ORALTAG

6 ADVERSE REACTIONS The following adverse reactions are described in greater detail in other sections: Hypersensitivity reactions [see Warnings and Precautions (5.2) ] The most common adverse reactions (incidence < 2%) are nausea, vomiting, and diarrhea ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Interpharma Praha at 1-877-886-7040 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience In studies involving 44 adult and 69 pediatric patients who received oral and intravenous iohexol for CT examinations of the abdomen, two reports of vomiting (2%) were noted. 6.2 Postmarketing Experience Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following adverse reactions have been reported following oral administration of the dilute, hypotonic solutions of iohexol (9 mgI/mL to 21 mgI/mL): Gastrointestinal: nausea, diarrhea

4 CONTRAINDICATIONS Oraltag is contraindicated in patients with a known hypersensitivity to iodinated contrast agents, including iohexol [see Warnings and Precautions (5.2) ] . Hypersensitivity to iodinated contrast agents, including iohexol

11 DESCRIPTION Oraltag (iohexol) is a radiographic contrast agent for oral solution. Oraltag is provided as a nonsterile white to off-white powder with 9.7 g iohexol (equivalent to 4.5 g of carbon bound iodine) in a 20-ounce beverage bottle. Each bottle is individually sealed in a foil laminated pouch. Oraltag consists of 100 percent iohexol and contains no excipients. Iohexol is designated chemically as N,N´-bis(2,3-dihydroxypropyl)-5-[N-(2,3-dihydroxypropyl)acetamido]-2,4,6-triiodoisophthalamide. It is a nonionic, water-soluble iodinated contrast medium with a molecular weight of 821.14 (carbon bound iodine content 46.36%). In aqueous solution each triiodinated molecule remains undissociated. The chemical structure is: Oraltag, when prepared at a concentration of 9 mgI/mL in water, has an osmolality of 30 mOsmol/kg water. The calculated osmolality of 21 mgI/mL in water is 55 mOsmol/kg water. The prepared solutions are hypotonic. Chemical Structure

2 DOSAGE AND ADMINISTRATION For oral use only: Adults : 1 to 2 bottles (4.5 g to 9 g iodine (I)) ( 2 ) Pediatric patients 3 to 18 years of age : less than 1 bottle to 2 bottles (less than 4.5 gI up to 9 gI) ( 2 ) Pediatric patients less than 3 years of age : up to 1 bottle (4.5 gI) ( 2 ) 2.1 Recommended Dosing For oral use only [see Warnings and Precautions (5.1) ] Refer to Table 1 for dosing information. Table 1 Dosing Guidelines for Oraltag Patient Age Recommended Dose Total volume of Oraltag administered will vary depending on the size of the patient Volume of Prepared Solution to Administer (at a concentration of 9 mgI per mL) Maximum Total Iodine Dose Adults Administer 4.5 g to 9 g of iodine (1 to 2 bottles of prepared solution), orally 500 mL to 1000 mL 9 grams 3 to 18 years of age Administer up to 9 g of iodine (from less than 1 bottle up to 2 bottles of prepared solution), orally 280 mL to 750 mL, depending on size of patient 9 grams Less than 3 years of age Administer up to 4.5 g of iodine (portion of 1 bottle of prepared solution), orally 120 mL to 300 mL, depending on size of patient 4.5 grams The variables of patient age, weight, or medical condition, may require adjustment of the concentration and/or volume of solution to be prepared for administration. If it is anticipated that the patient will have difficulty in consuming the required volume, a higher concentration of solution (up to 21 mgI per mL) can be prepared and a smaller volume administered (see Table 2). Table 2 Preparation of Higher Concentrations of Oraltag at Lower Volumes For Final Concentration (mgI/mL) Add Water or a Beverage Examples include infant formula, milk, juice, carbonated beverage or a sports drink to the Indicated Mark on the Bottle (mL) 9 500 12 375 15 300 18 250 21 214 2.2 Preparation and Administration Instructions Reconstitute Oraltag, supplied as a powder in a single use bottle, with water or other beverages just before its use Do not mix other pharmaceuticals with Oraltag Use the 5 fill lines premolded and labeled on the bottle to determine the volume for the 5 target concentrations (9, 12, 15, 18, and 21 mgI/mL) Administer Oraltag 20 to 60 minutes before image acquisition Protect prepared solution from strong daylight and direct exposure to sunlight Discard any unused portions

1 INDICATIONS AND USAGE Oraltag is indicated for use in computed tomography of the abdomen and pelvis to opacify bowel loops and delineate between normal loops and adjacent organs or areas of suspected pathology. Limitations of Use Oraltag is not indicated for diagnostic examination of the gastrointestinal tract. Oraltag is a radiographic contrast agent indicated for use in opacification of the gastrointestinal tract during computed tomography (CT) of the abdomen and pelvis ( 1 ) Limitations of Use Not indicated for diagnostic examination of the gastrointestinal tract ( 1 )

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Iohexol enhances imaging due to its high iodine content attenuating the beam of X-rays during CT examinations. Different tissues within the body attenuate X-rays to different degrees, and oral administration of iohexol allows for enhanced visualization due to the iodine present in bowel loops. 12.3 Pharmacokinetics Orally administered iohexol is very poorly absorbed from the normal gastrointestinal tract. Only 0.1 to 0.5% of the oral dose is excreted by the kidneys. This amount may increase in the presence of bowel perforation, bowel obstruction, or severe inflammatory bowel disease. Iohexol displays a low affinity for serum or plasma proteins and is poorly bound to serum albumin. No significant metabolism, deiodination or biotransformation occurs.

12.1 Mechanism of Action Iohexol enhances imaging due to its high iodine content attenuating the beam of X-rays during CT examinations. Different tissues within the body attenuate X-rays to different degrees, and oral administration of iohexol allows for enhanced visualization due to the iodine present in bowel loops.

12.3 Pharmacokinetics Orally administered iohexol is very poorly absorbed from the normal gastrointestinal tract. Only 0.1 to 0.5% of the oral dose is excreted by the kidneys. This amount may increase in the presence of bowel perforation, bowel obstruction, or severe inflammatory bowel disease. Iohexol displays a low affinity for serum or plasma proteins and is poorly bound to serum albumin. No significant metabolism, deiodination or biotransformation occurs.

20230105

17

3 DOSAGE FORMS AND STRENGTHS For oral solution: Oraltag is provided as a white to off-white powder of 9.7 g iohexol, (equivalent to 4.5 g of carbon bound iodine) in a single-use bottle. For oral solution: Each single use bottle contains 9.7 g iohexol (equivalent to 4.5 g carbon bound iodine)

ORALTAG Iohexol IOHEXOL IOHEXOL IODINE

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility No long-term animal studies have been performed to evaluate carcinogenic potential or mutagenesis. In animal reproduction studies, no evidence of impaired fertility was observed with intravenous administration of iohexol to rats and rabbits at doses up to 100 times the maximum recommended human intravenous dose.

NDA205383

ORALTAG

Iohexol

54702-501

HUMAN PRESCRIPTION DRUG

ORAL

PRINCIPAL DISPLAY PANEL - 9.7 g Bottle Label NDC 54702-501-21 Oraltag™ (iohexol) for oral solution 9.7 g of iohexol powder (equivalent to 4.5 g of carbon bound iodine) Single Use Bottle - Discard Unused Portion Prepared solution is 9-21 mgI/mL For Oral Use Only Nonsterile For indications and dosage, see prescribing information. Store at 20-25˚C (68-77˚F); excursions permitted to 15-30˚C (59-86˚F) [see USP] Protect prepared solutions of Oraltag from strong daylight and direct exposure to sunlight. Rx Only Manufactured for Interpharma Praha, a.s. Prague, Czech Republic by Ultra Seal Corporation New Paltz, New York PRINCIPAL DISPLAY PANEL - Bottle Label

Manufactured for Interpharma Praha, a.s., Prague, Czech Republic by Ultra Seal Corporation, New Paltz, New York.

17 PATIENT COUNSELING INFORMATION Hypersensitivity Reactions Advise patients about the risk of hypersensitivity reactions to Oraltag and the need to notify their healthcare provider if signs or symptoms of hypersensitivity reaction occur [see Warnings and Precautions (5.2) ] .

8.5 Geriatric Use 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.

8.4 Pediatric Use The safety and effectiveness of oral iohexol have been established in pediatric patients.

8.1 Pregnancy Risk Summary There are no human data on risks associated with the use of Oraltag during pregnancy. The background risk in the U.S. general population of major birth defects is 2% to 4% and risk of miscarriage is 15% to 20% of clinically recognized pregnancies. In animal reproduction studies, no evidence of fetal harm was observed with intravenous administration of iohexol to rats and rabbits at doses up to 100 times the maximum recommended human intravenous dose.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no human data on risks associated with the use of Oraltag during pregnancy. The background risk in the U.S. general population of major birth defects is 2% to 4% and risk of miscarriage is 15% to 20% of clinically recognized pregnancies. In animal reproduction studies, no evidence of fetal harm was observed with intravenous administration of iohexol to rats and rabbits at doses up to 100 times the maximum recommended human intravenous dose. 8.2 Lactation Risk Summary Iohexol administered intravenously is present in human milk at concentrations approximately 0.5% of the maternal dose; however, it is not known to what extent iohexol administered orally is present in human milk. Iodinated contrast is poorly excreted into human milk and is poorly absorbed by the gastrointestinal tract of a breastfed infant. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Oraltag and any potential adverse effects on the breastfed infant from Oraltag. Clinical Considerations Interruption of breastfeeding after exposure to iodinated contrast media is not necessary because the potential exposure of the breastfed infant to iodine is small. However, a lactating woman may consider interrupting breastfeeding and pumping and discarding breast milk for 10 hours (approximately 5 half-lives) after Oraltag administration in order to minimize potential drug exposure to a breastfed infant. 8.4 Pediatric Use The safety and effectiveness of oral iohexol have been established in pediatric patients. 8.5 Geriatric Use 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 Oraltag is supplied as a nonsterile white to off-white powder for oral solution in a single-use 20-ounce polyethylene terephthalate beverage bottle closed with a lined polypropylene cap. Each bottle is packaged in a sealed foil pouch. Twelve (12) bottles per pack (NDC 54702-501-52). Twenty-five (25) bottles per pack (NDC 54702-501-62). Storage Store at controlled room temperature, 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect prepared solutions of Oraltag from strong daylight and direct exposure to sunlight. Do not use if tamper-evident foil pouch has been opened.