Conray 400

Conray 400 is a sterile aqueous solution intended for intravascular administration as a diagnostic radiopaque medium. Conray 400 contains 66.8% w/v of iothalamate sodium which is monosodium 5-acetamido-2,4,6-triiodo-N-methylisophthalamate and has the following structural formula:

Each milliliter contains 668 mg of iothalamate sodium, 0.110 mg edetate calcium disodium as a stabilizer and 0.125 mg of monobasic sodium phosphate as a buffer. The solution contains approximately 24.2 mg (1.05 mEq) sodium in each milliliter of solution and provides 40% (400 mg/mL) organically bound iodine. Conray 400 has an osmolarity of approximately 1700 mOsmol per liter, an osmolality of approximately 2300 mOsmol per kilogram and is, therefore, hypertonic under conditions of use. The viscosity (cps) is approximately 7 at 25°C and 4.5 at 37°C. The pH is 6.5-7.7. Conray 400 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.

General

Diagnostic 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. At all times a fully equipped emergency cart, or equivalent supplies and equipment, and personnel competent in recognizing and treating adverse reactions of all severity, or situations which may arise as a result of the procedure, should be immediately available. If a serious reaction should occur, immediately discontinue administration. Since severe delayed reactions have been known to occur, emergency facilities and competent personnel should be available for at least 30 to 60 minutes after administration. (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. 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 manifestations 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 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 of this type does not arbitrarily contraindicate the use of a contrast agent, when a diagnostic procedure is thought essential, but does call for caution. (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 pre-test since in these patients the incidence of reaction 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 pretreatment 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 been reported in these patients, and 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 hemocystinuria 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. (See PRECAUTIONS, General.)
4. Inform your physician about any other medications you are currently taking including non-prescription drugs.

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 fertility or harm to the fetus due to Conray 400. 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 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.)

It is advisable that Conray 400 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 during administration a minor reaction occurs 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 and discoloration prior to administration.

Following intravenous injection, Conray 400 is rapidly excreted by the kidneys. Conray 400 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 3-8 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 400 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 25-50 mL. Children 14 years of age and over, of average weight, may receive the adult dose. The total dose is normally injected within 30-90 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 15-30 seconds. The dosage for children is reduced in proportion to age and body weight. The following approximate schedule is recommended for infants and children based on a dosage of about 0.5 mL/kg of body weight.