FDA label 0AAAA03E-B258-45EC-89C8-06E1353F57EF

WARNINGS—General 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 insure 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 the development of thromboembolic events. For these reasons, meticulous angiographic techniques are recommended 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 to decrease but not eliminate the likelihood of in vitro clotting. Excretory urography is potentially hazardous in patients with multiple myeloma. In some of those patients, therapeutically resistant anuria resulting in progressive uremia, renal failure, and eventually death has followed this procedure. Although neither the contrast agent nor dehydration has been proved separately to be the cause of anuria in myelomatous patients, it has been speculated that the combination of both may be causative. The risk of excretory urography in myelomatous patients is not a contraindication to the procedure; however, they require special precautions. Partial dehydration in the preparation of these patients for the examination is not recommended since this may predispose to the precipitation of myeloma protein in the renal tubules. Myeloma, which occurs most commonly in persons over age 40, should be considered before instituting urographic procedures. Contrast media may promote sickling in individuals who are homozygous for sickle cell disease when the material is injected intravenously or intra-arterially. Administration of radiopaque materials to patients known or suspected of having pheochromocytoma should be performed with extreme caution. If, in the opinion of the physician, the possible benefits of such procedures outweigh the considered risks, the procedures may be performed; however, the amount of radiopaque medium injected should be kept to an absolute minimum. The blood pressure should be assessed throughout the procedure and measures for treatment of a hypertensive crisis should be available. Recent reports of thyroid storm occurring following the intravascular use of iodinated radiopaque diagnostic 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 diatrizoate salts. Contrast media administered for cardiac catheterization and angiocardiography may cause cellular injury to circulating lymphocytes. Chromosomal damage in humans includes inhibition of mitosis, increases in the number of micronuclei, and chromosome aberrations. The damages appear to be related to the contrast medium itself rather than to the x-ray radiation. It is to be noted that those agents have not been adequately tested in animal or laboratory systems. Urography should be performed with caution in patients with severely impaired renal function and patients with combined renal and hepatic disease. Subcutaneous extravasation causes transitory stinging, chiefly because of hypertonic cellulitis. If the volume extravasated is small, ill effects are very unlikely. However, if the extravasation is extensive, especially in poorly vascularized areas (e.g., dorsum of the foot or hand), and especially in the presence of vascular disease, skin slough may occur. Injection of sterile water to dilute or addition of spreading agents to speed absorption have not been successful and may aggravate the condition. Selective spinal arteriography or arteriography of trunks providing spinal branches can cause mild to severe muscle spasm. However, serious neurologic sequelae, including permanent paralysis, could occur with even small doses of the 76 percent concentration. In patients with subarachnoid hemorrhage, a rare association between contrast administration and clinical deterioration, including convulsions and death, has been reported. Therefore, administration of intravascular iodinated ionic contrast media in these patients should be undertaken with caution.

ADVERSE REACTIONS—General Approximately 95 percent of adverse reactions accompanying the intravascular use of diatrizoate salts are of mild to moderate severity. However, life-threatening reactions and fatalities, mostly of cardiovascular origin, have occurred. Adverse reactions to injectable contrast media fall into two categories: chemotoxic reactions and idiosyncratic reactions. Chemotoxic reactions result from the physicochemical properties of the contrast media, the dose, and the speed of injection. All hemodynamic disturbances and injuries to organs or vessels perfused by the contrast 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 speed of 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 short duration; the severe reactions are life-threatening and treatment is urgent and mandatory. The reported incidence of adverse reactions to contrast media in patients with a history of allergy are twice that of the general population. Patients with a history of previous reactions to a contrast medium are three times more susceptible than other patients. However, sensitivity to contrast media does not appear to increase with repeated examinations. Most adverse reactions to injectable contrast media appear within one to three minutes after the start of injection, but delayed reactions may occur. Adverse reactions are grouped by organ system and listed below by decreasing order of occurrence and with an approximate incidence of occurrence. Significantly more severe reactions are listed before the other reactions regardless of frequency. Greater Than 1 in 100 Patients Body as a Whole: Reported incidences of death range from 6.6 per 1 million (0.00066 percent) to 1 in 10,000 patients (0.01 percent). Most deaths occur during injection or 5 to 10 minutes later, the main feature being cardiac arrest with cardiovascular disease as the main aggravating factor. Isolated reports of hypotensive collapse and shock following urography are found in the literature. The incidence of shock is estimated to occur in 1 out of 20,000 (0.005 percent) patients. Cardiovascular System: The most frequent adverse reaction to diatrizoate salts is vasodilation (feeling of warmth). The estimated incidence is 49 percent. Digestive System: Nausea 6 percent, vomiting 3 percent. Nervous System: Paresthesia 6 percent, dizziness 5 percent. Respiratory System: Rhinitis 1 percent, increased cough 2 percent. Skin and Appendages: Urticaria 1 percent. Pain at the injection site is estimated to occur in about 12 percent of the patients undergoing urography. Pain is usually due to extravasation. Painful hot erythematous swelling above the venipuncture site was estimated to occur in more than one percent of the patients undergoing phlebography. Special Senses: Perversion of taste 11 percent. Urogenital System: Osmotic nephrosis of the proximal tubular cells is estimated to occur in 23 percent of patients following excretory urography. Less Than 1 in 100 Patients Other infrequently reported reactions without accompanying incidence rates are listed below, grouped by organ system. Body as a Whole: Malaria relapse, uremia, high creatinine and BUN (see PRECAUTIONS—General, Drug/Laboratory Test Interactions ), thrombocytopenia, leukopenia, and anemia. Cardiovascular System: Cerebral hematomas, hemodynamic disturbances, sinus bradycardia, transient electrocardiographic abnormalities, ventricular fibrillation, petechiae, chest pain, and cardiac arrest. Digestive System: Severe unilateral or bilateral swelling of the parotid and submaxillary glands. Nervous System: Convulsions, paralysis, and coma. (See PRECAUTIONS—General. ) Respiratory System: Asthma, dyspnea, laryngeal edema, pulmonary edema, and bronchospasm. Skin and Appendages: Extravasation necrosis, urticaria with or without pruritus, mucocutaneous edema, and angioneurotic edema. Special Senses: Bilateral ocular irritation, lacrimation, itching, conjunctival chemosis, infection, and conjunctivitis. Urogenital: Renal failure, pain.