscopic retrograde cholangiopancreatography should only be performed bypersonnel skilled and experienced with the procedure, and careful attention totechnique is essential for the success and safety of the procedure. Fluor­oscopy is
mandatory during injection to prevent over distention of the duct systems.
Adverse Reactions
Adverse reactions that have occurred which are attributable to either the procedureor to Conray, include nausea, vomiting, fever, severe abdominal pain, duodenal wall
intravasation, septicemia, pancreatitis and perforation of the common bile duct
associated with pathology.
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 under fluoroscopic control
employing the minimal dose that is adequate to visualize the common bile duct,
the pancreatic duct, or both duct systems. The dosage will vary greatly dependingon the pathological findings and can range from 10 to 100 mL for visualization of thecommon 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 24hours.
CONTRAST ENHANCEMENT OF COMPUTED TOMOGRAPHIC (CT)
BRAIN IMAGING
TumorsConray may be useful to enhance the demonstration of the presence andextent 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.
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. General infarctions of recent onset may be better visualized with the contrast
enhancement, while some infarctions are obscured if contrast media are used. The useof iodinated contrast media results in contrast enhancement in about 60% of cerebral
infarctions studied from one to four weeks from the onset of symptoms.
Sites of active infection may also be enhanced following contrast medium
administration.
Arteriovenous malformations and aneurysms will show contrast enhancement. In thecase of these vascular lesions, the enhancement is probably dependent on the iodine
content of the circulating blood pool.
The opacification of the inferior vermis following contrast medium administration has
resulted in false positive diagnoses 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.
Usual Dosage
The usual dosage in adults and children is 2 mL/kg (1 mL/lb) by intrave­n ous
administration, not to exceed a total dose of 150 mL. In most cases, scanning may
be performed immediately after completion of administration; however, when fastscanning equipment (less than 1 minute) is used, consideration should be given to
waiting approximately 5 minutes to allow for maximum contrast enhancement.
CRANIAL COMPUTERIZED ANGIOTOMOGRAPHY
Conray may be administered for cranial computerized angiotomography whennecessary to visualize the cerebral vessels to detect cerebrovascular lesions and toevaluate the anatomical relationship between the cerebral blood vessels and otherparenchymal or space occupying lesions.

CONTRAST ENHANCEMENT IN BODY COMPUTED TOMOGRAPHY1

Patient Preparation
No special patient preparation is required for contrast enhancement in body CT. In
patients undergoing abdominal or pelvic examination, opacification of the bowel may
be valuable in scan interpretation.
Precautions
In addition to the general precautions previously described, it is advisable toensure that patients are adequately hydrated prior to examination. Patient motion,
including respiration, can markedly affect image quality, therefore, patient cooperation
is essential. The use of an intravascular contrast medium can obscure tumors inpatients undergoing CT evaluation of the liver resulting in a false negative diagnosis.
Dynamic CT scanning is the procedure of choice for malignant tumor enhancement(see CLINICAL PHARMACOLOGY).
Usual Dosage
Conray may be administered by bolus injection, by rapid infusion or by a combinationof 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 isrequired 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 todefine the area of interest followed by bolus injections of 20 to 50 mL to clarify selectedscans.
INTRAVENOUS DIGITAL SUBTRACTION ANGIOGRAPHY
Intravenous digital subtraction angiography (IV DSA) is a radiographic modality
which allows dynamic imaging of the arterial system following intravenous injection ofiodinated x-ray contrast media through the use of image intensification, enhancementof 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 most frequently examined by intravenous DSA are theheart, including coronary by-pass grafts; the pulmonary arteries; the arteries of thebrachiocephalic circulation; the aortic arch; the abdominal aorta and its major branches
including the celiac, mesenterics and renal arteries; the iliac arteries; and the arteries ofthe extremities.
Patient Preparation
No special patient preparation is required for intravenous digital subtraction
angiography. However, it is advisable to ensure that patients are well hydrated prior to
examination.
Precautions
In addition to the general precautions previously described, the risks associatedwith IV DSA are those usually attendant with catheter procedures and include
intramural injections, vessel dissection and tissue extravasation. Small test
injections of contrast medium made under fluoroscopic observation toensure the catheter tip is properly positioned, and in the case of peripheral placementthat the vein is of adequate size, will reduce this potential.
Patient motion, including respiration and swallowing, can result in marked image
degradation yielding non-diagnostic studies. Therefore, patient cooperation isessential.

shortened examination time. The limitations of arterial DSA include: reduced spatial
resolution; limited field size; and the inability to conduct simultaneous biplaneexaminations.
Patient Preparation
No special patient preparation is required for arterial DSA. However, it is advisable toensure that patients are well hydrated prior to examination.
Precautions
In addition to the general precautions described, the risks associated with arterial DSA
are those usually attendant with catheter procedures. Following the procedure, gentle
pressure hemostasis is required, followed by observation and immobilization of thelimb for several hours to prevent hemorrhage from the site of arterial puncture.
Usual Dosage
The following dosage schedule for adults should serve only as a guide since the volume
administered, the concentration selected and the flow rate will be determined by
the resolution of the equipment being used. As a general rule, the volume used andthe flow rates for arterial DSA are 50% or less than that used for conventional film
arteriography. Diagnostic studies have been obtained using Conray undiluted (28.2%
iodine), diluted 1:1 (14.1% iodine), and diluted 1:2 (9.4% iodine). Sodium Chloride
Injection USP or Water for Injection USP may be used for dilution.
The following doses, equivalent in iodine content to undiluted Conray, have been used.
Carotid or vertebral arteries:
Aortic Arch:
Subclavian and brachial arteries:
Major branches of the aorta:
Lumbar aorta (bifurcation):

3-8 mL
15-25 mL
5-15 mL
5-20 mL
10-25 mLHOW SUPPLIED

Conray® Glass Vials/Bottles
		
25x30 mL vials
		
25x50 mL vials
		
12x100 mL bottles
		
12x150 mL bottles

NDC Number
0019-0953-23
0019-0953-05
0019-0953-10
0019-0953-50

Storage
Store below 30˚C (86˚F). Exposing this product to very cold temperatures may resultin crystallization of the salt. If this occurs, the container should be brought to room
temperature. Shake vigorously to assure complete dissolution of any crystals. The
speed of dissolution may be increased by heating with circulating warm air. Before use,
examine the product to assure that all solids are redissolved, and that the container
and closure have not been damaged.
This preparation is sensitive to light and must be protected from strong daylight ordirect exposure to the sun.
As with all contrast media, glass containers should be inspected prior to use to ensurethat breakage or other damage has not occurred during shipping and handling. All
containers should be inspected for closure integrity. Damaged containers should not
be used.
Reference
1 Young, S. W., Turner, R.J., Castel­lino, R. A.: “A strategy for the contrast enhancementof malignant tumors using dynamic computed tomography and intravascularpharmacokinetics,” Radiology, 137:137-147, October 1980.
Manufactured by:
Liebel-Flarsheim Company LLC
Raleigh, NC 27616
Made in USA
GBT 0953A0817
Revised 08/17

Adverse Reactions
See section on general Adverse Reactions.
Usual Dosage
Conray 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 segmentof the corresponding vena cava. For peripheral injections, the catheter is introduced
at the antecubital fossa into the appropriate size arm vein. In order to reduce thepotential 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 dose range is 20 to 40 mL. Injections
may be repeated as necessary.
Central catheter injections are usually made with a power injector with aninjection rate of between 10 and 30 mL/second. When making peripheral
injections, rates of 12 to 20 mL/second should be used, depending on the size ofthe 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) of 5% Dextrose in water or normal
saline.
ARTERIAL DIGITALSUBTRACTION ANGIOGRAPHY

Usual Dosage
Conray may be administered by intravenous bolus injection, or by bolus injection
followed by rapid infusion.
For bolus injection, the usual dose in adults and children is 0.5 to 1.0 mL/kg at
an injection rate of 2 mL/second with scanning begun immediately afteradministration. This dose may be repeated as necessary. The total dose perprocedure should not exceed 200 mL, and in children the total dose is reduced inapproximate proportion to age and body weight.

Arterial digital subtraction angiography provides images similar in quality toconventional film-screen systems. The advantages of arterial DSA whencompared to standard film angiography include: the use of less contrast medium;the use of lower concentrations for some procedures; a decreased need forselective arterial catheterization reducing the possibility of dislodging
atheromatous plaques or significantly reducing the blood flow in the artery; and a

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