iopamidol

Recent Major Changes Indications and Usage, CT cerebral ventriculography ( 1 )-Removed 1/2026

1 INDICATIONS AND USAGE Iopamidol Injection, USP 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 * Specific concentrations are recommended for each type of imaging procedure. ( 2.2 , 2.3 , 2.4 ) 1.1 Intra-arterial Procedures* 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* Excretory urography in adults and pediatric patients Computed tomography (CT) of head and body in adults and pediatric patients Peripheral venography in adults * Specific concentrations of Iopamidol Injection, USP are recommended for each type of imaging procedure [see Dosage and Administration ( 2.2 , 2.3 , 2.4 )].

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 ) See full prescribing information for important dosage and administration information. ( 2.1 ) 2.1 Important Dosing and Administration Information Iopamidol Injection, USP is for intra-arterial or intravenous use only and must not be administered intrathecally [see Warnings and Precautions ( 5.1 )] . Specific concentrations of Iopamidol Injection, USP are recommended for each type of imaging procedure [see Dosage and Administration ( 2.2 , 2.3 , 2.4 )] . Individualize the volume, concentration, and injection rate of iopamidol injection according to the specific dosing tables [see Dosage and Administration ( 2.2 , 2.3 , 2.4 )] . 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 Iopamidol Injection, USP administration [see Warnings and Precautions ( 5.3 )] . Use aseptic technique for all handling and administration of Iopamidol Injection, USP. Iopamidol Injection, USP 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 Iopamidol Injection, USP for particulate matter or discoloration before administration. Do not administer Iopamidol Injection, USP if particulate matter or discolorations are observed. Do not mix Iopamidol Injection, USP with other drugs or inject in intravenous lines containing other drugs or total nutritional admixtures. Iopamidol Injection, USP 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 Iopamidol Injection, USP 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 intra-arterial procedures in adults are shown in Table 2. Table 2: Recommended Concentrations and Volumes of Iopamidol Injection, USP for Intravenous Procedures in Adults Imaging Procedure Concentration (mg Iodine/mL) Volume to Administer Excretory Urography 250 300 370 50 mL to 100 mL by rapid injection 50 mL by rapid injection 40 mL by rapid injection CT of the Head 250 300 130 mL to 240 mL 100 mL to 200 mL CT of Body 250 300 370 130 mL to 240 mL by rapid infusion or bolus injection 100 mL to 200 mL by rapid infusion or bolus injection 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 2.4 Recommended Dosage in Pediatric Patients The recommended doses in pediatric patients are shown in Table 3. Table 3: Recommended Concentrations and Volumes per Body Weight of I …

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 200 50 mL Single-Dose Vial 250 50 mL Single-Dose Vial 300 30 mL, 50 mL, 100 mL Single-Dose Vial 370 50 mL, 75 mL, and 100 mL Single-Dose Vial Injection: 200 mg Iodine/mL, 250 mg Iodine/mL, 300 mg Iodine/mL, and 370 mg Iodine/mL in single-dose vials ( 3 )

4 CONTRAINDICATIONS None. None ( 4 )

6 ADVERSE REACTIONS The following adverse reactions are described in greater detail in other sections: 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%) are pain, hot flashes, burning sensation, nausea, and warmth. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Slate Run Pharmaceuticals, Inc. at 1-888-341-9214 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 in Adults The safety of iopamidol injection was evaluated in 2,246 adult patients receiving iopamidol injection by intra-arterial or intravenous route in clinical studies. Table 4 shows the common adverse reactions (>1%). Table 4: Adverse Reactions Reported in >1% of Patients Receiving Intra-arterial or Intravenous Injection of Iopamidol in Clinical Studies Adverse Reaction Iopamidol Injection (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 iopamidol injection: 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 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. 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of iopamidol injection. 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, photophobia Gastrointestinal disorders : retching, abdominal pain, salivary hypersecretion, salivary gland enlargement General disorders and administration site conditions : injection site pain, malaise Immune system disorders : anaphylaxis characterized by cardiovascular, respiratory, and cutaneous ma …

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, iopamidol injection 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 agents. Re-evaluate eGFR 48 hours after the imaging procedure and reinstitute metformin use only after renal function is stable. Radioactive Iodine Administration of iopamidol injection 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 iopamidol injection 7.2 Drug-Laboratory Test Interactions Protein-Bound Iodine Test Iodinated contrast agents, including iopamidol injection, will temporarily increase protein-bound iodine in blood. Avoid protein-bound iodine test for at least 16 days following administration of iopamidol injection . However, thyroid function tests that do not depend on iodine estimations, e.g., triiodothyronine (T 3 ) resin uptake and total or free thyroxine (T 4 ) assays, are not affected.

8 USE IN SPECIFIC POPULATIONS Lactation: A lactating woman may pump and discard breast milk for 10 hours after iopamidol injection 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 iopamidol injection and any potential adverse effects on the breastfed infant from iopamidol injection 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 iopamidol injection administration in order to minimize drug exposure to a breastfed infant. 8.4 Pediatric Use The safety and effectiveness of iopamidol injection for lumbar and thoracic myelography and CT myelography have been established in pediatric patients aged 2 years and older. Pediatric patients at higher risk of experiencing adverse reactions during and after any iodinated contrast agent 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. Thyroid function tests indicative of thyroid dysfunction, characterized by hypothyroidism or transient thyroid suppression have been reported following iodinated contrast agent administration in pediatric patients, including term and preterm neonates; Some patients were treated for hypothyroidism. After exposure to iodinated contrast agent, 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 ( 5.6 ) and Adverse Reactions ( 6.2 )] . The safety and effectiveness of iopamidol injection for lumbar and thoracic myelography and CT myelography have not been established in pediatric patients younger …

12.1 Mechanism of Action Intravascular injection of iopamidol opacifies those vessels where the contrast agent is present, permitting radiographic visualization through attenuation of photons. In imaging of the body, iodinated contrast agents diffuse from the vessels into the extravascular space. In normal brain with an intact blood-brain barrier, contrast does not diffuse into the extravascular space. In patients with a disrupted blood-brain barrier, contrast agent accumulates in the extravascular space in the region of disruption.

11 DESCRIPTION Iopamidol Injection, USP is a radiographic contrast agent for intra-arterial or intravenous 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 C 17 H 22 I 3 N 3 O 8 , and the following structural formula: Iopamidol Injection, USP is a sterile, clear, colorless to pale yellow solution available in four concentrations of iodine: Iopamidol Injection, USP, 200 mg iodine/mL: Each mL contains 408 mg iopamidol (providing 200 mg organically bound iodine) and the following inactive ingredients: 0.26 mg edetate calcium disodium (providing 0.029 mg (0.001 mEq) sodium) and 1 mg tromethamine. Iopamidol Injection, USP, 250 mg iodine/mL: Each mL contains 510 mg iopamidol (providing 250 mg organically bound iodine) and the following inactive ingredients: 0.33 mg edetate calcium disodium (providing 0.036 mg (0.002 mEq) sodium) and 1 mg tromethamine. Iopamidol Injection, USP, 300 mg iodine/mL: Each mL contains 612 mg iopamidol (providing 300 mg organically bound iodine) and the following inactive ingredients: 0.39 mg edetate calcium disodium (providing 0.043 mg (0.002 mEq) sodium) and 1 mg tromethamine. Iopamidol Injection, USP, 370 mg iodine/mL: Each mL contains 755 mg iopamidol (providing 370 mg organically bound iodine) and the following inactive ingredients: 0.48 mg edetate calcium disodium (providing 0.053 mg (0.002 mEq) sodium) and 1 mg tromethamine. The pH of Iopamidol Injection, USP has been adjusted to 6.5 to 7.5 with hydrochloric acid and/or sodium hydroxide. Physicochemical characteristics are shown in Table 5. Iopamidol Injection, USP is hypertonic as compared to plasma and cerebrospinal fluid (approximately 285 and 301 mOsm/kg water, respectively). Table 5: Physicochemical Characteristics of Iopamidol Injection, USP 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 image-01.jpg

10 OVERDOSAGE Doses above 3,000 mg iodine in adults and 2,400 mg iodine in pediatric patients aged 2 years and older may result in an increased frequency and severity of adverse reactions including seizures. Treatment of an overdose is directed toward the support of all vital functions and prompt institution of symptomatic therapy. Iopamidol can be removed by dialysis.

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Iopamidol Injection, USP 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 50 mL Single-dose vial Carton of 1 70436-211-80 250 50 mL Single-dose vial Carton of 10 70436-125-82 300 30 mL Single-dose vial Carton of 10 70436-219-52 300 50 mL Single-dose vial Carton of 10 70436-219-62 300 100 mL Single-dose vial Carton of 10 70436-219-82 370 50 mL Single-dose vial Carton of 10 70436-127-52 370 75 mL Single-dose vial Carton of 10 70436-127-62 370 100 mL Single-dose vial Carton of 10 70436-127-82 Storage and Handling Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Protect from light.