OMNIPAQUE

1 INDICATIONS AND USAGE OMNIPAQUE is a radiographic contrast agent indicated for intrathecal, intra-arterial, intravenous, oral, rectal, intraarticular, and body cavity imaging procedures in adults and pediatric patients. ( 1 ) 1.1 Intrathecal Procedures ‡ OMNIPAQUE is indicated for: Myelography and computerized tomography (CT) myelography (lumbar, thoracic, cervical, total columnar) in adults and pediatric patients aged 2 weeks and older CT cisternography in adults and pediatric patients aged 2 weeks and older 1.2 Intra-arterial Procedures ‡ OMNIPAQUE is indicated for: Cardiac ventriculography in adults and pediatric patients Aortography including studies of aorta and its branches in adults and pediatric patients Selective coronary arteriography in adults Cerebral arteriography in adults Peripheral arteriography in adults Intra-arterial digital subtraction angiography (IA-DSA) of the head, neck, abdominal, renal, and peripheral vessels in adults Pulmonary angiography in pediatric patients 1.3 Intravenous Procedures ‡ OMNIPAQUE is indicated for: Excretory urography in adults and pediatric patients CT of the head and body in adults and pediatric patients Peripheral venography (phlebography) in adults Intravenous digital subtraction angiography (IV-DSA) of the head, neck, abdominal, renal, and peripheral vessels in adults 1.4 Oral or Rectal Procedures ‡ OMNIPAQUE is indicated for: Radiographic examination of the gastrointestinal (GI) tract in adults and pediatric patients CT of the abdomen and pelvis in conjunction with intravenous administration of OMNIPAQUE in adults and pediatric patients 1.5 Intraarticular Procedures ‡ OMNIPAQUE is indicated for: Arthrography in adults 1.6 Body Cavity Procedures ‡ OMNIPAQUE is indicated for: Endoscopic retrograde pancreatography (ERP) and cholangiopancreatography (ERCP) in adults Herniography in adults Hysterosalpingography in adults Voiding cystourethrography (VCU) in pediatric patients ‡ Specific dosage forms, concentrations, and presentations of OMNIPAQUE are recommended for each type of imaging procedure [see Dosage and Administrations (2.2 , 2.3 , 2.4 , 2.5 , 2.6 , 2.7 , 2.8 , 2.9) and Warnings and Precautions (5.1 , 5.2) ].

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Risks Associated with Intrathecal Administration of OMNIPAQUE Injection 140 mg Iodine/mL and 350 mg Iodine/mL [see Warnings and Precautions (5.1) ] Risks Associated with Parenteral Administration of OMNIPAQUE Oral Solution [see Warnings and Precautions (5.2) ] Hypersensitivity Reactions [see Warnings and Precautions (5.3) ] Acute Kidney Injury [see Warnings and Precautions (5.4) ] Cardiovascular Adverse Reactions [see Warnings and Precautions (5.5) ] Thromboembolic Events [ see Warnings and Precautions (5.6) ] Thyroid Dysfunction in Pediatric Patients 0 to 3 Years of Age [see Warnings and Precautions (5.9) ] Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.12) ] Most common adverse reactions (incidence ≥ 1%) in adult patients Intrathecal: Headaches, pain including backache, neckache, stiffness and neuralgia, nausea, vomiting, dizziness Intra-arterial or intravenous: Pain, vision abnormalities (including blurred vision and photomas), headache, taste perversion, arrhythmias including premature ventricular contractions (PVCs) and premature atrial contractions (PACs), angina/chest pain, nausea Oral: Diarrhea, nausea, vomiting, abdominal pain, flatulence, headache Body Cavity: Pain, swelling, heat sensation ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact GE Healthcare at 1-800-654-0118 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Intrathecal Administration Adults Adverse reactions (≥1%) in 1,531 adult patients following intrathecal administration of OMNIPAQUE in clinical trials are presented in Table 16. Table 16. Adverse Reactions (≥1%) in in Adult Patients Following Intrathecal Administration of OMNIPAQUE in Clinical Trials System Organ Class Adverse Reaction Incidence N=1,531 Nervous system disorders Headaches 18% Musculoskeletal and connective tissue disorders Pain including backache, neckache, stiffness, neuralgia 8% Gastrointestinal disorders Nausea 6% Vomiting 3% Nervous System disorders Dizziness 2% Other adverse reactions (<1%) were: Ear and labyrinth disorders : tinnitus, vertigo Eye disorders : photophobia General disorders and administration site conditions : sensation of heat Metabolism and nutrition disorders : loss of appetite Musculoskeletal and connective tissue disorders : feeling of heaviness Nervous system disorders : drowsiness, hypertonia, neuralgia, neurological changes, paresthesia, syncope Renal and urinary disorders : difficulty in micturition Skin and subcutaneous tissue disorders : sweating Vascular disorders : hypertension, hypotension Pediatric Patients The adverse reactions reported in pediatric patients following intrathecal administration of OMNIPAQUE were generally similar to those reported in adults. A total of 152 pediatric patients were administered OMNIPAQUE 180 mg iodine/mL intrathecally by lumbar puncture for pediatric myelography in clinical trials. Adverse reactions (≥1%) are presented in Table 17. Table 17. Adverse Reactions (≥1%) in Pediatric Patients Following Intrathecal Administration of OMNIPAQUE 180 mg iodine/mL by Lumbar Puncture for Myelography in Clinical Trials System Organ Class Adverse Reaction Incidence N=152 Nervous system disorders Headache 9% Gastrointestinal disorders Vomiting 6% Musculoskeletal and connective tissue disorders Backache 1.3% Other adverse reactions (<1%) were: Gastrointestinal disorders: stomachache General disorders and administration site conditions: fever Nervous system disorders : neurological changes Psychiatric disorders : visual hallucination Skin and subcutaneous tissue disorders : hives Intra-arterial or Intravenous Administration Adults Adverse reactions (≥1%) in 1,485 adult patients following intra-arterial or intravenous administration of OMNIPAQUE in clinical trials are presented in Table 18. Table 18. Adverse Reactions (≥1%) in Adult Patients Following Intra-arterial or Intravenous Administration of OMNIPAQUE in Clinical Trials System Organ Class Adverse Reaction Incidence (N=1,485) Cardiac disorders Arrhythmias including PVCs and PACs 2% Nervous system disorders Pain 3% Vision abnormalities including blurred vision and photomas 2% Taste perversion 1% Gastrointestinal disorders Nausea 2% Other adverse reactions (<1%) were: Cardiac disorders: hypotension, cardiac failure, asystole, bradycardia, tachycardia, vasovagal reaction Respiratory, thoracic and mediastinal disorders: dyspnea, rhinitis, coughing, laryngitis Gastrointestinal disorders : vomiting, diarrhea, dyspepsia, cramp, dry mouth General disorders and administration site conditions: fever, shivering Nervous system disorders: cerebral infarction, convulsion, hemiparesis, motor and speech dysfunction, nystagmus, paresthesia, somnolence, transient ischemic attack, vertigo including dizziness and lightheadedness Musculoskeletal and connective tissue disorders: still neck Skin and subcutaneous tissue disorders : urticaria, abscess, pruritus, purpura Psychiatric disorders : anxiety, syncope Pediatric Patients Adverse reactions reported in pediatric patients following intra-arterial or intravenous administration of OMNIPAQUE were generally similar in quality and frequency to those reported in adults. A total of 391 pediatric patients in clinical trials were administered OMNIPAQUE 240 mg iodine/mL, 300 mg iodine/mL, or 350 mg iodine/mL by intra-arterial or intravenous injection for pediatric cardiac ventriculography, excretory urography, and CT head imaging. Adverse reactions (≥1%) were vomiting (2%) and nausea (1%). Other adverse reactions (<1%) were: Cardiac disorders: Ventricular tachycardia, 2:1 heart block, hypertension, anemia General disorders and administration site conditions: Pain, fever Nervous system disorders: Convulsion, taste abnormality Respiratory, thoracic and mediastinal disorders: Congestion, apnea Endocrine disorders: Hypoglycemia Skin and subcutaneous tissue disorders: Rash Oral or Rectal Administration for Examination of the Gastrointestinal Tract Adults A total of 54 adult patients were administered undiluted OMNIPAQUE 350 mg iodine/mL by oral route for radiographic examination of the gastrointestinal tract in clinical trials. Adverse reactions (≥1%) are presented in Table 19. Table 19. Adverse Reactions (≥1%) in Adult Patients Following Oral Administration of Undiluted OMNIPAQUE 350 mg Iodine/mL in Clinical Trials System Organ Class Adverse Reaction Incidence N=54 Gastrointestinal disorders Diarrhea 42% Nausea 15% Vomiting 11% Abdominal Pain 7% Flatulence 2% Nervous system disorders Headache 2% Pediatrics Patients A total of 58 pediatric patients were administered OMNIPAQUE by oral or rectal administration in clinical trials. Adverse reactions (≥1%) are presented in Table 20. Table 20. Adverse Reactions (≥1%) in Pediatric Patients Following Oral or Rectal Administration of OMNIPAQUE in Clinical Trials System Organ Class Adverse Reaction Incidence N=58 Gastrointestinal disorders Diarrhea 36% Vomiting 9% Nausea 5% Abdominal pain 2% General disorders and administration site conditions Fever 5% Skin and subcutaneous tissue disorders Urticaria 2% Vascular disorders Hypotension 2% Oral Administration for CT of the Abdomen in Conjunction with Intravenous Administration Adults A total of 44 adult patients received diluted OMNIPAQUE (4-9 mg iodine/mL) by oral route in conjunction with intravenously injected OMNIPAQUE 300 mg iodine/mL for CT examination of the abdomen in clinical trials. Adverse reactions (≥1%) were limited to a single report of vomiting (2.3%). Pediatric Patients A total of 69 pediatric patients received diluted OMNIPAQUE (9-29 mg iodine/mL) by oral route in conjunction with intravenously administered OMNIPAQUE 240 mg iodine/mL or OMNIPAQUE 300 mg iodine/mL for CT examination of the abdomen in clinical trials. Adverse reactions (≥1%) were limited to a single report of vomiting (1.4%). Intraarticular Administration Arthrography in Adults A total of 285 adult patients received OMNIPAQUE 240 mg iodine/mL, 300 mg iodine/mL, or 350 mg iodine/mL for various body cavity examinations in clinical trials. The most frequent adverse reactions (≥1%) were administration site pain (26%) and swelling (22%) in arthrography. Patients also experienced heat (7%). Body Cavity Use VCU in Pediatric Patients No new adverse reactions associated with the use of OMNIPAQUE for VCU procedures were reported in 51 pediatric patients studied. 6.2 Post-marketing Experience The following adverse reactions have been identified during post-approval use of OMNIPAQUE. 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. General Immune system disorders: Hypersensitivity reactions, anaphylactic or anaphylactoid reactions, anaphylactic or anaphylactoid shock including life-threatening or fatal anaphylaxis General disorders and administration site conditions: Pyrexia, chills, pain and discomfort, asthenia, administration site conditions including extravasation Intrathecal Administration Nervous system disorders: Meningism, aseptic meningitis, seizures or status epilepticus, disorientation, coma, depressed or loss of consciousness, transient contrast-induced toxic encephalopathy (including amnesia, hallucination, paralysis, paresis, speech disorder, aphasia, dysarthria), restlessness, tremors, hypoesthesia Musculoskeletal and connective tissue disorders : Pain, muscle spasms or spasticity Psychiatric disorders: Confusional state, agitation, anxiety Eye disorders: Transient visual impairment including cortical blindness Renal and urinary disorders: Acute kidney injury Intra-arterial or Intravenous Administration Cardiac disorders: Severe cardiac complications (including cardiac arrest, cardiopulmonary arrest), shock, peripheral vasodilatation, palpitations, vasospasm including spasm of coronary arteries, myocardial infarction, syncope, cyanosis, pallor, flushing, chest pain Vascular disorders: Vasospasm and thrombophlebitis following intravenous injection Blood and lymphatic system disorders: Neutropenia Nervous system disorders: Disorientation, coma, depressed or loss of consciousness, transient contrast-induced toxic encephalopathy (including amnesia, hallucination, paralysis, paresis, speech disorder, aphasia, dysarthria), restlessness, tremors, hypoesthesia Psychiatric disorders: Confusional state, agitation Eye disorders: Eye irritation or itchiness, periorbital edema, ocular or conjunctival hyperemia, lacrimation Renal and urinary disorders: Acute kidney injury, toxic nephropathy (CIN), transient proteinuria, oliguria or anuria, increased serum creatinine Gastrointestinal disorders: Abdominal pain, pancreatitis aggravated, salivary gland enlargement Endocrine disorders: Hyperthyroidism, hypothyroidism Respiratory, thoracic and mediastinal disorders: Respiratory distress, respiratory failure, pulmonary edema, bronchospasm, laryngospasm, throat irritation, throat tightness, laryngeal edema, wheezing, chest discomfort, asthmatic attack Skin and subcutaneous tissue disorders: Contrast media reactions range from mild (e.g., pleomorphic rashes, drug eruption, erythema and skin discoloration, blisters, hyperhidrosis, angioedema, localized areas of edema) to severe (e.g., Stevens-Johnson syndrome and toxic epidermal necrolysis [SJS/TEN], bullous or exfoliative dermatitis, acute generalized exanthematous pustulosis [AGEP] and drug reaction with eosinophilia and systemic symptoms [DRESS]) Oral Administration Gastrointestinal disorders: Dysphagia, abdominal pain Body Cavity Administration Gastrointestinal disorders: Pancreatitis Musculoskeletal and connective tissue disorders: Arthritis (arthrography) Hysterosalpingography : Injection of OMNIPAQUE for hysterosalpingography is associated with immediate, transient pain. Monitor injection pressure and volume instilled to minimize pain and to avoid disruptive distention of the uterus and fallopian tubes. Fluoroscopic monitoring is recommended. Nervous system disorders : Pain (49%), somnolence and fever each with an individual incidence of 3% Gastrointestinal disorders : Nausea (3%)

4 CONTRAINDICATIONS OMNIPAQUE for hysterosalpingography is contraindicated during pregnancy or suspected pregnancy, menstruation or when menstruation is imminent, within 6 months after termination of pregnancy, within 30 days after conization or curettage, when signs of infection are present in any portion of the genital tract including the external genitalia, and when reproductive tract neoplasia is known or suspected because of the risk of peritoneal spread of neoplasm. Hysterosalpingography during pregnancy (or suspected pregnancy), menstruation (or when menstruation is imminent), within 6 months after termination of pregnancy, within 30 days after conization or curettage, when signs of infection are present in any portion of the genital tract, including the external genitalia, and when reproductive tract neoplasia is known or suspected. ( 4 )

11 DESCRIPTION Iohexol is a nonionic radiographic contrast agent available as: OMNIPAQUE (iohexol) injection for intrathecal, intra-arterial, intravenous, oral, rectal, intraarticular, and body cavity use OMNIPAQUE (iohexol) oral solution for oral use The chemical name of iohexol is Bis(2,3-dihydroxypropyl)-5-[ N -(2,3-dihydroxypropyl)-acetamido]-2,4,6- triiodoisophthalamide with a molecular weight of 821.14 (iodine content 46.36%). Iohexol has the following structural formula: OMNIPAQUE injection is a sterile, pyrogen-free, colorless to pale yellow solution available in five concentrations of iodine: OMNIPAQUE 140 mg iodine/mL: Each mL contains 302 mg iohexol (providing 140 mg organically bound iodine) and the following inactive ingredients: 0.1 mg edetate calcium disodium and 1.21 mg tromethamine. OMNIPAQUE 180 mg iodine/mL: Each mL contains 388 mg iohexol (providing 180 mg organically bound iodine) and the following inactive ingredients: 0.1 mg edetate calcium disodium and 1.21 mg tromethamine. OMNIPAQUE 240 mg iodine/mL: Each mL contains 518 mg iohexol (providing 240 mg organically bound iodine) and the following inactive ingredients: 0.1 mg edetate calcium disodium and 1.21 mg tromethamine. OMNIPAQUE 300 mg iodine/mL: Each mL contains 647 mg iohexol (providing 300 mg organically bound iodine) and the following inactive ingredients: 0.1 mg edetate calcium disodium and 1.21 mg tromethamine. OMNIPAQUE 350 mg iodine/mL: Each mL contains 755 mg iohexol (providing 350 mg organically bound iodine) and the following inactive ingredients: 0.1 mg edetate calcium disodium and 1.21 mg tromethamine. OMNIPAQUE oral solution is a sterile, pyrogen-free, colorless to pale yellow solution available in two concentrations of iodine: OMNIPAQUE oral solution 9 mg iodine/mL: Each mL contains 19 mg iohexol (providing 9 mg organically bound iodine) and the following inactive ingredients: 0.1 mg edetate calcium disodium and 1.21 mg tromethamine. OMNIPAQUE oral solution 12 mg iodine/mL: Each mL contains 26 mg iohexol (providing 12 mg organically bound iodine) and the following inactive ingredients: 0.1 mg edetate calcium disodium and 1.21 mg tromethamine. The pH is adjusted between 6.8 and 7.7 with hydrochloric acid or sodium hydroxide. OMNIPAQUE injection and OMNIPAQUE oral solution contain no preservatives and no ingredient made from a gluten-containing grain (wheat, barley, or rye). OMNIPAQUE injection and OMNIPAQUE oral solution have the following physical properties: Table 21. Physicochemical Properties of OMNIPAQUE Dosage Form Concentration (mg iodine/mL) Osmolality By vapor-pressure osmometry. (mOsmol/kg water) Absolute Viscosity (cP) Specific Gravity 20°C 37°C 37°C Injection 140 322 2.3 1.5 1.164 180 408 3.1 2.0 1.209 240 520 5.8 3.4 1.280 300 672 11.8 6.3 1.349 350 844 20.4 10.4 1.406 Oral solution 9 38 1.1 0.8 1.011 12 45 1.1 0.8 1.014 OMNIPAQUE injection has osmolalities from approximately 1.1 to 3 times that of plasma (285 mOsmol/kg water) or cerebrospinal fluid (301 mOsmol/kg water) as shown in the above table and are hypertonic . OMNIPAQUE oral solution is hypotonic. Chemical Structure

2 DOSAGE AND ADMINISTRATION For each imaging procedure, specific dosage forms, concentrations, and presentations are recommended. Individualize the concentration and volume according to the specific dosing tables and accounting for factors such as age, body weight, and condition of the patient, and the equipment and imaging technique used. ( 2.2 , 2.3 , 2.4 , 2.5 , 2.6 , 2.7 , 2.8 , 2.9 ) See full prescribing information for complete dosing and administration information. ( 2 ) 2.1 Important Dosage and Administration Instructions Specific dosage forms, concentrations, and presentations of OMNIPAQUE are recommended for each type of imaging procedure [see Dosage and Administration (2.2 , 2.3 , 2.4 , 2.5 , 2.6 , 2.7 , 2.8 , 2.9) and Warnings and Precautions (5.1 , 5.2) ]. Individualize the volume, strength, and rate of administration of OMNIPAQUE injection according to the specific dosing tables [see Dosage and Administration (2.2 , 2.3 , 2.4 , 2.5 , 2.6 , 2.7 , 2.8 , 2.9) ] . Consider factors such as age, body weight, vessel size, blood flow rate within the vessel, anticipated pathology, degree and extent of opacification required, structures or area to be examined, disease processes affecting the patient, and equipment and technique to be employed. Hydrate patients before and after administration of OMNIPAQUE injection [see Warnings and Precautions (5.4) ]. Use aseptic technique for all handling and administration of OMNIPAQUE injection. Administer OMNIPAQUE injection at either body (37°C, 98.6°F) or room temperature (20°C to 25°C, 68°F to 77°F). Do not mix OMNIPAQUE injection with, or inject in intravenous lines containing, other drugs or total nutritional admixtures except when OMNIPAQUE injection is administered in an automated contrast injection system or contrast management system suitable for simultaneous injection of OMNIPAQUE injection and 0.9% Sodium Chloride Injection [see Dosage and Administration (2.10 , 2.11) ]. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Each container of OMNIPAQUE injection and OMNIPAQUE oral solution in single-dose containers are intended for one procedure only. Discard any unused portion. 2.2 Recommended Dosage for Intrathecal Procedures in Adults The recommended doses for intrathecal procedures in adults are shown in Table 1. Administer over 1 minute to 2 minutes. If sequential or repeat examinations are required, allow at least 48 hours for clearance of the drug from the body before repeat administration; however, whenever possible, 5 days to 7 days is recommended. If CT myelography is performed, delay imaging by several hours to reduce the degree of contrast. Table 1. Recommended Concentrations and Volumes of OMNIPAQUE Injection for Intrathecal Procedures in Adults Imaging Procedure Injection Type Concentration (mg Iodine/mL) Volume to Administer Lumbar Myelography Lumbar 180 Use single-dose containers or 500 mL Pharmacy Bulk Packages [see Dosage and Administration (2.11) ]. 10 mL to 17 mL 240 7 mL to 12.5 mL Thoracic Myelography Lumbar Cervical 240 6 mL to 12.5 mL 300 6 mL to 10 mL Cervical Myelography Lumbar 240 6 mL to 12.5 mL 300 6 mL to 10 mL C1-2 180 7 mL to 10 mL 240 6 mL to 12.5 mL 300 4 mL to 10 mL Total Columnar Myelography Lumbar 240 6 mL to 12.5 mL 300 6 mL to 10 mL CT Cisternography Lumbar 180 10 mL to 17 mL 240 7 mL to 12.5 mL 2.3 Recommended Dosage for Intra-arterial Procedures in Adults The recommended doses for intra-arterial procedures in adults are shown in Table 2. Table 2. Recommended Concentrations and Volumes of OMNIPAQUE Injection for Intra-arterial Procedures in Adults Imaging Procedure Concentration (mg Iodine/mL) Volume to Administer per Single Injection for Selective Injection Sites Maximum Cumulative Total Dose Cardiac Ventriculography 350 Use single-dose containers or a 500 mL Pharmacy Bulk Package [see Dosage and Administration (2.11) ]. 40 mL (Range of 30 mL to 60 mL) may be combined with selective coronary arteriography 250 mL Aortography and Selective Visceral Arteriography 300 Aorta (aortic arch, ascending aorta): 50 mL to 80 mL Abdominal aorta and its branches (celiac, mesenteric, hepatic, and splenic arteries): 30 mL to 60 mL Renal arteries: 5 mL to 15 mL 290 mL 350 250 mL Aortic root and arch study when used alone 350 50 mL (Range of 20 mL to 75 mL) 250 mL Selective Coronary Arteriography 350 5 mL (Range of 3 mL to 14 mL) 250 mL Cerebral Arteriography 300 Common carotid artery: 6 mL to 12 mL Internal carotid artery: 8 mL to 10 mL External carotid artery: 6 mL to 9 mL Vertebral artery: 6 mL to 10 mL 290 mL Peripheral Arteriography Aortofemoral Runoffs 300 30 mL to 90 mL 290 mL 350 20 mL to 70 mL 250 mL Selective Arteriogram 300 10 mL to 60 mL 290 mL 350 10 mL to 30 mL 250 mL IA-DSA (head, neck, abdominal, renal, and peripheral vessels) 140 Aorta: 20 mL to 45 mL at 8 mL/sec to 20 mL/sec Carotid artery: 5 mL to 10 mL at 3 mL/sec to 6 mL/sec Femoral artery: 9 mL to 20 mL at 3 mL/sec to 6 mL/sec Vertebral artery: 4 mL to 10 mL at 2 mL/sec to 8 mL/sec Renal arteries: 6 mL to 12 mL at 3 mL/sec to 6 mL/sec Other branches of aorta (includes subclavian, axillary, innominate, and iliac): 8 mL to 25 mL at 3 mL/sec to 10 mL/sec 250 mL 2.4 Recommended Dosage for Intravenous Procedures in Adults The recommended doses for intravenous procedures in adults are shown in Table 3. Table 3. Recommended Concentrations and Volumes of OMNIPAQUE Injection for Intravenous Procedures in Adults Imaging Procedure Concentration (mg Iodine/mL) Volume to Administer Excretory Urography 300 Use single-dose containers or 500 mL Pharmacy Bulk Packages [see Dosage and Administration (2.11) ]. 0.6 mL/kg to 1.2 mL/kg body weight (maximum dose is 102 mL) 350 CT Head 240 120 mL to 250 mL by infusion 300 Use single-dose containers, 500 mL Imaging Bulk Packages or Pharmacy Bulk Packages, or 150 mL single-dose bottles with an automated contrast injection system or contrast management system [see Dosage and Administration (2.10 , 2.11 , 2.12) ]. 70 mL to 150 mL by rapid injection 350 80 mL by rapid injection Body 300 50 mL to 200 mL by rapid injection 350 60 mL to 100 mL by rapid injection Peripheral Venography (phlebography) 240 20 mL to 150 mL per leg 300 40 mL to 100 mL per leg IV-DSA (head, neck, abdominal, renal, and peripheral vessels) 350 30 mL to 50 mL at 7.5 mL/sec to 30 mL/sec using a pressure injector Frequently three or more doses may be required; the maximum cumulative total dose is 250 mL 2.5 Recommended Dosage for Oral Procedures in Adults Recommended Dosage for Radiographic Examination of the GI Tract in Adults The recommended dose for radiographic examination of the GI tract in adults is 50 mL to 100 mL of OMNIPAQUE injection 350 mg iodine/mL administered undiluted orally. Recommended Dosage for CT of the Abdomen and Pelvis in Conjunction with Intravenous Administration of OMINIPAQUE Injection in Adults The recommended oral dose using diluted OMNIPAQUE injection or OMNIPAQUE oral solution and concurrent intravenous doses for CT of the abdomen and pelvis in adults are shown in Table 4. Table 4. Recommended Concentrations and Volumes of Diluted OMNIPAQUE Injection or OMNIPAQUE Oral Solution for Oral Administration and Concurrent Intravenous OMNIPAQUE Injection for CT of the Abdomen and Pelvis in Adults Concentration (mg Iodine/mL) Volume to Administer Administration Instructions Oral Dose Using Diluted OMNIPAQUE Injection 6 mg Iodine/mL to 12 mg Iodine/mL of Diluted OMNIPAQUE Injection See Table 5 for dilution instructions of OMNIPAQUE injection 500 mL to 1,000 mL Administer the oral dose all at once or over a period of up to 45 minutes if there is difficulty in consuming the required volume. Use a higher iodine concentration of the diluted product if a smaller volume needs to be administered (see Table 5 ). Oral Dose Using OMNIPAQUE Oral Solution 9 mg Iodine/mL or 12 mg Iodine/mL of OMNIPAQUE Oral Solution 500 mL to 1,000 mL Administer the oral dose all at once or over a period of up to 45 minutes if there is difficulty in consuming the required volume. Intravenous Dose of OMNIPAQUE injection in Conjunction with Oral Administration 300 Use single-dose containers, 500 mL Imaging or Pharmacy Bulk Packages, or 150 mL single-dose bottles with an automated contrast injection system or contrast management system [see Dosage and Administration (2.10 , 2.11 , 2.12) ]. 100 mL to 150 mL Administer up to 40 minutes AFTER consumption of the oral dose. Preparation of Diluted OMNIPAQUE Injection for Oral Administration for CT of the Abdomen and Pelvis in Adults Prepare the diluted OMNIPAQUE injection in water, carbonated beverage, milk, infant formula, or juice just prior to administration according to Table 5. Discard any unused portion after the procedure. Table 5. Volumes of OMNIPAQUE Injection and Added Liquid to Dilute OMNIPAQUE Injection for Oral Administration for CT of the Abdomen in Adults Concentration of Diluted OMNIPAQUE injection (mg iodine/mL) Dilution Method 1 Dilution Method 2 Dilution Method 3 Volume of OMNIPAQUE 240 mg Iodine/mL (mL) Volume of Added Liquid Use water, carbonated beverage, milk, infant formula, or juice. (mL) Volume of OMNIPAQUE 300 mg Iodine/mL (mL) Volume of Added Liquid (mL) Volume of OMNIPAQUE 350 mg Iodine/mL (mL) Volume of Added Liquid (mL) 6 25 975 20 980 17 983 9 38 962 30 970 26 974 12 50 950 40 960 35 965 15 63 937 50 950 43 957 18 75 925 60 940 52 948 21 88 912 70 930 60 940 2.6 Recommended Dosage for Intraarticular Procedures in Adults The recommended doses for intraarticular procedures in adults are shown in Table 6. Use passive or active manipulation to disperse the medium throughout the joint space. Table 6. Recommended Concentrations and Volumes of OMNIPAQUE Injection for Intraarticular Procedures in Adults Imaging Procedure Location Concentration (mg Iodine/mL) Volume to Administer Double Contrast/Single Contrast Arthrography Knee 240 Use single-dose containers or 500 mL Pharmacy Bulk Packages [see Dosage and Administration (2.11) ]. 5 mL to 15 mL Lower volumes recommended for double-contrast examinations; higher volumes recommended for single-contrast examinations. 300 5 mL to 15 mL 350 5 mL to 10 mL Shoulder 300 10 mL Temporomandibular 300 0.5 mL to 1 mL 2.7 Recommended Dosage for Body Cavity Procedures in Adults The recommended doses for body cavity procedures in adults are shown in Table 7. Volume to administer may vary depending on individual anatomy and/or disease state. Table 7. Recommended Concentrations and Volumes of OMNIPAQUE Injection for Body Cavity Procedures in Adults Imaging Procedure Concentration (mg Iodine/mL) Volume to Administer Route of Administration Endoscopic retrograde pancreatography (ERP) and cholangiopancreatography (ERCP) 240 Use single-dose containers or 500 mL Pharmacy Bulk Packages [see Dosage and Administration (2.11) ]. 10 mL to 50 mL Intraductal Herniography 240 15 mL to 20 mL Intraperitoneal 300 Hysterosalpingography 240 50 mL Intrauterine 2.8 Recommended Dosage for Intrathecal, Intra-arterial, and Intravenous Procedures in Pediatric Patients Recommended Dosage for Intrathecal Procedures in Pediatric Patients Aged 2 Weeks and Older Recommended doses based on age for intrathecal procedures in pediatric patients aged 2 weeks and older are shown in Table 8. Administer over 1 minute to 2 minutes. If sequential or repeat examinations are required, allow at least 48 hours for clearance of the drug from the body before repeat administration; however, whenever possible, 5 days to 7 days is recommended. If CT myelography is performed, delay imaging by several hours to reduce the degree of contrast. Table 8: Recommended Concentrations and Volumes of OMNIPAQUE Injection Based on Age for Intrathecal Procedure in Pediatric Patients Aged 2 Weeks and Older Imaging Procedure Injection Type Age Concentration (mg Iodine/mL) Volume to Administer Myelography Lumbar Thoracic Cervical Total Columnar CT cisternography Lumbar 2 weeks up to 3 months 180 Use single-dose containers . 2 mL to 4 mL 3 months up to 36 months 4 mL to 8 mL 3 years up to 7 years 5 mL to 10 mL 7 years up to 13 years 5 mL to 12 mL 13 years to 18 years 6 mL to 15 mL Recommended Dosage for Intra-arterial Procedures in Pediatric Patients The recommended doses for intra-arterial procedures in pediatric patients are shown in Table 9. Table 9. Recommended Concentrations and Volumes of OMNIPAQUE Injection per Body Weight for Intra-arterial Procedures in Pediatric Patients Imaging Procedure Concentration (mg Iodine/mL) Volume per Body Weight to Administer per Single Injection Maximum Cumulative Volume Cardiac Ventriculography 300 Use single-dose containers or 500 mL Pharmacy Bulk Packages [see Dosage and Administration (2.11) ]. 1.75 mL/kg (Range of 1.5 mL/kg to 2 mL/kg) 6 mL/kg up to a total volume of 290 mL 350 1.25 mL/kg (Range of 1 mL/kg to 1.5 mL/kg) 5 mL/kg up to a total volume of 250 mL Aortography (aortic root, aortic arch, and descending aorta) 350 1 mL/kg 5 mL/kg up to a total volume of 250 mL Pulmonary Angiography 350 1 mL/kg 5 mL/kg up to a total volume of 250 mL Recommended Dosage for Intravenous Procedures in Pediatric Patients The recommended doses for intravenous procedures in pediatric patients are shown in Table 10. Table 10. Recommended Concentrations and Volumes of OMNIPAQUE Injection per Body Weight for Intravenous Procedures in Pediatric Patients Imaging Procedure Concentration (mg Iodine/mL) Volume per Body Weight to Administer Excretory Urography 300 Use single-dose containers or 500 mL Pharmacy Bulk Packages [see Dosage and Administration (2.11) ]. 0.5 mL/kg to 3 mL/kg (Maximum single dose: 116 mL) CT of the Head and Body 240 1 mL/kg to 2 mL/kg (with maximum 3 mL/kg) (Maximum single dose: 116 mL) 300 Use single-dose containers, 500 mL Imaging or Pharmacy Bulk Packages, or 150 mL single-dose bottles with an automated contrast injection system or contrast management system [see Dosage and Administration (2.10 , 2.11 , 2.12) ]. 2.9 Recommended Dosage for Oral or Rectal and Body Cavity Procedures in Pediatric Patients Recommended Dosage for Radiographic Examination of the GI Tract in Pediatric Patients The recommended doses for radiographic examination of the GI tract are shown in Table 11. Administer orally or rectally. Table 11. Recommended Concentrations and Volumes of OMNIPAQUE Injection Based on Age for Radiographic Examination of the GI Tract in Pediatric Patients Age Concentration (mg iodine/mL) Oral Volume Rectal Volume Less than 3 months 180 Use single-dose containers or 500 mL Pharmacy Bulk Packages [see Dosage and Administration (2.11) ] . 5 mL to 30 mL May be a larger volume than the volume given orally (up to 300 mL) 3 months to 3 years 180 , 240 , or 300 Up to 60 mL 4 years to 10 years Up to 80 mL Greater than 10 years Up to 100 mL Recommended Dosage for CT of the Abdomen and Pelvis in Conjunction with Intravenous Administration of OMNIPAQUE in Pediatric Patients The recommended oral dose using diluted OMNIPAQUE injection or OMNIPAQUE oral solution and concurrent intravenous dose for CT of the abdomen and pelvis in pediatric patients are shown in Table 12. Table 12. Recommended Concentrations and Volumes of Diluted OMNIPAQUE Injection or OMNIPAQUE Oral Solution for Oral Administration and Concurrent Intravenous OMNIPAQUE Injection for CT of the Abdomen and Pelvis in Pediatric Patients Concentration (mg Iodine/mL) Volume to Administer Administration Instructions Maximum Dose by Age or Body Weight Oral Dose Using Diluted OMNIPAQUE Injection 9 mg Iodine/mL to 21 mg Iodine/mL of Diluted OMNIPAQUE Injection See Table 13 for dilution instructions of OMNIPAQUE injection 180 mL to 750 mL Administer the oral dose all at once or over a period of up to 45 minutes if there is difficulty in consuming the required volume. Use a higher iodine concentration of the diluted product if a smaller volume needs to be administered (see Table 13 ). less than 3 years old: 5 grams iodine 3 years old to 18 years old: 10 grams iodine Oral Dose Using OMNIPAQUE Oral Solution 6 mg Iodine/mL or 12 mg Iodine/mL of OMNIPAQUE Oral Solution 180 mL to 750 mL Administer the oral dose all at once or over a period of up to 45 minutes if there is difficulty in consuming the required volume. less than 3 years old: 5 grams iodine 3 years old to 18 years old: 10 grams iodine Intravenous Dose in Conjunction with Oral Administration 240 or 300 Use single-dose containers, 500 mL Imaging or Pharmacy Bulk Packages, or 150 mL single-dose bottles with an automated contrast injection system or contrast management system [see Dosage and Administration (2.10 , 2.11 , 2.12) ]. 2 mL/kg body weight (with a range of 1 mL/kg to 2 mL/kg) Administer up to 60 minutes AFTER consumption of the oral dose. 3 mL/kg (maximum single dose: 116 mL) Preparation of Diluted OMNIPAQUE Injection for Oral Administration for CT of the Abdomen and Pelvis in Pediatric Patients Prepare the diluted OMNIPAQUE injection in water, carbonated beverage, milk, infant formula, or juice just prior to administration according to Table 13. Discard any unused portion after the procedure. Table 13. Volumes of OMNIPAQUE Injection and Added Liquid to Dilute OMNIPAQUE Injection for Oral Administration for CT of the Abdomen and Pelvis in Pediatric Patients Concentration of Diluted OMNIPAQUE injection (mg iodine/mL) Dilution Method 1 Dilution Method 2 Dilution Method 3 Volume of OMNIPAQUE 240 mg iodine/mL (mL) Volume of Added Liquid Use water, carbonated beverage, milk, infant formula, or juice. (mL) Volume of OMNIPAQUE 300 mg Iodine/mL (mL) Volume of Added Liquid (mL) Volume of OMNIPAQUE 350 mg Iodine/mL (mL) Volume of Added Liquid (mL) 6 25 975 20 980 17 983 9 38 962 30 970 26 974 12 50 950 40 960 35 965 15 63 937 50 950 43 957 18 75 925 60 940 52 948 21 88 912 70 930 60 940 Recommended Dosage for Voiding Cystourethrography in Pediatric Patients Voiding cystourethrography (VCU) can be performed in conjunction with excretory urography [see Dosage and Administration (2.8) ] . The concentration of diluted OMNIPAQUE injection may vary depending upon the patient's size and age and with the technique and equipment used. Volume ranges of diluted OMNIPAQUE injection 50 mg iodine/mL and 100 mg iodine/mL are shown in Table 14. Dilute OMNIPAQUE injection with Sterile Water for Injection according to Table 15, utilizing aseptic technique, just prior to use. Discard any unused portion after the procedure. Table 14. Volume Ranges of Diluted OMNIPAQUE Injection for VCU in Pediatric Patients Concentration of Diluted OMNIPAQUE Injection See Table 15 below for dilution instructions of OMNIPAQUE injection. (mg iodine/mL) Volume to Administer 50 50 mL to 600 mL by intravesical administration 100 50 mL to 300 mL by intravesical administration Table 15. Volumes of OMNIPAQUE Injection and Sterile Water for Injection to Dilute OMNIPAQUE Injection for VCU in Pediatric Patients Concentration of Diluted OMNIPAQUE injection (mg iodine/mL) Dilution Method 1 Dilution Method 2 Dilution Method 3 Volume of OMNIPAQUE 240 mg Iodine/mL (mL) Volume of Sterile Water for Injection (mL) Volume of OMNIPAQUE 300 mg Iodine/mL (mL) Volume of Sterile Water for Injection (mL) Volume of OMNIPAQUE 350 mg Iodine/mL (mL) Volume of Sterile Water for Injection (mL) 50 100 380 100 500 100 600 60 100 300 100 400 100 483 70 100 243 100 330 100 400 80 100 200 100 275 100 338 90 100 167 100 233 100 289 100 100 140 100 200 100 250 2.10 Directions for Use of the 500 mL Bottles of OMNIPAQUE Injection 300 mg Iodine/mL and 350 mg Iodine/mL as Imaging Bulk Package OMNIPAQUE injection 300 mg iodine/mL and OMNIPAQUE injection 350 mg iodine/mL in 500 mL bottles may be used as an Imaging Bulk Package (IBP) for intravenous use [see Dosage and Administration (2.4 , 2.8) ] . When used as an IBP, check the appropriate box on the container label to indicate that the selected container is to be utilized as an Imaging Bulk Package. This container is for use only with an automated contrast injection system, contrast management system, or contrast media transfer set approved or cleared for use with this contrast agent in this IBP. See device labeling for information on devices indicated for use with this IBP and techniques to help assure safe use. Use the OMNIPAQUE IBP and 0.9% Sodium Chloride Injection USP in a room designated for radiological procedures that involve administration of a contrast agent. Using aseptic technique, penetrate the container closure only one time with a suitable sterile component of the automated contrast injection system, contrast management system, or contrast media transfer set cleared for use with the OMNIPAQUE IBP. If 0.9% Sodium Chloride Injection USP is used with the OMNIPAQUE IBP, prepare the 0.9% Sodium Chloride Injection USP sterile port in accordance with the dosage and administration section of its approved prescribing information and affix the saline tag provided with the OMNIPAQUE IBP on the 0.9% Sodium Chloride Injection USP container. Once the OMNIPAQUE IBP and 0.9% Sodium Chloride Injection containers are punctured, do not remove them from the work area during the entire period of use. Maintain the OMNIPAQUE IBP in an inverted position such that container contents are in continuous contact with the dispensing set. After the container closure is punctured, if the integrity of the OMNIPAQUE IBP, the 0.9% Sodium Chloride Injection, and the delivery system cannot be assured through direct continuous supervision, discard the IBP, 0.9% Sodium Chloride Injection USP, and all associated disposables for the contrast media transfer set. A maximum time from initial puncture is 8 hours. Discard any unused portion. 2.11 Directions for Use of the 500 mL Bottles of OMNIPAQUE Injection 300 mg Iodine/mL and 350 mg Iodine/mL as Pharmacy Bulk Package OMNIPAQUE injection 300 mg iodine/mL and OMNIPAQUE injection 350 mg iodine/mL in 500 mL bottles contain many single doses and may be used as a Pharmacy Bulk Package (PBP). When used as a PBP, check the appropriate box on the container label to indicate that the selected container is to be utilized as a Pharmacy Bulk Package. This container is not for direct infusion; it is for use in pharmacy admixture service to dispense aliquots using a suitable dispensing set under a laminar flow hood or equivalent clean air compounding area using aseptic technique. Penetrate the container closure only one time, utilizing a suitable transfer device and aseptic technique. The withdrawal of container contents should be accomplished without delay. However, should this not be possible, a maximum time of 8 hours from initial closure entry is permitted to complete fluid transfer operations. Do not remove the container from the aseptic area during the entire 8-hour period. The temperature of the container should not exceed 37°C (98.6°F), after the closure has been entered. Discard any unused portion after 8 hours from the initial closure entry. 2.12 Directions for Use of the 150 mL Bottles of OMNIPAQUE Injection 300 mg Iodine/mL and 350 mg Iodine/mL with an Automated Contrast Injection System or Contrast Management System OMNIPAQUE injection 300 mg iodine/mL and OMNIPAQUE injection 350 mg iodine/mL in 150 mL bottles may be used with a contrast media management system cleared for use with OMNIPAQUE injection 300 mg iodine/mL and 350 mg iodine/mL in 150 mL bottles. See device labeling for information on device indications, instructions for use, and techniques to help assure safe use. Using aseptic technique, penetrate the container closure only one time with a suitable sterile component of the contrast media management system cleared for use with OMNIPAQUE 300 mg iodine/mL and 350 mg iodine/mL in 150 mL bottles. Once the container is punctured, do not remove the bottle from the work area during the entire period of use. Maximum use time is 4 hours after initial puncture. Each bottle is for one procedure only. Discard unused portion.

10 OVERDOSAGE The adverse effects of overdosage in intra-arterial or intravenous administration are life-threatening and affect mainly the pulmonary and cardiovascular systems. The symptoms include: cyanosis, bradycardia, acidosis, pulmonary hemorrhage, convulsions, coma, and cardiac arrest. Treatment of an overdosage is directed toward the support of all vital functions, and prompt institution of symptomatic therapy. Iohexol can be dialyzed.

7 DRUG INTERACTIONS 7.1 Drug-Drug Interactions Metformin In patients with renal impairment, metformin can cause lactic acidosis. Iodinated contrast agents appear to increase the risk of metformin-induced lactic acidosis, possibly as a result of worsening renal function. Stop metformin at the time of, or prior to, OMNIPAQUE administration in patients with an eGFR between 30 and 60 mL/min/1.73 m 2 ; in patients with a history of hepatic impairment, alcoholism or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging procedure, and reinstitute metformin only after renal function is stable. Radioactive Iodine OMNIPAQUE may interfere with thyroid uptake of radioactive iodine (I-131 and I-123) and decrease therapeutic and diagnostic efficacy. Avoid thyroid therapy or testing for up to 6 weeks post OMNIPAQUE. 7.2 Drug-Laboratory Test Interactions Protein-Bound Iodine Test Iodinated contrast agents, including OMNIPAQUE, will temporarily increase protein-bound iodine in blood. Do not perform protein-bound iodine test for at least 16 days following administration of OMNIPAQUE. However, thyroid function tests that do not depend on iodine estimation, e.g., T 3 resin uptake or direct thyroxine assays, are not affected.

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The iodine atoms in iohexol provide attenuation of X-rays in direct proportion to the concentration of iohexol. Since concentration changes over time, iohexol provides time-dependent image contrast which may assist in visualizing body structures. 12.2 Pharmacodynamics Intrathecal Administration The initial concentration and volume of the contrast medium, in conjunction with patient manipulation and the volume of cerebrospinal fluid (CSF) into which the contrast medium is placed, will determine the extent of the contrast that can be achieved. Following intrathecal injection in conventional radiography, OMNIPAQUE 180 mg iodine/mL, 240 mg iodine/mL, and 300 mg iodine/mL will continue to provide contrast for at least 30 minutes. Slow diffusion of iohexol takes place throughout the CSF with subsequent absorption into the bloodstream. At approximately 1 hour following injection, contrast will no longer be sufficient for conventional myelography. After administration into the lumbar subarachnoid space, computerized tomography shows the presence of contrast medium in the thoracic region in about 1 hour, in the cervical region in about 2 hours, and in the basal cisterns in 3 to 4 hours. Intravenous or Intra-arterial Administration Following intravenous or intra-arterial administration of OMNIPAQUE, the degree of contrast enhancement is directly related to the iodine concentration of an administered dose; peak iodine blood concentrations occur immediately (15 seconds to 120 seconds) following rapid intravenous injection. The time to maximum contrast enhancement can vary, depending on the organ, from the time that peak blood iodine concentrations are reached to one hour after intravenous bolus administration. When a delay between peak blood iodine concentrations and peak contrast is present, it suggests that radiographic contrast enhancement is at least in part dependent on the accumulation of iodine containing agent within the lesion and outside the blood pool. Oral Administration Orally administered OMNIPAQUE produces visualization of the gastrointestinal tract. Less than 1% of orally administered iohexol is recovered in the urine, suggesting minimal amounts are absorbed from the normal gastrointestinal tract. This amount may increase in the presence of bowel perforation or bowel obstruction. Intraarticular Administration Visualization of the joint spaces can be accomplished by direct injection of contrast medium. For intraarticular cavities, the injected iohexol is absorbed into the surrounding tissue and subsequently absorbed into systemic circulation. Body Cavity Administration For most body cavities, the injected iohexol is absorbed into the surrounding tissue and subsequently absorbed into systemic circulation. Examinations of the uterus (hysterosalpingography) and bladder (voiding cystourethrography) involve the almost immediate drainage of contrast medium from the cavity upon conclusion of the radiographic procedure. 12.3 Pharmacokinetics Following the intravenous administration of iohexol (between 500 mg iodine/kg to 1,500 mg iodine/kg) to 16 adult subjects, apparent first-order terminal elimination half-life was 12.6 hours and total body clearance was 131 (98 to 165) mL/min. Clearance was not dose dependent. Absorption As evidenced by the amount recovered in urine, <1% of orally administered iohexol is absorbed from the normal gastrointestinal tract. This amount may increase in the presence of bowel perforation or bowel obstruction. Distribution In 16 adult subjects (receiving between 500 mg iodine/kg to 1,500 mg iodine/kg intravenous iohexol) the plasma volume of distribution was165 (108 to 219) mL/kg. In five adult patients receiving 16 mL to 18 mL of OMNIPAQUE (180 mg iodine/mL) by lumbar intrathecal injection the plasma volume of distribution was 559 (350 to 849) mL/kg. Elimination Metabolism No significant metabolism, deiodination or biotransformation occurs. Excretion Following intravenous, intra-arterial or intrathecal administration, iohexol is excreted unchanged by glomerular filtration. Approximately 90% of the intravenously injected iohexol dose is excreted within the first 24 hours. Following intravenous or intraarterial administration, peak urine concentration occurs in the first hour after injection.

12.1 Mechanism of Action The iodine atoms in iohexol provide attenuation of X-rays in direct proportion to the concentration of iohexol. Since concentration changes over time, iohexol provides time-dependent image contrast which may assist in visualizing body structures.

12.2 Pharmacodynamics Intrathecal Administration The initial concentration and volume of the contrast medium, in conjunction with patient manipulation and the volume of cerebrospinal fluid (CSF) into which the contrast medium is placed, will determine the extent of the contrast that can be achieved. Following intrathecal injection in conventional radiography, OMNIPAQUE 180 mg iodine/mL, 240 mg iodine/mL, and 300 mg iodine/mL will continue to provide contrast for at least 30 minutes. Slow diffusion of iohexol takes place throughout the CSF with subsequent absorption into the bloodstream. At approximately 1 hour following injection, contrast will no longer be sufficient for conventional myelography. After administration into the lumbar subarachnoid space, computerized tomography shows the presence of contrast medium in the thoracic region in about 1 hour, in the cervical region in about 2 hours, and in the basal cisterns in 3 to 4 hours. Intravenous or Intra-arterial Administration Following intravenous or intra-arterial administration of OMNIPAQUE, the degree of contrast enhancement is directly related to the iodine concentration of an administered dose; peak iodine blood concentrations occur immediately (15 seconds to 120 seconds) following rapid intravenous injection. The time to maximum contrast enhancement can vary, depending on the organ, from the time that peak blood iodine concentrations are reached to one hour after intravenous bolus administration. When a delay between peak blood iodine concentrations and peak contrast is present, it suggests that radiographic contrast enhancement is at least in part dependent on the accumulation of iodine containing agent within the lesion and outside the blood pool. Oral Administration Orally administered OMNIPAQUE produces visualization of the gastrointestinal tract. Less than 1% of orally administered iohexol is recovered in the urine, suggesting minimal amounts are absorbed from the normal gastrointestinal tract. This amount may increase in the presence of bowel perforation or bowel obstruction. Intraarticular Administration Visualization of the joint spaces can be accomplished by direct injection of contrast medium. For intraarticular cavities, the injected iohexol is absorbed into the surrounding tissue and subsequently absorbed into systemic circulation. Body Cavity Administration For most body cavities, the injected iohexol is absorbed into the surrounding tissue and subsequently absorbed into systemic circulation. Examinations of the uterus (hysterosalpingography) and bladder (voiding cystourethrography) involve the almost immediate drainage of contrast medium from the cavity upon conclusion of the radiographic procedure.

12.3 Pharmacokinetics Following the intravenous administration of iohexol (between 500 mg iodine/kg to 1,500 mg iodine/kg) to 16 adult subjects, apparent first-order terminal elimination half-life was 12.6 hours and total body clearance was 131 (98 to 165) mL/min. Clearance was not dose dependent. Absorption As evidenced by the amount recovered in urine, <1% of orally administered iohexol is absorbed from the normal gastrointestinal tract. This amount may increase in the presence of bowel perforation or bowel obstruction. Distribution In 16 adult subjects (receiving between 500 mg iodine/kg to 1,500 mg iodine/kg intravenous iohexol) the plasma volume of distribution was165 (108 to 219) mL/kg. In five adult patients receiving 16 mL to 18 mL of OMNIPAQUE (180 mg iodine/mL) by lumbar intrathecal injection the plasma volume of distribution was 559 (350 to 849) mL/kg. Elimination Metabolism No significant metabolism, deiodination or biotransformation occurs. Excretion Following intravenous, intra-arterial or intrathecal administration, iohexol is excreted unchanged by glomerular filtration. Approximately 90% of the intravenously injected iohexol dose is excreted within the first 24 hours. Following intravenous or intraarterial administration, peak urine concentration occurs in the first hour after injection.

20241017

18

3 DOSAGE FORMS AND STRENGTHS Injection and Oral Solution: Colorless to pale yellow solution available in the following presentations: Dosage Form Concentration (mg of iodine/mL) Package Size Package Type Injection 140 50 mL Single-Dose Bottle 180 10 mL Single-Dose Vial 240 10 mL and 20 mL Single-Dose Vial 50 mL and 100 mL Sigle-Dose Bottle 300 10 mL Single-Dose Vial 30 mL, 50 mL, 100 mL, 125 mL, and 150 mL Single-Dose Bottle 500 mL OMNIPAQUE injection 300 mg iodine/mL and OMNIPAQUE injection 350 mg iodine/mL in bottles of 500 mL can be used as either an Imaging Bulk Package or a Pharmacy Bulk Package [see Dosage and Administration (2.10 , 2.11) ]. Imaging or Pharmacy Bulk Package 350 50 mL, 75 mL, 100 mL, 125 mL, 150 mL, and 200 mL Single-Dose Bottle 500 mL Imaging or Pharmacy Bulk Package Oral Solution 9 500 mL Single-Dose Bottle 12 500 mL Single-Dose Bottle Injection: 140 mg iodine/mL, 180 mg iodine/mL, and 240 mg iodine/mL in single-dose vials/bottles; 300 mg iodine/mL and 350 mg iodine/mL in single-dose vials/bottles and imaging or pharmacy bulk package Oral Solution: 9 mg iodine/mL and 12 mg iodine/mL ( 3 )

OMNIPAQUE Iohexol Iohexol Iohexol IODINE tromethamine edetate calcium disodium hydrochloric acid sodium hydroxide colorless to pale yellow OMNIPAQUE Iohexol Iohexol Iohexol IODINE tromethamine edetate calcium disodium hydrochloric acid sodium hydroxide colorless to pale yellow OMNIPAQUE Iohexol Iohexol Iohexol IODINE tromethamine edetate calcium disodium hydrochloric acid sodium hydroxide colorless to pale yellow OMNIPAQUE Iohexol Iohexol Iohexol IODINE tromethamine edetate calcium disodium hydrochloric acid sodium hydroxide colorless to pale yellow OMNIPAQUE Iohexol Iohexol Iohexol IODINE tromethamine edetate calcium disodium hydrochloric acid sodium hydroxide colorless to pale yellow OMNIPAQUE Iohexol Iohexol Iohexol IODINE tromethamine edetate calcium disodium hydrochloric acid sodium hydroxide colorless to pale yellow OMNIPAQUE Iohexol Iohexol Iohexol IODINE tromethamine edetate calcium disodium hydrochloric acid sodium hydroxide colorless to pale yellow

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term animal studies have not been performed with iohexol to evaluate carcinogenic potential. Iohexol was not genotoxic in a series of studies, including the Ames test, the mouse lymphoma TK locus forward mutation assay, and a mouse micronucleus assay. Iohexol did not impair the fertility of male or female rats when repeatedly administered at intravenous dosages up to 4 g iodine/kg.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term animal studies have not been performed with iohexol to evaluate carcinogenic potential. Iohexol was not genotoxic in a series of studies, including the Ames test, the mouse lymphoma TK locus forward mutation assay, and a mouse micronucleus assay. Iohexol did not impair the fertility of male or female rats when repeatedly administered at intravenous dosages up to 4 g iodine/kg.

NDA018956

OMNIPAQUE

Iohexol

0407-1411

HUMAN PRESCRIPTION DRUG

INTRATHECAL,ORAL,RECTAL

PRINCIPAL DISPLAY PANEL - 140 mgI/mL Bottle Label NDC 0407-1401-52 50 mL OMNIPAQUE™ (iohexol) Injection 140 mgI/mL NOT FOR INTRATHECAL USE in +PLUSPAK™ (polymer bottle) PRINCIPAL DISPLAY PANEL - 140 mgI/mL Bottle Label

Indications and Usage, CT cerebral ventriculography (1.1) - Removed 10/2024 Dosage and Administration ( 2.6 , 2.10 , 2.11 ) 10/2024

Distributed by GE Healthcare Inc., Marlborough, MA 01752 U.S.A. OMNIPAQUE is a trademark of GE HealthCare or one of its subsidiaries. GE is a trademark of General Electric Company used under trademark license. © 2024 GE HealthCare

17 PATIENT COUNSELING INFORMATION Hypersensitivity Reactions Advise the patient concerning the risk of hypersensitivity reactions that can occur both during and after OMNIPAQUE administration. Advise the patient to report any signs or symptoms of hypersensitivity reactions during the procedure and to seek immediate medical attention for any signs or symptoms experienced after discharge [see Warnings and Precautions (5.3) ]. Advise patients to inform their physician if they develop a rash after receiving OMNIPAQUE [see Warnings and Precautions (5.12) ]. Acute Kidney Injury Advise the patient concerning appropriate hydration to decrease the risk of contrast-induced acute kidney injury [see Warnings and Precautions (5.4) ] . Extravasation If extravasation occurs during injection, advise patients to seek medical care for progression of symptoms [see Warnings and Precautions (5.7) ]. Lactation Advise a lactating woman that interruption of breastfeeding is not necessary. However, to avoid any exposure, a lactating woman may consider pumping and discarding breast milk for 10 hours after OMNIPAQUE administration [see Use in Specific Populations (8.2) ]. Thyroid Dysfunction Advise parents/caregivers about the risk of developing thyroid dysfunction after OMNIPAQUE administration. Advise parents/caregivers about when to seek medical care for their child to monitor for thyroid function [see Warnings and Precautions (5.9) ].

14 CLINICAL STUDIES The safety and effectiveness of OMNIPAQUE for CT of the head were evaluated in three clinical studies. Each study also used an ionic high-osmolar iodinated contrast agent as a comparator. A total of 280 patients were randomized to administration of either OMNIPAQUE (n=142) or the comparator (n=138). OMNIPAQUE patients had a mean age of 52 years (range 16 to 85), 41% were women, and were administered a mean of 692 mg iodine/kg (range 337 to 1,250 mg iodine/kg) by intravenous injection with OMNIPAQUE 240 mg iodine/mL (1 study) or 300 mg iodine/mL (2 studies). Efficacy was determined from investigator ratings of quality of contrast enhancement (none, poor, good, or excellent; only scans rated as good or excellent were considered diagnostic). The percentage of OMNIPAQUE-enhanced scans rated as good or excellent was 100% in the two studies using OMNIPAQUE 300 mg iodine/mL, and 79% in the third study using OMNIPAQUE 240 mg iodine/mL.

8.5 Geriatric Use In clinical studies of OMNIPAQUE for CT of the head and body, 52 (17%) of patients were 70 and over. No overall differences in safety were observed between these patients and younger patients. Other reported clinical experience has not identified differences in safety and effectiveness between the elderly and younger patients. Iohexol is substantially excreted by the kidney, and the risk of adverse reactions to iohexol may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

8.4 Pediatric Use Intrathecal Use The safety and effectiveness of OMNIPAQUE have been established in pediatric patients aged 2 weeks and older for myelography and CT myelography (lumbar, thoracic, cervical, total columnar) and for CT cisternography. Use of OMNIPAQUE is supported by controlled clinical studies in adults for myelography, in addition to clinical studies in pediatric patients undergoing myelography. The safety and effectiveness of OMNIPAQUE have not been established for intrathecal use in pediatric patients less than 2 weeks of age. The safety and effectiveness of OMNIPAQUE for CT cerebral ventriculography have not been established in pediatric patients. Intra-arterial or Intravenous Use Cardiac Ventriculography, Aortography, and Pulmonary Angiography The safety and effectiveness of OMNIPAQUE have been established in pediatric patients from birth to 17 years of age for cardiac ventriculography, aortography, and pulmonary angiography. Use of OMNIPAQUE is supported by controlled clinical studies in adults for cardiac ventriculography and aortography, in addition to controlled clinical studies in pediatric patients undergoing cardiac ventriculography, including aortography. Excretory Urography The safety and effectiveness of OMNIPQUE have been established in pediatric patients from birth to 17 years of age for excretory urography. Use of OMNIPAQUE is supported by controlled clinical studies in adults for urography, in addition to controlled clinical studies in pediatric patients undergoing urography and clinical safety data in pediatric patients down to birth. CT of the Head and Body The safety and effectiveness of OMNIPAQUE have been established in pediatric patients from birth to 17 years of age for CT imaging of the head and body. Use of OMNIPAQUE is supported by controlled clinical studies in adults for head and body CT, in addition to clinical studies in pediatric patients undergoing head CT and in 69 pediatric patients undergoing CT of the abdomen after oral administration of diluted OMNIPAQUE plus intravenous administration of OMNIPAQUE. Selective Coronary Arteriography, Cerebral and Peripheral Arteriography, Intra-arterial Digital Subtraction Angiography, Peripheral Venography, and Intravenous Digital Subtraction Angiography The safety and effectiveness of OMNIPAQUE have not been established in pediatric patients for selective coronary arteriography, cerebral or peripheral arteriography, intra-arterial digital subtraction angiography, peripheral venography, and intravenous digital subtraction angiography. Oral or Rectal Use Examination of the GI Tract The safety and effectiveness of OMNIPAQUE have been established in pediatric patients, from birth to 17 years of age for examination of the GI tract. Use of OMNIPAQUE is supported by controlled studies in adults for examination of the GI tract, in addition to clinical studies in pediatric patients undergoing examination of the GI tract. CT of the Abdomen and Pelvis in Conjunction with Intravenous Use The safety and effectiveness of OMNIPAQUE for CT of the abdomen and pelvis have been established in pediatric patients from birth to 17 years of age. Use is supported by clinical trials in adults, in addition to clinical studies in 69 pediatric patients undergoing CT of the abdomen. Intraarticular Use The safety and effectiveness of OMNIPAQUE have not been established in pediatric patients for arthrography. Body Cavity Use Voiding Cystourethrography OMNIPAQUE is indicated for use in pediatric patients from birth to 17 years of age for voiding cystourethrography (VCU). Use for voiding cystourethrography is supported by clinical studies in 51 pediatric patients undergoing VCU. ERCP, Herniography, and Hysterosalpingography The safety and effectiveness of OMNIPAQUE have not been established in pediatric patients for ERCP, herniography, or hysterosalpingography. In general, the frequency of adverse reactions in pediatric patients was similar to that seen in adults [ s ee Adverse Reactions (6.1) ] . Pediatric patients at higher risk of experiencing adverse events during contrast-medium administration may include those having asthma, a sensitivity to medication and/or allergens, congestive heart failure, a serum creatinine greater than 1.5 mg/dL or those less than 12 months of age. Thyroid function tests indicative of thyroid dysfunction, characterized by hypothyroidism or transient thyroid suppression have been reported following iodinated contrast media administration in pediatric patients, including term and preterm neonates. Some patients were treated for hypothyroidism. After exposure to iodinated contrast media, individualize thyroid function monitoring in pediatric patients 0 to 3 years of age based on underlying risk factors, especially in term and preterm neonates [see Warnings and Precautions (5.9) and Adverse Reactions (6.2) ] .

8.1 Pregnancy Risk Summary Hysterosalpingography is contraindicated in pregnant women due to the potential risk to the fetus from an intrauterine procedure [see Contraindications (4) ]. There are no data with iohexol use in pregnant women to inform any drug-associated risks. Iohexol crosses the placenta and reaches fetal tissues in small amounts ( see Data ) . In animal reproduction studies, no developmental toxicity occurred with intravenous iohexol administration to rats and rabbits at doses up to 0.4 (rat) and 0.5 (rabbit) times the maximum recommended human intravenous dose ( see Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Human Data Literature reports show that intravenously administered iohexol crosses the placenta and is visualized in the digestive tract of exposed infants after birth. Animal Data Iohexol was neither embryotoxic nor teratogenic in either rats or rabbits at the following dose levels tested: 1.0, 2.0, 4.0 g iodine/kg in rats, administered intravenously to 3 groups of 25 dams once daily during days 6 through 15 of pregnancy; 0.3, 1.0, 2.5 g iodine/kg in rabbits, administered intravenously to 3 groups of 18 rabbits dosed once a day during days 6 through 18 of pregnancy.

8 USE IN SPECIFIC POPULATIONS Lactation: A lactating woman may pump and discard breast milk for 10 hours after OMNIPAQUE administration. ( 8.2 ) 8.1 Pregnancy Risk Summary Hysterosalpingography is contraindicated in pregnant women due to the potential risk to the fetus from an intrauterine procedure [see Contraindications (4) ]. There are no data with iohexol use in pregnant women to inform any drug-associated risks. Iohexol crosses the placenta and reaches fetal tissues in small amounts ( see Data ) . In animal reproduction studies, no developmental toxicity occurred with intravenous iohexol administration to rats and rabbits at doses up to 0.4 (rat) and 0.5 (rabbit) times the maximum recommended human intravenous dose ( see Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Human Data Literature reports show that intravenously administered iohexol crosses the placenta and is visualized in the digestive tract of exposed infants after birth. Animal Data Iohexol was neither embryotoxic nor teratogenic in either rats or rabbits at the following dose levels tested: 1.0, 2.0, 4.0 g iodine/kg in rats, administered intravenously to 3 groups of 25 dams once daily during days 6 through 15 of pregnancy; 0.3, 1.0, 2.5 g iodine/kg in rabbits, administered intravenously to 3 groups of 18 rabbits dosed once a day during days 6 through 18 of pregnancy. 8.2 Lactation Risk Summary Published literature reports that breast feeding after intravenous iohexol administration to the mother would result in the infant receiving an oral dose of approximately 0.7% of the maternal intravenous dose; however, lactation studies have not been conducted with oral, intrathecal, or intracavity administration of iohexol. There is no information on the effects of the drug on the breastfed infant or on milk production. Iodinated contrast agents are excreted unchanged in human milk in very low amounts with poor absorption from the gastrointestinal tract of a breastfed infant. Exposure to iohexol to a breastfed infant can be minimized by temporary discontinuation of breastfeeding (see Clinical Considerations ). The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for OMNIPAQUE and any potential adverse effects on the breastfed infant from OMNIPAQUE or from the underlying maternal condition. Clinical Considerations Interruption of breastfeeding after exposure to iodinated contrast agents 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 elimination half-lives) after OMNIPAQUE administration to minimize drug exposure to a breastfed infant. 8.4 Pediatric Use Intrathecal Use The safety and effectiveness of OMNIPAQUE have been established in pediatric patients aged 2 weeks and older for myelography and CT myelography (lumbar, thoracic, cervical, total columnar) and for CT cisternography. Use of OMNIPAQUE is supported by controlled clinical studies in adults for myelography, in addition to clinical studies in pediatric patients undergoing myelography. The safety and effectiveness of OMNIPAQUE have not been established for intrathecal use in pediatric patients less than 2 weeks of age. The safety and effectiveness of OMNIPAQUE for CT cerebral ventriculography have not been established in pediatric patients. Intra-arterial or Intravenous Use Cardiac Ventriculography, Aortography, and Pulmonary Angiography The safety and effectiveness of OMNIPAQUE have been established in pediatric patients from birth to 17 years of age for cardiac ventriculography, aortography, and pulmonary angiography. Use of OMNIPAQUE is supported by controlled clinical studies in adults for cardiac ventriculography and aortography, in addition to controlled clinical studies in pediatric patients undergoing cardiac ventriculography, including aortography. Excretory Urography The safety and effectiveness of OMNIPQUE have been established in pediatric patients from birth to 17 years of age for excretory urography. Use of OMNIPAQUE is supported by controlled clinical studies in adults for urography, in addition to controlled clinical studies in pediatric patients undergoing urography and clinical safety data in pediatric patients down to birth. CT of the Head and Body The safety and effectiveness of OMNIPAQUE have been established in pediatric patients from birth to 17 years of age for CT imaging of the head and body. Use of OMNIPAQUE is supported by controlled clinical studies in adults for head and body CT, in addition to clinical studies in pediatric patients undergoing head CT and in 69 pediatric patients undergoing CT of the abdomen after oral administration of diluted OMNIPAQUE plus intravenous administration of OMNIPAQUE. Selective Coronary Arteriography, Cerebral and Peripheral Arteriography, Intra-arterial Digital Subtraction Angiography, Peripheral Venography, and Intravenous Digital Subtraction Angiography The safety and effectiveness of OMNIPAQUE have not been established in pediatric patients for selective coronary arteriography, cerebral or peripheral arteriography, intra-arterial digital subtraction angiography, peripheral venography, and intravenous digital subtraction angiography. Oral or Rectal Use Examination of the GI Tract The safety and effectiveness of OMNIPAQUE have been established in pediatric patients, from birth to 17 years of age for examination of the GI tract. Use of OMNIPAQUE is supported by controlled studies in adults for examination of the GI tract, in addition to clinical studies in pediatric patients undergoing examination of the GI tract. CT of the Abdomen and Pelvis in Conjunction with Intravenous Use The safety and effectiveness of OMNIPAQUE for CT of the abdomen and pelvis have been established in pediatric patients from birth to 17 years of age. Use is supported by clinical trials in adults, in addition to clinical studies in 69 pediatric patients undergoing CT of the abdomen. Intraarticular Use The safety and effectiveness of OMNIPAQUE have not been established in pediatric patients for arthrography. Body Cavity Use Voiding Cystourethrography OMNIPAQUE is indicated for use in pediatric patients from birth to 17 years of age for voiding cystourethrography (VCU). Use for voiding cystourethrography is supported by clinical studies in 51 pediatric patients undergoing VCU. ERCP, Herniography, and Hysterosalpingography The safety and effectiveness of OMNIPAQUE have not been established in pediatric patients for ERCP, herniography, or hysterosalpingography. In general, the frequency of adverse reactions in pediatric patients was similar to that seen in adults [ s ee Adverse Reactions (6.1) ] . Pediatric patients at higher risk of experiencing adverse events during contrast-medium administration may include those having asthma, a sensitivity to medication and/or allergens, congestive heart failure, a serum creatinine greater than 1.5 mg/dL or those less than 12 months of age. Thyroid function tests indicative of thyroid dysfunction, characterized by hypothyroidism or transient thyroid suppression have been reported following iodinated contrast media administration in pediatric patients, including term and preterm neonates. Some patients were treated for hypothyroidism. After exposure to iodinated contrast media, individualize thyroid function monitoring in pediatric patients 0 to 3 years of age based on underlying risk factors, especially in term and preterm neonates [see Warnings and Precautions (5.9) and Adverse Reactions (6.2) ] . 8.5 Geriatric Use In clinical studies of OMNIPAQUE for CT of the head and body, 52 (17%) of patients were 70 and over. No overall differences in safety were observed between these patients and younger patients. Other reported clinical experience has not identified differences in safety and effectiveness between the elderly and younger patients. Iohexol is substantially excreted by the kidney, and the risk of adverse reactions to iohexol may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. 8.6 Renal Impairment The clearance of iohexol decreases with increasing degree of renal impairment and results in delayed opacification of the urinary system. In addition, preexisting renal impairment increases the risk for acute kidney injury [see Warnings and Precautions (5.4) ] . Iohexol can be removed by dialysis.

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied OMNIPAQUE (iohexol) injection and OMNIPAQUE (iohexol) oral solution are colorless to pale yellow solutions available in the following presentations: Dosage Form Concentration (mg iodine/mL) Package Size Package Type & Material Sale Unit NDC Injection 140 50 mL Single-Dose Polymer Bottles Boxes of 10 0407-1401-52 180 10 mL Single-Dose Glass Vials Boxes of 10 0407-1411-10 240 10 mL Single-Dose Glass Vials Boxes of 10 0407-1412-10 20 mL Single-Dose Glass Vials Boxes of 10 0407-1412-20 50 mL Single-Dose Polymer Bottles Boxes of 10 0407-1412-30 100 mL Single-Dose Polymer Bottles Boxes of 10 0407-1412-33 300 10 mL Single-Dose Glass Vials Boxes of 10 0407-1413-10 30 mL Single-Dose Polymer Bottles Boxes of 10 0407-1413-59 50 mL Single-Dose Polymer Bottles Boxes of 10 0407-1413-61 100 mL Single-Dose Polymer Bottles Boxes of 10 0407-1413-63 125 mL Single-Dose Glass Bottles Boxes of 10 0407-1413-53 150 mL Single-Dose Polymer Bottles Boxes of 10 0407-1413-65 500 mL OMNIPAQUE injection 300 mg iodine/mL and OMNIPAQUE injection 350 mg iodine/mL in bottles of 500 mL can be used as either an Imaging Bulk Package or a Pharmacy Bulk Package [see Dosage and Administration (2.10 , 2.11) ] . Imaging or Pharmacy Bulk Package Polymer Bottles Boxes of 10 0407-1413-72 350 50 mL Single-Dose Polymer Bottles Boxes of 10 0407-1414-89 75 mL Single-Dose Polymer Bottles Boxes of 10 0407-1414-90 100 mL Single-Dose Polymer Bottles Boxes of 10 0407-1414-91 125 mL Single-Dose Glass Bottles Boxes of 10 0407-1414-76 150 mL Single-Dose Polymer Bottles Boxes of 10 0407-1414-93 200 mL Single-Dose Polymer Bottles Boxes of 10 0407-1414-94 500 mL Imaging or Pharmacy Bulk Package Polymer Bottles Boxes of 10 0407-1414-72 Oral Solution 9 500 mL Single-Dose Polymer Bottles Boxes of 10 0407-1415-09 12 500 mL Single-Dose Polymer Bottles Boxes of 10 0407-1416-12 The container closure system components (bottle, vial, stopper, and cap) of OMNIPAQUE injection and OMNIPAQUE oral solution are not made with natural rubber latex. Storage and Handling OMNIPAQUE Injection: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. May be stored in a contrast media warmer for up to one month, not to exceed 37°C (98.6°F). OMNIPAQUE Oral Solution: Store between 0°C and 30°C (32°F to 86°F). Protect from light. Do not freeze. Discard any product that is inadvertently frozen, as freezing may compromise the closure integrity of the immediate container.

Storage and Handling OMNIPAQUE Injection: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. May be stored in a contrast media warmer for up to one month, not to exceed 37°C (98.6°F). OMNIPAQUE Oral Solution: Store between 0°C and 30°C (32°F to 86°F). Protect from light. Do not freeze. Discard any product that is inadvertently frozen, as freezing may compromise the closure integrity of the immediate container.

WARNING: RISKS ASSOCIATED WITH INTRATHECAL ADMINISTRATION OF OMNIPAQUE INJECTION 140 mg IODINE/mL and 350 mg IODINE/mL Use only the OMNIPAQUE iodine concentrations and presentations recommended for intrathecal procedure [see Dosage and Administration (2.2 , 2.8) ]. Intrathecal administration of OMNIPAQUE of a wrong iodine concentration, even if inadvertent, may cause death, convulsions, seizures, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, rhabdomyolysis, hyperthermia, and brain edema [see Warnings and Precautions (5.1) ]. WARNING: RISKS ASSOCIATED WITH INTRATHECAL ADMINISTRATION OF OMNIPAQUE INJECTION 140 and 350 mg IODINE/mL Use only the iodine concentrations and presentations recommended for intrathecal procedures. Intrathecal administration of a wrong iodine concentration, even if inadvertent, may cause death, convulsions, seizures, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, rhabdomyolysis, hyperthermia, and brain edema. ( 2.2 , 2.8 , 5.1 )