ISOVUE is indicated for:

ISOVUE is indicated for:

†Specific concentrations of ISOVUE are recommended for each type of imaging procedure [see Dosage and Administration (2.2, 2.3, 2.4)].

The recommended doses for intra-arterial procedures in adults are shown in Table 1.

<div class="scrollingtable"><table border="1"> <caption> <span>Table 1: Recommended Concentrations and Volumes of ISOVUE for Intra-arterial Procedures in Adults</span> </caption> <colgroup> <col width="20*"/> <col width="16*"/> <col width="31*"/> <col width="20*"/> </colgroup> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">Imaging Procedure</span></td><td class="Botrule Lrule Rrule Toprule"><span class="Bold">Concentration (mg Iodine/mL)</span></td><td class="Botrule Lrule Rrule Toprule"><span class="Bold">Volume to Administer per Single Injection for Selected Injection Sites</span></td><td class="Botrule Lrule Rrule Toprule"><span class="Bold">Maximum Cumulative Total Dose</span></td> </tr> <tr class="Botrule Lrule Rrule Toprule"> <td valign="top">Cerebral Arteriography</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">300</td><td class="Botrule Lrule Rrule Toprule">8 mL to 12 mL by carotid puncture or transfemoral catheterization</td><td class="Botrule Lrule Rrule Toprule" valign="top">90 mL</td> </tr> <tr> <td valign="top">Peripheral Arteriography</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">300</td><td class="Botrule Lrule Rrule Toprule"> <ul class="Disc"> <li>5 mL to 40 mL into the femoral artery or subclavian artery</li> <li>25 mL to 50 mL into the aorta for a distal runoff</li> </ul> </td><td class="Botrule Lrule Rrule Toprule" valign="top">250 mL</td> </tr> <tr class="Botrule Lrule Rrule Toprule"> <td class="Botrule Lrule Rrule Toprule" valign="top">Selective Visceral Arteriography and Aortography</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">370</td><td class="Botrule Lrule Rrule Toprule"> <ul class="Disc"> <li>Up to 10 mL for the renal arteries</li> <li>Up to 50 mL into the larger vessels such as the aorta or celiac artery</li> </ul> </td><td class="Botrule Lrule Rrule Toprule" valign="top">225 mL</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="top">Coronary Arteriography and Cardiac Ventriculography</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">370</td><td class="Botrule Lrule Rrule Toprule"> <ul class="Disc"> <li>2 mL to 10 mL for selective coronary artery injection</li> <li>25 mL to 50 mL for cardiac ventriculography or for nonselective opacification of multiple coronary arteries following injection at the aortic root</li> </ul> </td><td class="Botrule Lrule Rrule Toprule" valign="top">200 mL</td> </tr> </tbody> </table></div>

The recommended doses for intra-arterial procedures in adults are shown in Table 2.

<div class="scrollingtable"><table border="1"> <caption> <span>Table 2: Recommended Concentrations and Volumes of ISOVUE for Intravenous Procedures in Adults</span> </caption> <colgroup> <col width="20*"/> <col width="22*"/> <col width="53*"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First Lrule Rrule Toprule"> <td><span class="Bold">Imaging Procedure</span></td><td class="Botrule Lrule Rrule Toprule"><span class="Bold">Concentration (mg Iodine/mL) </span></td><td><span class="Bold">Volume to Administer</span></td> </tr> <tr class="Botrule Lrule Rrule Toprule"> <td rowspan="3">Excretory Urography</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">250</td><td>50 mL to 100 mL by rapid injection</td> </tr> <tr class="Botrule Lrule Rrule Toprule"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top">300</td><td>50 mL by rapid injection</td> </tr> <tr class="Botrule Lrule Rrule Toprule"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top">370</td><td>40 mL by rapid injection</td> </tr> <tr class="Botrule Lrule Rrule Toprule"> <td rowspan="2">CT of the Head</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">250</td><td>130 mL to 240 mL</td> </tr> <tr class="Botrule Lrule Rrule Toprule"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top">300</td><td>100 mL to 200 mL</td> </tr> <tr class="Botrule Lrule Rrule Toprule"> <td rowspan="3">CT of the Body</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">250</td><td>130 mL to 240 mL by rapid infusion or bolus injection</td> </tr> <tr class="Botrule Lrule Rrule Toprule"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top">300</td><td>100 mL to 200 mL by rapid infusion or bolus injection</td> </tr> <tr class="Botrule Lrule Rrule Toprule"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top">370</td><td>80 mL to 160 mL by rapid infusion or bolus injection</td> </tr> <tr class="Botrule Last Lrule Rrule Toprule"> <td>Peripheral Venography</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">200</td><td>25 mL to 150 mL per lower extremity; the maximum total dose is 350 mL</td> </tr> </tbody> </table></div>

The recommended doses in pediatric patients are shown in Table 3.

<div class="scrollingtable"><table border="1"> <caption> <span>Table 3: Recommended Concentrations and Volumes per Body Weight of ISOVUE for Intra- arterial and Intravenous Procedures in Pediatric Patients</span> </caption> <colgroup> <col width="19*"/> <col width="21*"/> <col width="20*"/> <col width="32*"/> </colgroup> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Imaging Procedure</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Concentration (mg Iodine/mL) </span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Volume per Body Weight to Administer</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Maximum Dose</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="4"><span class="Italics"><span class="Bold">Intra-arterial Procedures</span></span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top">Angiocardiography</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">370</td><td class="Botrule Lrule Rrule Toprule" valign="top">0.5 mL/kg to 2 mL/kg per single injection</td><td class="Botrule Lrule Rrule Toprule"><span class="Underline">Maximum Cumulative Dose by Weight</span> <ul class="Disc"> <li>Neonates: 5 mL/kg</li> <li>Aged 4 weeks and older: 8 mL/kg</li> <li>Do not exceed maximum cumulative doses by age below.</li> </ul> <p class="First"> <a name="p259410301734380457"></a><span class="Underline">Maximum Cumulative Dose by Age</span> </p> <ul class="Disc"> <li>&lt;2 years 40 mL</li> <li>2 years to 4 years 50 mL</li> <li>5 years to 9 years 100 mL</li> <li>10 years to 18 years 125 mL</li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="4"><span class="Bold"><span class="Italics">Intravenous Procedures</span></span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="2">Excretory Urography</td><td align="center" class="Botrule Lrule Rrule Toprule">250</td><td class="Botrule Lrule Rrule Toprule">1.2 mL/kg to 3.6 mL/kg</td><td class="Botrule Lrule Rrule Toprule">120 mL</td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule">300</td><td class="Botrule Lrule Rrule Toprule">1 mL/kg to 3 mL/kg</td><td class="Botrule Lrule Rrule Toprule">100 mL</td> </tr> <tr> <td class="Botrule Last Lrule Rrule Toprule" rowspan="2">CT of the Head and Body</td><td align="center" class="Botrule Lrule Rrule Toprule">250</td><td class="Botrule Lrule Rrule Toprule">1.2 mL/kg to 3.6 mL/kg</td><td class="Botrule Lrule Rrule Toprule">120 mL</td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule Toprule">300</td><td class="Botrule Lrule Rrule Toprule">1 mL/kg to 3 mL/kg</td><td class="Botrule Lrule Rrule Toprule">100 mL</td> </tr> </tbody> </table></div>

Injection: Clear, colorless to pale yellow solution available in the following concentrations of iodine:

{ "type": "p", "children": [], "text": "\nInjection: Clear, colorless\nto pale yellow solution available in the following concentrations\nof iodine:" }

<div class="scrollingtable"><table border="1"> <colgroup> <col/> <col/> <col/> </colgroup> <tbody class="Headless"> <tr class="Botrule First Lrule Rrule Toprule"> <td><span class="Bold">Concentration (mg Iodine/mL)</span></td><td class="Botrule Lrule Rrule Toprule"><span class="Bold">Package Size </span></td><td><span class="Bold">Package Type</span></td> </tr> <tr class="Botrule Lrule Rrule Toprule"> <td align="center">200</td><td class="Botrule Lrule Rrule Toprule">200 mL</td><td>Single-Dose Bottle</td> </tr> <tr class="Botrule Lrule Rrule Toprule"> <td align="center">250</td><td class="Botrule Lrule Rrule Toprule">100 mL</td><td>Single-Dose Bottle</td> </tr> <tr class="Botrule Lrule Rrule Toprule"> <td align="center" rowspan="2">300</td><td class="Botrule Lrule Rrule Toprule">30 mL and 50 mL</td><td>Single-Dose Vial</td> </tr> <tr class="Botrule Lrule Rrule Toprule"> <td class="Botrule Lrule Rrule Toprule">100 mL and 150 mL</td><td>Single-Dose Bottle</td> </tr> <tr class="Botrule Lrule Rrule Toprule"> <td align="center" class="Botrule Last Lrule Rrule Toprule" rowspan="2">370</td><td class="Botrule Lrule Rrule Toprule">50 mL</td><td>Single-Dose Vial</td> </tr> <tr class="Botrule Last Lrule Rrule Toprule"> <td class="Botrule Lrule Rrule Toprule">75 mL, 100 mL, 125 mL, and 150 mL </td><td>Single-Dose Bottle</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"1\">\n<colgroup>\n<col/>\n<col/>\n<col/>\n</colgroup>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First Lrule Rrule Toprule\">\n<td><span class=\"Bold\">Concentration (mg Iodine/mL)</span></td><td class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">Package Size </span></td><td><span class=\"Bold\">Package Type</span></td>\n</tr>\n<tr class=\"Botrule Lrule Rrule Toprule\">\n<td align=\"center\">200</td><td class=\"Botrule Lrule Rrule Toprule\">200 mL</td><td>Single-Dose Bottle</td>\n</tr>\n<tr class=\"Botrule Lrule Rrule Toprule\">\n<td align=\"center\">250</td><td class=\"Botrule Lrule Rrule Toprule\">100 mL</td><td>Single-Dose Bottle</td>\n</tr>\n<tr class=\"Botrule Lrule Rrule Toprule\">\n<td align=\"center\" rowspan=\"2\">300</td><td class=\"Botrule Lrule Rrule Toprule\">30 mL and 50 mL</td><td>Single-Dose Vial</td>\n</tr>\n<tr class=\"Botrule Lrule Rrule Toprule\">\n<td class=\"Botrule Lrule Rrule Toprule\">100 mL and 150 mL</td><td>Single-Dose Bottle</td>\n</tr>\n<tr class=\"Botrule Lrule Rrule Toprule\">\n<td align=\"center\" class=\"Botrule Last Lrule Rrule Toprule\" rowspan=\"2\">370</td><td class=\"Botrule Lrule Rrule Toprule\">50 mL</td><td>Single-Dose Vial</td>\n</tr>\n<tr class=\"Botrule Last Lrule Rrule Toprule\">\n<td class=\"Botrule Lrule Rrule Toprule\">75 mL, 100 mL, 125 mL, and 150\nmL </td><td>Single-Dose Bottle</td>\n</tr>\n</tbody>\n</table></div>" }

None.

{ "type": "p", "children": [], "text": "\nNone." }

Intrathecal administration, even if inadvertent, can cause death, convulsions, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, seizures, rhabdomyolysis, hyperthermia, and brain edema. ISOVUE is for intra-arterial or intravenous use only and must not be administered intrathecally [see Dosage and Administration (2.1)].

ISOVUE can cause life-threatening or fatal hypersensitivity reactions including anaphylaxis. Manifestations include respiratory arrest, laryngospasm, bronchospasm, angioedema, and shock [see Adverse Reactions (6.2)]. Most severe reactions develop shortly after the start of injection (e.g., within 1 to 3 minutes), but delayed reactions can also occur. There is increased risk of hypersensitivity reactions in patients with a history of previous reactions to contrast agents, and allergic disorders (i.e., bronchial asthma, allergic rhinitis, and food allergies) or other hypersensitivities.

Premedication with antihistamines or corticosteroids to avoid or minimize possible allergic reactions does not prevent serious life-threatening reactions but may reduce both their incidence and severity. Obtain a history of allergy, hypersensitivity, or hypersensitivity reactions to iodinated contrast agents and always have emergency resuscitation equipment and trained personnel available prior to ISOVUE administration. Monitor all patients for hypersensitivity reactions.

Acute kidney injury, including renal failure, may occur after ISOVUE administration. Risk factors include: pre-existing renal insufficiency, dehydration, diabetes mellitus, congestive heart failure, advanced vascular disease, elderly age, concomitant use of nephrotoxic or diuretic medications, multiple myeloma or other paraproteinemias, and repetitive or large doses of ISOVUE.

Use the lowest necessary dose of ISOVUE in patients with renal impairment. Adequately hydrate patients prior to and following ISOVUE administration. Do not use laxatives, diuretics, or preparatory dehydration prior to ISOVUE administration.

ISOVUE increases the circulatory osmotic load and may induce acute or delayed hemodynamic disturbances in patients with congestive heart failure, severely impaired renal function, combined renal and hepatic disease, and combined renal and cardiac disease, particularly when repetitive or large doses are administered. Fatal cardiovascular reactions have occurred mostly within 10 minutes of ISOVUE injection; the main feature was cardiac arrest with cardiovascular disease as the main underlying factor. Hypotensive collapse and shock have occurred. Cardiac decompensation, serious arrhythmias, and myocardial ischemia or infarction can occur during coronary arteriography and ventriculography.

The administration of ISOVUE may cause pulmonary edema in patients with heart failure. Based upon published reports, deaths associated with the administration of iodinated contrast agents range from 6.6 per 1 million (0.00066 percent) to 1 in 10,000 patients (0.01 percent). Use the lowest necessary dose of ISOVUE in patients with congestive heart failure and always have emergency resuscitation equipment and trained personnel available. Monitor all patients for severe cardiovascular reactions.

Serious, in some cases fatal, thromboembolic events, including myocardial infarction and stroke, can occur during angiographic procedures. During these procedures, increased thrombosis and activation of the complement system occurs. Risk factors for developing thromboembolic events include: length of procedure, catheter and syringe material, underlying disease state, and concomitant medications.

To minimize thromboembolic events, use meticulous angiographic techniques and minimize the length of the procedure. Avoid blood remaining in contact with syringes containing iodinated contrast agents, which increases risk of clotting. Avoid angiocardiography in patients with homocystinuria because of the risk of inducing thrombosis and embolism.

Extravasation can occur with ISOVUE administration, particularly in patients with severe arterial or venous disease. Inflammation, blistering, skin necrosis, and compartment syndrome have been reported following extravasation. In addition, injection site reactions such as pain and swelling at the injection site can also occur [see Adverse Reactions (6.2)]. Ensure intravascular placement of catheters prior to injection. Monitor patients for extravasation and advise patients to seek medical care for progression of symptoms.

Thyroid storm has occurred after the intravascular use of iodinated agents in patients with hyperthyroidism or with an autonomously functioning thyroid nodule. Evaluate the risk in such patients before use of ISOVUE.

Thyroid dysfunction characterized by hypothyroidism or transient thyroid suppression has been reported after both single exposure and multiple exposures to iodinated contrast agents in pediatric patients 0 years to 3 years of age.

Younger age, very low birth weight, prematurity, underlying medical conditions affecting thyroid function, admission to neonatal or pediatric intensive care units, and congenital cardiac conditions are associated with an increased risk of hypothyroidism after iodinated contrast agent exposure. Pediatric patients with congenital cardiac conditions may be at greatest risk given that they often require high doses of contrast during invasive cardiac procedures.

An underactive thyroid during early life may be harmful for cognitive and neurological development and may require thyroid hormone replacement therapy. After exposure to iodinated contrast agents, individualize thyroid function monitoring based on underlying risk factors, especially in term and preterm neonates.

Hypertensive crisis in patients with pheochromocytoma has occurred with iodinated contrast agents. Closely monitor patients when administering ISOVUE if pheochromocytoma or catecholamine-secreting paragangliomas are suspected. Inject the minimum amount of ISOVUE necessary and have measures for treatment of hypertensive crisis readily available.

Iodinated contrast agents can promote sickling in individuals who are homozygous for sickle cell disease. Hydrate patients prior to and following ISOVUE administration and use only if the necessary imaging information cannot be obtained with alternative imaging modalities.

Severe cutaneous adverse reactions (SCAR) may develop from 1 hour to several weeks after intravascular contrast agent administration. These reactions include Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS). Reaction severity may increase and time to onset may decrease with repeat administration of a contrast agent; prophylactic medications may not prevent or mitigate severe cutaneous adverse reactions. Avoid administering ISOVUE to patients with a history of a severe cutaneous adverse reaction to ISOVUE.

ISOVUE can interfere with protein-bound iodine test [see Drug Interactions (7.2)].

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 ISOVUE was evaluated in 2,246 adult patients receiving ISOVUE by intra-arterial or intravenous route in clinical studies. Table 4 shows the common adverse reactions (>1%).

<div class="scrollingtable"><table border="1" width="621"> <caption> <span>Table 4: Adverse Reactions Reported in &gt;1% of Patients Receiving Intra-arterial or Intravenous Injection of ISOVUE in Clinical Studies</span> </caption> <colgroup> <col width="48*"/> <col width="50*"/> </colgroup> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Adverse Reaction</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">ISOVUE <br/>(N=2,246) <br/>%</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Pain</td><td align="center" class="Botrule Lrule Rrule Toprule">2.8</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Hot flashes </td><td align="center" class="Botrule Lrule Rrule Toprule">1.5</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Burning sensation</td><td align="center" class="Botrule Lrule Rrule Toprule">1.4</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Nausea</td><td align="center" class="Botrule Lrule Rrule Toprule">1.2</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule">Warmth</td><td align="center" class="Botrule Lrule Rrule Toprule">1.1</td> </tr> </tbody> </table></div>

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 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.

The following adverse reactions have been identified during post approval use of ISOVUE. 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 manifestations (e.g., chest tightness, laryngeal edema, periorbital edema, facial edema); delayed hypersensitivity reactions including generalized maculopapular rash, erythema, pruritus, localized blistering, skin peeling

Musculoskeletal disorders: compartment syndrome following extravasation, muscle spasm, musculoskeletal pain, muscular weakness

Nervous system disorders: coma, seizure, tremors, syncope, depressed level of consciousness or loss of consciousness, encephalopathy

Psychiatric disorders: confusional state

Respiratory system disorders: respiratory arrest, respiratory failure, acute respiratory distress syndrome, respiratory distress, apnea, asthma, sneezing, choking, laryngeal edema, bronchospasm, rhinitis

Skin and subcutaneous tissue disorders: Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis (AGEP), erythema multiforme and drug reaction with eosinophilia and systemic symptoms (DRESS), skin necrosis, face edema

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, ISOVUE administration in patients with an eGFR between 30 and 60 mL/min/1.73 m2; 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 ISOVUE 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 ISOVUE.

Protein-Bound Iodine Test

Iodinated contrast agents, including ISOVUE, will temporarily increase protein-bound iodine in blood. Avoid protein-bound iodine test for at least 16 days following administration of ISOVUE. However, thyroid function tests that do not depend on iodine estimations, e.g., triiodothyronine (T3) resin uptake and total or free thyroxine (T4) assays are not affected.

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.

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.

The safety and effectiveness of ISOVUE have been established in pediatric patients for angiocardiography, excretory urography, and contrast computed tomography (head and body).

Pediatric patients at higher risk of experiencing adverse reactions during and after contrast medium 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 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 years to 3 years of age based on underlying risk factors, especially in term and preterm neonates [see Warning and Precautions (5.8) and Adverse Reactions (6.2)].

The safety and effectiveness of ISOVUE for cerebral, peripheral, and selective visceral arteriography, aortography, coronary arteriography, cardiac ventriculography, and peripheral venography have not been established in pediatric patients.

Iopamidol is excreted by the kidney, and the risk of adverse reactions to ISOVUE may be greater in patients with renal impairment. Because patients 65 years of age and older are more likely to have renal impairment, care should be taken in dose selection, and it may be useful to monitor renal function [see Warnings and Precautions (5.3) and Use in Specific Populations [8.6]).

The clearance of iopamidol 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 (5.3)]. Iopamidol can be removed by dialysis.

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.

{ "type": "p", "children": [], "text": "\nThe manifestations of overdosage are life-threatening and affect\nmainly the pulmonary and cardiovascular systems. Treatment of an overdose\nis directed toward support of all vital functions and the prompt institution\nof symptomatic therapy. Iopamidol can be removed by dialysis." }

ISOVUE (iopamidol) injection is a radiographic contrast agent for intra-arterial or intravenous use.

{ "type": "p", "children": [], "text": "\nISOVUE (iopamidol) injection\nis a radiographic contrast agent for intra-arterial or intravenous\nuse." }

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:

{ "type": "p", "children": [], "text": "\nIopamidol is\ndesignated chemically as (S)-N,N’-bis[2-hydroxy-1-(hydroxymethyl)-ethyl]-2,4,6-triiodo-5-\nlactamidoisophthalamide with a molecular weight of 777.09, an empirical\nformula of C17H22I3N3O8, and the following structural formula:" }

ISOVUE is a sterile, clear, colorless to pale yellow solution available in four concentrations of iodine:

{ "type": "p", "children": [], "text": "\nISOVUE is a sterile, clear, colorless to\npale yellow solution available in four concentrations of iodine:" }

{ "type": "ul", "children": [ "ISOVUE 200 mg iodine/mL: Each mL contains 408 mg iopamidol\n(providing 200 mg organically bound iodine) and the following inactive\ningredients: 0.26 mg edetate calcium disodium (providing 0.029 mg\n(0.001 mEq) sodium) and 1 mg tromethamine.", "ISOVUE 250 mg iodine/mL: Each mL contains 510 mg iopamidol\n(providing 250 mg organically bound iodine) and the following inactive\ningredients: 0.33 mg edetate calcium disodium (providing 0.036 mg\n(0.002 mEq) sodium) and 1 mg tromethamine.", "ISOVUE 300 mg iodine/mL: Each mL contains 612 mg iopamidol\n(providing 300 mg organically bound iodine) and the following inactive\ningredients: 0.39 mg edetate calcium disodium (providing 0.043 mg\n(0.002 mEq) sodium) and 1 mg tromethamine.", "ISOVUE 370 mg iodine/mL: Each mL contains 755 mg iopamidol\n(providing 370 mg organically bound iodine) and the following inactive\ningredients: 0.48 mg edetate calcium disodium (providing 0.053 mg\n(0.002 mEq) sodium) and 1 mg tromethamine." ], "text": "" }

The pH of ISOVUE has been adjusted to 6.5 to 7.5 with hydrochloric acid and/or sodium hydroxide.

{ "type": "p", "children": [], "text": "\nThe pH of ISOVUE has\nbeen adjusted to 6.5 to 7.5 with hydrochloric acid and/or sodium hydroxide." }

Physicochemical characteristics are shown in Table 5. ISOVUE is hypertonic as compared to plasma and cerebrospinal fluid (approximately 285 and 301 mOsm/kg water, respectively).

{ "type": "p", "children": [], "text": "\nPhysicochemical characteristics\nare shown in Table 5. ISOVUE is hypertonic as compared to plasma and\ncerebrospinal fluid (approximately 285 and 301 mOsm/kg water, respectively)." }

<div class="scrollingtable"><table border="1"> <caption> <span>Table 5: Physicochemical Characteristics of ISOVUE</span> </caption> <colgroup> <col width="36*"/> <col align="center" width="13*"/> <col align="center" width="13*"/> <col align="center" width="13*"/> <col align="center" width="13*"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First Lrule Rrule Toprule"> <td><span class="Bold">Concentration (mg Iodine/mL) </span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">200</span></td><td align="center"><span class="Bold">250</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">300</span></td><td align="center"><span class="Bold">370</span></td> </tr> <tr class="Botrule Lrule Rrule Toprule"> <td>Osmolality @ 37°C (mOsm/kg water) </td><td align="center" class="Botrule Lrule Rrule Toprule">413</td><td align="center">524</td><td align="center" class="Botrule Lrule Rrule Toprule">616</td><td align="center">796</td> </tr> <tr class="Botrule Lrule Rrule Toprule"> <td>Viscosity (cP) @ 37°C</td><td align="center" class="Botrule Lrule Rrule Toprule">2.0</td><td align="center">3.0</td><td align="center" class="Botrule Lrule Rrule Toprule">4.7</td><td align="center">9.4</td> </tr> <tr class="Botrule Lrule Rrule Toprule"> <td>Viscosity (cP) @ 20°C</td><td align="center" class="Botrule Lrule Rrule Toprule">3.3</td><td align="center">5.1</td><td align="center" class="Botrule Lrule Rrule Toprule">8.8</td><td align="center">20.9</td> </tr> <tr class="Botrule Last Lrule Rrule Toprule"> <td>Specific Gravity @ 37°C</td><td align="center" class="Botrule Lrule Rrule Toprule">1.227</td><td align="center">1.281</td><td align="center" class="Botrule Lrule Rrule Toprule">1.339</td><td align="center">1.405</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"1\">\n<caption>\n<span>Table 5: Physicochemical Characteristics of ISOVUE</span>\n</caption>\n<colgroup>\n<col width=\"36*\"/>\n<col align=\"center\" width=\"13*\"/>\n<col align=\"center\" width=\"13*\"/>\n<col align=\"center\" width=\"13*\"/>\n<col align=\"center\" width=\"13*\"/>\n</colgroup>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First Lrule Rrule Toprule\">\n<td><span class=\"Bold\">Concentration (mg Iodine/mL) </span></td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">200</span></td><td align=\"center\"><span class=\"Bold\">250</span></td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">300</span></td><td align=\"center\"><span class=\"Bold\">370</span></td>\n</tr>\n<tr class=\"Botrule Lrule Rrule Toprule\">\n<td>Osmolality @ 37°C (mOsm/kg water) </td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">413</td><td align=\"center\">524</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">616</td><td align=\"center\">796</td>\n</tr>\n<tr class=\"Botrule Lrule Rrule Toprule\">\n<td>Viscosity (cP) @ 37°C</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">2.0</td><td align=\"center\">3.0</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">4.7</td><td align=\"center\">9.4</td>\n</tr>\n<tr class=\"Botrule Lrule Rrule Toprule\">\n<td>Viscosity (cP) @ 20°C</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">3.3</td><td align=\"center\">5.1</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">8.8</td><td align=\"center\">20.9</td>\n</tr>\n<tr class=\"Botrule Last Lrule Rrule Toprule\">\n<td>Specific Gravity @ 37°C</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">1.227</td><td align=\"center\">1.281</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">1.339</td><td align=\"center\">1.405</td>\n</tr>\n</tbody>\n</table></div>" }

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.

Following administration of ISOVUE, the degree of enhancement is related to the iodine concentration in the tissue of interest. However, the exposure-response relationships and time course of pharmacodynamic response of iopamidol have not been fully characterized.

Distribution

Plasma concentrations of iodine fall within 5 to 10 minutes due to distribution into the vascular and extracellular fluid compartments. Equilibration with the extracellular compartments is reached in about 10 minutes.

The apparent volume of distribution suggests that iopamidol is distributed evenly between blood and extracellular fluid. Iopamidol may be visualized in the renal parenchyma within 30 to 60 seconds following rapid intravenous administration. Iopamidol did not bind to serum or plasma proteins at 1 hour after administration.

Elimination

The plasma half-life is approximately 2 hours; the half-life is not dose dependent.

Metabolism

Iopamidol does not undergo significant metabolism, deiodination, or biotransformation.

Excretion

Iopamidol is excreted primarily through the kidneys. In patients with normal renal function, the cumulative urinary excretion for iopamidol, expressed as a percentage of administered intravenous dose, is approximately 35% to 40% at 60 minutes, 80% to 90% at 8 hours, and 90% or greater in the 72- to 96- hour period after administration. In patients with normal renal function, approximately 1% or less of the administered dose appears in cumulative 72- to 96-hour fecal samples.

Long-term studies in animals have not been performed with iopamidol to evaluate carcinogenic potential. No evidence of genetic toxicity was obtained in in vitro tests. In animal reproduction studies performed on rats, intravenously administered iopamidol did not induce adverse effects on fertility or general reproductive performance.

How Supplied

{ "type": "p", "children": [], "text": "\nHow Supplied\n" }

ISOVUE (iopamidol) injection is a clear, colorless to pale yellow solution available in the following presentations:

{ "type": "p", "children": [], "text": "\nISOVUE (iopamidol) injection is a clear, colorless to pale yellow solution available in the following presentations:" }

<div class="scrollingtable"><table border="1" width="751"> <colgroup align="center"> <col width="16*"/> <col width="15*"/> <col width="20*"/> <col width="15*"/> <col width="14*"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First Lrule Rrule Toprule"> <td><span class="Bold">Concentration (mg Iodine/mL) </span></td><td class="Botrule Lrule Rrule Toprule"><span class="Bold">Package Size</span></td><td><span class="Bold">Package Type </span></td><td class="Botrule Lrule Rrule Toprule"><span class="Bold">Sale Unit</span></td><td><span class="Bold">NDC</span></td> </tr> <tr class="Botrule Lrule Rrule Toprule"> <td>200</td><td class="Botrule Lrule Rrule Toprule">200 mL</td><td>Single-Dose Bottle </td><td class="Botrule Lrule Rrule Toprule">Carton of 10 </td><td>0270-1314-15</td> </tr> <tr class="Botrule Lrule Rrule Toprule"> <td>250</td><td class="Botrule Lrule Rrule Toprule">100 mL</td><td>Single-Dose Bottle </td><td class="Botrule Lrule Rrule Toprule">Carton of 10 </td><td>0270-1317-02</td> </tr> <tr class="Botrule Lrule Rrule Toprule"> <td rowspan="4">300</td><td class="Botrule Lrule Rrule Toprule">30 mL </td><td>Single-Dose Vial</td><td class="Botrule Lrule Rrule Toprule">Carton of 10 </td><td>0270-1315-25</td> </tr> <tr class="Botrule Lrule Rrule Toprule"> <td class="Botrule Lrule Rrule Toprule">50 mL</td><td>Single-Dose Vial</td><td class="Botrule Lrule Rrule Toprule">Carton of 10 </td><td>0270-1315-30</td> </tr> <tr class="Botrule Lrule Rrule Toprule"> <td class="Botrule Lrule Rrule Toprule">100 mL</td><td>Single-Dose Bottle </td><td class="Botrule Lrule Rrule Toprule">Carton of 10 </td><td>0270-1315-35</td> </tr> <tr class="Botrule Lrule Rrule Toprule"> <td class="Botrule Lrule Rrule Toprule">150 mL</td><td>Single-Dose Bottle </td><td class="Botrule Lrule Rrule Toprule">Carton of 10 </td><td>0270-1315-50</td> </tr> <tr class="Botrule Lrule Rrule Toprule"> <td class="Botrule Last Lrule Rrule Toprule" rowspan="5">370</td><td class="Botrule Lrule Rrule Toprule">50 mL</td><td>Single-Dose Vial</td><td class="Botrule Lrule Rrule Toprule">Carton of 10 </td><td>0270-1316-30</td> </tr> <tr class="Botrule Lrule Rrule Toprule"> <td class="Botrule Lrule Rrule Toprule">75 mL</td><td>Single-Dose Bottle </td><td class="Botrule Lrule Rrule Toprule">Carton of 10 </td><td>0270-1316-52</td> </tr> <tr class="Botrule Lrule Rrule Toprule"> <td class="Botrule Lrule Rrule Toprule">100 mL</td><td>Single-Dose Bottle </td><td class="Botrule Lrule Rrule Toprule">Carton of 10 </td><td>0270-1316-35</td> </tr> <tr class="Botrule Lrule Rrule Toprule"> <td class="Botrule Lrule Rrule Toprule">125 mL</td><td>Single-Dose Bottle </td><td class="Botrule Lrule Rrule Toprule">Carton of 10 </td><td>0270-1316-04</td> </tr> <tr class="Botrule Last Lrule Rrule Toprule"> <td class="Botrule Lrule Rrule Toprule">150 mL</td><td>Single-Dose Bottle </td><td class="Botrule Lrule Rrule Toprule">Carton of 10 </td><td>0270-1316-37</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"1\" width=\"751\">\n<colgroup align=\"center\">\n<col width=\"16*\"/>\n<col width=\"15*\"/>\n<col width=\"20*\"/>\n<col width=\"15*\"/>\n<col width=\"14*\"/>\n</colgroup>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First Lrule Rrule Toprule\">\n<td><span class=\"Bold\">Concentration (mg Iodine/mL) </span></td><td class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">Package Size</span></td><td><span class=\"Bold\">Package Type </span></td><td class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">Sale Unit</span></td><td><span class=\"Bold\">NDC</span></td>\n</tr>\n<tr class=\"Botrule Lrule Rrule Toprule\">\n<td>200</td><td class=\"Botrule Lrule Rrule Toprule\">200 mL</td><td>Single-Dose Bottle </td><td class=\"Botrule Lrule Rrule Toprule\">Carton of 10 </td><td>0270-1314-15</td>\n</tr>\n<tr class=\"Botrule Lrule Rrule Toprule\">\n<td>250</td><td class=\"Botrule Lrule Rrule Toprule\">100 mL</td><td>Single-Dose Bottle </td><td class=\"Botrule Lrule Rrule Toprule\">Carton of 10 </td><td>0270-1317-02</td>\n</tr>\n<tr class=\"Botrule Lrule Rrule Toprule\">\n<td rowspan=\"4\">300</td><td class=\"Botrule Lrule Rrule Toprule\">30 mL </td><td>Single-Dose Vial</td><td class=\"Botrule Lrule Rrule Toprule\">Carton of 10 </td><td>0270-1315-25</td>\n</tr>\n<tr class=\"Botrule Lrule Rrule Toprule\">\n<td class=\"Botrule Lrule Rrule Toprule\">50 mL</td><td>Single-Dose Vial</td><td class=\"Botrule Lrule Rrule Toprule\">Carton of 10 </td><td>0270-1315-30</td>\n</tr>\n<tr class=\"Botrule Lrule Rrule Toprule\">\n<td class=\"Botrule Lrule Rrule Toprule\">100 mL</td><td>Single-Dose Bottle </td><td class=\"Botrule Lrule Rrule Toprule\">Carton of 10 </td><td>0270-1315-35</td>\n</tr>\n<tr class=\"Botrule Lrule Rrule Toprule\">\n<td class=\"Botrule Lrule Rrule Toprule\">150 mL</td><td>Single-Dose Bottle </td><td class=\"Botrule Lrule Rrule Toprule\">Carton of 10 </td><td>0270-1315-50</td>\n</tr>\n<tr class=\"Botrule Lrule Rrule Toprule\">\n<td class=\"Botrule Last Lrule Rrule Toprule\" rowspan=\"5\">370</td><td class=\"Botrule Lrule Rrule Toprule\">50 mL</td><td>Single-Dose Vial</td><td class=\"Botrule Lrule Rrule Toprule\">Carton of 10 </td><td>0270-1316-30</td>\n</tr>\n<tr class=\"Botrule Lrule Rrule Toprule\">\n<td class=\"Botrule Lrule Rrule Toprule\">75 mL</td><td>Single-Dose Bottle </td><td class=\"Botrule Lrule Rrule Toprule\">Carton of 10 </td><td>0270-1316-52</td>\n</tr>\n<tr class=\"Botrule Lrule Rrule Toprule\">\n<td class=\"Botrule Lrule Rrule Toprule\">100 mL</td><td>Single-Dose Bottle </td><td class=\"Botrule Lrule Rrule Toprule\">Carton of 10 </td><td>0270-1316-35</td>\n</tr>\n<tr class=\"Botrule Lrule Rrule Toprule\">\n<td class=\"Botrule Lrule Rrule Toprule\">125 mL</td><td>Single-Dose Bottle </td><td class=\"Botrule Lrule Rrule Toprule\">Carton of 10 </td><td>0270-1316-04</td>\n</tr>\n<tr class=\"Botrule Last Lrule Rrule Toprule\">\n<td class=\"Botrule Lrule Rrule Toprule\">150 mL</td><td>Single-Dose Bottle </td><td class=\"Botrule Lrule Rrule Toprule\">Carton of 10 </td><td>0270-1316-37</td>\n</tr>\n</tbody>\n</table></div>" }

Storage and Handling

{ "type": "p", "children": [], "text": "\nStorage and Handling\n" }

Store at 20°C to 25°C (68°F to 77°F) [See USP controlled room temperature]. Protect from light.

{ "type": "p", "children": [], "text": "\nStore at 20°C to 25°C (68°F to 77°F) [See USP controlled room temperature]. Protect from light." }

Hypersensitivity Reactions

{ "type": "p", "children": [], "text": "\nHypersensitivity Reactions\n" }

Advise the patient concerning the risk of hypersensitivity reactions that can occur both during and after ISOVUE 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 (5.2)].

{ "type": "p", "children": [], "text": "\nAdvise the patient\nconcerning the risk of hypersensitivity reactions that can occur both\nduring and after ISOVUE administration. Advise the patient to report\nany signs or symptoms of hypersensitivity reactions during the procedure\nand to seek immediate medical attention for any signs or symptoms\nexperienced after discharge [see Warnings and Precautions\n(5.2)].\n" }

Advise patients to inform their physician if they develop a rash after receiving ISOVUE [see Warnings and Precautions (5.11)].

{ "type": "p", "children": [], "text": "\nAdvise patients to inform their physician\nif they develop a rash after receiving ISOVUE [see Warnings\nand Precautions (5.11)].\n" }

Acute Kidney Injury

{ "type": "p", "children": [], "text": "\nAcute\nKidney Injury\n" }

Advise the patient concerning appropriate hydration to decrease the risk of contrast induced kidney injury [see Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "\nAdvise the patient concerning appropriate hydration to decrease the\nrisk of contrast induced kidney injury [see Warnings and Precautions\n(5.3)].\n" }

Extravasation

{ "type": "p", "children": [], "text": "\nExtravasation\n" }

If extravasation occurs during injection, advise patients to seek medical care for progression of symptoms [see Warnings and Precautions (5.6)].

{ "type": "p", "children": [], "text": "\nIf extravasation occurs during\ninjection, advise patients to seek medical care for progression of\nsymptoms [see Warnings and Precautions (5.6)].\n" }

Thyroid Dysfunction

{ "type": "p", "children": [], "text": "\nThyroid Dysfunction\n" }

Advise parents/caregivers about the risk of developing thyroid dysfunction after ISOVUE administration. Advise parents/caregivers about when to seek medical care for their child to monitor for thyroid function [see Warnings and Precautions (5.8)].

{ "type": "p", "children": [], "text": "\nAdvise parents/caregivers about the risk of\ndeveloping thyroid dysfunction after ISOVUE administration. Advise\nparents/caregivers about when to seek medical care for their child\nto monitor for thyroid function [see Warnings and Precautions\n(5.8)].\n" }

Lactation

{ "type": "p", "children": [], "text": "\nLactation\n" }

Advise a lactating woman that interruption of breastfeeding is not necessary, however, to minimize exposure to a breastfed infant, a lactating woman may consider pumping and discarding breast milk for 10 hours after ISOVUE administration [see Use in Specific Populations (8.2)].

{ "type": "p", "children": [], "text": "\nAdvise a lactating woman that\ninterruption of breastfeeding is not necessary, however, to minimize\nexposure to a breastfed infant, a lactating woman may consider pumping\nand discarding breast milk for 10 hours after ISOVUE administration [see Use in Specific Populations (8.2)].\n" }

Manufactured for:Bracco Diagnostic Inc.Monroe Township, NJ 08831 Manufactured by: BIPSO GmbH78224 Singen (Germany) ISOVUE is a registered trademark of Bracco Diagnostics Inc.

{ "type": "p", "children": [], "text": "\nManufactured for:Bracco Diagnostic\nInc.Monroe Township, NJ 08831\nManufactured\nby: BIPSO GmbH78224 Singen (Germany)\nISOVUE is a registered trademark of Bracco Diagnostics\nInc." }

Revised December 2024

{ "type": "p", "children": [], "text": "\nRevised\nDecember 2024" }

Isovue 200: 200mL vial labelNDC 0270-1314-15

{ "type": "p", "children": [], "text": "\nIsovue 200: 200mL vial labelNDC 0270-1314-15" }

Isovue 250: 10x 100mL Box labelNDC 0270-1317-02

{ "type": "p", "children": [], "text": "\nIsovue 250: 10x 100mL Box labelNDC 0270-1317-02" }

Isovue 300: 100mL Box labelNDC 0270-1315-35

{ "type": "p", "children": [], "text": "\nIsovue 300: 100mL Box labelNDC 0270-1315-35" }

Isovue 370: 75mL Bottle labelNDC 0270-1316-52

{ "type": "p", "children": [], "text": "\nIsovue 370: 75mL Bottle labelNDC 0270-1316-52" }