FDA label 8a81e0bf-8693-49b0-9f9e-e5b3352dcaaf

NOT FOR INTRATHECAL USE

WARNINGS Severe Adverse Events-lnadvertent Intrathecal Administration Serious adverse reactions have been reported due to the inadvertent intrathecal administration of iodinated contrast media that are not indicated for intrathecal use. These serious adverse reactions include: death, convulsions, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, seizures, rhabdomyolysis, hyperthermia, and brain edema. Special attention must be given to insure that this drug product is not inadvertently administered intrathecally. General Nonionic iodinated contrast media inhibit blood coagulation, in vitro , less than ionic contrast media. Clotting has been reported when blood remains in contact with syringes containing nonionic contrast media. Serious, rarely fatal, thromboembolic events causing myocardial infarction and stroke have been reported during angiographic procedures with both ionic and nonionic contrast media. Therefore, meticulous intravascular administration technique is necessary, particularly during angiographic procedures, to minimize thromboembolic events. Numerous factors, including length of procedure, catheter and syringe material, underlying disease state, and concomitant medications may contribute to the development of thromboembolic events. For these reasons, meticulous angiographic techniques are recommended including close attention to guidewire and catheter manipulation, use of manifold systems and/or three way stopcocks, frequent catheter flushing with heparinized saline solutions, and minimizing the length of the procedure. The use of plastic syringes in place of glass syringes has been reported to decrease but not eliminate the likelihood of in vitro clotting. Caution must be exercised in patients with severely impaired renal function, those with combined renal and hepatic disease, or anuria, particularly when larger or repeat doses are administered. Radiopaque diagnostic contrast agents are potentially hazardous in patients with multiple myeloma or other paraproteinemia, particularly in those with therapeutically resistant anuria. Myeloma occurs most commonly in persons over age 40. Although neither the contrast agent nor dehydration has been proved separately to be the cause of anuria in myelomatous patients, it has been speculated that the combination of both may be causative. The risk in myelomatous patients is not a contraindication; however, special precautions are required. Contrast media may promote sickling in individuals who are homozygous for sickle cell disease when injected intravenously or intraarterially. Administration of radiopaque materials to patients known or suspected of having pheochromocytoma should be performed with extreme caution. If, in the opinion of the physician, the possible benefits of such procedures outweigh the considered risks, the procedures may be performed; however, the amount of radiopaque medium injected should be kept to an absolute minimum. The blood pressure should be assessed throughout the procedure and measures for treatment of a hypertensive crisis should be available. These patients should be monitored very closely during contrast enhanced procedures. Reports of thyroid storm following the use of iodinated radiopaque diagnostic agents in patients with hyperthyroidism or with an autonomously functioning thyroid nodule suggest that this additional risk be evaluated in such patients before use of any contrast medium. Thyroid Dysfunction in Pediatric Patients 0 to 3 Years of Age : Thyroid dysfunction characterized by hypothyroidism or transient thyroid suppression has been reported after both single exposure and multiple exposures to iodinated contrast media in pediatric patients 0 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 ICM 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 ICM, individualize thyroid function monitoring based on underlying risk factors, especially in term and preterm neonates. Severe Cutaneous Adverse Reactions : 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 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.

ADVERSE REACTIONS Adverse reactions following the use of iopamidol are usually mild to moderate, self-limited, and transient. In angiocardiography (597 patients), the adverse reactions with an estimated incidence of one percent or higher are: hot flashes 3.4%; angina pectoris 3.0%; flushing 1.8%; bradycardia 1.3%; hypotension 1.0%; hives 1.0%. In a clinical trial with 76 pediatric patients undergoing angiocardiography, 2 adverse reactions (2.6%) both remotely attributed to the contrast media were reported. Both patients were less than 2 years of age, both had cyanotic heart disease with underlying right ventricular abnormalities and abnormal pulmonary circulation. In one patient pre-existing cyanosis was transiently intensified following contrast media administration. In the second patient pre-existing decreased peripheral perfusion was intensified for 24 hours following the examination. (See “PRECAUTIONS” Section for information on high risk nature of these patients.) Intravascular injection of contrast media is frequently associated with the sensation of warmth and pain especially in peripheral arteriography and venography; pain and warmth are less frequent and less severe with ISOVUE (Iopamidol Injection) than with diatrizoate meglumine and diatrizoate sodium injection. The following table of incidence of reactions is based on clinical studies with ISOVUE in about 2246 patients. Adverse Reactions Estimated Overall Incidence System > 1% ≤ 1% Cardiovascular none tachycardia hypotension hypertension myocardial ischemia circulatory collapse S-T segment depression bigeminy extrasystoles ventricular fibrillation angina pectoris bradycardia transient ischemic attack thrombophlebitis Nervous pain (2.8%) burning sensation (1.4%) vasovagal reaction tingling in arms grimace faintness Digestive nausea (1.2%) vomiting anorexia Respiratory none throat constriction dyspnea pulmonary edema Skin and Appendages none rash urticaria pruritus flushing Body as a Whole hot flashes (1.5%) headache fever chills excessive sweating back spasm Special Senses warmth (1.1%) taste alterations nasal congestion visual disturbances Urogenital none urinary retention Regardless of the contrast agent employed, the overall estimated incidence of serious adverse reactions is higher with coronary arteriography than with other procedures. Cardiac decompensation, serious arrhythmias, or myocardial ischemia or infarction have been reported with ISOVUE and may occur during coronary arteriography and left ventriculography . Following coronary and ventricular injections, certain electrocardiographic changes (increased QTc, increased R-R, T-wave amplitude) and certain hemodynamic changes (decreased systolic pressure) occurred less frequently with ISOVUE (Iopamidol Injection) than with diatrizoate meglumine and diatrizoate sodium injection; increased LVEDP occurred less frequently after ventricular iopamidol injections. In aortography , the risks of procedures also include injury to the aorta and neighboring organs, pleural puncture, renal damage including infarction and acute tabular necrosis with oliguria and anuria, accidental selective filling of the right renal artery during the translumbar procedure in the presence of preexisting renal disease, retroperitoneal hemorrhage from the translumbar approach, and spinal cord injury and pathology associated with the syndrome of transverse myelitis. The following adverse reactions have been reported for Iopamidol: Cardiovascular : arrhythmia, arterial spasms, flushing, vasodilation, chest pain, cardiopulmonary arrest; Nervous System : confusion, paresthesia, dizziness, temporary cortical blindness, temporary amnesia, convulsions, paralysis, coma; Respiratory : increased cough, sneezing, asthma, apnea, laryngeal edema, chest tightness, rhinitis; Skin and Appendages : injection site pain usually due to extravasation and/or erythematous swelling, pallor, periorbital edema, facial edema; Urogenital : pain, hematuria; Special Senses : watery itchy eyes, lacrimation, conjunctivitis; Musculoskeletal : muscle spasm, involuntary leg movement; Body as a whole : tremors, malaise, anaphylactoid reaction (characterized by cardiovascular, respiratory and cutaneous symptoms), pain; Digestive : severe retching and choking, abdominal cramps. Some of these may occur as a consequence of the procedure. Other reactions may also occur with the use of any contrast agent as a consequence of the procedural hazard; these include hemorrhage or pseudoaneurysms at the puncture site, brachial plexus palsy following axillary artery injections, chest pain, myocardial infarction, and transient changes in hepatorenal chemistry tests. Arterial thrombosis, displacement of arterial plaques, venous thrombosis, dissection of the coronary vessels and transient sinus arrest are rare complications. General Adverse Reactions To Contrast Media Reactions known to occur with parenteral administration of iodinated ionic contrast agents (see the listing below) are possible with any nonionic agent. Approximately 95 percent of adverse reactions accompanying the use of other water-soluble intravascularly administered contrast agents are mild to moderate in degree. However, life-threatening reactions and fatalities, mostly of cardiovascular origin, have occurred. Reported incidences of death from the administration of other iodinated contrast media range from 6.6 per 1 million (0.00066 percent) to 1 in 10,000 patients (0.01 percent). Most deaths occur during injection or 5 to 10 minutes later, the main feature being cardiac arrest with cardiovascular disease as the main aggravating factor. Isolated reports of hypotensive collapse and shock are found in the literature. The incidence of shock is estimated to be 1 out of 20,000 (0.005 percent) patients. Adverse reactions to injectable contrast media fall into two categories: chemotoxic reactions and idiosyncratic reactions. Chemotoxic reactions result from the physicochemical properties of the contrast medium, the dose, and the speed of injection. All hemodynamic disturbances and injuries to organs or vessels perfused by the contrast medium are included in this category. Experience with iopamidol suggests there is much less discomfort (e.g. pain and/or warmth) with peripheral arteriography. Fewer changes are noted in ventricular function after ventriculography and coronary arteriography. Idiosyncratic reactions include all other reactions. They occur more frequently in patients 20 to 40 years old. Idiosyncratic reactions may or may not be dependent on the amount of drug injected, the speed of injection, the mode of injection, and the radiographic procedure. Idiosyncratic reactions are subdivided into minor, intermediate, and severe. The minor reactions are self-limited and of short duration; the severe reactions are life-threatening and treatment is urgent and mandatory. The reported incidence of adverse reactions to contrast media in patients with a history of allergy is twice that for the general population. Patients with a history of previous reactions to a contrast medium are three times more susceptible than other patients. However, sensitivity to contrast media does not appear to increase with repeated examinations. Most adverse reactions to intravascular contrast agents appear within one to three minutes after the start of injection, but delayed reactions may occur. Delayed reactions, usually involving the skin, may uncommonly occur within 2-3 days (range 1-7 days) after the administration of contrast (see PRECAUTIONS-General ). Delayed allergic reactions are more frequent in patients treated with immunostimulants, such as interleukin-2. In addition to the adverse drug reactions reported for iopamidol, the following additional adverse reactions have been reported with the use of other intravascular contrast agents and are possible with the use of any water-soluble iodinated contrast agent: Cardiovascular: cerebral hematomas, petechiae; Hematologic: neutropenia; Urogenital: osmotic nephrosis of proximal tubular cells, renal failure; Special Senses: conjunctival chemosis with infection; Endocrine: hyperthyroidism, hypothyroidism; Skin and Subcutaneous Tissue Disorders: Skin necrosis; Reactions range from mild (e.g. rash, erythema, pruritus, urticaria and skin discoloration) to severe: [e.g. Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS)].

<table ID="t565432" width="100%"><colgroup><col width="33%"/><col width="33%"/><col width="34%"/></colgroup><tbody><tr styleCode="First Toprule"><td colspan="3" align="center"><content styleCode="bold">Adverse Reactions</content></td></tr><tr styleCode="Toprule"><td/><td align="left">Estimated Overall Incidence</td><td/></tr><tr><td>System</td><td>&gt; 1%</td><td>&#x2264; 1%</td></tr><tr><td styleCode="Toprule" valign="top">Cardiovascular</td><td styleCode="Toprule" valign="top">none</td><td styleCode="Toprule">tachycardia hypotension hypertension myocardial ischemia circulatory collapse S-T segment depression bigeminy extrasystoles ventricular fibrillation angina pectoris bradycardia transient ischemic attack thrombophlebitis</td></tr><tr><td valign="top">Nervous</td><td valign="top">pain (2.8%) burning sensation (1.4%)</td><td>vasovagal reaction tingling in arms grimace faintness</td></tr><tr><td valign="top">Digestive</td><td valign="top">nausea (1.2%)</td><td>vomiting anorexia</td></tr><tr><td valign="top">Respiratory</td><td valign="top">none</td><td>throat constriction dyspnea pulmonary edema</td></tr><tr><td valign="top">Skin and Appendages</td><td valign="top">none</td><td>rash urticaria pruritus flushing</td></tr><tr><td valign="top">Body as a Whole</td><td valign="top">hot flashes (1.5%)</td><td>headache fever chills excessive sweating back spasm</td></tr><tr><td valign="top">Special Senses</td><td valign="top">warmth (1.1%)</td><td>taste alterations nasal congestion visual disturbances</td></tr><tr styleCode="Botrule Last"><td valign="top">Urogenital</td><td valign="top">none</td><td>urinary retention</td></tr></tbody></table>