Barium Sulfate

INDICATIONS AND USAGE E-Z-PAQUE is indicated for use in single contrast radiographic examinations of the esophagus, stomach, duodenum and small bowel to visualize the gastrointestinal tract (GI) in adult and pediatric patients. E-Z-PAQUE is a radiographic contrast agent indicated for use in single contrast radiographic examinations of the esophagus, stomach, duodenum and small bowel to visualize the gastrointestinal (GI) tract in adult and pediatric patients ( 1 )

DOSAGE AND ADMINISTRATION Adults: Recommended reconstituted oral dose is between 150 – 750 mL ( 2.1 ) Pediatric patients: adjust reconstituted dose based on relative GI volume ( 2.1 ) Must reconstitute supplied powder with water prior to use. See Full Prescribing Information for reconstitution instructions ( 2.2 ) 2.1 Recommended Dosage The optimal oral dose of E-Z-PAQUE will vary depending on the size and anatomy of the patient and the procedure being performed. The recommended oral dose of reconstituted E-Z-PAQUE: Adults: 150 to 750 mL, 169 to 450 g barium sulfate, depending on the reconstituted concentration [see Dosage and Administration ( 2.2 )] . Volumes closer to 150 mL are recommended for examination of the esophagus and stomach. Volumes up to 750 mL are recommended for examination of the small bowel. Pediatric Patients: Adjust dose of reconstituted E-Z-PAQUE based on GI volume. For examinations of the upper GI tract, administer a volume sufficient to fully distend the esophagus or stomach. For small bowel examinations: Age birth to less than 2 years: 30 mL to 75 mL. Age 2 years to less than 17 years: 75 mL to 480 mL. 2.2 Instructions for Reconstitution The reconstituted concentration will vary, depending on the procedure being performed. A barium suspension up to 115% w/v is recommended for examinations of the esophagus and upper GI A barium suspension of 60% w/v is recommended for examinations of the small bowel. Reconstitute the E-Z-PAQUE prior to administration according to the following instructions: Tap bottle on a hard surface (right side up) several times to compact the product in the bottle. Add water to the blue line marked ‘Initial Fill Line’ on the bottle. Replace cap securely on the bottle. Invert bottle and tap with fingers to mix contrast into the water. Shake vigorously for 30 seconds; wait 5 minutes. Add more water as needed to achieve the desired % w/v concentration using the fill lines marked on the bottle. Then, re-shake vigorously for 30 seconds. To use with straw, remove adhesive label on top of cap. Remove cap and use straw to push out cap liner; replace cap. 2.3 Administration Instructions Use immediately after reconstitution. Ensure patients have nothing by mouth for the following time period prior to the examination: Neonates and infants < 3 months 2 hours Infants 3-12 months 3 hours > 12 months of age 4 hours Discard any unused suspension. Encourage patients to maintain hydration following the barium sulfate procedure.

WARNINGS AND PRECAUTIONS Emergency equipment and trained personnel should be immediately available for treatment of a serious hypersensitivity reaction ( 5.1 ) Intra-abdominal leakage: Caution is recommended in patient conditions like GI fistula, ulcer, inflammatory bowel disease, appendicitis or diverticulitis, severe stenosis or obstructing lesions of the GI tract ( 5.2 ) Patients should maintain adequate hydration in days following a barium sulfate procedure to avoid obstruction or impaction caused by baroliths ( 5.3 ) Aspiration: Caution is recommended in patients with history of food aspiration and in patients with known swallowing disorders ( 5.4 ) E-Z-HD is not intended for pediatric use from birth through 11 years of age ( 8.4 ) 5.1 Hypersensitivity Reactions Barium sulfate preparations contain a number of excipients, including natural and artificial flavors and may induce serious hypersensitivity reactions. The manifestations include hypotension, bronchospasm and other respiratory impairments, dermal reactions including rashes, urticaria, and itching. A history of bronchial asthma, atopy, or a previous reaction to a contrast agent may increase the risk for hypersensitivity reactions. Emergency equipment and trained personnel should be immediately available for treatment of a hypersensitivity reaction. 5.2 Intra-abdominal Barium Leakage The use of E-Z-HD is contraindicated in patients at high risk of perforation of the GI tract [see Contraindications ( 4 )]. Administration of E-Z-HD may result in leakage of barium from the GI tract in the presence of conditions such as carcinomas, GI fistula, inflammatory bowel disease, gastric or duodenal ulcer, appendicitis, or diverticulitis, and in patients with a severe stenosis at any level of the GI tract, especially if it is distal to the stomach. The barium leakage has been associated with peritonitis and granuloma formation. 5.3 Delayed Gastrointestinal Transit and Obstruction Orally administered barium sulfate may accumulate proximal to a constricting lesion of the colon, causing obstruction or impaction with development of baroliths (inspissated barium associated with feces) and may lead to abdominal pain, appendicitis, bowel obstruction, or rarely perforation. Patients with the following conditions are at higher risk for developing obstruction or baroliths: severe stenosis at any level of the GI tract, impaired GI motility, electrolyte imbalance, dehydration, on a low residue diet, taking medications that delay GI motility, constipation, pediatric patients with cystic fibrosis or Hirschsprung disease, and the elderly [see Use in Specific Populations ( 8.4 , 8.5 )] . To reduce the risk of delayed GI transit and obstruction, patients should maintain adequate hydration during and in the days following a barium sulfate procedure. Consider the administration of laxatives. 5.4 Aspiration Pneumonitis The use of E-Z-HD is contraindicated in patients at high risk of aspiration [see Contraindications ( 4 )] . Oral administration of barium is associated with aspiration pneumonitis, especially in patients with a history of food aspiration or with compromised swallowing mechanism. Vomiting following oral administration of barium sulfate may lead to aspiration pneumonitis. In patients at risk for aspiration, begin the procedure with a small ingested volume of E-Z-HD. Discontinue administration of E-Z-HD immediately if aspiration is suspected. 5.5 Systemic Embolization Barium sulfate products may occasionally intravasate into the venous drainage of the large bowel and enter the circulation as a "barium embolus" leading to potentially fatal complications which include systemic and pulmonary embolism, disseminated intravascular coagulation, septicemia and prolonged severe hypotension. Although this complication is exceedingly uncommon after oral administration of a barium sulfate suspension, monitor patients for potential intravasation when administering barium sulfate. 5.6 Risk with Hereditary Fructose Intolerance E-Z-HD contains sorbitol which may cause severe reactions if ingested by patients with hereditary fructose intolerance, such as: vomiting, hypoglycemia, jaundice, hemorrhage, hepatomegaly, hyperuricemia, and kidney failure. Before administration of E-Z-HD assess patients for a history of hereditary fructose intolerance and avoid use in these patients.

CONTRAINDICATIONS VARIBAR PUDDING is contraindicated in patients with: - known or suspected perforation of the gastrointestinal (GI) tract; - known obstruction of the GI tract; - high risk of GI perforation such as those with a recent GI perforation, acute GI hemorrhage or ischemia, toxic megacolon, severe ileus, post GI surgery or biopsy, acute GI injury or burn, or recent radiotherapy to the pelvis; - high risk for aspiration such as those with known or suspected tracheo-esophageal fistula or obtundation; - known hypersensitivity to barium sulfate or any of the excipients of VARIBAR PUDDING. VARIBAR PUDDING is contraindicated in patients with: Known or suspected perforation of the gastrointestinal (GI) tract ( 4 ) Conditions associated with high risk for GI perforation ( 4 ) Known obstruction of the GI tract ( 4 ) Patients with trachea-esophageal fistula ( 4 ) Known hypersensitivity to barium sulfate or any of the excipients of VARIBAR PUDDING ( 4 )

Drug Interactions The presence of barium sulfate formulations in the GI tract may alter the absorption of therapeutic agents taken concomitantly. In order to minimize any potential change in absorption, the separate administration of barium sulfate from that of other agents should be considered.

ADVERSE REACTIONS The following adverse reactions have been identified from spontaneous reporting or clinical studies of barium sulfate administered orally. Because the reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or to establish a causal relationship to drug exposure: Nausea, vomiting, diarrhea and abdominal cramping Serious adverse reactions and fatalities include aspiration pneumonitis, barium sulfate impaction, intestinal perforation with consequent peritonitis and granuloma formation, vasovagal and syncopal episodes. Common adverse reactions include nausea, vomiting, diarrhea and abdominal cramping ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Bracco Diagnostics Inc at 1-800-257-5181 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Due to its high atomic number, barium (the active ingredient in VARIBAR THIN LIQUID) is opaque to x-rays and therefore acts as a positive contrast agent for radiographic studies. 12.2 Pharmacodynamics Barium sulfate is biologically inert and has no known pharmacological effects. 12.3 Pharmacokinetics Under physiological conditions, barium sulfate passes through the gastrointestinal tract in an unchanged form and is absorbed only in small, pharmacologically insignificant amounts.