CONRAY- iothalamate meglumine injection
Liebel-Flars heim Company LLC---------Augus t 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)-D-glucitol 5-acetamido2,4,6 triiodo-N-methylisophthalamate (salt), and has the following structural formula:

Each milliliter contains 600 mg of iothalamate meglumine, 0.09 mg edetate calcium disodium as astabilizer and 0.125 mg of monobasic sodium phosphate as a buffer. The solution provides 28.2% (282mg/mL) organically bound iodine. Conray has an osmolarity of approximately 1000 mOsmol per liter, anosmolality of approximately 1400 mOsmol per kilogram and is, therefore, hypertonic under conditionsof use. The viscosity (cps) is approximately 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 thekidneys and is excreted unchanged in the urine by glomerular filtration. The pharmacokinetics ofintravascularly administered radiopaque contrast media are usually 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 pelvesoccurs, 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.
Injectable iodinated contrast agents are excreted either through the kidneys or through the liver. These
two 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.
Iothalamate salts cross the placental barrier in humans and are excreted unchanged in human milk.
The biliary system, pancreatic duct or joint spaces may be visualized by the direct injection of contrast
medium into the region to be studied.
CT Scanning of the Head
When used for contrast enhancement in computed tomographic brain scanning, the degree ofenhancement is directly related to the amount of iodine administered. Rapid injection of the entire doseyields peak blood iodine concentrations immediately following the injection, which fall rapidly over the
next five to ten 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 theextracellular 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, depending on the peak iodine
levels achieved and the cell type of the lesion. This lag suggests that the contrast enhancement of theimage is at least in part dependent on the accumulation of iodine within the lesion and outside the bloodpool.
In brain scanning, the contrast medium (Conray) does not accumulate in normal brain tissue due to thepresence of the “blood brain barrier.” The increase in x-ray absorption in the normal brain is due to thepresence 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 and aneurysms, isdependent on the iodine content of the circulating blood pool.
When used for cranial computerized angiotomography, rapid bolus injection and/or infusion combinedwith 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 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 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 of certain lesions in somesites with greater assurance than is possible with unenhanced CT and in supplying additional features ofthe 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.
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 acontinuous scanning technique (a series of 2 to 3 second scans beginning at the injection - dynamic CT

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 non-vascularized lesion, may
be distinguished from vascularized solid lesions by comparing enhanced and unenhanced scans; nonvascularized lesions show no change in CT number, whereas vascularized lesions would show anincrease. The latter might be benign, malignant or normal, but it is unlikely that it would be a cyst,
hematoma, or other non-vascularized lesion.
Because unenhanced scanning may provide adequate information in the individual patient, the decision toemploy contrast enhancement, which is associated with additional risk and increased exposure, should
be based upon a careful evaluation of clinical, other radiological, and unenhanced CT findings.
INDICATIONS AND USAGE
Conray is indicated for use in excretory urography, cerebral angiography, peripheral arteriography,
venography, arthrography, direct cholangiography, endoscopic retrograde cholangiopancreatography,
contrast enhancement of computed tomographic 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 andevaluation of lesions in the liver, pancreas, kidneys, abdominal aorta, mediastinum, abdominal cavity andretroperitoneal 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 in establishing diagnoses of certain
lesions in these sites with greater assurance than is possible with CT alone, and in supplying additionalfeatures of the lesions. In other cases, the contrast agent may allow visualization of lesions not seen
with CT alone, or may help to define suspicious lesions seen with unenhanced CT (see CLINICALPHARMACOLOGY). Subsets of patients in whom delayed body CT scans might be helpful have notbeen identified. Inconsistent results have been reported and abnormal and normal tissues may be
isodense during the time frame used for delayed CT scanning. The risks of such indiscriminate use ofcontrast media are well known and such use is not recommended. At present, consistent results havebeen 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 contraindicated in patients with coagulation defects andprolonged prothrombin times. Endoscopic retrograde cholangiopancreatography is contraindicatedduring an acute attack of pancreatitis or during severe clinically evident cholangitis and in patients inwhom endoscopy is prohibited.
WARNINGSSEVERE ADVERSE EVENTS - INADVERTENT INTRATHECAL ADMINISTRATION:
Serious adverse reactions have been reported due to the inadvertent intrathecal administration ofiodinated 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 than nonionic contrast media.
Nonetheless, it is prudent to avoid prolonged contact of blood with syringes containing ionic 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,
catheter and syringe material, underlying disease state and concomitant medications may contribute to thedevelopment of thromboembolic 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 with heparinized saline solutions and minimizing
the length of the procedure. The use of plastic syringes in place of glass syringes has been reported todecrease, but not eliminate, the likelihood of in vitro clotting.
Serious or fatal reactions have been associated with the administration of iodine-containing radiopaquemedia. 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 of vessels supplying the spinal cord.
The intravascular injection of a contrast medium should never be made following the administration ofvasopressors since they strongly potentiate neurologic effects.
In patients with subarachnoid hemorrhage, a rare association between contrast administration and clinicaldeterioration, including convulsions and death, has been reported. Therefore, administration of
intravascular iodinated ionic contrast media in these 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 has developed, resulting in progressive uremia, renal failure andeventually death. Although neither the contrast agent nor dehydration has separately proved to be thecause of anuria in myeloma, it has been speculated that the combination of both may be causative factors.
The risk in myelomatous patients is not a contraindication to the procedure; however, partial dehydrationin 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 beensuccessful 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 shouldbe performed with extreme caution. If, in the opinion of the physician, the possible benefits of suchprocedures outweigh the considered risks, the procedures may be performed; however, the amount ofradiopaque medium injected should be kept to an absolute minimum. The blood pressure should beassessed throughout the procedure, and measures for treatment of a hypertensive crisis should beavailable.
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 theadministration of iodine-containing radiopaque media for the contrast enhancement of CT brain images.
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. Patientswith combined renal and hepatic disease, those with severe hypertension or congestive heart failure,
and recent renal transplant recipients may present an additional risk.
Renal failure has been reported in patients with liver dysfunction who were given an oralcholecystographic agent followed by an intravascular iodinated radiopaque agent, and also in patientswith occult renal disease, notably diabetics and hypertensives. In these classes of patients, there should
be no fluid restriction and every attempt made to maintain normal hydration, prior to contrast medium
administration, since dehydration is the single most important factor influencing further renal
impairment.
Acute renal failure has been reported in diabetic patients with diabetic nephropathy and in susceptible

non-diabetic patients (often elderly with pre-existing renal disease) following the administration ofiodinated 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 with endotoxemia and/or
those with elevated body temperatures.
Reports of thyroid storm occurring following the intravascular use of iodinated radiopaque agents inpatients with hyperthyroidism or with an autonomously functioning thyroid nodule, suggest that thisadditional 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 andradioactive iodine uptake studies. Such tests, if indicated, should be performed prior to theadministration of this preparation.
Severe Cutaneous Advers e 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 administration of contrast agent;prophylactic medications may not prevent or mitigate severe cutaneous adverse reactions. Avoid
administering Conray to patients with a history of 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 in recognizing
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 andcompetent personnel should be available for at least 30 to 60 minutes after administration (seeADVERSE 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 vasculardisease and diabetic patients.
Severe reactions to contrast media often resemble allergic responses. This has prompted the use of
several provocative pretesting methods, none of which can be relied on to predict severe reactions. No
conclusive relationship between severe reactions and antigen-antibody reactions or other manifestationsof allergy has been established. The possibility of an idiosyncratic reaction in patients who havepreviously received a contrast medium without ill effect should always be considered. Prior to theinjection of any contrast medium, the patient should be questioned to obtain a medical history withemphasis on allergy and hypersensitivity. A positive history of bronchial asthma or allergy, including
food, 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 pre-testing in predicting the potential for reaction,although not necessarily the severity or type of reaction in the individual case. A positive history ofthis type does not arbitrarily 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 be considered for patients
who present with a strong allergic history, a previous reaction to a contrast medium, or a positive
pretest, since the incidence of reaction in these patients is two to three times that of the general
population. Adequate doses of corticosteroids should be started early enough prior to contrast medium
injection to be effective and should continue through the time of injection and for 24 hours after
injection. Antihistamines should be administered within 30 minutes of the contrast medium injection.
Recent reports indicate that such 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 in young or uncooperative
children and in selected adult patients; however, a higher incidence of adverse reactions has beenreported 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 andincrease the duration of contact of the contrast agent.
Angiography should be avoided whenever possible in patients with homocystinuria because of the riskof 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 (see PRECAUTIONS, General).
4. Inform your physician about any other medications you are currently taking, including nonprescription drugs.
5. Consult with your physician if, at some future date, any thyroid tests are planned. The iodine in thisagent may interfere with later thyroid tests.
6. Advise patients to inform their physician if they develop a rash after receiving Conray.
Carcinogenes is , Mutagenes is , Impairment of Fertility
No long-term animal studies have been performed to evaluate carcinogenic potential. However, animalstudies 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 humandose and have revealed no evidence of impaired fertility or harm to the fetus due to Conray. There are,however, no adequate and well controlled studies in pregnant women. Because animal reproduction
studies are not always predictive of human response, this drug should be used during pregnancy only ifclearly needed.
Nurs ing Mothers
Iothalamate salts are excreted unchanged in human milk. Because of the potential for adverse effects innursing infants, bottle feedings should be substituted for breast feedings for 24 hours following theadministration 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 andidiosyncratic reactions.

Chemotoxic reactions result from the physio-chemical properties of the contrast media, the dose andspeed of injection. All hemodynamic disturbances and injuries to organs or vessels perfused by thecontrast medium are included in this category.
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 speedof injection, the mode of injection and the radiographic procedure. Idiosyncratic reactions are
subdivided into minor, intermediate and severe. The minor reactions are self-limited and of shortduration; the severe reactions are life-threatening and treatment is urgent and mandatory.
Fatalities have been reported following the administration of iodine-containing contrast agents. Basedupon clinical literature, the incidence of death is reported to range from one in 10,000 (0.01 percent) toless than one in 100,000 (0.001 percent).
The following adverse reactions have been observed in conjunction with the use of iodine-containing
contrast agents.
The most frequent adverse reactions are nausea, vomiting, facial flush and a feeling 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 andmaculopapular rash. Dry mouth. Sweating. Conjunctival 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 of more severe andinfrequent 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: Generalized vasodilation, flushing and venospasm. Occasionally, thrombosis
or rarely, thrombophlebitis. Red blood cell clumping and agglutination, crenation and interference inclot formation. Extremely rare cases of disseminated intravascular coagulation resulting in death havebeen 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.
Endocrine reactions: Thyroid function tests indicative of hypothyroidism or transient thyroid
suppression have been uncommonly reported following iodinated contrast media administration to adultand pediatric patients, including infants. Some patients 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. Stevens-Johnson syndrome and toxic epidermal
necrolysis (SJS/TEN), acute generalized exanthematous pustulosis (AGEP) and drug reaction witheosinophilia and systemic symptoms (DRESS)].
Technique reactions: Extravasation with burning pain, hematomas, ecchymosis and tissue 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 of transverse myelitis, visual field losses which
are usually transient but may be permanent, coma and death.
Other reactions: Headache, trembling, shaking, chills without fever and lightheadedness. Temporary
renal shutdown or other nephropathy.
(Adverse reactions to specific procedures receive comment under that procedure.)
OVERDOSAGE
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. 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 LD 50
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 administeredprior 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 thereaction 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 syringewith the contrast medium because of a potential for chemical incompatibility.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior toadministration.
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 thecalyces 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 isrecommended for the day preceding the examination and a laxative is given the evening before theexamination, unless contraindicated.
Precautions
Infants and small children should not have any fluid restrictions prior to excretory urography. Injectionsof Conray represent an osmotic load which, if superimposed on increased serum osmolality due topartial dehydration, may magnify hypertonic dehydration (see WARNINGS and PRECAUTIONS,
General concerning preparatory dehydration).
Advers e Reactions
See section on general Adverse Reactions.
Us ual Dos age
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, 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 bodyweight:Under 6 months of

5 mL

age
6-12 months
1-2 years
2-5 years
5-8 years
8-12 years
12-14 years

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 or embolism, and migraine.
Advers e Reactions
The major sources of cerebral arteriographic adverse reactions appear to be related to repeatedinjections of the contrast material, administration of doses higher than those recommended, the presenceof 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 and not listed under
the general Adverse Reactions include stroke, amnesia and respiratory difficulties.
Cardiovascular reactions that may occur with some frequency are bradycardia and decrease in systemic
blood pressure. The blood pressure change is transient and usually requires no treatment.
Us ual Dos age
The usual dosage employed varies with the site and method of injection and the age, condition andweight of the patient. In adults, carotid and vertebral angiography, by either the percutaneous needle orcatheter 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 asingle 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 inapproximate proportion to age and body weight.
PERIPHERAL ARTERIOGRAPHY AND VENOGRAPHY

Conray may be injected to visualize the arterial and venous peripheral circulation. Arteriograms of theupper and lower extremities may be obtained by any of the established techniques. Most frequently, apercutaneous 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 notreatment; however, the blood pressure should be monitored 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 considered following theprocedure. 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 andfluoroscopy is recommended. This is especially important in patients with severe arterial or venous
disease.
Advers e Reactions
In addition to the general adverse reactions previously described, hemorrhage and thrombosis haveoccurred 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 havebeen reported following venography.
Us ual Dos age
Peripheral Arteriography: In adults a single rapid injection of 20 to 40 mL is normally sufficient tovisualize the entire extremity. The dose for children is reduced in proportion 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 flushedwith either 5% dextrose in water (D5W) or normal saline (Sodium Chloride Injection USP) or thecontrast medium should be removed by leg massage and/or leg elevation.
ARTHROGRAPHY
Precautions
In addition to the general precautions previously described, strict aseptic technique is required toprevent 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 ofexcessive 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.
Advers e 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.
Us ual Dos age
Arthrography is usually performed under local anesthesia. The amount of contrast agent required issolely 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, hipShoulder,
ankle
Other

5-15 mL
5-10 mL
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 of either filtered room air or carbon
dioxide is introduced for examination of the knee and lesser volumes for other joints. The concomitant
use of epinephrine 1:1000 will reduce the rate of contrast medium absorption as well as the productionof synovial fluids and consequent dilution of the medium.
DIRECT CHOLANGIOGRAPHY
Precautions
In addition to the general precautions previously described, in the presence of acute pancreatitis, direct
cholangiography, if necessary, should be employed with caution, 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 areavailable. The patient should be carefully monitored for at least 24 hours to ensure prompt detection ofbile leakage and hemorrhage. Appropriate premedication of the patient is recommended and drugs
which are cholespastic, such as morphine, should be avoided. Respiratory movements should becontrolled during introduction of the needle.
Advers e 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 inliver 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 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 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.
Dos age and Adminis tration
It is advisable that Conray be at or close to body temperature when injected. The injection is madeslowly 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 ofthe 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 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 selectedpatients for the differential diagnosis of jaundice due to extrahepatic biliary obstruction or parenchymal
disease. The procedure is only employed where oral or intravenous cholangiography and otherprocedures have failed to provide the necessary information. In obstructed cases, percutaneoustranshepatic cholangiography is used to determine the cause and site of obstruction to help plansurgery. 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 and safety 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 be diluted 1:1 with Sodium Chloride injection
USP 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 berepeated for exposures in different planes and repositioning of the patient, if necessary, should be donewith care. If a duct is not readily located by aspiration, successive small doses of 1 to 2 mL of themedium are injected into the liver as the needle is gradually withdrawn, until a duct is visualized by xray.
If no duct can be located after 3 or 4 attempts, the procedure should be terminated. Inability to enter aduct by a person experienced in the technique is generally considered to be strongly suggestive ofhepatocellular disease.
ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY
Endoscopic retrograde cholangiopancreatography (ERCP) is indicated in carefully selected patientswith known or suspected pancreatic or biliary tract disease when other diagnostic procedures havefailed 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 by personnel skilled andexperienced with the procedure, and careful attention to technique is essential for the success andsafety of the procedure. Fluoroscopy is mandatory during injection to prevent over distention of theduct systems.
Advers e Reactions
Adverse reactions that have occurred which are attributable to either the procedure or to Conray,include nausea, vomiting, fever, severe abdominal pain, duodenal wall intravasation, septicemia,
pancreatitis and perforation of the common bile duct associated with pathology.
Dos age and Adminis tration

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 anappropriate antiperistaltic agent.
The contrast medium should be injected slowly under fluoroscopic control employing the minimal dosethat is adequate to visualize the common bile duct, the pancreatic duct, or both duct systems. The dosage
will vary greatly depending on the pathological findings and can range from 10 to 100 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.
CONTRAST ENHANCEMENT OF COMPUTED TOMOGRAPHIC (CT) BRAIN IMAGING
TumorsConray may be useful to enhance the demonstration of the presence and extent of certain malignancies
such as: gliomas including malignant gliomas, glioblastomas, astrocytomas, oligodendrogliomas andgangliomas; 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 oflow 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-Neoplas tic 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 someinfarctions are obscured if contrast media are used. The use of iodinated contrast media results incontrast enhancement in about 60% of cerebral infarctions studied from one to four weeks from theonset of symptoms.
Sites of active infection may also be enhanced following contrast medium administration.
Arteriovenous malformations and aneurysms will show contrast enhancement. In the case of these
vascular lesions, the enhancement is probably dependent on the iodine content of the circulating bloodpool.
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 isadvisable to ensure that patients are well hydrated prior to examination.
Us ual Dos age
The usual dosage in adults and children is 2 mL/kg (1 mL/lb) by intravenous administration, not toexceed a total dose of 150 mL. In most cases, scanning may be performed immediately after completionof 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.
CRANIAL COMPUTERIZED ANGIOTOMOGRAPHY
Conray may be administered for cranial computerized angiotomography when necessary to visualize thecerebral vessels to detect cerebrovascular lesions and to evaluate the anatomical relationship between

the cerebral blood vessels and other parenchymal or space occupying lesions.
Us ual Dos age
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 after administration. This dose may be repeated asnecessary. The total dose per procedure should not exceed 200 mL, and in children the total dose isreduced in approximate proportion to age and body weight.
In adults, when the 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 doseis reduced in approximate proportion to age and body weight.
CONTRAST ENHANCEMENT IN BODY COMPUTED TOMOGRAPHY1
Conray may be administered when necessary to visualize vessels and organs in patients undergoing CTof the chest, abdomen and pelvis.
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 to ensure that patients areadequately hydrated prior to examination. Patient motion, including respiration, can markedly affectimage 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. Dynamic CT scanning is the procedure of choice for malignant tumor enhancement (seeCLINICAL PHARMACOLOGY).
Us ual Dos age
Conray 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 specificlesions, 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 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 of iodinated x-ray contrast media throughthe 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 most frequently examined by intravenous DSA are the heart, including coronary
by-pass grafts; the pulmonary arteries; the arteries of the brachiocephalic 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 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 associated with IV DSA are thoseusually attendant with catheter procedures and include intramural injections, vessel dissection 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 ofadequate size, will reduce this potential.
Patient motion, including respiration and swallowing, can result in marked image degradation yielding
non-diagnostic studies. Therefore, patient cooperation is essential.
Advers e Reactions
See section on general Adverse Reactions.
Us ual Dos age
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 intoeither 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 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 dose range is 20 to 40 mL. Injections may be repeated asnecessary.
Central catheter injections are usually made with a power injector with an injection 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 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) of 5% Dextrose in water or normal saline.
ARTERIAL DIGITAL SUBTRACTION ANGIOGRAPHY
Arterial digital subtraction angiography provides images similar in quality to conventional film-screen
systems. The advantages of arterial DSA when compared to standard film angiography include: the useof less contrast medium; the use of lower concentrations for some procedures; a decreased need forselective arterial catheterization reducing the possibility of dislodging atheromatous plaques orsignificantly reducing the blood flow in the artery; and a shortened examination time. The limitations ofarterial DSA include: reduced spatial resolution; limited field size; and the inability to conductsimultaneous biplane examinations.
Patient Preparation
No special patient preparation is required for arterial DSA. However, it is advisable to ensure thatpatients are well hydrated prior to examination.
Precautions
In addition to the general precautions described, the risks associated with arterial DSA are thoseusually attendant with catheter procedures. Following the procedure, gentle pressure hemostasis isrequired, followed by observation and immobilization of the limb for several hours to preventhemorrhage from the site of arterial puncture.
Us ual Dos age
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 and the flow rates for arterial DSA are 50% or less than thatused 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:
3-8 mL
Aortic Arch:
15-25 mL
Subclavian and brachial arteries: 5-15 mL
Major branches of the aorta:
5-20 mL
Lumbar aorta (bifurcation):
10-25 mLHOW SUPPLIED
Conray® Glas s Vials /Bottles NDC Number
25x30 mL vials
0019-0953-23
25x50 mL vials
0019-0953-05
12x100 mL bottles
0019-0953-10
12x150 mL bottles
0019-0953-50
Storage
Store below 30°C (86°F). Exposing this product to very cold temperatures may result in crystallizationof the salt. If this occurs, the container should be brought to room temperature. Shake vigorously toassure complete dissolution of any crystals. The speed of dissolution may be increased by heating withcirculating warm air. Before use, examine the product to assure that all solids are redissolved, and thatthe container and closure have not been damaged.
This preparation is sensitive to light and must be protected from strong daylight or direct exposure to
the sun.
As with all contrast media, glass containers should be inspected prior to use to ensure that breakage orother 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 enhancement of malignant
tumors using dynamic computed tomography and intravascular pharmacokinetics,” Radiology, 137:137147, October 1980.
Manufactured by:
Liebel-Flarsheim Company LLC
Raleigh, NC 27616
Made in USA
GBT 0953A0817
Revised 08/17

Package Label Principal Dis play Panel - 150mL Bottle
For Intravas cular Us e
Sterile Solution
Conray®
150mL
NDC 0019-0953-50
Iothalamate Meglumine Injection USP 60%
282 mg/mL Organically Bound Iodine
NOT FOR INTRATHECAL USE
Rx Only
Protect from light • Store below 30°C (86°F).
Each mL contains 600 mg iothalamate meglumine, 0.09 mg edetate calcium disodium as a stabilizer, and0.125 mg monobasic sodium phosphate as a buffer.
Single dos e container • Dis card unus ed portion
Us ual Dos age: See Package Insert.
10390817
Manufactured by:
Liebel-Flarsheim Company LLC
Raleigh, NC 27616
Made in USA

CONRAYiothalamate meglumine injection

Product Information
Prod uct T yp e

HUMAN PRESCRIPTIO N DRUG

Route of Ad minis tration

INTRAVASCULAR

Ite m Cod e (S ource )NDC:0 0 19 -0 9 53

Active Ing redient/Active Moiety
Ing redient NameIO THALAMATE MEGLUMINE (UNII: XUW72GO P7W) (IO THALAMIC ACID UNII:16 CHD79 MIX)

Basis o f Streng th
IO THALAMATEMEGLUMINE

Streng th
6 0 0 mgin 1 mLInactive Ing redients
Ing redient Name

Streng th

EDETATE CALCIUM DISO DIUM (UNII: 25IH6 R4SGF)
SO DIUM PHO SPHATE, MO NO BASIC, UNSPECIFIED FO RM (UNII: 39 8 0 JIH2SW)

Packag ing#

Item Co de1

NDC:0 0 19 -0 9 5309

NDC:0 0 19 -0 9 5311

NDC:0 0 19 -0 9 5310

NDC:0 0 19 -0 9 5350

NDC:0 0 19 -0 9 5313

5
6

NDC:0 0 19 -0 9 5315

10 /14/20 0 3

12 in 1 BO X

10 /14/20 0 350 in 1 BO X

10 /14/20 0 350 in 1 BO X

10 /14/20 0 3

50 mL in 1 VIAL, GLASS; Type 0 : No t a Co mbina tio n Pro duc t
NDC:0 0 19 -0 9 5303

78

12 in 1 BO X

30 mL in 1 VIAL, GLASS; Type 0 : No t a Co mbina tio n Pro duc t

6
7

10 /14/20 0 3

150 mL in 1 BO TTLE, GLASS; Type 0 : No t a Co mbina tio n
Pro duc t

4
5

12 in 1 BO X

10 0 mL in 1 BO TTLE, GLASS; Type 0 : No t a Co mbina tio n
Pro duc t

3
4

10 /14/20 0 3

150 mL in 1 BO TTLE, GLASS; Type 0 : No t a Co mbina tio n
Pro duc t

2
3

12 in 1 BO X

Marketing End
Date

10 0 mL in 1 BO TTLE, GLASS; Type 0 : No t a Co mbina tio n
Pro duc t

1
2

Marketing Start
Date

Packag e Descriptio n

12 in 1 BO X

10 /14/20 0 3

10 0 mL in 1 VIAL, GLASS; Type 0 : No t a Co mbina tio n Pro duc t
NDC:0 0 19 -0 9 5323

25 in 1 BO X

10 /14/20 0 3

830 mL in 1 VIAL, GLASS; Type 0 : No t a Co mbina tio n Pro duc t

NDC:0 0 19 -0 9 539
05

25 in 1 BO X

9

50 mL in 1 VIAL, GLASS; Type 0 : No t a Co mbina tio n Pro duc t

10 /14/20 0 3

Marketing Information
Marke ting Cate goryNDA

Ap p lication Numb e r or Monograp h Citation
NDA0 1329 5Marke ting S tart Date

Marke ting End Date

10 /14/20 0 3

Labeler - Liebel-Flars heim Company LLC (057880002)
Establishment
Name

Ad d re s s

ID/FEIBus ine s s Op e rations

LIEBEL-FLARSHEIM CO MPANY LLC

10 9 0 249 8 4

ANALYSIS(0 0 19 -0 9 53) , MANUFACTURE(0 0 19 -0 9 53)

Establishment
Name
Juste sa Ima ge n, S.A.U.

Revised: 10/2018

Ad d re s s

ID/FEI
4770 20 325

Bus ine s s Op e rations
API MANUFACTURE(0 0 19 -0 9 53)

Liebel-Flarsheim Company LLC