ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. The following adverse reactions are described in greater detail in other sections:Hypersensitivity reactions [see Warnings and Precautions (5.2)] 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 population of uncertain size, it is not always possible to reliably estimate their frequency or establish 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. Gastrointestinal: nausea, diarrhea.

CLINICAL PHARMACOLOGY SECTION.

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 low affinity for serum or plasma proteins and is poorly bound to serum albumin. No significant metabolism, deiodination or biotransformation occurs.

DESCRIPTION SECTION.

11 DESCRIPTION. Oraltag (iohexol) is radiographic contrast agent for oral solution. Oraltag is provided as nonsterile white to off-white powder with 9.7 iohexol (equivalent to 4.5 of carbon bound iodine) in 20-ounce beverage bottle. Each bottle is individually sealed in 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 nonionic, water-soluble iodinated contrast medium with 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 concentration of 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.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. For oral use only:Adults: to bottles (4.5 to g iodine (I)) (2)Pediatric patients to 18 years of age: less than bottle to bottles (less than 4.5 gI up to gI) (2)Pediatric patients less than years of age: up to bottle (4.5 gI) (2). Adults: to bottles (4.5 to g iodine (I)) (2). Pediatric patients to 18 years of age: less than bottle to bottles (less than 4.5 gI up to gI) (2). Pediatric patients less than years of age: up to bottle (4.5 gI) (2). 2.1 Recommended Dosing. For oral use only[see Warnings and Precautions (5.1)]Refer to Table for dosing information.Table Dosing Guidelines for OraltagPatient AgeRecommended DoseTotal volume of Oraltag administered will vary depending on the size of the patient Volume of Prepared Solution to Administer (at concentration of mgI per mL)Maximum Total Iodine DoseAdultsAdminister 4.5 to g of iodine (1 to bottles of prepared solution), orally500 mL to 1000 mL9 grams3 to 18 years of ageAdminister up to g of iodine (from less than bottle up to bottles of prepared solution), orally280 mL to 750 mL, depending on size of patient9 gramsLess than years of ageAdminister up to 4.5 of iodine (portion of bottle of prepared solution), orally120 mL to 300 mL, depending on size of patient4.5 gramsThe 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, higher concentration of solution (up to 21 mgI per mL) can be prepared and smaller volume administered (see Table 2).Table Preparation of Higher Concentrations of Oraltag at Lower VolumesFor Final Concentration (mgI/mL)Add Water or BeverageExamples include infant formula, milk, juice, carbonated beverage or sports drink to the Indicated Mark on the Bottle(mL)950012375153001825021214. 2.2 Preparation and Administration Instructions. Reconstitute Oraltag, supplied as powder in single use bottle, with water or other beverages just before its useDo not mix other pharmaceuticals with OraltagUse the fill lines premolded and labeled on the bottle to determine the volume for the target concentrations (9, 12, 15, 18, and 21 mgI/mL)Administer Oraltag 20 to 60 minutes before image acquisitionProtect prepared solution from strong daylight and direct exposure to sunlightDiscard any unused portions. Reconstitute Oraltag, supplied as powder in single use bottle, with water or other beverages just before its use. Do not mix other pharmaceuticals with Oraltag. Use the fill lines premolded and labeled on the bottle to determine the volume for the 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.

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. How SuppliedOraltag is supplied as nonsterile white to off-white powder for oral solution in single-use 20-ounce polyethylene terephthalate beverage bottle closed with lined polypropylene cap. Each bottle is packaged in sealed foil pouch.Twelve (12) bottles per pack (NDC 54702-501-52).Twenty-five (25) bottles per pack (NDC 54702-501-62).StorageStore at controlled room temperature, 20 to 25C (68 to 77F); excursions permitted to 15 to 30C (59 to 86F) [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.

INDICATIONS & USAGE SECTION.

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 UseOraltag is not indicated for diagnostic examination of the gastrointestinal tract.. Oraltag is radiographic contrast agent indicated for use in opacification of the gastrointestinal tract during computed tomography (CT) of the abdomen and pelvis (1)Limitations of UseNot indicated for diagnostic examination of the gastrointestinal tract (1).

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL 9.7 Bottle Label. NDC 54702-501-21Oraltag(TM)(iohexol) for oral solution9.7 of iohexol powder(equivalent to 4.5 of carbon bound iodine)Single Use Bottle Discard Unused PortionPrepared solution is 9-21 mgI/mLFor Oral Use OnlyNonsterileFor indications and dosage, see prescribing information.Store at 20-25C (68-77F); excursions permitted to 15-30C (59-86F) [see USP]Protect prepared solutions of Oraltag from strong daylight and direct exposure to sunlight.Rx OnlyManufactured for Interpharma Praha, a.s.Prague, Czech Republicby Ultra Seal CorporationNew Paltz, New York. PRINCIPAL DISPLAY PANEL Bottle Label.

PREGNANCY SECTION.

8.1 Pregnancy. Risk SummaryThere 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.

SPL UNCLASSIFIED SECTION.

2.1 Recommended Dosing. For oral use only[see Warnings and Precautions (5.1)]Refer to Table for dosing information.Table Dosing Guidelines for OraltagPatient AgeRecommended DoseTotal volume of Oraltag administered will vary depending on the size of the patient Volume of Prepared Solution to Administer (at concentration of mgI per mL)Maximum Total Iodine DoseAdultsAdminister 4.5 to g of iodine (1 to bottles of prepared solution), orally500 mL to 1000 mL9 grams3 to 18 years of ageAdminister up to g of iodine (from less than bottle up to bottles of prepared solution), orally280 mL to 750 mL, depending on size of patient9 gramsLess than years of ageAdminister up to 4.5 of iodine (portion of bottle of prepared solution), orally120 mL to 300 mL, depending on size of patient4.5 gramsThe 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, higher concentration of solution (up to 21 mgI per mL) can be prepared and smaller volume administered (see Table 2).Table Preparation of Higher Concentrations of Oraltag at Lower VolumesFor Final Concentration (mgI/mL)Add Water or BeverageExamples include infant formula, milk, juice, carbonated beverage or sports drink to the Indicated Mark on the Bottle(mL)950012375153001825021214.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. 8.1 Pregnancy. Risk SummaryThere 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 SummaryIohexol 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 breastfed infant. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for Oraltag and any potential adverse effects on the breastfed infant from Oraltag.Clinical ConsiderationsInterruption of breastfeeding after exposure to iodinated contrast media is not necessary because the potential exposure of the breastfed infant to iodine is small. However, lactating woman may consider interrupting breastfeeding and pumping and discarding breast milk for 10 hours (approximately half-lives) after Oraltag administration in order to minimize potential drug exposure to 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.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. Hypersensitivity reactions: life-threatening or fatal reactions can occur. Resuscitation equipment and personnel should be available (5.2)Thyroid function test alterations: Oraltag may alter tests which depend on iodine estimation. Perform such tests prior to Oraltag administration (5.3). Hypersensitivity reactions: life-threatening or fatal reactions can occur. Resuscitation equipment and personnel should be available (5.2). Thyroid function test alterations: Oraltag may alter tests which depend on iodine estimation. Perform such tests prior to Oraltag administration (5.3). 5.1 Risks Associated with Inadvertent Parenteral Administration. Oraltag is not sterile product and is not suitable for parenteral route of administration. Serious adverse reactions such as sepsis can occur if administered parenterally. Do not administer Oraltag parenterally.. 5.2 Hypersensitivity Reactions. Administration of Oraltag can cause life-threatening hypersensitivity reactions including anaphylaxis [see Contraindications (4)]. Patients at increased risk include those with previous reaction to an iodinated contrast agent and allergic disorders (i.e., bronchial asthma, allergic rhinitis, and food allergies). Emergency resuscitation equipment and trained personnel should be available.. 5.3 Alteration of Thyroid Function Tests. Iodinated contrast agents may alter the results of thyroid function tests which depend on iodine estimation, e.g., radioactive iodine uptake test. Therefore, such testing, if indicated, should be performed prior to the administration of this preparation.