Iohexol

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.

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, an

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 m

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: cerebra

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.