PEDIATRIC USE SECTION.

Pediatric Use. See WARNINGS, and PRECAUTIONS, General.Local injury to the colonicmucosa, particularly in the presence of underlying disease which interfereswith intestinal viability, has been reported in cases where recommendeddoses and dilutions (see DOSAGE AND ADMINISTRATION) were not used; when extemporaneous dosage is elected, thepolysorbate 80 level in the dose may be contributing factor to injury.

PRECAUTIONS SECTION.

PRECAUTIONS. General. Diagnostic procedureswhich involve the use of radiopaque contrast agents should be carriedout under the direction of personnel with the prerequisite trainingand with thorough knowledge of the particular procedure to be performed.Appropriate facilities should be available for coping with any complicationof administration, as well as for treatment of reaction to the contrastmedium (see ADVERSE REACTIONS, and PRECAUTIONS, Information for the Patient).Rectal administrationof undiluted Gastrografin (Diatrizoate Meglumine and Diatrizoate SodiumSolution) in any patient, particularly with large doses and/or inthose with overdistention, has been reported to be associated withmucosal irritation.Cases of hyperthyroidismhave been reported with the use of oral contrast media. Some of thesepatients reportedly had multinodular goiters which may have been responsiblefor the increased hormone synthesis in response to excess iodine.Administration of an intravascular iodinated radiopaque diagnosticagent to hyperthyroid patient precipitated thyroid storm; similarsituation could follow administration of oral preparations of iodides.Therefore, caution should be exercised when administering enteralgastrointestinal radiopaque agents to hyperthyroid and euthyroid goiterouspatients.Consideration shouldbe given to the potential for precipitation of water-soluble contrastagents under conditions that may promote hyperacidity (i.e., fasting,emotional upset, or stress). Harmful effects directly attributableto precipitate formation have not been reported. However, the possibilityof interpreting the precipitate radiologically as an anatomical abnormality(i.e., ulceration of the stomach or small intestine) or injury, shouldbe kept in mind.. Information for the Patient. Patients should receive the following information andinstructions:This drug has been prescribed to perform an x-ray of thegastrointestinal tract.Inform the physician if pregnant or if allergic to iodine,any foods, or x-ray materials.The iodine in diatrizoate salts may interfere with somethyroid tests if these are needed in the future. Inform the attendingphysician at that time about this gastrointestinal study.This drug may cause abdominal cramping, nausea, vomiting,diarrhea, skin rashes, itching, heartburn, dizziness, or headachein some patients, but most reactions are mild and pass quickly.. This drug has been prescribed to perform an x-ray of thegastrointestinal tract.. Inform the physician if pregnant or if allergic to iodine,any foods, or x-ray materials.. The iodine in diatrizoate salts may interfere with somethyroid tests if these are needed in the future. Inform the attendingphysician at that time about this gastrointestinal study.. This drug may cause abdominal cramping, nausea, vomiting,diarrhea, skin rashes, itching, heartburn, dizziness, or headachein some patients, but most reactions are mild and pass quickly.. Drug/Laboratory Test Interactions. Thyroid FunctionTests. The resultsof protein bound iodine (PBI) and radioactive iodine uptake studies,which depend on iodine estimations, will not accurately reflect thyroidfunction for six months, and possibly as long as one year, followingthe administration of diagnostic enteral radiopaque media.Thyroid function tests, if indicated, generallyshould be performed prior to the administration of any iodinated agent.However, thyroid function can be evaluated after use of these agentsby using T3 resin uptake and total or freethyroxine (T4) assays which are not dependenton iodine estimations.. Pancreatic Tests. Small quantities ofcontrast medium in the intestinal tract may cause false low trypsinvalues when determined spectrophotometrically. Therefore, duodenalinstillation should not precede pancreatic function tests involvingspectrophotometric trypsin assays.Any test which might be affected by contrast media should be performedprior to administration of the contrast medium.. Carcinogenesis, Mutagenesis,Impairment of Fertility. Long-term studies in animals have not been performed to evaluatecarcinogenic or mutagenic potential, or possible impairment of fertilityin males or females.. Pregnancy. When administeredintravenously, diatrizoate salts cross the placenta and are evenlydistributed in fetal tissues.No teratogenic effects attributable to diatrizoate meglumine or diatrizoatesodium have been observed in teratology studies performed in animals.There are, however, no adequate and well-controlled studies in pregnantwomen. Because small amounts of these agents may be absorbed, andanimal teratology studies are not always predictive of human response,these agents should be used during pregnancy only when clearly needed.Procedures including radiation involve acertain risk related to the exposure of the fetus.. Nursing Mothers. Diatrizoate meglumine is excreted in breastmilk following intravascular administration.Because small amounts of enteral gastrointestinal radiopaqueagents may be absorbed following oral or rectal administration, cautionshould be exercised when they are administered to nursing woman.. Pediatric Use. See WARNINGS, and PRECAUTIONS, General.Local injury to the colonicmucosa, particularly in the presence of underlying disease which interfereswith intestinal viability, has been reported in cases where recommendeddoses and dilutions (see DOSAGE AND ADMINISTRATION) were not used; when extemporaneous dosage is elected, thepolysorbate 80 level in the dose may be contributing factor to injury.

PREGNANCY SECTION.

Pregnancy. When administeredintravenously, diatrizoate salts cross the placenta and are evenlydistributed in fetal tissues.No teratogenic effects attributable to diatrizoate meglumine or diatrizoatesodium have been observed in teratology studies performed in animals.There are, however, no adequate and well-controlled studies in pregnantwomen. Because small amounts of these agents may be absorbed, andanimal teratology studies are not always predictive of human response,these agents should be used during pregnancy only when clearly needed.Procedures including radiation involve acertain risk related to the exposure of the fetus.

SPL UNCLASSIFIED SECTION.

Thyroid FunctionTests. The resultsof protein bound iodine (PBI) and radioactive iodine uptake studies,which depend on iodine estimations, will not accurately reflect thyroidfunction for six months, and possibly as long as one year, followingthe administration of diagnostic enteral radiopaque media.Thyroid function tests, if indicated, generallyshould be performed prior to the administration of any iodinated agent.However, thyroid function can be evaluated after use of these agentsby using T3 resin uptake and total or freethyroxine (T4) assays which are not dependenton iodine estimations.

STORAGE AND HANDLING SECTION.

Storage. Protect from light. Store at 20-25C (68-77F)[See USP]; avoid excessive heat.

ADVERSE REACTIONS SECTION.

ADVERSE REACTIONS. Most adverse reactions to enteral diagnosticradiopaque agents are mild and transitory. Nausea, vomiting and/ordiarrhea, urticaria with erythema, hypoxia, acute dyspnea, tachyarrhythmia,and anaphylaxis have occurred following ingestion of the contrastmedium, particularly when high concentrations of large volumes ofsolution are administered. Severe changes in serum osmolarity andelectrolyte concentrations may produce shock-like states (see WARNINGS). It should be kept in mindthat serious or anaphylactoid reactions that may occur with intravascularadministration of radiopaque contrast agents are theoretically possiblefollowing administration by other routes.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

Carcinogenesis, Mutagenesis,Impairment of Fertility. Long-term studies in animals have not been performed to evaluatecarcinogenic or mutagenic potential, or possible impairment of fertilityin males or females.

CLINICAL PHARMACOLOGY SECTION.

CLINICAL PHARMACOLOGY. The most important characteristic of contrast media is the iodinecontent. The relatively high atomic weight of iodine contributes sufficientradiodensity for radiographic contrast with surrounding tissues.Diagnostic enteral radiopaque agents havefew known pharmacological effects. Diatrizoate meglumine and diatrizoatesodium exert mild laxative effect attributable to their high osmolarity.Diatrizoate meglumine and diatrizoate sodiumare sparingly absorbed from the intact gastrointestinal tract, andtherefore permit gastrointestinal opacification and delineation afteroral or rectal administration. Oral administration is used for radiographicevaluation of the esophagus, stomach and proximal small intestine.Rectal administration is used for examination of the colon; however,visualization of the distal small bowel is generally unsatisfactory,since the hypertonicity of the medium causes intraluminal diffusionof water with subsequent dilution of the medium. Enough absorptionfrom the gastrointestinal tract to permit incidental visualizationof the urinary tract has been reported; this should also be consideredwhen thyroid testing is being contemplated, since iodine-mediatedthyrotropic effects may occur (see PRECAUTIONS).

CONTRAINDICATIONS SECTION.

CONTRAINDICATIONS. Do not administer to patients with knownhypersensitivity to Gastrografin or any of its components.

DESCRIPTION SECTION.

DESCRIPTION. Gastrografin (Diatrizoate Meglumine and DiatrizoateSodium Solution) is palatable lemon-flavored water-soluble iodinatedradiopaque contrast medium for oral or rectal administration only.Each mL contains 660 mg diatrizoate meglumine and 100 mg diatrizoatesodium; pH has been adjusted to 6.0 to 7.6 with sodium hydroxide. Each mL contains approximately 4.8 mg (0.21 mEq) sodium and367 mg organically bound iodine. Inactive ingredients: edetate disodium,flavor, polysorbate 80, purified water, saccharin sodium, simethicone,and sodium citrate.Diatrizoatemeglumine is designated chemically as 1-deoxy-1-(methylamino)-D-glucitol3,5-diacetamido-2,4,6-triiodo-benzoate (salt); diatrizoate sodiumis monosodium 3, 5-diacetamido-2,4,6-triiodobenzoate. Structural formulas:. Gastrografin Structure.

DOSAGE & ADMINISTRATION SECTION.

DOSAGE AND ADMINISTRATION. General. This medium is not to be used forthe preparation of solutions for parenteral administration. Oral orrectal administration only. Discard any unused portion after procedure.The routine preparatory measuresemployed for barium studies are also appropriate for this agent.For pediatric and severely cachectic patientsthe maintenance of an intravenous fluid line may be advisable.. Radiographic Examinationof Segments of the Gastrointestinal Tract. Oral Administration: Adult oral dosagemay range from 30 to 90 mL (11 to 33 iodine), depending on the natureof the examination and the size of the patient. For infants and childrenless than years of age, 30 mL (11 iodine) are usually adequate;for children to 10 years of age, the suggested dose is 60 mL (22g iodine). These pediatric doses may be diluted 1:1, if desired, withwater, carbonated beverage, milk, or mineral oil. When used in infants,the solution may be given in nursing bottle. Pediatric doses mayalso be used in dehydrated and/or debilitated adult patients. 1:1dilution is also recommended when the contrast medium is used in elderlycachectic individuals.For veryyoung (under 10 kg) and debilitated children the dose should be diluted:1 part Gastrografin (Diatrizoate Meglumine and Diatrizoate SodiumSolution) in parts water is recommended.For Enemas or Enterostomy Instillations: Gastrografin should be diluted when it is used for enemas and enterostomyinstillations. When used as an enema, the suggested dilution for adultsis 240 mL (88 iodine) in 1,000 mL of tap water. For children under5 years of age, 1:5 dilution in tap water is suggested; for childrenover years of age, 90 mL (33 iodine) in 500 mL of tap water isa suitable dilution.. Tomography (Body Imaging). usual adult dose is 240 mL of diluteGastrografin solution prepared by diluting 25 mL (9.17 iodine) toone liter with tap water. Less dilute solutions [up to 77 mL (28.26g iodine) diluted to one liter with tap water] may be used when indicated.The dose is administered orally about 15 to 30 minutes prior to imagingin order to permit the contrast medium to reach the pelvic loops.

DRUG & OR LABORATORY TEST INTERACTIONS SECTION.

Drug/Laboratory Test Interactions. Thyroid FunctionTests. The resultsof protein bound iodine (PBI) and radioactive iodine uptake studies,which depend on iodine estimations, will not accurately reflect thyroidfunction for six months, and possibly as long as one year, followingthe administration of diagnostic enteral radiopaque media.Thyroid function tests, if indicated, generallyshould be performed prior to the administration of any iodinated agent.However, thyroid function can be evaluated after use of these agentsby using T3 resin uptake and total or freethyroxine (T4) assays which are not dependenton iodine estimations.. Pancreatic Tests. Small quantities ofcontrast medium in the intestinal tract may cause false low trypsinvalues when determined spectrophotometrically. Therefore, duodenalinstillation should not precede pancreatic function tests involvingspectrophotometric trypsin assays.Any test which might be affected by contrast media should be performedprior to administration of the contrast medium.

GENERAL PRECAUTIONS SECTION.

General. Diagnostic procedureswhich involve the use of radiopaque contrast agents should be carriedout under the direction of personnel with the prerequisite trainingand with thorough knowledge of the particular procedure to be performed.Appropriate facilities should be available for coping with any complicationof administration, as well as for treatment of reaction to the contrastmedium (see ADVERSE REACTIONS, and PRECAUTIONS, Information for the Patient).Rectal administrationof undiluted Gastrografin (Diatrizoate Meglumine and Diatrizoate SodiumSolution) in any patient, particularly with large doses and/or inthose with overdistention, has been reported to be associated withmucosal irritation.Cases of hyperthyroidismhave been reported with the use of oral contrast media. Some of thesepatients reportedly had multinodular goiters which may have been responsiblefor the increased hormone synthesis in response to excess iodine.Administration of an intravascular iodinated radiopaque diagnosticagent to hyperthyroid patient precipitated thyroid storm; similarsituation could follow administration of oral preparations of iodides.Therefore, caution should be exercised when administering enteralgastrointestinal radiopaque agents to hyperthyroid and euthyroid goiterouspatients.Consideration shouldbe given to the potential for precipitation of water-soluble contrastagents under conditions that may promote hyperacidity (i.e., fasting,emotional upset, or stress). Harmful effects directly attributableto precipitate formation have not been reported. However, the possibilityof interpreting the precipitate radiologically as an anatomical abnormality(i.e., ulceration of the stomach or small intestine) or injury, shouldbe kept in mind.

HOW SUPPLIED SECTION.

HOW SUPPLIED. Gastrografin (Diatrizoate Meglumineand Diatrizoate Sodium Solution USP) is available in packagesof:Twenty-four 30 mL single dose bottles (NDC 0270-0445-35).Twelve 120 mL single dose bottles (NDC 0270-0445-40).. Storage. Protect from light. Store at 20-25C (68-77F)[See USP]; avoid excessive heat.

INDICATIONS & USAGE SECTION.

INDICATIONS AND USAGE. Gastrografin (Diatrizoate Meglumine andDiatrizoate Sodium Solution) is indicated for radiographic examinationof segments of the gastrointestinal tract (esophagus, stomach, proximalsmall intestine, and colon). The preparation is particularly indicatedwhen more viscous agent such as barium sulfate, which is not water-soluble,is not feasible or is potentially dangerous.Gastrografin may also be used as an adjunct to contrastenhancement in computed tomography of the torso (body imaging); thepreparation is indicated, in conjunction with intravenous administrationof radiopaque contrast agent, when unenhanced imaging may not providesufficient definition in distinguishing normal loops of bowel fromadjacent organs or areas of suspected pathology.

INFORMATION FOR PATIENTS SECTION.

Information for the Patient. Patients should receive the following information andinstructions:This drug has been prescribed to perform an x-ray of thegastrointestinal tract.Inform the physician if pregnant or if allergic to iodine,any foods, or x-ray materials.The iodine in diatrizoate salts may interfere with somethyroid tests if these are needed in the future. Inform the attendingphysician at that time about this gastrointestinal study.This drug may cause abdominal cramping, nausea, vomiting,diarrhea, skin rashes, itching, heartburn, dizziness, or headachein some patients, but most reactions are mild and pass quickly.. This drug has been prescribed to perform an x-ray of thegastrointestinal tract.. Inform the physician if pregnant or if allergic to iodine,any foods, or x-ray materials.. The iodine in diatrizoate salts may interfere with somethyroid tests if these are needed in the future. Inform the attendingphysician at that time about this gastrointestinal study.. This drug may cause abdominal cramping, nausea, vomiting,diarrhea, skin rashes, itching, heartburn, dizziness, or headachein some patients, but most reactions are mild and pass quickly.

NURSING MOTHERS SECTION.

Nursing Mothers. Diatrizoate meglumine is excreted in breastmilk following intravascular administration.Because small amounts of enteral gastrointestinal radiopaqueagents may be absorbed following oral or rectal administration, cautionshould be exercised when they are administered to nursing woman.

OVERDOSAGE SECTION.

OVERDOSAGE. See WARNINGS regarding potential hypovolemia, hypotension, or shock. Themaintenance of an open intravenous fluid line for rehydration maybe advisable. See DOSAGE AND ADMINISTRATION for appropriate doses and dilutions. Treatment of an overdoseshould be directed toward the support of all vital functions, andprompt institution of symptomatic therapy.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

Gastrografin(R) 120 mL LabelNDC 0270-0445-40. Gastrografin label 120ml.

WARNINGS SECTION.

WARNINGS. Dehydration: Administration of hypertonicGastrografin solutions may lead to hypovolemia and hypotension dueto fluid loss from the intestine. 1 in 4.6 (1:4.6) dilution of Gastrografinyields an approximately isotonic 16.5 percent diatrizoate salts solution;less dilute solutions are hypertonic and may lead to intraluminalmovement of fluid with resulting hypovolemia. In young or debilitatedchildren and in elderly cachectic persons, the loss of plasma fluidmay be sufficient to cause shock-like state. If Gastrografin isused in infants and children (under 10 kg) or in dehydrated or debilitatedpatients, the solution must be prepared using the specific dilutionsdescribed in DOSAGE AND ADMINISTRATION. Indebilitated patients and in patients with electrolyte imbalances,postprocedural monitoring of hydration, serum osmolarity, electrolytesand clinical status is essential. In pediatric or severely debilitatedpatients, the maintenance of an open intravenous fluid line for rehydrationmay be advisable should hypotension or shock supervene. Electrolytedisturbances must be corrected prior to the administration of anyhypertonic Gastrografin solutions.Aspiration: Aspiration of Gastrografin into the trachea and airwaysmay result in serious pulmonary complications including, pulmonaryedema, pneumonitis or death Bronchial entry of any orally administeredcontrast medium causes copious osmotic effusion. Therefore, avoiduse of Gastrografin in patients with esophagotracheal fistula andminimize risks for pulmonary aspiration in all patients. If Gastrografinis given by nasogastric tube, the position of the tube in the stomachmust be verified before administration.Anaphylactic reactions: Anaphylactic reactions, includingfatalities, have been reported with the use of Gastrografin. Patientsat increased risk include those with history of previous reactionto contrast medium, patients with known sensitivity to iodine,and patients with known clinical hypersensitivity (bronchial asthma,hay fever, and food allergies). Medical personnel trained in the treatmentof anaphylactic reactions and the necessary drugs and medical equipmentshould always be readily available when Gastrografin is used.