Conray^{^®}(iothalamate meglumine injection USP 60%)

Important Safety Information

NOT FOR INTRATHECAL USE

Important Safety Information (Continued)

Indication and Usage
Conray^{^®} (Iothalamate Meglumine Injection USP 60%) is a prescription diagnostic radiopaque medium 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 and evaluation of lesions in the liver, pancreas, kidneys, abdominal aorta, mediastinum, abdominal cavity and retroperitoneal space. Conray 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 additional features of the lesions. In other cases, Conray may allow visualization of lesions not seen with CT alone, or may help to define suspicious lesions seen with unenhanced CT.

Contraindications
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 and prolonged prothrombin times. Endoscopic retrograde cholangiopancreatography is contraindicated during an acute attack of pancreatitis or during severe clinically evident cholangitis and in patients in whom endoscopy is prohibited. See Warnings and Precautions concerning hypersensitivity.

Warnings and Precautions
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. Serious or fatal reactions have been associated with the administration of iodine-containing radiopaque 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.

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 of vasopressors since they strongly potentiate neurologic effects.

In patients with subarachnoid hemorrhage, a rare association between contrast administration and clinical deterioration, including convulsions and death, has been reported.

A definite risk exists in the use of intravascular contrast agents in patients who are known to have multiple myeloma.
Administration of radiopaque materials to patients known or suspected to have pheochromocytoma should be performed with extreme caution.
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 used with caution, and only when the need for the examination dictates, since excretion of the medium may be impaired. Patients with combined renal and hepatic disease, 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 oral cholecystographic agent followed by an intravascular iodinated radiopaque agent and also in patients with 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 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 with endotoxemia and/or those with elevated body temperatures.
Reports of thyroid storm occurring following the intravascular use of iodinated radiopaque agents in patients with hyperthyroidism or with an autonomously functioning thyroid nodule, suggest that this additional risk be evaluated in such patients before use of this drug.
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 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.
The possibility of an idiosyncratic reaction in patients who have previously received a contrast medium without ill effect should always be considered. Prior to the injection of any contrast medium, the patient should be questioned to obtain a medical history with emphasis on allergy and hypersensitivity. A positive history of bronchial asthma, hay fever or allergy, including food, a family history of allergy, a known sensitivity to iodine per se, patients with a known clinical hypersensitivity to a contrast agent may imply a greater than usual risk.
Angiography should be avoided whenever possible in patients with homocystinuria because of the risk of inducing thrombosis and embolism.
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.
Following the arterial digital subtraction angiography procedure, gentle pressure hemostasis is required, followed by observation and immobilization of the limb for several hours to prevent hemorrhage from the site of arterial puncture.

Adverse Reactions
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.
Hypersensitivity reactions: Dermal manifestations of urticaria with or without pruritus, erythema maculopapular rash, dry mouth, sweating, conjunctival symptoms as well as 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 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: Generalized vasodilation, flushing and venospasm. Severe cardiovascular responses include rare cases of hypotensive shock, coronary insufficiency, cardiac arrhythmia, fibrillation and arrest.
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. 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 with eosinophilia 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.

Serious neurological reactions with cerebral angiography include stroke, amnesia and respiratory difficulties.

Use in Specific Populations

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 fertility or harm to the fetus due to Conray. There are, however, no adequate and well controlled studies in pregnant women. Conray should be used during pregnancy only if clearly needed. Iothalamate salts cross the placental barrier in humans and are excreted unchanged in human milk.
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 Conray.
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.
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.

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Conray^{^®} is used for organ or tissue enhancement in certain CT, X-ray and fluoroscopy imaging procedures for which it is approved.

Assists in the diagnosis of internal lesions¹
Solution provides 28.2% (282 mg/mL) organically bound iodine
Available in glass bottles and vials in a variety of fill sizes

For more information about Conray^{^®}, please see the Full Prescribing Information.

Physical Characteristics¹

	Osmolarity mOsmol/l	Osmolarity mOsmol/kg	mPa*s at 25˚C	Viscosity mPa*s at 37˚C
Conray^{^®}	1000	1400	6	4

Packaging