ISOVUE-M

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

1 INDICATIONS AND USAGE ISOVUE-M is indicated for: Lumbar and thoracic myelography, and computed tomography (CT) myelography in adults and pediatric patients aged 2 years and older Cervical and total columnar myelography and CT myelography in adults CT cisternography in adults Specific concentrations of ISOVUE-M are recommended for each type of imaging procedure [see Dosage and Administration ( 2.2 , 2.3 )]. ISOVUE-M is a radiographic contrast agent indicated for: Lumbar and thoracic myelography and computed tomography (CT) myelography in adults and pediatric patients aged 2 years and older Cervical and total columnar myelography in adults CT cisternography in adults ( 1 ) Specific concentrations of ISOVUE-M are recommended for each type of imaging procedure. ( 2.2 , 2.3 )

2 DOSAGE AND ADMINISTRATION Individualize the volume and concentration of ISOVUE-M according to the specific dosing tables based on patient age, body weight, and study to be performed. ( 2.2 , 2.3 ) See full prescribing information for important dosage and administration information. ( 2.1 ) 2.1 Important Dosage and Administration Information ISOVUE-M is for intrathecal use only. Specific concentrations of ISOVUE-M are recommended for each type of imaging procedure [see Dosage and Administration ( 2.2 , 2.3 )]. Individualize the volume, concentration, and injection rate of ISOVUE-M according to the dosing tables [see Dosage and Administration ( 2.2 , 2.3 )]. Consider factors such as age, body weight, anticipated pathology and degree and extent of opacification required, structure(s) or area to be examined, concomitant medical conditions, and imaging equipment and technique to be employed. Hydrate patients prior to and following ISOVUE-M administration [see Warnings and Precautions ( 5.2) ] . Use aseptic technique for all handling and administration of ISOVUE-M. ISOVUE-M 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-M for particulate matter and discoloration prior to administration whenever the solution and container permit. Do not administer ISOVUE-M if particulate matter or discoloration are observed. Do not mix ISOVUE-M with other drugs. ISOVUE-M is packaged in a single-dose vial and intended for one procedure only. Discard any unused portion. 2.2 Recommended Dosage for Intrathecal Procedures in Adults The recommended doses in adults are shown in Table 1 . Administer over 1 minute to 2 minutes. Allow at least 48 hours before repeat administration to avoid overdose; however, whenever possible, 5 days to 7 days is recommended. If CT myelography is performed, delay imaging by at least 4 hours to reduce the degree of contrast. Table 1: Recommended Concentrations and Volumes of ISOVUE-M for Intrathecal Procedures in Adults Imaging Procedure Concentration (mg Iodine/mL) Volume to Administer Injection Type Lumbar and thoracic myelography 200 10 mL to 15 mL Lumbar Cervical myelography 200 10 mL to 15 mL Lumbar 10 mL Lateral cervical 300 10 mL Lumbar Total columnar myelography 300 10 mL Lumbar CT cisternography 200 4 mL to 6 mL Lumbar 2.3 Recommended Dosage for Intrathecal Procedures in Pediatric Patients Aged 2 Years and Older The recommended doses based on age for pediatric patients aged 2 years and older are shown in Table 2. Administer over 1 minute to 2 minutes. Allow at least 48 hours before repeat administration to avoid overdose; however, whenever possible, 5 days to 7 days is recommended. If CT myelography is performed, delay imaging by at least 4 hours to reduce the degree of contrast. Table 2: Recommended Concentrations and Volumes of ISOVUE-M Based on Age for Intrathecal Procedures in Pediatric Patients Aged 2 Years and Older Imaging Procedure Age Concentration (mg Iodine/mL) Volume to Administer Injection Type Lumbar and thoracic myelography 2 years to 7 years 200 7 mL to 9 mL Lumbar 8 years to 12 years 8 mL to 11 mL Lumbar 13 years and older 10 mL to 12 mL Lumbar

3 DOSAGE FORMS AND STRENGTHS Injection: clear, colorless to pale yellow solution available in two concentrations of iodine: Concentration (mg of Iodine/mL) Package Size Package Type 200 10 mL Single-Dose Vial 300 15 mL Single-Dose Vial Injection: 200 mg Iodine/mL and 300 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: Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )] Acute Kidney Injury [see Warnings and Precautions ( 5.2 )] Increased Risk of Seizures [see Warnings and Precautions ( 5.3 )] Cardiovascular Adverse Reactions [see Warnings and Precautions ( 5.4 )] Thyroid Dysfunction in Pediatric Patients 0 to 3 Years of Age [see Warnings and Precautions ( 5.6 )] Severe Cutaneous Adverse Reactions [see Warnings and Precautions ( 5.9 )] Most common adverse reactions (incidence > 1%) are headache, nausea, vomiting, back pain, leg pain, neck pain, and hypotension. ( 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. The safety of ISOVUE-M was evaluated in 686 adult patients receiving ISOVUE-M intrathecally in clinical studies. Table 3 shows the common adverse reactions (>1%). These reactions usually occur 1 to 10 hours after injection, almost all occurring within 24 hours. Table 3: Adverse Reactions Reported in >1% of Patients Receiving Intrathecal Injection of ISOVUE-M in Clinical Studies Adverse Reaction ISOVUE-M (N=686) % Headache 16.4 Nausea 7.3 Vomiting 3.6 Back pain 2.2 Leg Pain 1.4 Neck Pain 1.1 Hypotension 1.1 The following additional adverse reactions occurred in ≤ 1% of patients receiving intrathecal injection of ISOVUE-M: Cardiovascular disorder: tachycardia, hypertension, chest pain Gastrointestinal: diarrhea, heartburn General disorders and administration site conditions: pyrexia, muscle weakness, hot flashes, malaise, fatigue, weakness, injection site pain Musculoskeletal: leg cramps, sciatica, cervicobrachial irritation, meningeal irritation, radicular irritation lumbosacral, other musculoskeletal pain, involuntary movement, burning sensation Nervous system: dizziness, paresthesia, confusion, hallucinations, lightheadedness, syncope, numbness, cold extremities, ataxia, irritability Urogenital: urinary retention Respiratory: dyspnea Skin and subcutaneous tissues : rash 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of ISOVUE-M and other iopamidol products. 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, transient ischemic attack, flushing, 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: chills, malaise Immune system disorders: anaphylaxis characterized by cardiovascular, respiratory, and cutaneous manifestations (e.g., chest tightness, laryngeal edema, periorbital edema, facial edema); delayed hypersensitivity reactions including generalized maculopapular rash, erythema, pruritus, localized blistering, skin peeling Infections and infestations: meningitis aseptic, meningitis bacterial as consequence of the procedural hazard Musculoskeletal disorders: muscle spasm, musculoskeletal pain …

8 USE IN SPECIFIC POPULATIONS Lactation: A lactating woman may pump and discard breast milk for 10 hours after ISOVUE-M 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- M and any potential adverse effects on the breastfed infant from ISOVUE-M 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-M administration in order to minimize drug exposure to a breastfed infant. 8.4 Pediatric Use The safety and effectiveness of ISOVUE-M 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 ISOVUE-M for lumbar and thoracic myelography and CT myelography have not been established in pediatric patients younger than 2 years of age. The safety and effectiveness of ISOVUE-M for …

11 DESCRIPTION ISOVUE-M (iopamidol) injection is a radiographic contrast agent for intrathecal 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: ISOVUE-M is a sterile, clear, colorless to pale yellow solution available in two concentrations of iodine: ISOVUE-M 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 sodium) and 1 mg tromethamine. ISOVUE-M 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 sodium) and 1 mg tromethamine. The pH of ISOVUE-M has been adjusted to 6.5 to 7.5 with hydrochloric acid and/or sodium hydroxide. Physicochemical characteristics are shown in Table 4 . ISOVUE-M is hypertonic as compared to plasma and cerebrospinal fluid (approximately 285 and 301 mOsm/kg water, respectively). Table 4: Physicochemical Characteristics of ISOVUE-M Concentration (mg Iodine/mL) 200 300 Osmolality @ 37°C (mOsm/kg water) 413 616 Viscosity (cP) @ 37°C 2.0 4.7 Viscosity (cP) @ 20°C 3.3 8.8 Specific Gravity @ 37°C 1.227 1.339 isovue-m-struct

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 ISOVUE-M (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 10 mL Single-Dose Vial Carton of 10 0270-1411-11 300 15 mL Single-Dose Vial Carton of 10 0270-1412-15 Storage and Handling Store at 20°C to 25°C (68°F to 77°F) [See USP controlled room temperature]. Protect from light.