E-Z-Paque

6 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

4 CONTRAINDICATIONS Liquid E-Z-PAQUE is contraindicated in patients with the following conditions: known or suspected perforation of the 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 of aspiration such as those with prior aspiration, tracheo-esophageal fistula, or obtundation known severe hypersensitivity to barium sulfate or any of the excipients of Liquid E-Z-PAQUE Known or suspected perforation of the GI tract ( 4 ) Known obstruction of the GI tract ( 4 ) Conditions associated with high risk of GI perforation or aspiration ( 4 ) Known severe hypersensitivity to barium sulfate or any of the excipients of Liquid E-Z-PAQUE ( 4 )

11 DESCRIPTION Liquid E-Z-PAQUE (barium sulfate) is a radiographic contrast agent supplied as a white to lightly colored barium sulfate suspension (60%w/v) for oral administration. The active ingredient barium sulfate is designated chemically as BaSO 4 with a molecular weight of 233.4 g/mol, a density of 4.5 g/cm 3 , and the following chemical structure: Liquid E-Z-PAQUE contains the following excipients: carboxymethyl cellulose sodium, citric acid, natural and artificial strawberry lemon cream flavor, polysorbate 80, potassium sorbate, purified water, saccharin sodium, simethicone emulsion, sodium benzoate, sodium citrate, sorbitol solution, xanthan gum. barium-sulfate-structure

2 DOSAGE AND ADMINISTRATION Adults: Recommended oral dose is 150 mL to 750 mL (87g to 435g of barium sulfate, respectively) ( 2.1 ) Pediatric patients: adjust dose based on relative GI volume ( 2.1 ) 2.1 Recommended Dosage The optimal oral dose of Liquid E-Z-PAQUE will vary depending on the size and anatomy of the patient and the procedure being performed. The recommended oral dose of Liquid E-Z-PAQUE: Adults: 150 to 750 mL (87 g to 435 g of barium sulfate, respectively). Volumes closer to 150 mL are recommended for examination of the esophagus and stomach and volumes up to 750 mL are recommended for examination of the small bowel Pediatric Patients: Adjust dose 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 Administration Instructions For oral use only Shake bottle vigorously for 30 seconds prior to oral administration to fully suspend product Administer undiluted 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

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

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Due to its high atomic number, barium (the active ingredient in Liquid E-Z-PAQUE) is opaque to x-rays and therefore acts as a positive contrast agent for radiographic studies. 12.3 Pharmacokinetics Under physiological conditions, barium sulfate passes through the gastrointestinal tract in an unchanged form and is absorbed only in pharmacologically insignificant amounts.

20201009

7

3 DOSAGE FORMS AND STRENGTHS Liquid E-Z-PAQUE oral suspension: 213 grams of barium sulfate supplied as a suspension (60 % w/v) in a single-dose bottle. Oral suspension 213 g barium sulfate (60% w/v) ( 3 )

E-Z-Paque barium sulfate Barium Sulfate Barium Sulfate CARBOXYMETHYLCELLULOSE SODIUM ANHYDROUS CITRIC ACID DIMETHICONE 350 DIMETHICONE 1000 POLYSORBATE 80 POTASSIUM SORBATE WATER SACCHARIN SODIUM SILICON DIOXIDE SODIUM BENZOATE TRISODIUM CITRATE DIHYDRATE SORBITOL XANTHAN GUM E-Z-Paque barium sulfate Barium Sulfate Barium Sulfate CARBOXYMETHYLCELLULOSE SODIUM ANHYDROUS CITRIC ACID DIMETHICONE 350 DIMETHICONE 1000 POLYSORBATE 80 POTASSIUM SORBATE WATER SACCHARIN SODIUM SILICON DIOXIDE SODIUM BENZOATE TRISODIUM CITRATE DIHYDRATE SORBITOL XANTHAN GUM

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility No animal studies have been performed to evaluate the carcinogenic potential of barium sulfate or potential effects on fertility.

NDA208143

E-Z-Paque

barium sulfate

32909-187

HUMAN PRESCRIPTION DRUG

ORAL

LIQUID E-Z-PAQUE 355 mL Carton and Label NDC: 32909-187-02 Liquid E-Z-Paque External Label Liquid E-Z-Paque Internal Label

17 PATIENT COUNSELING INFORMATION After administration advise patients to: Maintain adequate hydration Seek medical attention for worsening of constipation or slow gastrointestinal passage Seek medical attention for any delayed onset of hypersensitivity, such as: rash, urticaria, or respiratory difficulty Manufactured for Bracco Diagnostics Inc. Monroe Township, NJ 08831 by EZEM Canada Inc Anjou (Quebec) Canada H1J 2Z4 Revised February 2020 CL110101

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Liquid E-Z-PAQUE is not absorbed systemically following oral administration, and maternal use is not expected to result in fetal exposure to the drug [see Clinical Pharmacology ( 12.3 )] . 8.2 Lactation Risk Summary Liquid E-Z-PAQUE is not absorbed systemically by the mother following oral administration, and breastfeeding is not expected to result in exposure of the infant to Liquid E-Z-PAQUE [see Clinical Pharmacology ( 12.3 ) . 8.4 Pediatric Use The efficacy of Liquid E-Z-PAQUE in pediatric patients from birth to less than 17 years of age is based on successful opacification of the esophagus, stomach, and small bowel during single contrast radiographic procedures [see Clinical Pharmacology ( 12.1 )] . Safety and dosing recommendations in pediatric patients are based on clinical experience [see Dosage and Administration ( 2.1 )] . Liquid E-Z-PAQUE is contraindicated in pediatric patients with tracheo-esophageal fistula. [see Contraindications ( 4 )]. Pediatric patients with a history of asthma or food allergies may be at increased risk for development of hypersensitivity reactions [ see Warnings and Precautions ( 5.1 )]. Monitor pediatric patients with cystic fibrosis or Hirschsprung disease for bowel obstruction after use [see Warnings and Precautions ( 5.3 )] 8.5 Geriatric Use Clinical studies of Liquid E-Z-PAQUE do not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Liquid E-Z-PAQUE (barium sulfate) is a suspension (60% w/v) supplied as a unit dose in a single use HDPE plastic bottle containing 213 grams of barium sulfate in 355 mL. Provided as: 12 x 355 mL bottles (NDC 32909-187-02). Storage and Handling Store at USP controlled room temperature 20 to 25°C (68 to 77° F). Protect from freezing.