WARNINGS
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.
Serious or fatal reactions have been associated with the administration of iodine 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 injections of concentrated contrast media into arteries supplying the spinal cord. The injection of a contrast medium should never be made following the administration of vasopressors since they strongly potentiate neurologic effects. (See PRECAUTIONS pertaining to Aortography.)
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.
A definite risk exists in the use of intravascular contrast agents in patients who are known to have multiple myeloma. In such instances there has been anuria resulting in progressive uremia, renal failure and eventually death. Although neither the contrast agent nor dehydration has separately proved to be the cause of anuria in myeloma, it has been speculated that the combination of both may be the causative factor. The risk in myelomatous patients is not a contraindication to the procedures; however, 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. No form of therapy, including dialysis, has been successful in reversing this effect. Myeloma, which occurs most commonly in persons over age 40, should be considered before intravascular administration of a contrast agent.
Administration of radiopaque materials to patients known or suspected to have 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 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.
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.
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 should be 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 nondiabetic 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.
Avoid accidental introduction of this preparation into the subarachnoid space since even small amounts may produce convulsions and possible fatal reactions.
Convulsions have occurred in patients with primary or metastatic cerebral lesions following administration of contrast media for contrast enhancement of CT brain images.
PRECAUTIONS
General
Diagnostic procedures which involve the use of iodinated intravascular 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 types should always be 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 pretesting in predicting the potential for reactions, 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 pretest, 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 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.
The possibility of thrombosis should be borne in mind when percutaneous techniques are employed.
Consideration must be given to the functional ability of the kidneys before injecting this preparation.
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:
- Inform your physician if you are pregnant.
- Inform your physician if you are diabetic or if you have multiple myeloma, pheochromocytoma, homozygous sickle cell disease or known thyroid disease. (See WARNINGS.)
- 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.)
- Inform your physician about any other medications you are currently taking, including non-prescription drugs.
Drug/Laboratory Test Interactions: Iodine-containing contrast agents may alter the results of thyroid function tests which depend on iodine estimation, e.g., PBI and radioactive iodine uptake studies. Such tests, if indicated, should be performed prior to the administration of this preparation or delayed for about two weeks following administration.
Contrast agents may interfere with some chemical determinations made on urine specimens; therefore, urine should be collected before administration of the contrast medium or two or more days afterwards.
Following selective coronary arteriography, transient elevation of creatinine phosphokinase (CPK) has occurred in approximately 30% of patients tested.
Post-arteriographic changes in laboratory studies include transient elevations in BUN, serum creatinine and glucose.
Hypertonic solutions cause a decrease in hematocrit in vitro and in vivo, and shrinkage of red blood cells.
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: Diatrizoate sodium and diatrizoate meglumine administered intravenously cross the placenta and are evenly distributed in fetal tissues. No teratogenic effects attributable to diatrizoate sodium or diatrizoate meglumine have been observed in teratology studies performed in animals. There are, however, no adequate and well-controlled studies in pregnant women. Because animal teratology studies are not always predictive of human response, this agent should be used during pregnancy only if clearly needed.
Nursing Mothers: Diatrizoate salts are excreted 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.)
|
