ISOVUE

RECENT MAJOR CHANGES Indications and Usage, Oral Procedures ( 1.3 ) 10/2025 Dosage and Administration Recommended Dosage for Oral Procedures in Pediatric Patients and Adults ( 2.5 ) Directions for Dilution of ISOVUE for Oral Administration ( 2.6 ) 10/2025

1 INDICATIONS AND USAGE ISOVUE is a radiographic contrast agent indicated for: Intra-arterial Procedures † ( 1.1 ) Cerebral arteriography in adults Peripheral arteriography in adults Selective visceral arteriography and aortography in adults Coronary arteriography and cardiac ventriculography in adults Angiocardiography in pediatric patients Intravenous Procedures † ( 1.2 ) Excretory urography in adults and pediatric patients Computed tomography (CT) of head and body in adults and pediatric patients Peripheral venography in adults Oral Procedures † ( 1.3 ) CT of the abdomen and pelvis to delineate the gastrointestinal tract in adults and pediatric patients † Specific concentrations are recommended for each type of imaging procedure. ( 2.2 , 2.3 , 2.4 , 2.5 ) 1.1 Intra-arterial Procedures † ISOVUE is indicated for: Cerebral arteriography in adults Peripheral arteriography in adults Selective visceral arteriography and aortography in adults Coronary arteriography and cardiac ventriculography in adults Angiocardiography in pediatric patients 1.2 Intravenous Procedures † ISOVUE is indicated for: Excretory urography in adults and pediatric patients Computerized tomography (CT) of the head and body in adults and pediatric patients Peripheral venography in adults 1.3 Oral Procedures † ISOVUE is indicated for: CT of the abdomen and pelvis to delineate the gastrointestinal tract in adults and pediatric patients † Specific concentrations of ISOVUE are recommended for each type of imaging procedure [see Dosage and Administration ( 2.2 , 2.3 , 2.4 , 2.5 )].

2 DOSAGE AND ADMINISTRATION Individualize the volume and concentration according to the specific dosing tables accounting for factors such as age, body weight, size of the vessel, and the rate of blood flow within the vessel. ( 2.2 , 2.3 , 2.4 , 2.5 ) See full prescribing information for important dosage and administration information and dilution instructions. ( 2.1 , 2.6 ) 2.1 Important Dosing and Administration Information ISOVUE is for intra-arterial, intravenous, or oral use only. Do not administer intrathecally [see Warnings and Precautions ( 5.1 )] . Specific concentrations of ISOVUE are recommended for each type of imaging procedure [see Dosage and Administration ( 2.2 , 2.3 , 2.4 , 2.5 )]. Individualize the volume, concentration, and rate of administration of ISOVUE according to the specific dosing tables [see Dosage and Administration ( 2.2 , 2.3 , 2.4 , 2.5 )] . Consider factors such as: age, body weight, blood vessel size and blood flow rate, anticipated pathology and degree and extent of opacification required, structures or area to be examined, concomitant medical conditions, imaging equipment, and technique to be employed. Hydrate patients before and after ISOVUE administration [see Warnings and Precautions ( 5.3 )] . Use aseptic technique for all handling and administration of ISOVUE for intra-arterial and intravenous procedures. ISOVUE may be administered at either body temperature (37°C, 98.6°F) or room temperature (20°C to 25°C, 68°F to 77°F). Visually inspect ISOVUE for particulate matter or discoloration before administration. Do not administer ISOVUE if particulate matter or discolorations are observed. Do not mix ISOVUE with other drugs or inject in intravenous lines containing other drugs or total nutritional admixtures. ISOVUE single-dose containers are intended for one procedure only. Discard any unused portion. 2.2 Recommended Dosage for Intra-arterial Procedures in Adults The recommended doses for intra-arterial procedures in adults are shown in Table 1. Table 1: Recommended Concentrations and Volumes of ISOVUE for Intra-arterial Procedures in Adults Imaging Procedure Concentration (mg Iodine/mL) Volume to Administer per Single Injection for Selected Injection Sites Maximum Cumulative Total Dose Cerebral Arteriography 300 8 mL to 12 mL by carotid puncture or transfemoral catheterization 90 mL Peripheral Arteriography 300 5 mL to 40 mL into the femoral artery or subclavian artery 25 mL to 50 mL into the aorta for a distal runoff 250 mL Selective Visceral Arteriography and Aortography 370 Up to 10 mL for the renal arteries Up to 50 mL into the larger vessels such as the aorta or celiac artery 225 mL Coronary Arteriography and Cardiac Ventriculography 370 2 mL to 10 mL for selective coronary artery injection 25 mL to 50 mL for cardiac ventriculography or for nonselective opacification of multiple coronary arteries following injection at the aortic root 200 mL 2.3 Recommended Dosage for Intravenous Procedures in Adults The recommended doses for intravenous procedures in adults are shown in Table 2. Table 2: Recommended Concentrations and Volumes of ISOVUE for Intravenous Procedures in Adults Imaging Procedure Concentration (mg Iodine/mL) Volume to Administer Excretory Urography 250 50 mL to 100 mL by rapid injection 300 50 mL by rapid injection 370 40 mL by rapid injection CT of the Head 250 130 mL to 240 mL 300 100 mL to 200 mL CT of the Body 250 130 mL to 240 mL by rapid infusion or bolus injection 300 100 mL to 200 mL by rapid infusion or bolus injection 370 80 mL to 160 mL by rapid infusion or bolus injection Peripheral Venography 200 25 mL to 150 mL per lower extremity; the maximum total dose is 350 mL 300 15 mL to 100 mL per lower extremity; the maximum total dose is 230 mL 2.4 Recommended Dosage for Intra-arterial and Intravenous Procedures in Pediatric Patients The recommended doses for intra-arterial and intravenous procedures in pediatric patients are shown in Table 3. Table 3: Recommended Con …

3 DOSAGE FORMS AND STRENGTHS Injection: Clear, colorless to pale yellow solution available in the following concentrations of iodine: Concentration (mg Iodine/mL) Package Size Package Type 300 200 mL Imaging Bulk Package 500 mL Imaging Bulk Package 370 200 mL Imaging Bulk Package 500 mL Imaging Bulk Package Injection: 300 mg Iodine/mL and 370 mg Iodine/mL in imaging bulk packages for use only with an automated contrast injection system, contrast management system, or contrast media transfer set approved or cleared for use with these imaging bulk packages ( 2.5 , 3 )

4 CONTRAINDICATIONS None. None ( 4 )

6 ADVERSE REACTIONS The following adverse reactions are described in greater detail elsewhere in the labeling: Risks Associated with Intrathecal Administration [see Warnings and Precautions ( 5.1 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.2 )] Acute Kidney Injury [see Warnings and Precautions ( 5.3 )] Cardiovascular Adverse Reactions [see Warnings and Precautions ( 5.4 )] Thromboembolic Events [see Warnings and Precautions ( 5.5 )] Extravasation and Injection Site Reactions [see Warnings and Precautions ( 5.6 )] Thyroid Dysfunction in Pediatric Patients 0 to 3 Years of Age [see Warnings and Precautions ( 5.8 )] Severe Cutaneous Adverse Reactions [see Warnings and Precautions ( 5.11 )] Most common adverse reactions (incidence >1%) from intra-arterial or intravenous use are pain, hot flashes, burning sensation, nausea, and warmth. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bracco Diagnostics Inc. at 1-800-257-5181 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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. Adverse Reactions from Intra-arterial or Intravenous Use in Adults The safety of ISOVUE was evaluated in 2,246 adult patients receiving ISOVUE by intra-arterial or intravenous route in clinical studies. Table 6 shows the common adverse reactions (>1%). Table 6: Adverse Reactions Reported in >1% of Patients Receiving Intra-arterial or Intravenous Injection of ISOVUE in Clinical Studies Adverse Reaction ISOVUE (N=2,246) % Pain 2.8 Hot flashes 1.5 Burning sensation 1.4 Nausea 1.2 Warmth 1.1 The following adverse reactions occurred in ≤ 1% of patients receiving intra-arterial or intravenous injection of ISOVUE: Cardiovascular disorders: tachycardia, hypotension, hypertension, myocardial ischemia, circulatory collapse, S-T segment depression, bigeminy, extrasystoles, ventricular fibrillation, angina pectoris, bradycardia, transient ischemic attack, thrombophlebitis Gastrointestinal disorders: vomiting, anorexia General disorders: headache, fever, chills, excessive sweating, back spasm Nervous system disorders: vasovagal reaction, tingling in arms, grimace, faintness Renal and urinary disorders: urinary retention Respiratory: throat constriction, dyspnea, pulmonary edema Skin and subcutaneous tissues: rash, urticaria, pruritus, flushing Special senses: taste alterations, nasal congestion, visual disturbances Adverse Reactions from Intra-arterial Use in Pediatric Patients In a clinical trial with 76 pediatric patients undergoing angiocardiography, two adverse reactions (2.6%) were reported: worsening cyanosis and worsening peripheral perfusion. Adverse Reactions from Oral Use in Adult and Pediatric Patients There were no new adverse reactions from oral use of ISOVUE in adult and pediatric patients [see Clinical Studies ( 14 )]. 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of ISOVUE or other iopamidol-containing products by intra-arterial, intravenous, or oral administration. Because the reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or to establish a causal relationship to drug exposure. Blood and lymphatic system disorders: thrombocytopenia Cardiovascular disorders: cardiopulmonary arrest, cardiac decompensation, arrhythmias, myocardial infarction, shock, electrocardiographic changes (e.g., increased QTc, increased R-R, increased T-wave amplitude), decreased systolic pressure, deep vein thrombosis, arterial spasms, vasodilation, chest pain, pallor Endocrine disorders: hyperthyroidism, hypothyroidism Eye disorders: lacrimation increased, conjunctivitis, eye pruritus, transient blindness, visual disturbance, …

8 USE IN SPECIFIC POPULATIONS Lactation: A lactating woman may pump and discard breast milk for 10 hours after ISOVUE administration. ( 8.2) 8.1 Pregnancy Risk Summary Available data from published literature and postmarketing cases from decades of use with iopamidol during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Iopamidol crosses the placenta and reaches fetal tissues in small amounts ( see Data ). In animal reproduction studies, no adverse developmental outcomes were observed with intravenous administration of iopamidol to pregnant rats and rabbits during organogenesis at doses up to 2.7 and 1.4 times, respectively, the maximum recommended human dose ( see Data ). The 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 iopamidol crosses the placenta and is visualized in the digestive tract of exposed infants after birth. Animal Data Iopamidol did not affect fetal development and did not induce teratogenic changes in the offspring in either rats or rabbits at the following dose levels tested: 600 mg, 1,500 mg, or 4,000 mg iodine/kg in rats, administered intravenously once a day during days 6 through 15 of pregnancy; 300 mg, 800 mg, or 2,000 mg iodine/kg in rabbits, administered intravenously once a day during days 6 through 18 of pregnancy. 8.2 Lactation Risk Summary There are no data on the presence of iopamidol in human milk, the effects on the breastfed infant, or the effects on milk production. Iodinated contrast agents are present unchanged in human milk in very low amounts, with poor absorption from the gastrointestinal tract of a breastfed infant. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ISOVUE and any potential adverse effects on the breastfed infant from ISOVUE 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 half- lives) after ISOVUE administration in order to minimize drug exposure to a breastfed infant. 8.4 Pediatric Use The safety and effectiveness of ISOVUE have been established in pediatric patients for intra-arterial administration for angiocardiography and for intravenous administration for excretory urography and contrast computed tomography (head and body). The safety and effectiveness of ISOVUE have been established in pediatric patients for oral administration for CT of the abdomen and pelvis to delineate the gastrointestinal tract. Use of ISOVUE for this indication is supported by evidence from an adequate and well-controlled clinical study in adults (n=152) and pediatric patients 3 to 16 years of age (n=66) who underwent CT of the abdomen and pelvis with oral administration of ISOVUE and from additional safety data from post-approval use of enteral iopamidol in adult and pediatric patients [see Adverse Reactions ( 6.2 )] and Clinical Studies ( 14 )] . Pediatric patients at higher risk of experiencing adverse reactions during and after ISOVUE administration may include those having asthma, sensitivity to medication or allergens, cyanotic heart disease, congestive heart failure, or 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 …

1.3 Oral Procedures † ISOVUE is indicated for: CT of the abdomen and pelvis to delineate the gastrointestinal tract in adults and pediatric patients † Specific concentrations of ISOVUE are recommended for each type of imaging procedure [see Dosage and Administration ( 2.2 , 2.3 , 2.4 , 2.5 )].

11 DESCRIPTION ISOVUE (iopamidol) injection is a radiographic contrast agent for intra-arterial, intravenous, or oral use. Iopamidol is designated chemically as (S)-N,N’-bis[2-hydroxy-1-(hydroxymethyl)-ethyl]-2,4,6-triiodo-5- lactamidoisophthalamide with a molecular weight of 777.09, an empirical formula of C17H22I3N3O8, and the following structural formula: ISOVUE is a sterile, clear, colorless to pale yellow solution available in four concentrations of iodine: ISOVUE 200 mg iodine/mL: Each mL contains 408 mg iopamidol (providing 200 mg bound iodine) and the following inactive ingredients: 0.26 mg edetate calcium disodium (providing 0.029 mg sodium) and 1 mg tromethamine. ISOVUE 250 mg iodine/mL: Each mL contains 510 mg iopamidol (providing 250 mg bound iodine) and the following inactive ingredients: 0.33 mg edetate calcium disodium (providing 0.036 mg sodium) and 1 mg tromethamine. ISOVUE 300 mg iodine/mL: Each mL contains 612 mg iopamidol (providing 300 mg bound iodine) and the following inactive ingredients: 0.39 mg edetate calcium disodium (providing 0.043 mg sodium) and 1 mg tromethamine. ISOVUE 370 mg iodine/mL: Each mL contains 755 mg iopamidol (providing 370 mg bound iodine) and the following inactive ingredients: 0.48 mg edetate calcium disodium (providing 0.053 mg sodium) and 1 mg tromethamine. The pH of ISOVUE has been adjusted to 6.5 to 7.5 with hydrochloric acid and/or sodium hydroxide. Physicochemical characteristics are shown in Table 7. ISOVUE is hypertonic as compared to plasma and cerebrospinal fluid (approximately 285 and 301 mOsm/kg water, respectively). Table 7: Physicochemical Characteristics of ISOVUE Concentration (mg Iodine/mL) 200 250 300 370 Osmolality @ 37°C (mOsm/kg water) 413 524 616 796 Viscosity (cP) @ 37°C 2.0 3.0 4.7 9.4 Viscosity (cP) @ 20°C 3.3 5.1 8.8 20.9 Specific Gravity @ 37°C 1.227 1.281 1.339 1.405 iopamidol-structure

10 OVERDOSAGE The manifestations of overdosage are life-threatening and affect mainly the pulmonary and cardiovascular systems. Treatment of an overdose is directed toward support of all vital functions and the prompt institution of symptomatic therapy. Iopamidol can be removed by dialysis.

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied ISOVUE (iopamidol) injection is a clear, colorless to pale yellow solution available in the following presentations: Concentration (mg Iodine/mL) Package Size Package Type Sale Unit NDC 200 200 mL Single-Dose Bottle Carton of 10 0270-1314-15 250 100 mL Single-Dose Bottle Carton of 10 0270-1317-02 300 30 mL Single-Dose Vial Carton of 10 0270-1315-25 50 mL Single-Dose Vial Carton of 10 0270-1315-30 100 mL Single-Dose Bottle Carton of 10 0270-1315-35 150 mL Single-Dose Bottle Carton of 10 0270-1315-50 370 50 mL Single-Dose Vial Carton of 10 0270-1316-30 100 mL Single-Dose Bottle Carton of 10 0270-1316-35 125 mL Single-Dose Bottle Carton of 10 0270-1316-04 150 mL Single-Dose Bottle Carton of 10 0270-1316-37 Storage and Handling Store at 20°C to 25°C (68°F to 77°F) [See USP controlled room temperature]. Protect from light.