DailyMed Label: Diatrizoate Sodium

DailyMed Label: Diatrizoate Sodium

2006

DailyMed Prescription

Diatrizoate Sodium

Diatrizoate Sodium

Amersham Health Inc.

NDC: 0407-0766

HYPAQUE sodium, brand of diatrizoate sodium, is a radiopaque diagnostic agent, water-soluble organic iodide contrast medium. In pure form, it contains 59.87 percent organically bound iodine. The 50 percent (w/v) solution contains 300 mg iodine per mL and 0.8 mEq (18.1 mg) sodium per mL. It has an osmolality of 1515 mosm/kg (determined by VPO), and is hypertonic to blood. As a point of information only, a 10 percent solution (w/v) is isotonic. The viscosity (cp) is about 3.25 at 25° C and 2.34 at 37° C. Sodium carbonate and hydrochloric acid have been added to adjust pH between 6.5 and 7.7.The pKa is 3.4 for diatrizoic acid. If a solution of this medium is chilled, crystals may form but readily dissolve if the vial is placed in moderately hot water before use; cool to body temperature before injecting. The sterile aqueous solution is clear and nearly colorless. It is relatively thermostable and may be autoclaved without harmful effects, although it should be protected from strong light. The 50 percent solution contains edetate calcium disodium 1:10,000 as a sequestering stabilizing agent. Diatrizoate sodium is a triiodinated benzoic acid derivative, the sodium salt of 3,5-diacetamido-2,4,6-triiodobenzoate with a molecular weight of 635.90, and has the following structural formula:

HYPAQUE sodium 50 percent is indicated for excretory urography, cerebral and peripheral angiography, aortography, intraosseous venography, direct cholangiography, hysterosalpingography, splenoportography, and contrast enhancement of computed tomographic head imaging. Diatrizoate salts are used in small, medium, and large dose urography (see Dosage and Administration—EXCRETORY UROGRAPHY ). Visualization of the urinary tract can be achieved by either direct intravenous bolus injection, intravenous drip infusion, or incidentally following intra-arterial procedures.Visualization of the urinary tract is delayed in infants less than 1 month old, and in patients with urinary tract obstruction (see CLINICAL PHARMACOLOGY ). Injectable radiopaque contrast media may be used to refine diagnostic precision in areas of the brain which may not otherwise have been satisfactorily visualized. Radiopaque diagnostic agents may be useful to investigate the presence and extent of certain malignancies such as: gliomas including malignant gliomas, glioblastomas, astrocytomas, oligodendrogliomas and gangliomas, 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 of low grade or infiltrative glioma has not been demonstrated. In calcified lesions, there is less likelihood of enhancement. Following therapy, tumors may show decreased or no enhancement. The opacification of the inferior vermis following contrast media administration has resulted in false-positive diagnosis in a number of normal studies. The use of injectable radiopaque diagnostic agents may be beneficial in the image enhancement of nonneoplastic lesions. Cerebral infarctions of recent onset may be better visualized with contrast enhancement, while some infarctions are obscured if contrast media are used. The use of iodinated contrast media results in contrast enhancement in about 60 percent of cerebral infarctions studied from one to four weeks from the onset of symptoms. Sites of active infection may also be enhanced following contrast media administration. Arteriovenous malformations and aneurysms will show contrast enhancement. For these vascular lesions, the enhancement is probably dependent on the iodine content of the circulating blood pool. Hematomas and intraparenchymal bleeders seldom demonstrate any contrast enhancement. However, in cases of intraparenchymal clot, for which there is no obvious clinical explanation, contrast media administration may be helpful in ruling out the possibility of associated arteriovenous malformation. Diatrizoate salts are used for radiographic studies throughout the cardiovascular system. Intravascular radiopaque diagnostic agents of high concentration are not recommended for cerebral or spinal angiography (see CONTRAINDICATIONS—General ), and contrast agents with the lowest compatible viscosity and higher concentration of iodine (310 mg/mL to 480 mg/mL of bound iodine) must be used for angiocardiography. Contrast media approaching serum ionic content and osmolality have less potential for deleterious effects on the myocardium (see PRECAUTIONS—General, Drug Interactions ). Addition of chelating agents may contribute to toxicity in coronary angiography, and the sodium content of angiographic agents used in coronary arteriography is of crucial importance. In addition to the following general CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, and ADVERSE REACTIONS, there are additional listings in these categories under the particular procedures.

Preparation of the patient will vary with preference of the radiologist and the type of radiological procedure performed. Specific radiologic procedures used will depend on the state of the patient and the diagnostic indications. Individual doses should be tailored according to age, body size, and indication for examination. (See INDIVIDUAL INDICATIONS AND USAGE section for specific Dosage and Administration.) Solutions of radiopaque diagnostic agents for intravascular use should be at body temperature when injected and may need to be warmed before use. In the event that crystallization occurs, the solution may be clarified by placing the vial in a water bath at 40 ° C to 5O ° C and shaking gently for two to three minutes or until the solids redissolve. If particles still persist, do not use this vial but discard it. The solution should be protected from light and any unused portion remaining in the container should be discarded. Dilution and withdrawal of the, contrast agents should be accomplished under aseptic conditions with sterile syringes. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Avoid contaminating catheters, syringes, needles, and contrast media with glove powder or cotton fibers. Pediatric doses of injectable radiopaque diagnostic agents are generally determined on a weight basis and should be calculated for each patient individually. (See INDIVIDUAL INDICATIONS AND USAGE section .) Diatrizoate salts are incompatible in vitro with some antihistamines and many other drugs. It is believed that one of the chief causes of in vitro incompatibility is an alteration of pH. Turbidity of solutions of intravascular contrast medium occurs between pH 2.5 and 4.1. Another cause is chemical interaction; therefore, other pharmaceuticals should not be mixed with contrast agents in the same syringe.

HYPAQUE sodium 50 percent has no absolute contraindications in its recommended uses (see general WARNINGS and PRECAUTIONS ). Do not use HYPAQUE sodium 50 percent for myelography or for examination of dorsal cysts or sinuses which might communicate with the subarachnoid space. Even a small amount in the subarachnoid space may produce convulsions and result in fatality. (See also AORTOGRAPHY, Warnings .) Epidural injection is also contraindicated. Urography and large dose vascular procedures are contraindicated in dehydrated azotemic patients. (See also PRECAUTIONS—General .)

Diagnostic procedures which involve the use of radiopaque diagnostic agents should be carried out under the direction of personnel with the prerequisite training and with a thorough knowledge of the particular procedure to be performed. Appropriate facilities should be available for coping with any complication of the procedure, as well as for emergency treatment of severe reactions to the contrast agent itself. After parenteral administration of a radiopaque agent, competent personnel and emergency facilities should be available for at least 30 to 60 minutes since severe delayed reactions have occurred (see ADVERSE REACTIONS—General ). The possibility of a reaction, including serious, life-threatening, fatal, anaphylactic or cardiovascular reactions should always be considered (see ADVERSE REACTIONS ). It is of utmost importance that a course of action be carefully planned in advance for immediate treatment of serious reactions, and that adequate and appropriate personnel be readily available in case of any reaction. Preparatory dehydration for angiography and CT procedures is unnecessary and may be dangerous, contributing to acute renal failure in infants, young children, the elderly, patients with preexisting renal insufficiency, patients with advanced vascular disease, and diabetic patients. Dehydration in these patients seems to be enhanced by the osmotic diuretic action of urographic agents. Overnight fluid restriction for urography may be undesirable and is considered unnecessary when using this relatively high (50%) concentration. Although azotemia is not a contraindication, the medium should be used with great care in patients with advanced renal destruction associated with severe uremia. (See also EXCRETORY UROGRAPHY, Precautions .) Acute renal failure has been reported in diabetic patients with diabetic nephropathy and in susceptible nondiabetic patients (often elderly with preexisting renal disease) following excretory urography. Therefore, careful consideration of the potential risks should be given before performing this radiographic procedure in these patients. (See also EXCRETORY UROGRAPHY, Precautions—Preparatory Dehydration .) Immediately following surgery, excretory urography should be used with caution in renal transplant recipients. The possibility of an idiosyncratic reaction in susceptible patients should always be considered (see ADVERSE REACTIONS—General ). The susceptible population includes patients with a history of a previous reaction to a contrast media, patients with a known sensitivity to iodine per se, and patients with a known clinical hypersensitivity: bronchial asthma, hay fever, and food allergies. The occurrence of severe idiosyncratic reactions has prompted the use of several pretesting methods. However, pretesting cannot be relied upon to predict severe reactions and may itself be hazardous for the patient. It is suggested that a thorough medical history with emphasis on allergy and hypersensitivity, prior to injection of any contrast media, may be more accurate than pretesting in predicting potential adverse reactions. A positive history of allergies or hypersensitivity does not arbitrarily contraindicate the use of a contrast agent, where a diagnostic procedure is thought essential, but caution should be exercised (see ADVERSE REACTIONS—General ). Premedication with antihistamines or corticosteroids to avoid or minimize possible allergic reactions in such patients should be considered. Recent reports indicate that such pretreatment does not prevent serious life-threatening reactions, but may reduce both their incidence and severity. Due to the transitory increase in the circulatory osmotic load, injections of urographic agents should be used with caution in patients with congestive heart failure. Such patients should be observed for several hours following the procedure to detect delayed hemodynamic disturbances. 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 reduce cardiac output and increase the duration of exposure to the contrast agent. Seizure activity is rare (about 0.01%) on intravenous injection of ionic contrast media. However, in the higher doses used for CT in patients with brain metastases the incidence can be much higher (1% to 10%). In these patients prophylactic use of a small parenteral dose of a diazepam is suggested immediately before injection when extra high dose CT regimens are employed. In addition to the general precautions already described, excretory urography, angiography, and other uses also have hazards associated with the particular techniques employed. (See INDIVIDUAL INDICATIONS AND USAGE section .) Patients receiving injectable radiopaque diagnostic agents should be instructed to: Inform the physician if they are pregnant (see CLINICAL PHARMACOLOGY ). Inform the physician if they are diabetic or if they have multiple myeloma, pheochromocytoma, homozygous sickle cell disease or known thyroid disorder (see WARNINGS—General ). Inform the physician if they are allergic to any drugs, food, or if they have had any reactions to previous injections of dyes used for x-ray procedures (see PRECAUTIONS—General ). Inform the physician about any other medications they are currently taking, including nonprescription drugs, before they are administered this drug. Renal toxicity has been reported in a few patients with liver dysfunction who were given oral cholecystographic agents followed by urographic agents. Administration of intravascular urographic agents should therefore be postponed in any patient with a known or suspected hepatic or biliary disorder who has recently received a cholecystographic contrast agent. Addition of an inotropic agent to contrast agents may produce a paradoxical depressant response which can be deleterious to the ischemic myocardium. Diphenhydramine hydrochloride may cause precipitation when mixed in the same syringe with HYPAQUE sodium 50%. Under certain circumstances (pH, temperature, concentrations, time), diatrizoate solutions are incompatible with promethazine hydrochloride, diphenhydramine hydrochloride, brompheniramine maleate, or papaverine hydrochloride solutions. Do not prefill plastic syringes with HYPAQUE sodium 50% for prolonged periods (ie, for several hours or longer) before use. If any of these studies, which might be affected by contrast media are indicated, it is recommended that they be performed prior to administration of the contrast medium or two or more days afterwards. Diatrizoate salts interfere with several laboratory urine and blood tests. Coagulation: Diatrizoate salts significantly inhibit all stages of coagulation. The fibrinogen concentration, Factors V, VII, and VIII are decreased. Prothrombin time and thromboplastin time are increased. Platelet aggregation: High levels of plasma diatrizoates inhibit platelet aggregation. Serum calcium: Diatrizoate salts may decrease serum calcium levels. However, this depletion of serum calcium may also be the result of the addition of chelating agents (edetate disodium) in the preparation of certain contrast media. Red cell counts: Transitory decreases in red cell counts. Technetium-99m—RBC labeling interference. Leukocyte counts: Decrease. Urea nitrogen (BUN): Transitory increase (see CLINICAL PHARMACOLOGY ). Serum creatinine: Transitory increase. Contrast media which are excreted in the urine, may interfere with some laboratory determinations eg, proteinuria, specific gravity, osmolality, or bacterial cultures. Protein-bound iodine (PBI) and total serum organic iodine: Transient increase of both tests following urography have been noticed. The results of PBI and radioactive iodine uptake studies which depend on iodine estimations will not accurately reflect thyroid function for up to 16 days following administration of iodinated urographic media. However, thyroid function tests not depending on iodine estimations, eg, T3 resin uptake or free thyroxine assays are not affected. Long-term studies in animals have not been performed in order to evaluate carcinogenic potential, mutagenesis, or whether HYPAQUE sodium 50 percent can affect fertility in males or females. Animal reproduction studies have not been conducted with HYPAQUE sodium 50 percent. It is also not known whether HYPAQUE sodium 50 percent can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. HYPAQUE sodium 50 percent should be given to a pregnant woman only if clearly needed. It is not known whether use of these contrast agents during labor or delivery has immediate or delayed adverse effects on the fetus, prolongs the duration of labor or increases the likelihood that forceps delivery or other obstetrical intervention or resuscitation of the newborn will be necessary. Diatrizoate salts are excreted unchanged in human milk. Because of the potential adverse reactions, although it has not been established that serious adverse reactions occur in nursing infants, caution should be exercised when these contrast media are administered to a nursing woman. Infants and small children should not have any fluid restriction prior to excretory urography or any other procedures (see PRECAUTIONS—General ). Guidelines for pediatric dosages are presented in DOSAGE AND ADMINISTRATION—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.

Renal toxicity has been reported in a few patients with liver dysfunction who were given oral cholecystographic agents followed by urographic agents. Administration of intravascular urographic agents should therefore be postponed in any patient with a known or suspected hepatic or biliary disorder who has recently received a cholecystographic contrast agent. Addition of an inotropic agent to contrast agents may produce a paradoxical depressant response which can be deleterious to the ischemic myocardium. Diphenhydramine hydrochloride may cause precipitation when mixed in the same syringe with HYPAQUE sodium 50%. Under certain circumstances (pH, temperature, concentrations, time), diatrizoate solutions are incompatible with promethazine hydrochloride, diphenhydramine hydrochloride, brompheniramine maleate, or papaverine hydrochloride solutions. Do not prefill plastic syringes with HYPAQUE sodium 50% for prolonged periods (ie, for several hours or longer) before use.

Vials of 50 mL, rubber stoppered, box of 25 (NDC 0407-0766-04). Protect from light. Store at 15°C to 30°C (59° F to 86°F).

Intravascular injection of a radiopaque diagnostic agent opacifies those vessels in the path of the flow of the contrast medium, permitting radiographic visualization of the internal structures of the human body until significant hemodilution occurs. At physiologic pH, the water-soluble contrast media are completely dissociated into a radiopaque anion and a solubilizing cation. While circulating in tissue fluids, the compound remains ionized. However, it is not metabolized but excreted unchanged in the urine, each diatrizoate molecule remaining "obligated" to its sodium moiety. Following intravenous injection, the radiopaque diagnostic agents are immediately diluted in the circulating plasma. Equilibrium is reached with the extracellular compartment at about 10 minutes. Hence, the plasma concentration at 10 minutes is closely related to the dose corrected to body size. The pharmacokinetics of the intravenously administered radiopaque contrast media are usually best described by a two compartment model with a rapid alpha phase for drug distribution and a slow beta phase for drug elimination. In patients with normal renal function, the alpha and beta half-lives were respectively 30 minutes and 120 minutes for diatrizoate. But in patients with renal functional impairment, the elimination half-life for the beta phase can be prolonged up to several days. Injectable radiopaque diagnostic agents are excreted either through the liver or through the kidneys. These two excretory pathways are not mutually exclusive, but the main route of excretion seems to be governed by the affinity of the contrast medium for serum albumin. From 0% to 10% of diatrizoate sodium is bound to serum protein. Diatrizoate salts are excreted unchanged predominantly through the kidneys by glomerular filtration. The amount excreted by the kidney during any period of time is determined by the filtered load; ie, the product of plasma contrast media concentration and glomerular filtration rate. The plasma concentration is dependent upon the dose administered and the body size. The glomerular filtration rate varies with the body size, sex, age, circulatory dynamics, diuretic effect of the drug, and renal function. In patients with normal renal function the maximum urinary concentration of diatrizoate sodium occurs within 10 minutes with 12 percent of the administered dose being excreted. The mean values of cumulative urinary excretion for diatrizoate sodium expressed as percentage of administered dose are 38 percent at 60 minutes, 45 percent at 3 hours, and 94 to 100 percent at 24 hours. Urinary excretion of contrast media is delayed in infants younger than 1 month and in patients with urinary tract obstruction. The urinary iodine concentration is higher with the sodium salt of diatrizoic acid than with the meglumine salt. The liver and small intestine provide the major alternate route of excretion for diatrizoate. In patients free of severe renal disease, the fecal recovery is less than 2 percent of the administered dose. In patients with severe renal impairment the excretion of these contrast media through the gallbladder and into the small intestine sharply increases; up to 20 percent of the administered dose has been recovered in the feces in 48 hours. Saliva is a minor secretory pathway for injectable radiopaque diagnostic agents. In patients with normal renal function, minimal amounts of contrast media are secreted unchanged. However, in uremic patients small amounts of free iodides resulting from deiodination prior to administration or in vivo , have been detected in the saliva. Diatrizoate salts cross the placental barrier in humans by simple diffusion and appear to enter fetal tissue passively. No apparent harm to the fetus was observed when diatrizoate sodium and diatrizoate meglumine were injected intravenously 24 hours prior to delivery. However, abnormal neonatal opacification of the small intestine and colon were detected 4 to 6 days after delivery. Procedures including radiation involve a certain risk related to the exposure of the fetus. (See PRECAUTIONS—General, Pregnancy Category C .) Injectable radiopaque diagnostic agents are excreted unchanged in human milk. (See PRECAUTIONS—General, Nursing Mothers .) HYPAQUE sodium 50 percent can be administered as an intravenous bolus for brain tissue enhancement using computerized tomography. Increased tissue contrast differential for the scan is achieved either because of increased vascular (arterial, venous, or capillary bed) contrast or by blood brain barrier penetration of the medium (or its absence) in certain localized areas of disrupted vascular permeability. The degree of tissue enhancement caused by increased blood contrast is directly related to blood iodine content. However, the degree of enhancement due to extravascular accumulation of iodine resulting from blood brain barrier disruption will depend on the extent of disruption, the blood level of iodine, and the time delay prior to scanning. The nature of the pathology will determine whether an immediate or delayed scan is optimal. The anti-inflammatory and antiedema effects in patients receiving steroid therapy have interfered with the expected distribution of CT tissue enhancement on the scan in certain diseases.